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Charge transfer complexes (CTCs) are created when an electron donor reacts with an electron acceptor. Then, a new compound (CTC) is produced by forming hydrogen bonds or charge transfer. This review examines the production, features, and reported CTCs. This highlights recent advancements in utilizing CTCs across different sectors and explores their potential in upcoming uses, as well as the obstacles that must be overcome to create new CTCs and investigate their uses. These complexes have the characteristics of distinctive molecules that differ from traditional ionic, covalent, and coordination bonding. The review opening part summarizes CTCs, highlighting the connection between donors and acceptors in creating new molecular structures. Furthermore, this paper delves into applying density functional theory in examining intermolecular CTCs, emphasizing estimating structures, binding energies, and CT transitions. The review also discusses the different types of CTCs, such as protonic CTCs or hydrogen-bonded charge-transfer (HB-CT) complexes, and the thermodynamics involved in the process, which governs the relationship between the donor and the acceptor. Moreover, the paper emphasizes the diverse uses of CTCs in biological fields, thermoelectrics, photoconductors, light detectors, photocatalysts, material science, medicine, optoelectronic devices, NLO materials, chemo-sensors, electrical conductors, surface chemistry, molecular nanodevices, and photographic technology among other applications.

Background: Migraine is a multifactorial disorder in which headaches usually last from 4 to 72 hours. Sphenopalatine ganglion blockage (SPGB) has been used as a minimal invasive method for alleviating pain in severe headaches. Aim: We discuss our technique of performing SPGB and assessment of pain relief, before and after its application. We have also made an effort to study the prevalence of depression and quality of life by scoring patients of chronic migraine and assess how SPGB helps to reduce the incidence of depression and quality of life. Material and methods: Observational and interventional clinical study. Pain scores were recorded using the numeric rating score (NRS) prior to and 15 minutes after SPGB. Patients were also assessed for prevalence of depression and quality of life – based on 2 questionnaires (PHQ-9 and WHO-5) – before and 2 weeks after performing SPGB. Results: After intervention by SPGB, there was a statistically significant (p value <0.001) reduction of pain, the mean scores reduced from 7.41 +/- 2 to 2.02 +/- 1.57. Improvement in quality of life and a statistically significant reduction of depression scores after intervention were seen. The prevalence of depression significantly decreased after SPGB. Conclusion: SPGB is a minimally invasive, effective, focused and practical treatment for migraines. Improved quality of life and likelihood of reduction of depressive symptoms after SPGB will also alter the overall well-being of these patients.

Background:Pulmonary blastomas are rare and aggressive lung tumors that make up 0.25-0.5% of primary lung cancers and have a poor prognosis. They resemble tissue from the fetal lung and have both mesenchymal and epithelial components in their biphasic histology. Recent changes in classification by the World Health Organization (WHO) have separated well differentiated fetal adenocarcinoma (WDFA) and malignant pleuropulmonary blastoma (PPB) from classic biphasic pulmonary blastoma (BPB). This reclassification, along with their rarity, complicates the understanding of their epidemiology and clinical characteristics. The text discusses a clinical case and literature review, highlighting treatment challenges and the reliance on limited observational data and case reports for guidance.Key Clinical Message:This report aims to underscore the significance of pulmonary blastoma, a rare entity with limited literature, by contributing insights into its clinical features, diagnostic approaches, and treatment modalities. Additionally, it emphasizes the critical role of a multidisciplinary approach in the effective management of this complex and challenging disease.Case Presentation:A 41 years old male presented to outpatient department with the chief complaints of right sided chest pain since 2 months and mild breathlessness on exertion since 1 month .He had no others complaints of fever, cough, weight loss, anorexia, haemoptysis, paroxysmal nocturnal dyspnea but with time his disease progressed and he developed mild cough, pleural effusion, hypoxia. He was a former smoker for about 15 pack years. He also used to take alcohol occasionally 5 to 6 years back but then he stopped completely. He was a known case pf HIV diagnosed back in 2019 under his treatment on ARV with undetectable viral load since 07/02/2023. He got spontaneous pneumothorax in the left lung at the age of 23 for which he was treated via chest tube insertion. He had RTA back in 2005. On Examination he looked well, no palpable lymph nodes, no oral thrush, had no clubbing, he had a clear chest but absent breath sounds on the right side on auscultation.Investigations and Treatment:A mass was seen in the right upper and middle lobe on a chest radiograph. [see figure 1 and figure 2] A subsequent CT of the chest showed a right upper lobe pleural based mass. [see figure 4 and figure 5]A core biopsy using CT guidance of the right lung mass was performed which gave an impression of adenocarcinoma of the lung initially. A biopsy performed a month later revealed a scanty focus of a malignant neoplasm composed of nests of atypical, hyperchromatic cells. Adenocarcinoma with solid and acinar patterns as well as adenocarcinoma with acinar patterns and mesenchymal components (round and spindle-shaped cells) were all made more likely by morphology.Due to limited nature, prognostic indicators and molecular tests could not be conducted.A repeated biopsy revealed a malignant neoplasm with a biphasic morphology, comprising a hypercellular spindled stroma, desmin negative, SS18-SSX negative and B catenin focal positive, features favoring pulmonary blastoma. PET CT scan showed a large heterogeneously enhancing, lobulated right lung mass involving the right upper and middle lobes with some internal component of necrosis that appeared photopenic. The mass measured 13.4 x 7.6 x 11.9 cm [AP x TR x CC], SUV 12.9. It was invading the chest wall anteriorly at the level adjacent to the right 3rd rib without any obvious local bone erosion. No size significant or hypermetabolic mediastinal lymphadenopathy was appreciated. No suspicious pulmonary nodules in the rest of the lungs. No pleural effusion was seen. Bilateral axillary recesses appeared unremarkable. Sections through the brain parenchyma showed normal physiological tracer uptake without any focal abnormality. No significant and metabolically active bilateral cervical lymphadenopathy was appreciated. A tiny right supraclavicular node was appreciated which measured 0.5cm and was non-avid. Liver, spleen, pancreas, bilateral kidneys and adrenals appeared unremarkable. There was no significant and metabolically active abdominopelvic lymphadenopathy. Physiological FDG uptake was noted in the bowel without any locality.Bilateral inguinal recesses were clear. Homogeneous tracer distribution was noted throughout the visualized skeleton. No destructive osseous lesions. In short no hypermetabolic locoregional or distant metastasis. A repeated CT chest and abdomen with contrast showed interval increase, measuring 19 x 11 cm in the axial plane and 27 cm in its CC dimension. Previously, it measured 17 x 11 cm, and 17 cm respectively.It displayed several enhancing septations and a mixed solid cystic look.The right hemidiaphragm and liver were being inferiorly displaced by the mass that was spreading across the midline with a mediastinal shift to the left. SVC and IVC were pushed by the mass but they were patent. The right lung was encased by the mass, its upper lobe was relatively aerated while middle and lower lobes collapsed due to mass effect. The left lung showed normal aeration. No suspicious pulmonary nodules seen. No pneumothorax noted. This interval increase in the size of the mass indicated disease aggressiveness and progression. Involvement of the mediastinum made it T4 disease. Predicted stage was T4 N0 M0. Serial CT scans performed subsequently showed further progression with increasing areas of necrosis, increasing left cardiomediastinal shift and infiltration into the right pulmonary vein. There was also interval development of multifocal patches of ground glass appearance in the left lung lower lobe. The patient was initially assessed for resection of the mass and it was found to be unresectable. He was then started on chemotherapy (Carboplatin/Paclitaxel), twelve cycles of which were completed until the patient had stable disease on CT. He was offered surgery but explained that the tumor was borderline resectable.Conclusion and Results:A month later the patient developed worsening symptoms and signs of progression on CT after which XRT (chest wall) was planned. The patient was later put on symptomatic treatment and end of life care pathway owing to deteriorating clinical condition.DiscussionPulmonary blastoma is a rare and aggressive neoplasm of the lung, accounting for approximately 0.5% of all primary lung tumors.[1] They have morphological similarities to lung tissue from fetuses before four months of pregnancy.[2] Despite its rare occurrence, existence of Pulmonary blastoma is well documented.[3] PB was initially characterized by Barnett and Barnard in 1945 under the term ”embryonoma.”[4,5] In 1961, Spencer named the cancer due to the resemblance of its microscopic appearance to that of fetal lung tissue during the 10–16 week stage of development, known as the paraadenomal stage of lung development.[6,7]Spencer was the first to refer to the tumor as ”pulmonary blastoma,” assuming it was the pulmonary equivalent of nephroblastoma, and he recorded three occurrences.[6] An epithelial type of pulmonary blastoma with malignant yet well-organized glandular epithelium displaying embryonic traits was more recently reported by Kradin et al.8 and Kodama et al.9. The latter group referred to this tumor as well-differentiated adenocarcinoma that mimics fetal lung tubules.[9] Originally, pulmonary blastoma was described as a lung tumor that combined elements of sarcoma and carcinoma, with glandular and mesenchymal components that resemble embryos. Pulmonary blastoma was originally defined as a neoplasm of the lung.According to 2015 World Health Organization (WHO) Classification, PB has been classified under Pulmonary Sarcomatoid Carcinoma which is a heterogeneous category of Primary Lung Cancer.[10]A variety of malignant epithelial tumours (carcinomas) that histologically resemble sarcomas and either have or do not have the typical characteristics of non-small cell lung cancer (NSCLC) are referred to as pulmonary sarcomatoid carcinoma (PSC).[10] Therefore, this rare category of pulmonary neoplasms encompasses pleomorphic carcinoma, spindle cell carcinoma, giant cell carcinoma, pulmonary blastoma, and carcinosarcoma.[10] Childhood lung tumors are subdivided into 3 subtypes pulmonary blastoma, fetal adenocarcinoma, and pleuropulmonary blastoma (PPB).[11] The presence of both malignant and immature epithelial components is a characteristic of fetal adenocarcinomas.[11] In contrast, pleuropulmonary blastoma is defined by a malignant and immature mesenchymal proliferation.[11] The blastoma exhibits biphasic features, comprising both mesenchymal and epithelial malignant immature components that resemble lung tissue of 10 to 16 weeks of gestation.[11]Clinical Presenation:Patient usually presents with complaints of cough, hemoptysis, dyspnea, chest pain occurring because of the mass compressing the bronchi or pleura, fever, weight loss and recurrent pneumonia.[3,12] Occasionally spontaneous pneumothorax and neurological symptoms can develop too.[12] The tumors are frequently discovered by chance on chest radiographs, and about 40% of people with this illness have no symptoms.[3,12] Clinical evaluations may show reduced breath sounds in specific areas or other effects associated with cigarette smoking, with more than 80% of cases linked to a smoking history or asbestos exposure. The review by Van Loo indicates that the average age of CBPB patients is 39 years, and the male-to-female ratio is 1.5:1. [12]Diagnosis:Laboratory investigation abnormalities have been infrequent and non-specific, and there is no existing literature detailing specific laboratory findings associated with pulmonary blastoma. Pulmonary blastoma commonly appears as a large, well-defined unilateral mass in the peripheral lung, as noted in studies by Lee[13] and Koss et al.[3]Due to its location, a tissue diagnosis via bronchoscopy is only possible in about 25% of cases.[3] However, these tumors can be effectively visualized on thoracic ultrasound, with imaging results that align with CT findings.[14]Typical imaging characteristics include round or oval solid masses with smooth edges and lobed borders, usually without ”burr” formation.[15] Tumor invasion into adjacent structures can lead to complications such as obstructive pneumonia, pleural effusion, or atelectasis, complicating diagnosis and potentially leading to misdiagnosis in clinical practice.[15]Pulmonary blastoma on CT scans is identified by its dense and vesicular structure, which shows varying contrast uptake and features central necrosis.[12] It’s unclear how PET-CT is used to stage pulmonary blastoma, although some cases support their findings in terms of pathological staging. Due to the complex histology, preoperative diagnoses succeed in only about one-third of cases.[1] It’s critical to differentiate pulmonary blastoma from malignant tumors, such as primary and metastatic lung malignancies, as well as benign diseases like pleural fibroma and hamartoma.[16] Immunohistochemical staining is crucial for diagnosing pulmonary blastoma (PB). Tumor cells in the epithelial component test positive for keratin, epithelial membrane antigen, and TTF-1. Neuroendocrine cells within the tumor express CD56, Syn, or CgA. β-catenin shows nucleus-positive staining in glands and morula bodies, while vimentin is positive in mesenchymal components, with additional specific markers potentially found in heterodifferentiated areas.[15] In the case presented above, biopsy showed beta-catenin focal positivity as well owing to pulmonary blastoma diagnosis.Histology:Microscopically, the epithelial components of pulmonary blastoma (PB) resemble those of fetal lung tissue from 11 to 18 weeks of gestation, characterized by branched or back-to-back glandular hyperplasia, columnar cells with reduced cytoplasm, and small, uniform, round to oval nuclei with minimal atypia. Morula bodies are present in approximately 40% of PB cases.[15] The mesenchymal differentiation features include primitive oval or spindle cells, with allogenic differentiation, such as skeletal muscle, bone, and cartilage, observed in about 25% of cases. Occasional nuclear polymorphism and nuclear fissions may be noted. Additionally, adenocarcinoma or poorly differentiated carcinoma areas can be found in 30% to 50% of PB patients.[15,17]Management:Currently, there is no standard management for pulmonary blastoma (PB). Patients may benefit from a combination of surgery, radiotherapy, and chemotherapy. Surgical resection is typically the primary treatment for localized cases. Similar to non-small cell lung cancer (NSCLC), lobectomy is the most commonly performed surgical procedure for Pulmonary Blastoma patients.[18,19,20] For patients with late-stage disease, a comprehensive treatment strategy may be considered, incorporating surgery, chemotherapy, and radiotherapy.[21] While no single agent has been proven to be more effective than others, cisplatin is commonly utilized due to its effectiveness against primitive tumors.[16] The effectiveness of adjuvant therapy has not been confirmed through clinical trials; however, several case reports indicate positive outcomes with the use of adjuvant chemotherapy, either alone or in combination with radiotherapy.[22] A literature review has suggested that a regimen of cisplatin and etoposide may be suitable for adjuvant chemotherapy. [23] In a more recent study by Lewis et al. (2018), two patients who underwent surgical treatment received four cycles of adjuvant cisplatin-based chemotherapy followed by thoracic radiation, and both patients experienced long-term survival[24]. Metastasis occurs in about 43% of cases, frequently affecting the brain, mediastinum, pleura, diaphragm, liver, soft tissues in the limbs, submandibular glands, scrotum, and ovaries.[23,24] In the context of metastatic disease, chemotherapy is the primary treatment option; however, there are no established guidelines for specific regimens. Reviews by Cutler et al. (1998) [24] and more recently by Lewis et al. (2018) [25] have examined cases of patients who underwent chemotherapy. Initially, single-agent chemotherapy was attempted but yielded no clinical or objective responses.[23] Vila et al. were pioneers in using combination chemotherapy with chlorambucil and methotrexate in 1973.[25] Over the years, various cytotoxic regimens have been employed, including cisplatin-etoposide, with or without ifosfamide, as well as cyclophosphamide and vincristine-based treatments. [22] Other commonly used chemotherapeutic agents include carboplatin, doxorubicin, and paclitaxel. [22] There are only a limited number of reports on the molecular alterations found in PB, and even fewer that are suitable for targeted therapies. [22] Two cases have been documented where the tumor exhibited a ROS1 rearrangement. In the first case, fluorescence in situ hybridization (FISH) revealed a ROS1 rearrangement in 7 out of 50 tumor cells (14%).[26] In the second case, the patient had a detectable CD74–ROS1 rearrangement and showed a positive response to crizotinib, presenting a new treatment option for PB.[27] Evidence regarding other molecular alterations is still limited; however, in the absence of established therapies and considering the adenocarcinoma component of the tumor, it is reasonable to investigate potential targetable mutations.[28] Additionally, while some cases of PB have shown high expression of PD-L1, there have been no published studies on the use of immunotherapeutic agents for this condition.[29]Prognosis:The prognosis for pulmonary blastoma is generally poor, with two-thirds of patients dying within two years and a five-year survival rate of only 16%.[16] Tumor size at diagnosis is a key factor influencing prognosis, with tumors smaller than 5 cm associated with better outcomes.[16] Poor prognosis is also linked to tumor metastasis and recurrence despite surgical resection.[16] Notably, 43% of tumors recur within the first year, often spreading to locations such as the brain and mediastinum.[3] Recurrence typically occurs within the first year following diagnosis or not at all.[30]Conclusion:We present a case of classic biphasic pulmonary blastoma, a rare type of lung cancer that typically affects younger patients and is linked to a poorer outcome compared to more common lung cancers. Pulmonary blastoma is an infrequent and aggressive cancer characterized by a poor outlook. Its rapid growth and biphasic nature complicate diagnosis, and any delays in identifying the condition can adversely impact patient outcomes. The absence of a specific treatment for this cancer poses a significant challenge, as selecting the right therapeutic agents is complicated by its intricate structure, which requires a combination of therapies targeting different components. Moreover, the rarity of this cancer complicates the establishment of an effective treatment plan. As a result, treatment regimens must be tailored to the individual needs of each patient. Pulmonary blastoma (PB) displays distinctive microscopic characteristics reminiscent of fetal lung tissue at 11 to 18 weeks of gestation. Key features include branched glandular hyperplasia and columnar cells with small uniform, round to oval nuclei with minimal atypia. Given the rarity of these cases, there is a critical need for multicenter collaboration to create databases, facilitate large clinical trials, and develop therapeutic guidelines.Ethical Considerations:The study used anonymised data from Hospital Information System after obtaining written informed consent from deceased patient’s brother and approval from Institutional Review Board.Author Contributions:Dr. Farwa Aftab: Contributed to data curation, investigation, and drafting the original manuscript.Dr. Alishba Amjid: Contributed to investigation and drafting the original manuscript.Dr. Sumbal Saeed: Contributed to investigation and drafting the original manuscript.Dr. Haseeb Ahsin (Corresponding Author): Responsible for conceptualization, formal analysis, project administration, supervision, validation, and writing—review and editing of the manuscript.Dr. Fattahullah Khan: Contributed to supervision and writing—review and editing of the manuscript.All authors have read and approved the final version of the manuscript and agree to be accountable for all aspects of the work, ensuring accuracy and integrity.The authors declare no conflict of interest.References:Francis D, Jacobsen M: Pulmonary blastoma. Curr Top Pathol 1983, 73:265–294.Fung CH, Lo JW, Yonan TN, Milloy FJ, Hakami MM, Changus GW: Pulmonary blastoma. An ultrastructural study with a brief review of literature and a discussion of pathogenesis. Cancer 1997, 39:153–163Koss MN, Hochholzer L, O’Leary T. Pulmonary blastomas. Cancer. 1991;67:236881. doi: 10.1002/1097-0142(19910501)67:9<2368::aid-cncr2820670926>3.0.co;2g.Barnett N, Barnard WG. Some unusual thoracic tumors. BR J Surg 1945; 32: 441457.Barnard WG. Embryoma of the lung. Thorax 1952; 7: 229–301.Spencer H. Pulmonary blastomas. J Pathol Bacteriol, 1961; 82: 161–165.Travis W, Brambilla E, Muller-Hermelink H, Harris C. World Health Organization classification of tumors: pathology and genetics of tumors of the lung, pleura, thymus and heart. IARC Press: Lyon; 2004.Kradin RL, Kirkham SE, Young RH, Dickersin G, Mark E. Pulmonary blastoma with argyrophil cells and lacking sarcomatous features (pulmonary endodermal tumor resembling fetal lung). Am JSurg Pathol 1982; 6: 165- 172.Kodama T, Shimosato Y, Watanabe S, Koide T, Naruke T, Shimase J. Six cases of well differentiated adenocarcinoma simulating fetal lung tubules in pseudoglandular stage: Comparison with pulmonary blastoma. Am JSurg Paihol 1984; 8:735-744.Baldovini C, Rossi G, Ciarrocchi A. Approaches to Tumor Classification in Pulmonary Sarcomatoid Carcinoma. Lung Cancer (Auckl). 2019 Dec 5;10:131-149. doi: 10.2147/LCTT.S186779. PMID: 31824199; PMCID: PMC6901065.Mlika M, Anjum F, El Mezni F. Pleuropulmonary Blastoma. [Updated 2023 Apr 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK534211Van Loo S, Boeykens E, Stappaerts I, Rutsaert R. Classic biphasic pulmonary blastoma: A case report and review of the literature. Lung Cancer, 2011; 73: 127Lee HJ, Goo JM, Kim KW, Im JG, Kim JH. Pulmonary blastoma: radiologic findings in five patients. Clin Imaging. 2004;28:113–8. doi: 10.1016/S0899-7071(03)00240-Bini A, Ansaloni L, Grani G, Grazia M, Pagani D, Stella F, Bazzocchi R: Pulmonary blastoma: report of 2 cases. Surg Today 2001, 31:438–442.Liu Q, Li F, Wang L, et al. Pulmonary blastoma with a good prognosis: a case report and review of the literature. Journal of International Medical Research.2024;52(6). doi: 10 .1177 /03000605241254 778.Smyth et al.: Pulmonary blastoma: a case report and review of the literature. BMC Research Notes 2014 7:294.Jain TK, Singh H, Kumar R, et al. Real Time F-18 FDG PET-CT-Guided Metabolic Biopsy Targeting Differential FDG Avidity in a Pulmonary Blastoma. Nucl Med Mol maging 2020; 54: 261–263.Brodowska-Kania D, Kotwica E, Paturej A, et al. What do we know about pulmonary blastoma?: review of literature and clinical case report. Nagoya J Med Sci. 2016; 78(4): 507–516, doi: 10.18999/nagjms.78.4.507, indexed in Pubmed: 28008207.Kim K, Gupta S, Gupta S, et al. Incidental early diagnosis of biphasic pulmonary blastoma in a patient with history of stage IV lung adenocarcinoma. Thorac Cancer. 2020; 11(10): 3029–3033, doi: 10.1111/1759-7714.13629, indexed in Pubmed: 32833349.Liman ST, Altinok T, Topcu S, et al. Survival of biphasic pulmonary blastoma. Respir Med. 2006; 100(7): 1174–1179, doi: 10.1016/j.rmed.2005.10.026, indexed in Pubmed: 16332433. 48. Kouvaris JR, Gogou PV, Papacharalampous XN, et al. SolitaryXiu, Y., Jiang, L., & Liu, W. (2015). Classic biphasic pulmonary blastoma with brain and axillary metastases: a case report with molecular analysis and review of literature. International Journal of Clinical and Experimental Pathology, 8(1), 983.Tsamis I, Chachali SP, Gomatou G, et al. Pulmonary blastoma: a comprehensive overview of a rare entity. Adv Respir Med 2021 ; 89: 511-519.Cutler CS, Michel RP, Yassa M, et al. Pulmonary blastoma: case report of a patient with a 7-year remission and review of chemotherapy experience in the world literature. Cancer. 1998; 82(3): 462–467, doi: 10.1002/(sici)1097- 0142(19980201)82:3<462::aid-cncr6>3.0.co;2-r, indexed in Pubmed: 9452262.Lewis JA, Petty WJ, Urbanic J, et al. Cure of oligometastatic classic biphasic pulmonary blastoma using aggressive tri-modality treatment: case series and review of the literature. Cureus. 2018; 10(11): e3586, doi: 10.7759/cureus.3586, indexed in Pubmed: 30656089. 63.Vila R, McCoy JJ, McCall RE. Pulmonary blastoma, report of a case. Journal of the South Carolina Medical Association. 1973; 69(7): 251–6, indexed in Pubmed: 4515901.Jenkins TM, Morrissette JJD, Kucharczuk JC, et al. ROS1 rearrangement in a case of classic biphasic pulmonary blastoma. Int J Surg Pathol. 2018; 26(4): 360–363, doi: 10.1177/1066896917749928, indexed in Pubmed: 29295663.Meng Z, Chen P, Zang F, et al. A patient with classic biphasic pulmonary blastoma harboring CD74-ROS1 fusion responds to crizotinib. Onco Targets Ther. 2018; 11: 157–161, doi: 10.2147/ OTT.S150001, indexed in Pubmed: 29343973.30.. Luo Z, Cao C, Xu N, et al. Classic biphasic pulmonary blastoma: a case report and review of the literature. J Int Med Res. 2020; 48(10): 300060520962394, doi: 10.1177/0300060520962394, indexed in Pubmed: 33107372. 27.Bosch-Barrera J, Holguin F, Baldó X, et al. Neoadjuvant Chemoradiotherapy Treatment for a Classic Biphasic Pulmonary Blastoma with High PD-L1 Expression. Anticancer Res. 2015; 35(9): 4871–4875, indexed in Pubmed: 26254381.Larsen H, Sorensen JB: Pulmonary blastoma: a review with special emphasis on prognosis and treatment. Cancer Treat Rev. 1996, 22: 145-160.

Aortopulmonary window with Tetralogy of Fallot is a rare cardiac defect with very few reported cases in literature. We report an incidentally detected type 1 aortopulmonary window during routine intraoperative transesophageal echocardiography which helped to tailor the anaesthetic and surgical plan for better post-operative outcome.

The E. coli H7:O157 was the subject of many studies. It is characterized by producing Shiga toxins, abdominal illness, and developing resistance to antimicrobial agents. A total 20 fecal samples tested positive for E. coli H7:O157 from patients showed the typical symptoms of the infection, and another 20 from animals were collected. The bacterium was isolated, identified, and classified using culture medium, and molecular methods. Results obtained from classification of E. coli H7:O157 showed it is highly similar to E. coli H7:O157 strain Sakai. The genes rpoB, stx, waa, and rfbO were deposited in the NCBI website under accession no. PP059841, OR939814, PP059843, and PP059842 respectively. The mutant sequences of waa sites K, L, Y were analyzed to determine the shifting in their function, cell wall formation, and the ability to develop antibiotic resistance the mutant E. coli H7:O157 compared to the wild type. We found that the resistance to antibiotics in mutant E. coli H7:O157 increased significantly when compared to the wild type. Animals. The explanation for this may be attributed to the waa K, and waa L by preventing theentry of antimicrobial agents into the bacterial cell.

Three three-dimensional Hofmann-type metal-organic frameworks (MOFs) [Fe(bpn){Ag(CN) 2} 2]·Ph 2S ( 1·Ph 2 S, bpn = 1,4-di(pyridin-4-yl)naphthalene, Ph 2S = diphenylsulfide), [Fe(bpn){Ag(CN) 2} 2]·Ph 2SO ( 1·Ph 2 SO, Ph 2SO = diphenylsulfoxide) and [Fe(bpn){Ag(CN) 2} 2]·Ph 2SO 2 ( 1·Ph 2 SO 2, Ph 2SO 2 = diphenylsulfone) were synthesized by employing sulfur-containing aromatic guests varying in oxidation states. 1·Ph 2 S performed a complete four-step spin crossover (SCO) behavior with the sequence of HS↔LS 1/3HS 2/3↔LS 1/2HS 1/2↔LS 2/3HS 1/3↔LS, while an incomplete two-step SCO profile with the sequence of HS↔LS 1/3HS 2/3↔LS 2/3HS 1/3 and a faint SCO behavior at low temperature for 1·Ph 2 SO and 1·Ph 2 SO₂. Photomagnetic experiments indicate the light-induced excited spin-state trapping (LIESST) effect in 1·Ph 2 S and the bi-directional LIESST effect for 1·Ph 2 SO and 1·Ph 2 SO₂. Variable-temperature structural analyses reveal the evolution of host-guest synergy and highlight the mechanism of adaptive deformation of guests mediated by phenyl rotation amid spin transition. As the oxidation state of sulfur-containing guests increases, the host-guest cooperation within the lattice is limited by the steric effect, which stabilizes the high-spin state and consequently diminishes the SCO capability in this system. These results demonstrated herein open a new perspective on host-guest chemistry within SCO frameworks.

The Fuzhou cattle breed, native to northeast China, is widely recognized for its adaptability, disease resistance, and docility. Despite being known for these qualities, its population has declined recently, and there is a significant lack of genomic studies on this species. We sequenced 21 samples from a primary breeding farm to determine the genetic structure, diversity, and selection signature to address this. Additionally, we combined 100 published genomic datasets from diverse geographical regions to characterize the genomic variation of Fuzhou cattle. In population structure analysis, Fuzhou cattle show a predominantly East Asian taurine ancestry, with stronger genetic affinities to Hanwoo and Yanbian cattle. Despite high nucleotide diversity within the Bos taurine lineage, genetic diversity analysis also revealed significant levels of inbreeding in Fuzhou cattle populations, indicating the need for conservation. Utilizing various methods such as θπ, iHS, F ST, π-ratio, and XP-EHH, we identified genes associated with traits like growth, meat quality, energy metabolism, and immunity. Several genes related to cold adaptation were identified, including PLIN5, PLB1, and CPT2. As a result of these findings, the genetic resources of Fuzhou cattle can be preserved and conserved.

Clinical Commentary: Atypical myopathy associated with Box Elder in EuropeKnowles, E.J. and Piercy, R.J.The Royal Veterinary College, Royal College Street, LondonThe case report by Jahn et al (REF when available) describes a case of Atypical Myopathy in Europe caused by ingestion of the protoxin hypoglycin A (HGA) from Box Elder seedlings. This is an important report. It reminds clinicians in Europe that trees other than The European Sycamore (Acer pseudoplatanus) may contain HGA and of the potential for other unfamiliar plant species to cause pasture-associated toxicities.After many years of research, the pathogenesis of Atypical Myopathy, also known as Seasonal Pasture Myopathy, is now well understood. The severe myopathy results from ingestion of the seeds or seedlings of European Sycamore (Acer pseudoplatanus) in Europe and the Box Elder (Acer negundo) in the USA (Westermann et al. 2008, Valberg et al. 2013). The seeds, seedlings and leaves of these trees contain the protoxin HGA, and to a lesser extent its analogue methylenecyclopropylglycine (MCPrG) (Bochnia et al. 2019a). These protoxins are metabolised to the active toxins Methylenecyclopropylacetyl-CoA (MCPA-CoA) and MCPrG-CoA respectively at tissue-specific rates and primarily in skeletal muscle (Sander et al. 2023). The toxic effects mainly occur in the highly-oxidative ‘slow-twitch’ type I muscle fibres such as the postural muscles, masseters, diaphragm and cardiac muscle (Cassart et al. 2007). The primary toxin, MCPA-CoA inhibits acyl-CoA dehydrogenase enzymes involved in the beta-oxidation of fatty acids and catabolism of branched-chain amino acids resulting in failure of mitochondrial energy generation and subsequently muscle cell death (Westermann et al. 2008). Inhibition of Acyl-CoA dehydrogenase enzymes causes an accumulation of their acyl-CoA substrates and the carnitine and glycine conjugates of those substrates in serum and urine, a characteristic metabolic profile known as multiple acyl-CoA dehydrogenase deficiency (MADD) (Westermann et al. 2008). The accumulation of acylcarnitines together with the protoxins (HGA and MCPrG) and the carnitine conjugates of the toxins (MCPA-carnitine and MCPF-carnitine) can be detected in serum by liquid-chromatography-mass-spectometry (LCMS) (Valberg et al. 2013, Bochnia et al. 2019, González-Medina et al. 2021).In many cases a diagnosis of Atypical Myopathy can be made relatively confidently based on the characteristic clinical signs, serum biochemical changes, the seasonal occurrence and, in Europe, the presence of Sycamore (Acer psuedoplatanus) seeds or seedlings on the pasture (González-Medina et al. 2017, Dunkel et al. 2018). Detection of serum HGA or MCPA-carnitine by LCMS may be useful to confirm the diagnosis and may be particularly useful to identify sub-clinically affected cases, or those with less-severe or unusual presentations or when a toxic (tree) source cannot readily be identified.HGA or MCPA-carnitine has been detected in the serum of horses co-grazing with affected cases (Baise et al. 2016, Bochniaet al. 2018, Renaud et al. 2024). Whilst these co-grazing horses were apparently healthy it is unknown whether clinical signs would have been apparent if they had undertaken higher levels of exercise or if they could have been precipitated by a greater negative energy balance, requiring a greater reliance on metabolism of stored fats. It is therefore plausible that HGA could affect the exercise performance of a much greater number of horses than those with overt clinical signs.Identification of serum HGA or MCPA-carnitine can also be useful in cases such as the case described by Jahn et al (REF when available) in which Box Elder but not Sycamore trees were present on the pasture. Whilst the presence of Box Elder had been reported on one European pasture grazed by an AM affected horse previously, Sycamore was also present on that pasture (Votion et al. 2014) and to the author’s knowledge, confirmed Box Elder related Atypical Myopathy has not been reported previously in Europe.Many clinicians in Europe will not be familiar with the Box Elder tree as an alternative source of HGA, However, given that the Box Elder has been identified as a major invasive species in forests in the European Union (Campagnaro et al. 2018) it is likely to be responsible for further cases of Atypical Myopathy in Europe in future. Clinicians should also be aware of the potential for many other trees of theAcer family to that are grown in gardens or as ornamental trees to contain HGA. HGA has been identified in the sugar maple (Acer saccharum) , Japanese maple (Acer palmatum) , trident maple (Acer buergerianum) , paperbark maple (Acer griseum), Himalayan maple (Acer oblongum), mountain maple (Acer spicatum), big leaf maple (Acer macrophyllum) , full moon maple (Acer japonicum), lime-leafed maple (Acer distylum) and Siebold’s maple (Acer sieboldianum). (Fowden and Pratt 1973, Novotná et al. 2023). Given the potential for the winged samaras of these species to spread widely in windy conditions it is plausible that cases of Atypical myopathy could occur if these species are grown in gardens adjoining paddocks.Acylcarnitine profiling combined with HGA/ MCPA-carnitine assays may also be clinically useful to identify unusual cases of Atypical Myopathy, other pasture toxicities and inborn errors of metabolism. For example, a rare case of Atypical Myopathy was diagnosed using these methods in a newborn foal in which the mare had suffered from Atypical Myopathy during pregnancy (Karlíková et al. 2018). In another case, severe clinical signs in a newborn foal resulted from suspected concurrent Atypical Myopathy with inborn metabolic disease (Sanderet al. 2021). Finally, acylcarnitine profiling was also successfully used to identify an inborn form of MADD without HGA toxicity in a paint foal (Pinn et al. 2018).Recently, acylcarnitine profiling was also used to identify cases of Marsh mallow (Malva parviflora) toxicity in which it is proposed that malvalic and/or sterculic acid inhibit very-long chain acyl-CoA dehydrogenase, thus slowing the beta-oxidation of very-long chain fatty acids (Bauquier et al. 2017). Acylcarnitine profiles have also revealed suspected disorders of fatty acid metabolism without the detection on HGA MCPA-carnitine in serum samples submitted to the authors’ laboratory (unpublished data) and there is likely that as yet unidentified pasture-associated toxicities occur in the UK and Europe.In conclusion, the interesting case report by Jahn et al (REF) is an important reminder to clinicians in Europe of the potential forAcer species other than Sycamore to cause Atypical Myopathy. Acyl-carnitine profiles and detection of HGA/ MCPA-carnitine by LCMS can be a useful diagnostic aid in myopathy cases.ReferencesBaise, E., Habyarimana, J.A., Amory, H., Boemer, F., Douny, C., Gustin, P., Marcillaud-Pitel, C., Patarin, F., Weber, M. and Votion, D.M. (2016) Samaras and seedlings of Acer pseudoplatanus are potential sources of hypoglycin A intoxication in atypical myopathy without necessarily inducing clinical signs. Equine Vet J 48 , 414–417.Bauquier, J., Stent, A., Gibney, J., Jerrett, I., White, J., Tennent-Brown, B., Pearce, A. and Pitt, J. (2017) Evidence for marsh mallow (Malva parviflora) toxicosis causing myocardial disease and myopathy in four horses. Equine Vet J 49 , 307–313.Bochnia, M., Sander, J., Ziegler, J., Terhardt, M., Sander, S., Janzen, N., Cavalleri, J.M.V., Zuraw, A., Wensch-Dorendorf, M. and Zeyner, A. (2019a) Detection of MCPG metabolites in horses with atypical myopathy.PLoS One 14 .Bochnia, M., Sander, J., Ziegler, J., Terhardt, M., Sander, S., Janzen, N., Cavalleri, J.M.V., Zuraw, A., Wensch-Dorendorf, M. and Zeyner, A. (2019b) Detection of MCPG metabolites in horses with atypical myopathy.PLoS One 14 .Bochnia, M., Scheidemann, W., Ziegler, J., Sander, J., Vollstedt, S., Glatter, M., Janzen, N., Terhardt, M. and Zeyner, A. (2018) Predictive value of hypoglycin A and methylencyclopropylacetic acid conjugates in a horse with atypical myopathy in comparison to its cograzing partners.Equine Vet Educ 30 , 24–28.Campagnaro, T., Brundu, G. and Sitzia, T. (2018) Five major invasive alien tree species in European Union forest habitat types of the Alpine and Continental biogeographical regions. J Nat Conserv 43 , 227–238.Cassart, D., Baise, E., Cherel, Y., Delguste, C., Antoine, N., Votion, D., Amory, H., Rollin, F., Linden, A., Coignoul, F. and Desmecht, D. (2007) Morphological alterations in oxidative muscles and mitochondrial structure associated with equine atypical myopathy. Equine Vet J 39 , 26–32.Dunkel, B., Ryan, A., Haggett, E. and Knowles, E.J. (2018) Atypical myopathy in the South-East of England: Clinicopathological data and outcome in hospitalised horses. Equine Vet Educ . https://doi.org/10.1111/eve.12895Fowden, L. and Pratt, H.M. (1973) Cyclopropylamino acids of the genus Acer: Distribution and biosynthesis. Phytochemistry 12 , 1677–1681.González-Medina, S., Hyde, C., Lovera, I. and Piercy, R.J. (2021) Detection of hypoglycin A and MCPA-carnitine in equine serum and muscle tissue: Optimisation and validation of a LC-MS-based method without derivatisation. Equine Vet J 53 , 558–568.González-Medina, S., Ireland, J.L., Piercy, R.J., Newton, J.R. and Votion, D.M. (2017) Equine atypical myopathy in the UK: Epidemiological characteristics of cases reported from 2011 to 2015 and factors associated with survival. Equine Vet J 49 , 746–752.Karlíková, R., Široká, J., Mech, M., Friedecký, D., Janečková, H., Mádrová, L., Hrdinová, F., Drábková, Z., Dobešová, O., Adam, T. and Jahn, P. (2018) Newborn foal with atypical myopathy. J Vet Intern Med 32 , 1768–1772.Novotná, T., Jahn, P., Šamonilová, E., Kabešová, M., Pospíšilová, S. and Maršálek, P. (2023) Hypoglycin A in Acer genus plants. Toxicon 234 , 107271.Pinn, T.L., Divers, T.J., Southard, T., De Bernardis, N.P., Wakshlag, J.J. and Valberg, S. (2018) Persistent hypoglycemia associated with lipid storage myopathy in a paint foal. J Vet Intern Med 32 , 1442.Renaud, B., Kruse, C.J., François, A.C., Cesarini, C., van Loon, G., Palmers, K., Boemer, F., Luis, G., Gustin, P. and Votion, D.M. (2024) Large-scale study of blood markers in equine atypical myopathy reveals subclinical poisoning and advances in diagnostic and prognostic criteria. Environ Toxicol Pharmacol 110 , 104515.Sander, J., Terhardt, M. and Janzen, N. (2021) Severe Inhibition of Long-Chain Acyl-CoA Enoylhydratase (EC 4.2.1.74) in a Newborn Foal Suffering From Atypical Myopathy. Front Vet Sci 8 , 765623.Sander, J., Terhardt, M., Janzen, N., Renaud, B., Kruse, C.J., François, A.C., Wouters, C.P., Boemer, F. and Votion, D.M. (2023) Tissue Specific Distribution and Activation of Sapindaceae Toxins in Horses Suffering from Atypical Myopathy. Animals (Basel) 13 .Valberg, S.J., Sponseller, B.T., Hegeman, A.D., Earing, J., Bender, J.B., Martinson, K.L., Patterson, S.E. and Sweetman, L. (2013) Seasonal pasture myopathy/atypical myopathy in North America associated with ingestion of hypoglycin A within seeds of the box elder tree.Equine Vet J 45 , 419–426.Votion, D.-M., van Galen, G., Sweetman, L., Boemer, F., de Tullio, P., Dopagne, C., et al. (2014) Identification of methylenecyclopropyl acetic acid in serum of European horses with atypical myopathy. Equine Vet J 46 , 146–149.Westermann, C.M., Dorland, L., Votion, D.M., de Sain-van der Velden, M.G.M., Wijnberg, I.D., Wanders, R.J.A., Spliet, W.G.M., Testerink, N., Berger, R., Ruiter, J.P.N. and van der Kolk, J.H. (2008) Acquired multiple Acyl-CoA dehydrogenase deficiency in 10 horses with atypical myopathy. Neuromuscular Disorders 18 , 355–364.

NK cells are an innate class of lymphocytes in the human body that can achieve non-specific killing of tumor cells without MHC restriction or prior sensitization. In recent years, targeted killing of tumor cells has become possible due to the development of diverse biological technology, particularly the chemical chimeric antigen receptors (CAR), and other technologies. CAR gives NK cells a new magic, and its extracellular domains of the recognition region are usually single-chain antibodies (scFv), which can be targeted to specific antigens. CAR-NK cells have shown excellent results in several preclinical studies and clinical trials for hematologic malignancies. However, their clinical application in the treatment of solid tumors is still insufficient. Currently, the treatment of gynecological tumors relies mainly on surgery, chemotherapy, and radiotherapy, which are often accompanied by significant side effects and limited efficacy. CAR-T cell therapy has shown efficacy in certain gynecological tumors. However, side effects that are still urgent problems in clinical applications such as Graft-Versus-Host Disease (GVHD) and Cytokine Release Syndrome (CRS) have been observed. In contrast, CAR-NK cell therapy shows potential advantages in this area. Based on the above, this review mainly focuses on the development of CAR-NK cell constructs and their promising applications for immunotherapy of gynecological malignancies, aiming to provide references for clinical trials and clinical studies.

Background: Long COVID significantly impacts various body systems, particularly the respiratory system. This study aimed to analyze the lung ventilatory function and diffusion capacity of patients with severe SARS-CoV-2 pneumonia at different time points during a 24-month follow-up course. Methods: Ventilatory function and lung diffusion capacity of the lung were assessed 6, 12, 18, and 24 months after hospital discharge. Patients underwent spirometry and lung volume measurements. Ventilatory parameters and DLCO and KCO normalization were defined as achieving values > 80% predicted. Results: A total of 222 patients admitted to the Intensive Care Unit (ICU) of the ASST - Spedali Civili di Brescia, Brescia, Italy, who survived severe SARS-CoV-2 pneumonia were enrolled. Among the 172 patients who completed the study, 140 (85.59%) achieved normalization of ventilatory parameters and DLCO and KCO. The median time to recovery was 4.5 months, and the hazard ratio (HR) reduced by 2% as each year of age increased. The median time to normalize ventilatory parameters (VC, FVC, FEV 1, Tiffeneau index, TLC, and KCO) was 1.5 months, while the median time to VA normalization was 4.5 months. Male gender reduces the normalization odds of the Tiffeneau index and Alveolar Volume (VA). The median time to DLCO normalization was 9 months, with HR reduced by 3.1% as each year of age increased and augmented by 226% in obese subjects. Conclusions: 24 months after hospital discharge, 19% of patients had persistent ventilatory and/or diffusive defects. Our study documented that male sex, age, and obesity impact the normalization odds of ventilatory function and diffusive capacity of the lung. These findings underline the chronic nature of lung damage following severe COVID-19 pneumonia and the need for long-term follow-ups .

The ability to prioritize threatening stimuli in attention has been well-documented, but its manifestation in individuals with high autistic traits remains debated. This study used a dot-probe task and event-related potentials (ERPs) to examine early (N2pc) and late (SPCN) stages of attentional processing in individuals with high (HAT) and low (LAT) autistic traits. The results revealed no significant group differences in early attentional orienting, as indicated by similar N2pc responses. However, a divergence was observed in the later stages, with the HAT group showing a sustained attention to threat, evidenced by a prominent SPCN. This suggests that individuals with high autistic traits have difficulty disengaging from threatening stimuli. These findings contribute to our understanding of social threat processing in autism spectrum disorder and underscore the importance of targeting attentional control in interventions for this population.

Human, animal and plant populations are at risk of large outbreaks of infectious diseases called ‘epidemics’. Despite the potential for strong antagonistic co-evolution between host and parasite infection traits, epidemiological research has often focussed on studying any given epidemic in isolation. Therefore, I propose a simple ‘Disease Cycle’ model that seeks to link the size of past and future epidemics of disease within the context of ongoing environmental perturbation. Specifically, I review some of the contemporary literature about evolutionary topics that are relevant to the Disease Cycle. I focus on three key axes of (co)evo-epidemiology, including (i) the link between epidemic size and the strength of selection, (ii) changes in host-parasite diversity as a result of the (co)evolution of host resistance or parasite infectivity and (iii) how either host or parasite population genetic diversity could impact on future epidemic size. I identify missing links in the Disease Cycle that could be filled by future work, but overall, I find compelling evidence supporting this model. Future work should focus on understanding how host (and parasite) population genetic diversity could impact on the variability of disease and how the strength of host or parasite-mediated selection might be linked to epidemic size. This Disease Cycle model can encourage the scientific community to conceptualise disease as part of an ongoing battle between the evolution of hosts and parasites that allows us to view epidemiology through a coevolutionary lens.

Restoration and protection of kelp forest ecosystems is critical to maintain marine biodiversity, support coastal communities, and meet global conservation targets such as the Kunming-Montreal Global Biodiversity Framework's 30x30 and Kelp Forest Challenge. Much of the success of kelp forest restoration and protection depends heavily on selecting ecologically suitable sites that align with species-specific environmental requirements. This paper introduces a novel kelp forest restoration site selection tool that synthesizes the realized environmental niche of 105 kelp species across 25 biophysical factors. Using over 426,000 global observations of kelp and high-resolution oceanographic datasets, the tool provides quantitative niche data summarized by species and ecoregion. It incorporates key variables such as temperature, salinity, light, and nutrient availability, offering users practical guidance to identify optimal restoration sites. Accessible via an interactive web application, the tool supports conservation practitioners, policymakers, and researchers by enabling evidence-based site selection, maximizing restoration success, and informing broader marine ecosystem management. This tool represents a significant advancement in kelp forest conservation, facilitating global restoration efforts and contributing to the ambitious goal of restoring one million hectares of kelp forest by 2040. Future developments will address qualitative ecological factors and socio-cultural considerations to enhance its utility.

Plant hydraulics govern water transport linking root to mesophyll surfaces, affecting gas-exchange, survival, and growth. Xylem and leaf structural and functional characteristics vary widely among Pinus species, even when growing under similar conditions. We quantified the variation of xylem anatomy, hydraulic function, and within-tree hydraulic resistivity distribution, among five widely ranging southern US species: Pinus echinata, P. elliottii, P. palustris, P. taeda, and P. virginiana. We found that, across species, needle length (NL) explained most of the variation in needle hydraulic properties. Resistivity to water flow in needles through tracheids’ bordered-pits decreased from ~99% to 8% with increasing NL; total tracheid resistivity in branches and roots was partitioned between bordered-pits and lumens similarly regardless of NL. Mean annual precipitation typical of the species’ climatic range (CR) accounted for the variation in root hydraulic properties. Despite strong root-to-branch correlations of several attributes, neither NL nor CR explained the variation of any branch attribute. The results suggest that NL dominates needle xylem anatomy and function in a manner consistent with increasing hydraulic efficiency with NL, but CR produces genetic differences resulting in increased resistance to more negative xylem pressures with decreasing precipitation, at a cost of reduced hydraulic efficiency.

Stylosanthes guianensis is a dominant pasture legume in tropical and subtropical regions. Anthracnose, a fungal disease caused by Colletotrichum gloeosporioides (C. gloeosporioides), significantly limits the production of S. guianensis. Phenylalanine ammonia-lyase (PAL), the rate-limiting enzyme in the phenylpropanoid pathway, plays a vital role in regulating plant resistance to pathogens. However, its function in the stylo’s resistance against anthracnose requires further exploration. In this study, a core collection (28 accessions) representing 237 S. guianensis accessions was established based on phenotypic data and SSR (Simple Sequence Repeat) molecular marker data. The PAL activity in response to C. gloeosporioides was correlated with the resistance phenotypes in the core collection. Five members of the SgPAL gene family were identified from previous transcriptomic data. Among these, SgPAL1 and SgPAL2 showed a significant positive correlation with the PAL activity across the core collection after inoculation. Biochemical analyses, subcellular localization study, and expression pattern analyses demonstrated that SgPAL1 and SgPAL2 displayed PAL activity, localized in the cytoplasm, and were induced by C. gloeosporioides inoculation. Furthermore, overexpression (OE) of SgPAL1 and SgPAL2 in Arabidopsis enhanced resistance against C. gloeosporioides. The transcriptomic analyses of SgPAL1 and SgPAL2 OE lines revealed the up-regulation of the key genes regulating the lignin synthesis. Consistently, the total lignin content and the ratio of G to S monomers were also higher in SgPAL1 and SgPAL2 OE lines than in wild type plant after inoculation. These results imply that SgPAL1 and SgPAL2 may enhance plant resistance against C. gloeosporioides by increasing lignin content and the G/S ratio. In conclusion, this study provides an effective core germplasm collection for advancing the genetic breeding of S. guianensis, and characterize SgPAL1 and SgPAL2 as promising targets for improving crop resistance against anthracnose.

Being diagnosed with cancer is a pivotal moment in a person’s life and changes biographies fundamentally, especially in terms of temporality and physicality. Modern concepts of maintenance therapy or therapeutic abstinence are at odds with typical desire of patients to fight the disease radically. Decisions about therapeutic goals are caught between medical-scientific expertise on the one hand and life-world judgements and values on the other. This makes it particularly challenging to reconcile different preferences and norms. This study aims to analyse values in the context of the challenging human experience of cancer. We hypothesise that established quantitative measures and even more patient-centred assessment tools such as PROMs may not be adequate to capture therapeutic success as understood by patients. Semi-structured interviews will be carried out with participants with gynaecological or colorectal cancer. We propose a mixed methods approach to identify participants’ values, individual treatment goals, and expectations. Outcomes of the study are defined as: 1) ethical analysis of values in the context of human experiences with cancer 2) reconstruction of values triggering individual treatment goals and positive and negative expectations 3) comparison of ethical concepts of successful life with situational values of patients with evidence-based (medical-scientific) preferences. This results in following secondary objectives: 1) Establishing a strategy for patient-centred adaptation of clinical evaluation of therapeutic concepts of escalation, maintenance or abstinence, 2) modelling of a well operationalised clinical strategy for therapeutic goal setting, 3) teaching this strategy, including the clinical oncological, ethical and communicative requirements, as part of medical education.

This study introduces a novel graphical multi-factor authentication (MFA) algorithm that integrates user image hashes and dynamic image grids with cell addresses (DIGCA) to optimize storage requirements with robust security. The algorithm stores image hashes rather than actual images, significantly reducing storage space while maintaining security integrity. In contrast to the existing image recognition algorithm, the algorithm shows a drastic reduction of 99.9% in storage requirements. Performance analysis demonstrates that the algorithm provides a high level of accuracy with a 95.36% success rate in user authentication over an extended period. Again, the image grid and cell addresses prove an ample password space and entropy. With the minimum assumption grid size, it achieves a password space of 1.36 × 10 !" , Which makes it virtually impossible for an attacker to guess the correct combination. The results underscore the algorithm's potential as a superior alternative to existing MFA schemes, offering both security and practicality in modern authentication systems.

Background: Developing manual platelet-rich plasma (PRP) methods in donkeys improves cost-efficient field management in a species often treated under resource limitations. Objectives: To compare asinine PRP manually produced by single and double centrifugation. Study design: Ex vivo experimental study. Methods: Whole blood (WB) from 6 healthy donkeys was collected into sodium citrate vacutainer tubes for single centrifugation processing and an acid-citrate-phosphate-dextrose-adenine blood bag for double centrifugtation processing to produce, respectively, PRP1 and PRP2. Concentrations of platelets ([PLT]), leukocyte ([WBC]), and erythrocytes ([RBC]), and activities of platelet-derived growth factor-BB (PDGF-BB) and transforming growth factor beta 1 (TGF-β1) were assessed in WB, PRP1, PRP2. Results were compared by Friedman’s and Dunn’s multiple comparison test. Spearman’s rank was used to assess the correlation between [PLT] in WB, PRP1, and PRP2. Results: Both centrifugation protocols concentrated platelets 1.8–5.2-fold, reduced WBC 1.1–50.4-fold, and decreased RBC at least 829-fold compared to WB. PRP2 yielded a higher [PLT] and platelet enrichment factor than PRP1. However, PRP 1 possessed lower [WBC] and greater WBC reduction factor than PRP2. PDGF-BB and TGF-β1 activities were higher in PRP2 than PRP1 and WB. Growth factor activities were not significantly different between PRP1 and WB. There was weak and moderate correlation of baseline [PLT] to that of PRP2 (r = 0.4) and PRP1 (r = 0.62), respectively; neither was statistically significant ( p > 0.05). PRP2 yielded higher platelet enrichment and growth factor activities despite greater WBC and RBC contamination than PRP1. Main limitations: Non-randomized collection methods. Conclusions: Manual, noncommercial methods of equine PRP preparation can be used to produce PRP in donkeys. Double centrifugation yielded a more concentrated platelet product with higher leukocyte contamination than single centrifugation. The clinical utility of leukocyte contaminated PRP and its optimal platelet concentration, in vivo efficacy, and safety warrent further investigation.

The American Migraine Foundation estimates that over 39 million Americans and over 1 billion people worldwide suffer from some form of migraine. Treatment of migraine generally falls into two categories: treatment of attacks once they have begun, and prophylactic prevention, including lifestyle changes. The use of phytocannabinoids to reduce both the frequency and severity of migraine is widely documented in both scientific, grey, and popular literature. This review provides descriptions of both pre-clinical and clinical studies involving the treatment of migraine with phytocannabinoids as well as the involvement of endocannabinoids and endocannabinoid-like compounds in migraine pathology, including the receptors and associated mechanisms. Currently unanswered questions and areas for further exploration are discussed.

Background: Venetoclax-based (ven) combinations have become a standard of care for acute myeloid leukemia (AML) patients ineligible for intensive chemotherapy. However, the associated risk of infectious adverse events (IAEs) remains a significant clinical concern. Aims: This study aimed to evaluate the incidence, characteristics, and risk factors for IAEs in newly diagnosed AML patients treated with venetoclax combinations in a real-world setting. Methods and Results: We conducted a retrospective cohort study of AML patients treated with ven in combination with hypomethylating agents or low-dose cytarabine (LDAC), with analyses performed on a treatment cycle basis. Clinical and laboratory data, including IAE characteristics, duration of neutropenia, and concomitant medications, were collected, and grade ≥2 IAEs were included according to CTCAE v5.0 criteria. The cohort included 143 treatment cycles of 43 patients, with a median neutropenia duration of 13 days (5–35). A total of 34 (23.8%) grade ≥2 IAEs occurred, with an incidence of 1 per 121 patient-days. Multivariate analysis identified prolonged neutropenia (days, OR=1.037, p=0.005) and interacting concomitant medications (OR=9.99, p<0.001) as independent risk factors for IAEs. The rate of invasive fungal infections was as low as 3.5%, and the use of antifungal or antibacterial prophylaxis was not associated with a reduction in the rate of IAEs. Conclusion: IAEs remain a substantial risk in venetoclax-treated AML patients, particularly during prolonged neutropenia and with concomitant drug interactions. Optimizing venetoclax regimens and careful management of interacting medications may mitigate these risks.

Climate change, increased needs for food, industry and mitigation of environmental impacts are currently driving changes in agricultural practices. Moreover, increasing demand for plant-based protein in substitution to animal protein or to reduce soybean importations is driving cultivation of high-protein crops. Legumes are such crops that play a critical role in this process. Amongst them, white lupin is a so-called orphan species, i.e. associated with relatively little cultivated surface area worldwide and limited agronomic knowledge. Lupin is nevertheless very promising since seeds contain a high content of storage proteins with interesting nutritional properties. Also, it has low fertilisation requirements since it forms root clusters allowing efficient phosphorus (P) acquisition, along with symbiotic nitrogen (N) fixation by nodules. Nevertheless, lupin cultivation faces important challenges such as yield variability, slow vegetative development or susceptibility to weeds diseases and water stress, for example. Lupin has an enormous potential for resource-saving practices such as intercropping with non-legumes, because of niche complementarity for N acquisition and facilitation of P transfer to the associated species, which can in turn mitigate weeds and pests, and ensure yield stability. To overcome several bottlenecks associated with lupin cultivation (e.g. nutrient utilisation, drought resistance or limiting the impact of weeds), genetic, metabolic, and agronomic research is required in order to define ideotypes that are particularly well-fitted to sustainable agricultural practices such as intercropping, with optimal protein yield. This is one of the purposes of the trans-disciplinary research programme PULSAR, funded by France 2030, which aims to unlock several bottlenecks in lupin utilisation in agronomy. Keywords: Lupinus albus, intercropping, metabolism, cluster root, France 2030 PULSAR projectHighlightsWhite lupin has is a legume with high potential for plant-based protein production. PULSAR is a project funded by France 2030 to study lupin unique physiological traits and overcome several challenges associated with lupin cultivation with emphasis on intercropping.

The rising prevalence of metabolic dysfunction related fatty liver disease (MASLD) is related to the increased mortality and substantial health care costs, which constitutes a major global health challenge. Currently, effective treatment options for MASLD is still in need. Metabolic inflammation is a typical feature of MASLD. Management of metabolic inflammation represents a significant strategy for the treatment of MASLD. Non-steroidal anti-inflammatory drugs (NSAIDs), known for their anti-inflammatory and analgesic properties, are widely used in various inflammatory diseases. Recent clinical investigations revealed that certain NSAIDs can prevent the progression of MASLD, which brings hope for the treatment of MASLD. However, concerns on the accurate application, as well as the potential mechanisms are still unknown. In this study, we summarized the update of NSAIDs in the treatment of MASLD, and systematically discussed their potential mechanisms in treating MASLD, aiming to provide new research directions for the management of MASLD.

Browntop millet (Brachiaria ramosa L. Stapf) holds cultural and agricultural significance in Southern India, serving as both a staple food for humans and fodder for livestock. Recently, its high fiber and protein content has gained public attention, making it popular as a nutritious grain. However, despite its nutritional benefits, the limited genomic information available for browntop millet has hindered breeding efforts. To address this knowledge gap, an assessment was made to test the transferability of SSR (Simple Sequence Repeat) primers from finger millet to browntop millet, aiming to identify genetic polymorphism. In this study, 27 accessions of browntop millet were subjected to SSR analysis using 100 SSR primers developed for finger millet. Among the 100 primers tested, five were mono-nucleotide, 38 were di-nucleotide, 42 were tri-nucleotide, and 15 were tetra-nucleotide repeats. Initial screening of 100 primers on 100 primers on two browntop millet accessions GPUBT-2 and IC617953 showed 40 per cent and 42 per cent transferability. Among the 30 amplified primers screened on both browntop millet genotypes, one was a mono-nucleotide repeat, 16 were di-nucleotide repeats, and 13 were tri-nucleotide repeats. The analysis revealed that di-nucleotide repeats were the most common repeat type. 30 primers which showed amplification in both genotypes were used for screening 27 browntop millet genotypes. The PIC values of all the polymorphic loci for 25 browntop millet genotypes varied from 0 to 0.68, major allele frequency varied from 0.40 to 1, allele number varied from 1 to 5 and genetic diversity varied from 0 to 0.72. Cluster analysis combining morphological and molecular markers based on UPGMA method resulted in two major clusters. These findings demonstrate the potential for utilizing genomic resources from related millet species and highlight opportunities to enhance browntop millet breeding programs.