Recently, two invasive Aedes mosquito species, Ae. japonicus and Ae. koreicus, are circulating in several European countries posing potential health risks to humans and animals. Vector control is the main option to prevent mosquito-borne diseases, and an accurate genome sequence of these mosquitoes is essential to better understand their biology and to develop effective control strategies. Here, we present a de novo genome assembly of the Ae. japonicus (Ajap1) and Ae. koreicus (Akor1) based on a hybrid approach that combines Oxford Nanopore long reads and Illumina short reads data. Their quality was ascertained using various metrics. Masking of repetitive elements, gene prediction and functional annotation was performed. Sequence analysis revealed a very high presence of repetitive DNA and, among others, thermal adaptation genes and insecticide-resistance genes. Through the RNAseq analysis of larvae and adults of Ae. koreicus and Ae. japonicus exposed to different temperatures (15 and 28°C) we also identified genes showing a differential temperature-dependent activation. The assembly of Akor1 and Ajap1 genomes constitutes the first updated collective knowledge of the genomes of both mosquito species, providing the possibility of understanding key mechanisms of their biology such as the ability to adapt to harsh climates and to develop insecticide-resistance mechanisms.

A secretory carcinoma with NTRK3 break-apart molecular rearrangement: A case report on a tumor initially diagnosed as a mucoepidermoid carcinoma.Authors declare no conflict of interestData are available from the digital archieves and laboratories of Policlinico G.B. Rossi, Verona, Italy.Key points: Secretory Carcinoma, Salivary Glands, Mucoepidermoid Carcinoma, Oral Oncology, NTRK3

Background: Modulation of the cardiac autonomic nervous system (ANS) is a promising adjuvant therapy in the treatment of atrial fibrillation (AF). In pre-clinical models, pulsed field (PF) energy has the advantage of selectively ablating the epicardial ganglionated plexi (GP) that govern the ANS. Objective: This study aims to demonstrate the feasibility and safety of epicardial ablation of the GPs with PF during cardiac surgery with a primary efficacy outcome of prolongation of the atrial effective refractory period (AERP).  Methods: In a single-arm, prospective analysis, patients with or without a history of AF underwent epicardial GP ablation with PF during coronary artery bypass grafting (CABG). AERP was determined immediately pre- and post- GP ablation to assess cardiac ANS function. Holter monitors were performed to determine rhythm status and Heart Rate Variability (HRV) at baseline and at 1 month post-procedure.   Conclusions:  This study demonstrates the safety and feasibility of epicardial ablation of the GP using PF to modulate the ANS during cardiac surgery. Large, randomized analyses are necessary to determine whether epicardial PF ablation can offer a meaningful impact on the cardiac ANS and reduce AF. Results: Of 24 patients, 23 (96%) received the full ablation protocol. No device-related adverse effects were noted. GP ablation resulted in a 20.7% ± 19.9% extension in AERP (P < 0.001). Post-operative AF was observed in 7 (29%) patients. Holter monitoring demonstrated an increase in mean heart rate (74.0±8.7 vs 80.6±12.3, P=0.01). There were no significant changes in HRV. There were no study-related complications.

Image processing is the set of operations performed to extract “information” from the image. An interesting problem in digital image processing is the restoration of degraded images. It often happens that the resulting image is different from the expected image. Our problem will therefore be to recover an image close to the original image from a poor quality image (that has been skewed by Gaussian and additive noise). There are a lot of algorithms on how we can improve the broken image in better quality. We present in this paper our numerical results obtained with the models of Tichonov regularization, ROF, Vese Osher, anisotropic and isotropic TV denoising algorithms.

A document by Kamal Acharya. Click on the document to view its contents.

Title: Sirolimus-induced DRESS syndrome in a stem cell transplant patient.Authors: Fortunato CASSALIA1, Alice SPILLER1, Roberto SALMASO1, Francesca CAROPPO1,2, Anna BELLONI FORTINA1,2Affiliations:Dermatology Unit, Department of Medicine (DIMED), University of Padua, Padua, Italy.Pediatric Dermatology Unit, Department of Women and Children’s Health, University of Padua, Padua, Italy.Corresponding Author: Francesca Caroppo, MD Unit of Dermatology, Department of Medicine University of Padova, Italy Via Vincenzo Gallucci 4, 35121, Padova, Italy e-mail: francesca.caroppo@outlook.itKeywords:Word count: 1329Tables: NoneFigure: 3References: 9Conflicts of interest: NoneAcknowledgements: NoneAuthor Contributions: All authors contributed to designing and conducting the work, drafting, and revising the manuscript and approved the final version for submission.ABSTRACTBACKGROUND: We present a case of sirolimus-induced DRESS syndrome in a stem cell transplant patient. Sirolimus is an immunosuppressive drug that inhibits the mTOR pathway. It is commonly used in organ transplants to prevent rejection. While no sirolimus-induced DRESS cases have been reported, allergic reactions with everolimus, a similar drug, have been documented. DRESS syndrome is a severe drug reaction characterized by fever, rash, and organ involvement. Diagnosis is based on clinical findings and laboratory tests. Early recognition, discontinuation of the drug, and supportive care are crucial in managing DRESS syndrome, often involving systemic corticosteroids.CASE REPORT A 24-year-old man who had undergone haplo-TESE transplantation for acute lymphatic leukaemia presented with diffuse itchy eczematous lesions. Initially diagnosed as atopic dermatitis, he received topical steroid therapy and NB-UVB phototherapy, but his condition worsened. Two months later, he returned to the emergency department with eczematous patches, xerosis, fever, chills, and generalized edema. His medical history included relapses of leukaemia, acute cutaneous graft-versus-host disease (GVHD), and Evans syndrome. He had been on sirolimus immunosuppressive therapy before the onset of symptoms. A skin biopsy revealed spongiotic dermatitis with dermal eosinophils, suggestive of drug reaction or atopic reaction. Based on the severity of the symptoms and histological findings, the patient was diagnosed with sirolimus-induced DRESS syndrome. Sirolimus was discontinued, and oral steroid therapy was initiated, leading to significant improvement. At the one-month follow-up, the patient was symptom-free and had lost the gained weight.CONCLUSION Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus have been documented. And since sirolimus and everolimus, both mTOR inhibitors, share a common mechanism of action, therapeutic indications, pharmacokinetics, adverse effects and drug interactions, it cannot be ruled out that sirolimus may trigger DRESS syndrome in patients with risk factors. In our case, the patient’s history characterized by stem cell transplantation and multiple immunosuppressive therapies may have contributed to the development of DRESS syndrome after beginning sirolimus therapy. This case may be the first evidence of sirolimus-induced DRESS syndrome in a stem cell transplant patient and highlights how early diagnosis, discontinuation of the culprit drug and appropriate management are crucial for a favourable outcome.BACKGROUND We present a case of sirolimus-induced DRESS syndrome1in a stem cell transplant patient. Sirolimus, also known as rapamycin, is an immunosuppressive and antiproliferative drug that inhibits the mammalian target of rapamycin (mTOR) pathway2. It has a wide range of clinical applications and has been extensively studied in various fields of medicine. Sirolimus is commonly used in solid organ transplants to prevent acute rejection and improve transplant survival with the advantage of reducing the nephrotoxicity associated with calcineurin inhibitors3. Although no cases of sirolimus-induced DRESS syndrome have been reported, allergic reactions with eosinophilia induced by everolimus, a similar drug of the mTOR inhibitor family, have been documented. In particular, cases of drug reaction with eosinophilia and systemic symptoms (DRESS) caused by an everolimus-eluting stent have been reported4. DRESS syndrome, also known as drug-induced hypersensitivity syndrome (DIHS), is a severe adverse drug reaction characterized by fever, skin rash, multi-organ involvement and eosinophilia. The pathogenesis of the DRESS syndrome remains unclear, involving a complex interaction between drug metabolism, immune dysregulation and genetic factors. Skin manifestations vary from maculopapular eruptions to severe exfoliative dermatitis, while organ involvement often involves the liver, kidneys, lungs and haematological system. Other systemic symptoms may include lymphadenopathy, myocarditis and interstitial nephritis. The diagnosis of DRESS syndrome is based on the recently validated RegiSCAR score5 which considers clinical findings, temporal relationship with drug exposure and blood tests. Early recognition and discontinuation of the involved drug are crucial for the management of DRESS syndrome. Supportive care and careful monitoring of organ function are essential, while symptomatic treatment aims to improve symptoms. Systemic corticosteroids are often administered to suppress the immune response6.CASE REPORTA 24-year-old boy, who had previously undergone haplo-TESE transplantation (transplantation of haploidentical haematopoietic stem cells for acute lymphatic leukaemia, presented to the dermatology outpatient clinic for the onset of a diffuse eruption with itchy eczematous lesions. The initial clinical presentation was diagnosed as atopic dermatitis and topical steroid therapy was recommended. In the following days, due to the lack of clinical response and the worsening of the skin eruption, about two months later the patient returned to the emergency department complaining of diffuse xerosis mixed with eczematous, itchy, finely scaling patches. In addition, the patient complained of fever and chills and significant and consistent oedema all over his body. He also reported a weight gain of 9 kg in the last month and eosinophilia >20% with leukopenia (Figure 1). The medical history revealed that the patient was diagnosed with acute lymphatic leukaemia in 2003 and underwent treatment according to the AIEOP LLA 2000 protocol (Prednisone, Vincristine, Daunorubicin, L-asparaginase, methotrexate, 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone). In 2015, the patient developed a relapse for which he was treated according to the AIEOP protocol BFM 2009 concluded in 2017 (Prednisone, Vincristine, Daunorubicin, L-asparaginase, methotrexate, 6-Mercaptopurine, Cyclophosphamide, Cytarabine, Dexamethasone). However, in 2018, the patient developed a new relapse and therefore underwent haplo-TESE stem cell transplantation. Unfortunately, in 2019, the patient suffered an acute cutaneous GVHD for which he underwent treatment with oral cyclosporine in combination with tacrolimus that led to a rapid improvement of the skin manifestations. Unfortunately, in 2020 he was diagnosed with Evans syndrome and was treated with oral steroids; once the acute phase was over, the patient started immunosuppressive therapy with sirolimus 2 mg/die. Given the history and the severity of the clinical picture, the patient was hospitalized and a skin biopsy with histological examination was performed. The result of the histological examination revealed a hyperkeratosis with focally confluent spongiosis and irregular acanthosis of the epidermide. The underlying superficial dermis shows a modest infiltrate of lymphocytes, plasma cells and eosinophils, the latter also observed in the deep dermis. Specific histochemical stains did not reveal the presence of mucins and fungi (Alcial Blue and PAS) while immunohistochemical reactions for T and B lymphocytes excluded the clinical hypothesis of GVHD. The morphological picture depicts a spongiotic dermatitis with a discrete presence of dermal eosinophils suggesting the possibility of drug reaction vs. atopic reaction (Figure 2). Considering the clinical picture and the histological examination, the diagnosis of DRESS syndrome induced by sirolimus was made7. The drug was withdrawn and scaled-up oral steroid therapy was instituted, after 3 weeks of therapy the patient ceased taking the oral steroid. At the follow-up visit after one month the oedema was in remission, the patient no longer complained of any symptoms and had lost the previously accumulated kg (Figure 3).DISCUSSION The case described presents a 24-year-old boy with a complex medical history, including a previous diagnosis of acute lymphatic leukaemia and subsequent relapses, which required intensive treatments such as stem cell transplantation and immunosuppressive therapy. The patient presented to the dermatology outpatient clinic with diffuse itchy eczematous lesions, initially diagnosed as atopic dermatitis. Despite topical steroid therapy, the patient’s condition worsened with dry, itchy patches mixed with xerosis concomitant with fever, swelling, weight gain and abnormal blood results. Skin biopsy ruled out the diagnosis of graft-versus-host disease (GVHD). Based on the clinical presentation, histological findings and history of sirolimus therapy, the diagnosis of sirolimus-induced DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) syndrome was made. Sirolimus was discontinued and the patient started oral steroid therapy, which was gradually reduced and finally discontinued. After three weeks of treatment, the patient’s symptoms improved, including remission of oedema, and at the one-month follow-up visit the patient was asymptomatic and had lost the weight gained during the illness. DRESS syndrome is a severe form of drug reaction in which skin manifestations and systemic involvement are associated. The onset time is usually longer than in other delayed skin reactions, on average 6-8 weeks after the introduction of the responsible drug. It is a severe idiosyncratic T-cell mediated reaction, classified as a type Vb and sometimes IVc delayed hypersensitivity reaction. DRESS is presumed to result from a complex interaction between drug exposure (such as vaccines or biological drugs), genetic predisposition and/or viral reactivation, and the development of this serious clinical condition would appear to be the result of the cumulative effect of aligned risks1. Early recognition and discontinuation of the culprit drug are crucial for the management of DRESS syndrome. Systemic corticosteroids are often used to suppress the inflammatory response and supportive care is provided for any organ involvement6. Although no cases of sirolimus-induced DRESS syndrome are reported in the literature, allergic reactions with eosinophilia induced by everolimus have been described. In particular, cases of drug reaction with eosinophilia and systemic symptom syndrome caused by an everolimus-eluting stent have been reported4. Sirolimus and everolimus both belong to the class of drugs called mTOR inhibitors and share several features8, including: (1) Mechanism of action: Sirolimus and everolimus act by inhibiting the mammalian target of rapamycin (mTOR); (2) therapeutic indications: both are used in immunosuppressive therapy to prevent organ rejection in transplant patients. (3) Pharmacokinetics: both are administered orally and are rapidly absorbed. They have a large volume of distribution and are extensively metabolised in the liver. (4) Adverse effects: They have common adverse effects including immunosuppression, which may increase the risk of infection, delay wound healing and altered response to vaccines. Other potential side effects include hyperlipidaemia (elevated blood lipid levels), peripheral oedema, gastrointestinal disorders, and metabolic abnormalities; (5) drug interactions: both drugs are metabolised by cytochrome P450 enzymes, which may lead to potential drug interactions with other drugs that act on these enzymes9. It is important to consider these interactions when prescribing or administering these drugs. In our case, the patient’s history of previous intensive treatments, stem cell transplantation and immunosuppressive therapies may have contributed to immune system dysregulation and the onset of DRESS syndrome following the initiation of sirolimus therapy. Timely diagnosis, discontinuation of the drug and appropriate management led to the resolution of symptoms and general improvement of the patient’s condition. The case emphasizes the importance of careful monitoring and consideration of potential adverse drug reactions in patients undergoing complex treatment regimes. This case could be the first evidence of DRESS syndrome induced by sirolimus in a stem cell transplant patient.FIGURE 1 Eczematous, itchy, finely scaling patches and significant and consistent oedema.FIGURE 2 Flap of skin with hyperkeratosis, focally confluent spongiosis and irregular acanthosis of the epider-mide. Modest infiltrate of lymphocytes, plasma cells and eosinophils, in the deep dermis.FIGURE 3 One month after withdrawal of SirolimusREFERENCESRamirez, G. A., Ripa, M., Burastero, S., et al . (2023). Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS): Focus on the Pathophysiological and Diagnostic Role of Viruses. Microorganisms, 11(2), 346.https://doi.org/10.3390/microorganisms11020346Mao, B., Zhang, Q., Ma, L., et al. (2022). Overview of Research into mTOR Inhibitors. Molecules (Basel, Switzerland), 27(16), 5295.https://doi.org/10.3390/molecules27165295Hahn, D., Hodson, E. M., Hamiwka, L. A., et al. (2019). Target of rapamycin inhibitors (TOR-I; sirolimus and everolimus) for primary immunosuppression in kidney transplant recipients. The Cochrane database of systematic reviews, 12(12), CD004290.https://doi.org/10.1002/14651858.CD004290.pub3Bianchi, L., Caraffini, S., & Lisi, P. (2014). Drug reaction with eosinophilia and systemic symptoms syndrome caused by an everolimus-eluting stent. International journal of dermatology, 53(4), e286–e288.https://doi.org/10.1111/ijd.12112Kardaun, S. H., Sekula, P., Valeyrie-Allanore, L., et al (2013). Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study. The British journal of dermatology, 169(5), 1071–1080. https://doi.org/10.1111/bjd.12501Calle, A. M., Aguirre, N., Ardila, et al. (2023). DRESS syndrome: A literature review and treatment algorithm. The World Allergy Organization journal, 16(3), 100673. https://doi.org/10.1016/j.waojou.2022.100673Jindal, R., Chugh, R., Chauhan, P., et al (2022). Histopathological Characterization of Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) and Comparison with Maculopapular Drug Rash (MPDR). Indian dermatology online journal, 13(1), 32–39.https://doi.org/10.4103/idoj.idoj_452_21Yan, X., Huang, S., Yang, Y., et al (2022). Sirolimus or Everolimus Improves Survival After Liver Transplantation for Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis. Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Granata, S., Dalla Gassa, A., Carraro, A., et al (2016). Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects. International journal of molecular sciences, 17(5), 735. https://doi.org/10.3390/ijms17050735

Colorectal cancer is one of the most prevalent malignancies worldwide, and long-term chronic colitis is considered to be an important factor in the etiological study of colorectal cancer. As an emerging detection technology, the non-invasive, non-ionizing, and fingerprint spectroscopic features of terahertz technology have tremendous application prospects in disease diagnosis. Therefore, this study aims to explore the value of terahertz technology in colitis-related cancers by constructing an inflammation-associated mouse colorectal cancer model. In this paper, we found that the terahertz spectroscopy technique can effectively distinguish colitis-associated cancer from normal tissue, and for the first time, we searched that 1.8 THz may be the best terahertz frequency for diagnosing colorectal cancer in mice, suggesting that we can use the terahertz technique for rapid diagnosis of colorectal cancer histopathology.

The case report by Navarro-Lopez et al., (2023) in this issue describes a thorough differential diagnosis in an equine with acute neurological disease. Rabies was confirmed by direct fluorescent antibody test (DFA). Rabies virus (RABV) was isolated from brain tissue of the ill mare by intracerebral inoculation in sucking mice. Sequencing and phylogenetic inference allowed the identification of the rabies virus variant (RVV) associated with this case. Thus, Navarro-Lopez et al., reported that the rabid mare got infected with a rabies virus variant associated with skunks. This clinical commentary elaborates on the seemingly rare skunk rabies across North America (NA) highlighting its relevance in human and animal health that have remained somehow neglected

The increasing trend of transformation of land at the expense of fertile agricultural land is becoming troublesome and threatens food security worldwide. The scenario is more severe at the rural-urban interface and the agrarian land on the outskirt of larger cities is at greater risk, however, the extensive literature is not readily available in the Nepalese context. This study focuses on the land use patterns and variables shaping farmers’ choices for the future use of land in Dhading, Nepal. The analysis of land use patterns showed that, between 2013 and 2022, productive agricultural land decreased by 60.28% while non-farm use of land increased by 93.14% in the study area of Dhunibeshi Municipality, Dhading. The cross-sectional survey data among vegetable farming households showed that 36% of the household were eager to switch from farming to non-farm use of their land in the near future. Based on binary logistic regression, land ownership, the share of family income from vegetable production, the proposal received for land conversion, and proximity variables like distance between farmland to the closest non-farm firm, were found to be statistically significant in shaping the farmers’ decisions on agricultural land conversion. The land ownership and lower family income from agriculture activities were identified as major push factors, while the proximity of the farm to non-farm firms, and proposals for urban use of land were identified as major pull factors for land conversion. The widespread adoption of low-cost production strategies in agriculture, and effective implementation of a land-use policy could contribute towards sustainable agricultural land management in the future.

A document by Sowmya Sagireddy. Click on the document to view its contents.

Magnetoelastic switching in multiferroic nanomagnets with a small voltage is a promising substitute for current charge-based CMOS devices. Here, we study strain-mediated multiferroic majority logic gate by solving Landau-Lifshitz-Gilbert equation and establish an energy- efficient CMOS compatible equivalent circuit analogy to capacitor's I- V characteristics. We can easily simulate nanomagnet logic units using this tool. After that, the circuit is verified by SPICE simulations. Results show that the output voltage polarity is determined by the majority of input voltage polarity with ultralow energy consumption, working similarly to majority logic function. The SPICE circuit model shows ultralow energy consumption because of the conserved dynamic current, which can serve as a promising logic unit, consequently, integrated into large-scale nanomagnetic logic circuits and even a nanomagnetic chip.

Previous studies have established the association of sex with gene and protein expression. This study investigated the association of sex with the abundance of endogenous urinary peptides, using capillary electrophoresis-coupled to mass spectrometry datasets from 2008 healthy individuals and patients with type II diabetes, divided in one discovery and two validation cohorts. Statistical analysis using the Mann-Whitney test, adjusted for multiple testing, revealed 143 sex-associated peptides in the discovery cohort. Of these, 90 peptides were associated with sex in at least one of the validation cohorts and showed agreement in their regulation trends across all cohorts. The 90 sex-associated peptides were fragments of 29 parental proteins. Comparison with previously published transcriptomics data demonstrated that the genes encoding 16 of these parental proteins had sex-biased expression. The 143 sex-associated peptides were combined into a support vector machine-based classifier that could discriminate males from females in two independent sets of healthy individuals and patients with type II diabetes, with an AUC of 89% and 81%, respectively. Collectively, the urinary peptidome contains multiple sex-associated differences, which may enable a better understanding of sex-biased molecular mechanisms and the development of more accurate diagnostic, prognostic or predictive classifiers for each individual sex.

Variation in fitness components can be linked in some cases to variation of key traits. Metric traits that lie at the intersection of development, defense, and ecological interactions may be expected to experience strong environmental selection, informing our understanding of evolutionary and ecological processes. Here, we use quantitative genetic and population genomic methods to investigate disease dynamics in hybrid and non-hybrid populations. We focus our investigation on morphological and ecophysiological traits which inform our understanding of physiology, growth, and defense against a pathogen. In particular, we investigate stomata, microscopic pores on the surface of a leaf which regulate gas exhange during photosynthesis and are sites of entry for various plant pathogens. Stomatal patterning traits were highly predictive of disease risk. Admixture mapping identified a polygenic basis of disease resistance. Candidate genes for stomatal and disease resistance map to the same genomic regions, and are experienceing positive selection. Genes with functions for guard cell homeostasis, the plant immune system, components of constitutive defenses, and growth related transcription factors were identified. Our results indicate positive selection is filtering genetic variance from one of the parental species maladpated to a novel pathogen, and changing suites of stomatal traits which contribute to disease variation in natural populations.

INTRODUCTIONCharles Bonnet Syndrome(CBS) was first described in 1760 by Naturalist and philosopher Charles Bonnet, who first observed lifelike complex visual hallucinations in his grandfather Charles Lullis after bilateral cataract surgery(1); it was a neurologist George de Morsier who coined the term in 1938 after Charles Bonnet himself developed the condition(2). CBS, also known as ”phantom image”, is characterized by recurrent or persistent complex visual hallucinations in people with a disease of the visual system with intact insight, intellectual function and normal cognitive functioning without primary psychiatric disorders(3,4). With limited knowledge of CBS among physicians, the prevalence of CBS is underreported(4) even though 41-59% of the visually impaired experience elementary visual phenomena, and 11-15% exhibit complex hallucinations, due to a medical condition or artificially produced, such as in preparation for cataract surgery(5,6). The presence of varying inclusion criteria, inconsistent depth of questioning and limited patient disclosure for fear of being ridiculed may all contribute to underreporting(3,5). Visual hallucinations could be a sign of psychiatric disorders, neurological diseases, metabolic abnormalities, and the use or abuse of specific drugs(7). Both elementary forms(3) and complex visual hallucinations are reported in CBS(8); while glaucoma,cataract and age-related macular degeneration are the most common associated disorders, any ophthalmological conditions can lead to CBS(7), especially in significant visual impairment(9). A pituitary adenoma is rarely associated with CBS (10); however, reduced visual acuity or a visual field deficit can occur from the benign tumour’s compressing optic chiasm affecting one or both eyes(11).There are three main theories associated with the pathogenesis of CBS, and these are; the sensory deprivation or deafferentiation theory related to spontaneous excitation due to a loss of visual input to the brain(12), the release theory associated with excessive excitation and the consequent release of visual hallucinations(13,14), and the ”irritative theory” due to distal provocative injuries transmit abnormal input to the visual cortex leading to abnormal excitatory activity to the temporal and occipital lobes(15,16).Charles Bonnet syndrome is treated multifacetedly with pharmacotherapy, psychosocial therapy, maintaining appropriate eye care, and sensory stimulation. Generally, CBS is treated with antipsychotics and antidepressants(5), and in some cases, antiepileptic medications have also been used with variable benefits (17).An 81-year-old blind male presented with a three-year history of visual hallucinations after a recurrence of pituitary macroadenoma. His past psychiatric history is uneventful, and he has intact insight with no cognitive impairment. He improved on a low haloperidol dosage, with a few relapses, when he stops the medications.

The global interest in fatty acids is steadily rising due to their wealth of industrial potential ranging from cosmetics to biofuels. Unfortunately, certain fatty acids, such as monounsaturated C12, cannot be produced cost and energy-efficiently using conventional methods. Biosynthesis of fatty acids using microorganisms can overcome this drawback. However, rewiring a microbe’s metabolome for increased production remains challenging. To overcome this, sophisticated genome-wide metabolic network models have become available. These models predict the effect of genetic perturbations on the metabolism, thereby serving as a guide for metabolic pathways optimization. In this work, we used constraint-based modeling in combination with the algorithm Optknock to identify gene deletions in Escherichia coli that improve the C12 fatty acid production. Nine gene targets were identified that, when deleted, were predicted to increase C12 titers. Targets play a role in anaplerotic reactions, amino acid synthesis, carbon metabolism and cofactor-balancing. Subsequently, we constructed the corresponding (combinatorial) deletion mutants to validate the in silico predictions in vivo. Our highest producer (Δ maeB Δ ndk Δ pykA) reaches a titer of 6.7 mg/L, corresponding to a 7.5-fold increase in C12 fatty acid production. This study demonstrates that model-guided metabolic engineering is a useful tool to improve C12 fatty acid production.

Fermentation monitoring is a powerful tool for bioprocess development and optimisation. On-line metabolomics is a technology that is starting to gain attention as a bioprocess monitoring tool, allowing the direct measurement of many compounds in the fermentation broth at a very high time resolution. In this work, targeted on-line metabolomics was used to monitor 40 metabolites of interest during three Escherichia coli succinate production fermentation experiments every 5 minutes with a triple quadrupole mass spectrometer. This allowed capturing high time resolution biological data that can provide critical information for process optimisation. For 9 of these metabolites, simple univariate regression models were used to model compound concentration from their on-line mass spectrometry peak area. These on-line metabolomics univariate models performed comparably to vibrational spectroscopy multivariate PLS regressions models reported in the literature, which typically are much more complex and time consuming to build. In conclusion, this work shows how on-line metabolomics can be used to directly monitor many bioprocess compounds of interest and obtain rich biological and bioprocess data.

Changes in land use and climate change have been reported to reduce biodiversity of the environment and human microbiota. This may lead to inadequate and unbalanced stimulation of immunoregulatory circuits and ultimately, to clinical diseases, such as asthma and allergies. We summarised available empirical evidence on the role of inner and outer layers of biodiversity in the development of asthma, asthma-like symptoms, and allergic sensitization. We conducted a systematic search in SciVerse Scopus, PubMed MEDLINE, and Web of Science up to 5 December 2022 to identify relevant studies assessing the relations between inner and outer layers of biodiversity and the risk of asthma, wheezing and/or allergic sensitization. We applied random-effects models to calculate summary effect estimates. The protocol was registered in PROSPERO (CRD42022381725). Of 75 studies, 20 provided effect estimates for the meta-analysis showing an association between high outer layer biodiversity and a low risk of asthma development (Shannon diversity index: OR (95% CI) = 0.77 (0.55; 1.06); bacterial richness: OR (95% CI) = 0.74 (0.57; 0.96)). Although the evidence on the effect of inner layer biodiversity suggested that bacterial diversity was slightly higher among individuals with asthma, there was no clear evidence of a significant association between inner layer biodiversity and the risk of asthma, wheezing or allergic sensitization. The weight of evidence suggests that environmental exposure to high biodiversity may protect from the development of asthma, whereas there was no consistent evidence on any association between inner layer biodiversity and asthma, wheezing or allergic sensitization.

Background: Modelling atopic dermatitis (AD) in vitro is paramount to understand the disease pathophysiology and identify novel treatments. Previous studies have shown that the Th2 cytokines IL-4 and IL-13 induce AD-like features in keratinocytes in vitro. However, it has not been systematically researched whether the addition of Th2 cells, their supernatants or a 3D structure are superior to model AD compared to simple 2D cell culture with cytokines. Methods: For the first time, we investigated what in vitro option most closely resembles the disease in vivo based on single-cell RNA sequencing data (scRNA-seq) obtained from skin biopsies in a clinical study and published datasets of healthy and AD donors. In vitro models were generated with primary fibroblasts and keratinocytes, subjected to cytokine treatment or Th2 cell cocultures in 2D/3D. Gene expression changes were assessed using qPCR and Multiplex Immunoassays. Results: Of all cytokines tested, incubation of keratinocytes and fibroblasts with IL-4 and IL-13 induced the closest in vivo-like AD phenotype which was observed in the scRNA-seq data. Addition of Th2 cells to fibroblasts failed to model AD due to the downregulation of ECM-associated genes such as POSTN. While keratinocytes cultured in 3D showed better stratification than in 2D, changes induced with AD triggers did not better resemble AD keratinocyte subtypes observed in vivo. Conclusions: Taken together, our comprehensive study shows that the simple model using IL-4 or IL-13 in 2D most accurately models AD in fibroblasts and keratinocytes in vitro, which may aid the discovery of novel treatment options.

Self-efficacy (SE) is recognized as a main determinant of successful performance and may mediate the relationship between psychological performance enhancement techniques and sports performance. Identifying the cognitive–motor processes of superior performance can provide crucial information not only for accelerating the motor learning process but also for enhancing motor performance. The frontal midline theta power (Fmθ) reflects the level of top–down attention allocated to achieve a desired cognitive–motor behavior. Thus, this study investigated the effect of SE on the performance and Fmθ of golf players and explored the association between the objective measures of cortical dynamics and SE. Thirty-four skilled golfers were recruited (within-subject design) to perform 60 putts, and their electroencephalographic activity was recorded during the task. The SE score was measured using a visual analog scale ranging from 0 to 10 before each putt. Paired t test results revealed that trials with higher SE scores were associated with a higher putting success rate than trials with lower SE scores (53.3% vs 46.7%). Moreover, trials with higher SE scores were preceded by lower Fmθ than trials with lower SE scores (4.49 vs. 5.18). These findings suggested that higher SE was followed by less top–down attentional control, a characteristic of automatic processing, leading to better putting performance. Our findings support Bandura’s SE theory and elucidate the intermediate processes of SE by investigating the effect of the anticipation of outcomes on sports performance and attentional control before putting.

Background Recombinant factor IX Fc fusion protein (rFIX-Fc) is an extended half-life (EHL) factor concentrate administered to haemophilia B patients. So far, a population pharmacokinetic (PK) model has only been published for patients ≥12 years of age. Aim Assess the predictive performance of the published rFIX-Fc population PK model for patients of all ages and develop a model that describes rFIX-Fc PK using real world data. Methods We collected prospective and retrospective data from patients with haemophilia B (FIX activity level ≤5 IU/dL) treated with rFIX-Fc and included in the OPTI-CLOT TARGET study (NTR7523) or United Kingdom (UK)-EHL Outcome Registry (NCT02938156). Predictive performance was assessed by comparing predicted with observed FIX activity levels. A novel population PK model was constructed using nonlinear mixed-effects modelling. Results Real world data was obtained from 37 patients (median age: 16 years, range 2-71) of whom 14 were <12 years of age. Observed FIX activity levels were significantly higher than levels predicted using the published model, with a median prediction error (PE) of -48.8%. The novel model showed a lower median PE (3.4%) and better described rFIX-Fc PK, especially for children <12 years of age. In the novel model, an increase in age was correlated with a decrease in clearance (p<0.01). Conclusion The published population PK model significantly underpredicted FIX activity levels. The novel model better describes rFIX-Fc PK, especially for children <12 years of age. This study underlines the necessity to strive for representative population PK models, thereby avoiding extrapolation outside the studied population.

This study applies the generative adversarial network-based optimization approach to site selection and capacity determination of energy storage device in a power grid. Through the combination of modified long short-term memory and generative adversarial networks, the proposed method enhances the learning capability for the decision support of energy storage allocation. This method excels at the utilization of modified long short-term memory to ensure a better data-generation and data-discrimination in a generative adversarial network, enabling the achievement of effective data learning and deduction. To validate the feasibility of the proposed approach, a practical system as well as an example system are both examined under different scenarios, where the placement cost, peak load, and voltage deviation are all concerned. Test results gained from this study are beneficial for energy storage industry applications. In this study, a novel approach is proposed for site selection and capacity determination of energy storage devices in power grids by applying a generative adversarial network-based optimization method. The proposed approach combines modified long short-term memory and generative adversarial networks to enhance the learning capability for decision support of energy storage allocation. Specifically, the modified long short-term memory improves the data-generation and data-discrimination in the generative adversarial network, leading to effective data learning and deduction. To demonstrate the feasibility of our proposed approach, a practical system as well as an example system are tested under different scenarios, where the placement cost, peak load, and voltage deviation are all taken into considerations. Test results indicate the feasibility of the method, providing valuable insights for the energy storage industry.

A document by Jennifer Oliveira. Click on the document to view its contents.

Background Cancer is the leading cause of death among Asian Americans, who face barriers to cancer care. Cancer supportive care needs among Asian Americans remain understudied. Methods We recruited 47 Asian American adults with colorectal, liver, or lung cancer who spoke Chinese, English, or Vietnamese, and were starting or undergoing cancer treatment. We assessed cancer supportive care needs in four domains: cancer information, daily living, behavioral health, and language assistance. Hierarchical cluster analysis was used to identify clusters of participants based on their need profiles to further examine the association between need profiles and quality of life (QoL) assessed by the Functional Assessment of Cancer Therapy (FACT-G). Results Participants (mean age=57.6) included 72% males and 62% spoke English less than very well. Older participants (age >65) and those with annual income <$50K reported higher daily living needs. Men and younger participants (age <50) reported higher behavioral health needs. We found 3 clusters displaying distinct cancer supportive need profiles: Cluster 1 (28% of the sample) displayed high needs across all domains; Cluster 2 (51%) had low overall needs; and Cluster 3 (21%) had high needs for cancer information and daily living. Cluster 1 participants reported lowest QoL. Conclusions Cancer supportive care needs among Asian American patients with colorectal, liver and lung cancer were associated with patient characteristics and QoL. Understanding cancer supportive care needs will inform future interventions to improve care and QoL for Asian American cancer patients.

Spacecraft magnetic field measurements are frequently degraded by stray magnetic fields originating from onboard electrical systems. These interference signals can mask the natural ambient magnetic field, reducing the quality of scientific data collected. Traditional approaches involve positioning magnetometers on mechanical booms to minimize the influence of the spacecraft's stray magnetic fields. However, this method is impractical for resource-constrained platforms, such as CubeSats, which necessitate compact and cost-effective designs. In this work, we introduce an interference removal technique called Wavelet-Adaptive Interference Cancellation for Underdetermined Platforms (WAIC-UP). This method effectively eliminates stray magnetic field signals using multiple magnetometers, without requiring prior knowledge of the spectral content, location, or magnitude of the interference signals. WAIC-UP capitalizes on the distinct spectral properties of various interference signals and employs an analytical method to separate them from ambient magnetic field in the wavelet domain. We validate the efficacy of WAIC-UP through a statistical simulation of randomized 1U CubeSat interference configurations, as well as with real-world magnetic field signals generated by copper coils. Our findings demonstrate that WAIC-UP consistently retrieves the ambient magnetic field under various interference conditions and does so with orders of magnitude less computational time compared to other modern noise removal algorithms. By facilitating high-quality magnetic field measurements on boomless platforms, WAIC-UP presents new opportunities for small-satellite-based space science missions.