Background: Healthcare managers and administrators increasingly need to develop systems, structures, and operations capable of improving the patient experience performance of their organizations or service delivery units. Aim: To systematically review the effectiveness of organizational and service management interventions on standardized patient experience measure scores. Methods: Six scientific databases, specialty journals, and snowballing were used to identify English-language, peer-reviewed, contemporary studies (2015-2023) that examined the impact of service management or organizational interventions on the patient experience as a primary outcome. The studies needed to include inferential statistics on standardized, patient-reported experience measures. Two independent reviewers performed the eligibility decisions and risk-of-bias appraisals. Results: Nine papers were finally included. Three papers were on discrete, service-level interventions, including two randomized controlled trials (RCTs) and one pre-post study; one RCT achieved significant improvements by delaying the timing of bedside rounding versus maintaining the early morning schedule. One non-randomized controlled study and two pre-post studies addressed organization-wide approaches. Among those, one pre-post study achieved significant improvements by having site managers meet regularly with an organizational oversight committee to compare the units’ patient-experience performance and setting improvement expectations. Finally, three observational, multi-site comparative studies were included. These addressed self-reported improvement approaches, implementation of a nursing excellence certification program, and implementation of Patient Experience Offices. The latter was significantly associated with improved patient experience performance. Conclusion: Selected discrete service-level interventions and organizational approaches can lead to better patient experience outcomes, even though the evidence from the pre-post and observational studies should be interpreted with caution.

Title: A 19-year-old male with Truncus arteriosus type I : A rare case report from Syria.ABDULKADER BITARa ,Mouhammed Sleiaya,+, M-JABER KOJAKb , MOLHAM HOMSIa, Abdullah Alomara , OBADA AL TAWEKJIa, AHMAD ABDUL HAKIM ALHAMIDc, Saleh Takkemd.a Faculty of Medicine, Hama University, Hama, Syrian Arab Republic.b Faculty of Medicine, Internal medicine Department, Damascus university, Damascus , Syrian Arab Republic.c Faculty of Medicine, Al Hawash Private University, Damascus , Syrian Arab Republic.d Faculty of Medicine,Cardiology Department, Damascus University, Damascus, Syria*Corresponding author: Mouhammed Sleiay, Faculty of Medicine, Hama University, Hama, Syrian Arab Republic. email: abdmouh1234mouhmouh@gmail.com+ ABDULKADER BITARa ,Mouhammed Sleiaya,+, M-JABER KOJAKb , MOLHAM HOMSIa, Abdullah Alomara , OBADA AL TAWEKJIa, AHMAD ABDUL HAKIM ALHAMIDc, Saleh Takkemd are co-first authors. All contributed equally in this paper.Emails & ORCID:ABDULKADER BITAR:ibrahimabd751@gmail.comMouhammed Sleiay:abdmouh1234mouhmouh@gmail.comORCID: 0009-0003-8887-0739M-JABER KOJAK:mjkojak2000@gmail.comMOLHAM HOMSI:molhamhomsi901@gmail.comAbdullah Alomar:abdullahaloumar10@gmail.comOBADA AL TAWEKJI:altawekjy@gmail.comAHMAD ABDUL HAKIM ALHAMID:alhamidahmad933@gmail.comSaleh Takkem:drsalehtakkem35@gmail.com

Successful treatment of large left ventricular thrombosis during extracorporeal membrane oxygenation (ECMO）：a case report and review of the literatureXue-ting Yang, MM1**, Yi-jin Chen, MM1,2,3**, Han Zeng, MM1**, Lei Deng, MM1, Li Chang, MM1, Yi Li, MM1, Meng-long Song, MM1, Yang Zhang, MM1, Wei Peng, MM1, Dong-Wang, MM1,2,3, Hong-qiong Peng, MM1+, Hua Jiang, MD1,2+1 Emergency intensive care unit, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, 1st Ring Road, Chengdu 610072, Sichuan, China; 2 Institute for Emergency and Disaster Medicine, Sichuan Academy of Medical Science, Sichuan Provincial People’s Hospital, School of Medicine, University of Electronic Science and Technology of China, No. 32, West Second Section, 1st Ring Road, Chengdu610072, Sichuan, China; 3 University of Electronic Science and Technology of China, Chengdu 6100054, China.+Corresponding Author: Hong-qiong Peng, Emergency intensive care unite, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, 1st Ring Road, Chengdu 610072, Sichuan, China. Tel: +86-28-87393496, Email: 2294398778@qq.com. Hua Jiang, Emergency intensive care unite, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, No. 32, West Second Section, 1st Ring Road, Chengdu 610072, Sichuan, China. Tel: +86-28-87393881, Email: jianghua@uestc.edu.cn.**These authors have contributed equally to this workAuthor Contributions:Xue-ting Yang: Writing-original draft.Yi-jin Chen: Writing-original draft.Han Zeng: Writing-original draft.Lei Deng: Acquisition, analysis, or interpretation of data.Li Chang: Acquisition, analysis, or interpretation of data.Yi Li: Acquisition, analysis, or interpretation of data.Meng-long Song: Acquisition, analysis, or interpretation of data.Yang Zhang: Acquisition, analysis, or interpretation of data.Wei Peng: Acquisition, analysis, or interpretation of data.Dong-Wang: Writing-review and editing.Hong-qiong Peng: Supervision.Hua Jiang: Writing-review and editing, supervision and obtained funding.FundingThis work was supported by funding from the Sichuan Science and Technology Program (Grant ID: 2021YFS0378) to Hua Jiang.Conflict of interest statementAll authors have nothing to declare.Data availability statementThe corresponding author’s data supporting this study’s findings are available upon reasonable request.ConsentWritten informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.ORCIDYi-jin Chen https://orcid.org/0009-0009-8075-1093Key clinical messageWe report the case that a fulminant myocarditis patient was treated with Venoarterial extracorporeal membrane oxygenation (VA-ECMO) and experienced a rare complication of left ventricular giant thrombosis. After anticoagulation alone without surgical intervention, the thrombosis disappeared. This case illustrates anticoagulant alone therapy is safe and effective on treatment of giant left ventricular thrombosis during ECMO.Keywords: extracorporeal membrane oxygenation (ECMO), left ventricular (LV) thrombosis, anticoagulant.IntroductionExtracorporeal membrane oxygenation (ECMO) is widely used to patients with fulminant myocarditis, severe heart failure or respiratory failure or combined cardiorespiratory failure. It has been more than 50 years since ECMO was first successfully used to save the patient’s life. According to the return cycle, ECMO is classified by venoarterial extracorporeal membrane oxygenation (VA-ECMO) and venovenous extracorporeal membrane oxygenation (VV-ECMO). ECMO is a high-risk operation technique, which may cause fatal complications, such as massive bleeding, thrombosis and infection. This article hereby reported one case that left ventricular (LV) thrombosis occurred during ECMO and was successfully treated with anticoagulant alone without surgery.Case presentationA 28-year-old male (height 174cm, weighing 55kg) was admitted to the Emergency Intensive Care Unit (EICU) of our hospital on March 15, 2023 due to recurrent fever for 5 days. Electrocardiogram revealed V4-V6 ST segment elevation 0.05-0.2mv(Fig.1 panel A ) and hyper-sensitive troponin T（hs-cTnT）was 5135ng/L. Six hours after admission, ventricular fibrillation occurred suddenly. Electric defibrillation was immediately applied, and chest compression was continued. He was diagnosed with fulminant myocarditis and cardiogenic shock and was connected to VA-ECMO immediately. The initial speed was 9200/min, the blood flow was 3.6L/min, the norepinephrine was 1.5ug/(kg/min) and heparin anticoagulation was 1u/（kg/h）. Activated clotting time [ACT] was monitored every 4 hours, activated partial thromboplastin time [APTT], prothrombin time [PT], and anti-Xa were monitored four times a day. On March 17, 2023, echocardiography showed that thrombosis in the patient’s left ventricular (LV) (33*23mm in width, Fig.1 panel B, arrow). On March 20, 2023, the maximum diameter of the thrombosis was 47*12mm (Fig.1 panel C, arrow) and left ventricular ejection fraction (LVEF) (biplane Simpson method) was 54%.TreatmentBecause of poor cardiac function, the surgical procedure is not available. Thus, we strengthen anticoagulation treatment. Anticoagulant targets were adjusted to ACT>180s and APTT>60. Because of the high activity of antithrombin III, heparin anticoagulation was adjusted to 18u/(kg/h)，In addition, the maximum APTT was 121.5s(Fig.1 panel E, arrow). On March 20, 2023. the patient met weaning criteria. We faced a dilemma at this point: the thrombosis in the heart is still there, if we wean him from ECMO, there is a high risk of cardiac arrest. If we do not wean him from ECMO, we need to maintain systemic anticoagulation therapy and the APTT is significantly prolonged. Under such circumstances, sustained ECMO may cause lethal hemorrhage. We carefully evaluated all the risk facing the patient and determined that the possibility of lethal hemorrhage is much higher than cardiac arrest so we decided to wean him from ECMO. Then the anticoagulant regimen was adjusted to enoxaparin 6000iu every 12 hours hypodermic inject. On March 21,2023, there was no obvious abnormal echo in the LV with color Doppler echocardiography (Fig.1 panel D, arrow), and combined with the patient data, thrombosis was diminished after anticoagulant therapy. On day 13, patient was weaned from mechanical ventilation and continuing to use enoxaparin 3000iu hypodermic inject every 12 hours. Subsequently, the patient gradually stabilized and was discharged on the 29th day of hospitalization with no central neurological damage, and no other organ system failures.Conclusions and follow-upBased on our case and literature analysis, left ventricular thrombosis is one of the most serious complications during ECMO. At present, the treatment of left ventricular thrombosis during ECMO mainly includes drug therapy, surgical thrombectomy, and left ventricular load unloading, but there are no specific guidelines about this. The volume of thrombosis in this case is the largest of all surviving cases reported so far of left ventricular thrombosis during ECMO receiving non-surgical treatment only (Table.1).After 3 months of follow-up, the patient’s cardiac ultrasound showed LVEF was 42% and the formation of a left ventricular posterior wall aneurysm. After 9 months of follow-up, the patient’s cardiac ultrasound showed LVEF was 67% and the formation of a left ventricular posterior wall aneurysm. The patients had no special discomfort during the two follow-up visits.DiscussionThere were many complications during taking ECMO as a treatment, including: tearing of large vessels, massive bleeding (30%-70%) [1], and thrombosis. Left ventricular thrombosis is one of the rare but serious complications may lead to death. Many factors may cause thrombosis, and insufficient anticoagulation is one of them. Zhao et al. [2] suggested that the direct thrombin inhibitors (DTI), e.g., heparin, may prevent LV thrombosis. They suggest to use heparin to prolong the APTT to 50-60s. However, there is still no consensus on the target of heparin usage. In addition, researchers suggested to use ACT as monitoring marker to guide the anti-coagulate therapy, but the controversies are still existence [3-4].There are very few case reports on ventricular thrombosis of ECMO. We reviewed previous case reports of left ventricular thrombosis during ECMO treatment. We used keywords “Left ventricular thrombosis” and “extracorporeal membrane oxygenation” and retrieved relevant literatures through PubMed (from 1993 to December 2023). We found only eight case reports and one review article [5-13]. In these reports (Table.1), five patients had survived, three patients had deceased. In one review article, the authors reported patients with heart thrombosis and all deceased. Among the 5 survived patients, the treatments were different, one patient [13] was treated by adjusting anticoagulant to Tenecteplase 30mg administration through a ventilation catheter. Three patients [5, 9, 10] were received surgical thrombectomy, and one patient [6] was treated with a new technology -placed retrograde aortic root catheter for heparin infusion. To our knowledge, our patient is the only successful case that uses heparin/low molecular heparin to save the patient from LV thrombosis reported so far. In addition, the volume of thrombosis in our case is the largest of all reported survival cases by anticoagulation (Table.1).In addition, anti-RO-52 antibody and anti-mitochondrial antibody M2 subtype of this patient were found positive in admission. However, there is no evidence in the literature which anyone can confidently use to causally link this antibody and thrombosis.

Introduction:Neuroblastoma (NB) is the most common extracranial solid tumor in children. The median age at diagnosis was 19 months. It is characterized by clinical heterogeneity. Depending on the risk group, treatment ranges from observation to aggressive multimodal treatment. Stage and age are clinically predictive of outcome. Younger patients (usually defined as 18 months or younger) fared better [1]. Imaging is used to assess primary tumors and determine patterns of disease spread. 60% of tumors originate in the abdomen, with adrenal glands in 32% of cases; other sites are the chest (15%), pelvis (5%), neck (5%), and rarely the brain (1%). [2] Bone and bone marrow are the most common sites of metastatic disease, involving skeletal structures ranging from the skull and spine to the appendix skeleton, followed by the liver and skin. [3]We present a rare case of a patient with bone metastasis neuroblastoma of unknown primary site.

Recently, distal transradial artery access has obtained popularity for coronary diagnostic and interventional procedures due to favorable ergonomics and fewer vascular complications. There are still complications reported including hematoma and pseudoaneurysm formation with this new access, however, distal radial arteriovenous fistula is quite rare. We reported a rare case of a

Amoxicillin-induced DRESS syndrome without eosinophilia

With global climate change leading to an increase in the frequency of abnormally low temperatures, the yield of rice has significantly impacted. Due to extensive efforts over the past four decades, many genes involved in rice cold tolerance have been identified and cloned. Despite these endeavors, the molecular mechanisms of rice’s response to cold stress remain unclear. In this study, we used reverse genetics along with biochemical and molecular biology approaches to characterize OsRab6a, a small GTP-binding protein. Our findings revealed that OsRab6a positively regulates rice cold tolerance during both the bud and seedling stages. The expression of OsRab6a is induced by cold stress, particularly in seedling roots. Overexpression of OsRab6a enhances cold tolerance in transgenic rice, whereas the OsRab6a mutants exhibit the opposite phenotype. Furthermore, OsRab6a physically interacts with OsRAN2 under cold stress, functioning upstream of OsRAN2. These results suggest that OsRab6a plays an crucial role in regulating cold tolerance and the ABA signalling pathway. Our study elucidates the functional significance of OsRab6a in rice cold tolerance and provides potential strategies for enhancing the resilience of rice plants to cold stress.

Background and Aims: The primary healthcare (PHC) system is a comprehensive, equitable, and efficient approach to supporting health and social well-being by offering prevention, treatment, and rehabilitation services close to living environments. The PHC system in Iraq is currently facing issues that limit its effectiveness and efficiency. This research aims to discover strategies to enhance the PHC system in Iraq. Methods: We conducted a systematic search for articles on initiatives aimed at enhancing the PHC system, covering the period from 1980 to June 2024, using eight databases and Google Scholar. We included articles that met the criteria and analyzed them using the framework analysis approach with RevMan 5.3 software. Results: A total of 18,705 articles were extracted. After removing duplicates and items without full text, 15,971 studies remained for title and abstract review, of which 14,175 were removed. Finally, 18 research articles related to PHC strengthening were used. Data collection methods included checking databases (12 studies), interviews (6 studies), focus groups (3 studies), questionnaires, and archival data (15 studies). The majority of research (44.45%) was conducted in Baghdad. Conclusion: In the context of Society 5.0, smart technology’s practical applications in healthcare aim to enhance decision-making, patient care, and service delivery. Smart technologies can help nurses make clinical decisions in complex care situations and streamline procedures like paperwork. When rebuilding and strengthening the PHC system, addressing the historical, social, cultural, and economic variables is important.

Hydrogels show potential for microbiologically influenced corrosion protection but face limitations from weak mechanical properties and toxicity from chemical crosslinkers. Herein, we prepared a photocatalytic antibacterial hydrogel by using chitosan and sodium alginate with loaded 2D g-C3N4, showing strong tensile properties, low swelling rates and exceptional antibacterial rate against Escherichia coli and Staphylococcus aureus. The adsorption of bacteria by -NH2 and the generation of reactive oxygen species by 2D g-C3N4 are the main reasons for antibacterial activity. Additionally, the electron-rich microenvironment formed by -NH2 and -OH attracts the h+ generated by 2D g-C3N4 photocatalysis, thereby increasing the charge carrier separation efficiency. Density functional theory calculations also support this inference. The inclusion of 2D g-C3N4 nanomaterials changes the hydrogel structure, disrupting hydrogen bonds to expose more -NH2 groups that bind with H+ to enhance active adsorption. This innovative hydrogel presents a novel approach for safeguarding against microbial corrosion in marine settings.

We tested whether decreasing respiratory frequency would stabilise both behavioural attention and pupil diameter oscillatory activity, compared to a spontaneously breathing control group. Pupil diameter was used as a proxy measure for Locus Coeruleus (LC) activity in order to directly test a prediction from a dynamical systems model (Melnychuk et al 2018) that posits the LC as a mediating nexus between respiration and attention. A novel task was designed, Paced Auditory Cue Entrainment (PACE) task, in which participants responded rhythmically to auditory cues, providing a continuous measure of sustained attention, and additionally, a breath guide for the experimental group. In Experiment 1, the respiratory frequency was guided from 0.15 Hz → 0.1 Hz → 0.15 Hz. In Experiment 2, participants spent a longer duration in each frequency, guided at 0.15 Hz → 0.1 Hz only. The two experiments yielded highly consistent results. Despite no group differences in the variation of the timing of responses, the control group committed significantly more lapses of attention in contrast to the breathing group, which barely committed any of such errors. Additionally, the oscillatory activity of pupil diameter in the breathing group closely tracked the frequency of the instructed breathing, implicating the possibility of LC-noradrenaline activity being entrained by the breath intervention. From these findings we conclude that decreasing respiratory frequency did indeed stabilise attention, mitigating lapses, possibly through stabilising fluctuations in LC activity.

Background: The study examines alloparental care and adoption in the Sri Lankan leopard population at Yala National Park, Sri Lanka. Using the Multi Point Leopard Identification Method, it documents a remarkable instance: a leopard cub [YM 67] initially adopted by its maternal aunt [YF 46], and later by another female [YF 15] with no prior connection to the cub. We consider this behaviour is noteworthy in especially solitary animal species such as leopards. Methods: Our study was conducted for a period of two years and five months (from February 2021 to July 2023). Our observations highlight the dynamics of these adoptions and the behaviours exhibited. Altruistic acts, such as feeding, brushing, and shielding the cubs, were observed. These inspections challenge the conventional knowledge regarding leopard behaviours. Notably, YF 15’s adoption of YM 67, despite their lack of genetic relatedness, exemplifies a form of mutually beneficial reciprocal altruism, benefiting both parties. Discussion: The following study explains leopard adoptions using evolutionary theories like kin altruism and reciprocal altruism. It suggests factors such as genetic relatedness, mutual dependency, and possible misidentification influenced the act of adoption. These rare altruistic acts benefit the leopard population. Conclusion: Our study opposes traditional concepts of solitary Sri Lankan leopards. Altruistic behaviours, influenced by genetic relatedness and reciprocal benefits, emphasize social dynamics in predator populations. These findings enhance the understanding of evolutionary mechanisms and cooperative behaviours in maintaining population fitness in the Sri Lankan leopard population.

Chronic low back pain, typically managed through lumbar fusion, demands innovative approaches to enhance therapeutic outcomes. This study investigates the efficacy of small extracellular vesicles (sEVs) derived from bone marrow mesenchymal stem cells (BMSCs) cultured in three-dimensional (3D) scaffolds concurrently under electromagnetic fields (EMF) stimulation, aiming to enhance osteogenesis and angiogenesis in a rat lumbar fusion model. We utilize a composite of polycaprolactone and hydroxyapatite, engineered via 3D printing, to create the scaffolds. sEVs are harvested from BMSCs under three distinct conditions: standard 2D cultures, 3D scaffolds, and 3D scaffolds with EMF stimulation. Specifically, the sEVs from the EMF-stimulated 3D cultures (3D/E-sEVs) are incorporated into these scaffolds before being implanted into rat spines. Results reveal that 3D/E-sEVs markedly enhance both osteogenesis and angiogenesis. Further mechanistic investigations identify the PTEN/PI3K/AKT signalling pathway as essential in mediating these regenerative effects. Moreover, 3D PCL/HA scaffold loaded with 3D/E-sEVs promote lumbar fusion in a rat model. Conclusively, our findings demonstrate that 3D-printed PCL/HA scaffolds engineered with 3D/E-sEVs significantly promote bone regeneration and vascular formation, thereby improving lumbar fusion outcomes. This study highlights potential of integrating tissue engineering techniques with sEVs therapies to revolutionize the treatment of low back pain and enhance surgical success rates.

Motherhood is generally portrayed as a concept associated with love and happiness and is defined as the most sacred role attainable for women. However, the responsibilities imposed by the gender-based division of labor cause women to feel burned out, lonely, and guilty. In this study, women's perceptions of motherhood and womanhood roles and the effect of a group therapy experience through psychodrama on these perceptions were examined. For this purpose, the Parental Stress Scale was administered as a pre-test before the "Psychodrama-oriented Motherhood-Femininity Roles Group Program," as a post-test after the program was completed, and as a follow-up measuring tool one year after the program was completed. In the focus group interview conducted as a follow-up measurement, three open-ended questions were asked to determine the effectiveness of the study and the changes in the participants. The results of the analysis showed that the psychodrama method enabled the participants to gain insight into their role patterns and experiences, improve their empathy for others, display healthier behaviors, and develop their role repertoires through group therapy.

Despite the importance of attentional control deficits in the development of anxiety symptoms, insufficient studies take a developmental approach to understanding attentional control theory. The study aimed to understand the reciprocal association between attentional control and anxiety symptoms during transition into early adolescence. Using the longitudinal design, the study recruited 321 Chinese children from a primary school with the ages of 9 to 10 years. Children completed inventories to measure attentional control difficulties and anxiety symptoms three times with an interval of 6 months from Grades 3 to 5. Random intercept cross-lagged panel model revealed that attentional control difficulties did not predict the development of anxiety symptoms, and anxiety symptoms did not predict the development of attentional control difficulties from Wave 1 to Wave 2 and from Wave 2 to Wave 3. These findings casted doubt to attentional control theory in the developmental context. Preventions that improve adolescents' attentional control might not necessarily help reduce anxiety symptoms.

Background: Despite the recognition that depressive symptoms increase the risk of non-suicidal self-injury (NSSI) in adolescence, there are limited investigations of these associations and their mediators in adulthood. The current study examined the predictive validity of depressive symptoms on NSSI and perceived social support (PSS) characteristics and the mediating role of PSS domains in these relationships. Methods: Univariate group difference tests (i.e., t-tests and chi-square test of independence, 𝝌 2), regression, and mediation analyses were conducted with cross-sectional data from 435 community-based adults. Results: The findings indicate that individuals with clinically significant depressive symptoms were more likely to endorse a lifetime history of NSSI and greater rates of future self-rated risk. Clinically elevated depressive symptoms were associated with lower overall, familial, significant other, and friend PSS. Only familial PSS emerged as a significant predictor of self-rated future NSSI engagement likelihood and a statistical mediator between past-week depressive symptoms and prospective NSSI risk. Conclusions: These results may contribute to the advancement of assessment and intervention practices for depressive symptoms and NSSI in adulthood.

Authors details:1. Somee Rauniyar (Corresponding Author)Affiliation: Madan Bhandari Institute of Health Sciences (Hetauda Hospital), Makawanpur, NepalContribution: Conceptualization, Data curation, Formal Analysis, Investigation, Methodology, Project Administration, Resources, Supervision, Validation, Writing-original draft, Writing-review & editingSupervision, Writing- Original draft, Writing-review, and editingOrcid No: 0009-0007-5466-3183Email: rauniyarsomee4@gmail.com2. Deepak SubediAffiliation: Nepalese Army Institute of Health Sciences College of Medicine,Kathmandu, NepalContribution: Data curation, Formal Analysis, Investigation, Methodology, Supervision, Writing-original draft, Writing-review, and editingOrcid No: 0000-0001-8512-1482Email: subedideepak28@gmail.com3. Bishwodip BaralAffiliation: Sukraraj Tropical and Infectious and Disease Hospital, KathmanduContribution: Formal Analysis, Investigation, Methodology, Resources, Supervision, Validation, Writing-review, and editingOrcid No: 0000-0002-2066-7940Email: bishwodipbaral@gmail.com4. Pramod kumar KafleAffiliation: Chitwan Medical College and Teaching Hospital, Chitwan, NepalContribution: Data curation, Formal Analysis, Investigation, Methodology, Resources, Writing-review, and editingOrcid No: 0000-0003-3945-7190Email: pramodkafle18@gmail.com5. Neha BistaAffiliation: Madan Bhandari Institute of Health Sciences (Hetauda Hospital), Makawanpur, NepalContribution: Investigation, Methodology, Supervision, Validation, Writing-review, and editingWriting- Writing-review and editingOrcid No: 0009-0009-1934-6347Email: nehabista992@gmail.com6. Prajwal SapkotaAffiliation: Madan Bhandari Institute of Health Sciences (Hetauda Hospital), Makawanpur, NepalContribution: Formal analysis, Methodology, Resources, Writing-review, and editingOrcid No: - 0009-0009-5933-5837Email: dr.prajwalsapkota@gmail.com

A document by Reinhardt Rading. Click on the document to view its contents.

Objective: Radiation therapy (RT) is the primary neoadjuvant modality for pancreatic ductal adenocarcinoma (PDAC), especially in borderline resectable or unresectable presentations. Despite its central role, the therapeutic efficacy of RT is markedly hindered by inherent resistance mechanisms in pancreatic cancer cells, the specific determinants of which are not yet fully understood. This study aims to elucidate the potential of metformin in enhancing the synergistic effects of RT against PDAC.. Methods: Radiation therapy was confirmed to induce senescence in pancreatic cancer cell lines (PANC-1 and PANC-02) via immunofluorescence, SA-β-Gal staining, and immunoblot analysis. We assessed the resistance of senescent cancer cells to RT and examined the capacity of metformin to potentially reverse this resistance, employing SA-β-Gal staining, immunofluorescence, western blotting, and CCK8 assays. Results: RT increased the expression of senescence biomarkers (p21, p16, and SA-β-Gal activity) in residual cancer cells. Senescent cancer cells exhibited resistance to RT both in vitro and in vivo. Furthermore, metformin effectively reversed this RT-induced resistance in senescent cancer cells in both experimental settings. Mechanistically, we observed a reduction in the unfolded protein response in senescent pancreatic cancer cells treated with RT and metformin. Conclusion: This study demonstrates that combining RT with metformin represents a potent strategy to eliminate senescent pancreatic cancer cells, suggesting its potential as a novel neoadjuvant therapeutic approach for refractory tumors in clinical practice.

Objectives: Ovarian cancer has a limited immunotherapeutic response; hence, this study aimed to investigate the relationship between CXC-chemokine ligand 13 ( CXCL13) expression and overall survival (OS) rate, key immune pathways, degree of immune cell infiltration, and PD-1 checkpoint blockade. Methods: A total of 703 differentially expressed genes (DEGs) were obtained from “The Cancer Genome Atlas” (TCGA) database based on the immune and stromal scores of 379 OC patients for getting the targeted gene CXCL13. The association between CXCL13 and OS in OC patients, biological function annotation of CXCL13, and its correlation with immune components were assessed. Results: The results indicated that upregulated CXCL13 expression was positively correlated with good OC patient prognosis. CXCL13 expression was associated with six immune-related pathways, ten immune cells, and PD-1 in the OC microenvironment. Moreover, high expression of CXCL13 was related to a better tumor response and a more extended tumor-stable stage after PD-1 blocking therapy in IMvigor210. Conclusions: The study concluded that CXCL13 could be a prognostic marker and a potential immunotherapy target for OC patients, especially PD-1 checkpoint blockade.

This paper aims to establish the global well-posedness of the free boundary problem for the incompressible viscous resistive magnetohydrodynamic (MHD) equations. Under the framework of Lagrangian coordinates, a unique global solution exists in the half-space provided that the norm of the initial data in the critical homogeneous Besov space B _ p , 1 – 1 + N / p ( R + N ) is sufficiently small, where p∈[ N,2 N–1). Building upon prior work such as (Danchin and Mucha, J. Funct. Anal. 256 (2009) 881–927) and (Ogawa and Shimizu, J. Differ. Equations 274 (2021) 613–651) in the half-space setting, we establish maximal L 1 -regularity for both the Stokes equations without surface stress and the linearized equations of the magnetic field with zero boundary condition. The existence and uniqueness of solutions to the nonlinear problems are proven using the Banach contraction mapping principle.

Developing safe and high energy density batteries is a significant challenge, especially for Li-ion configurations. Using Li-metal as the negative electrode could greatly boost energy density but requires the replacement of liquid electrolytes by solid‑state electrolytes (SSEs) to work properly and safely. Non‑volatile SSEs may prevent dendrite growth related to inhomogeneous Li electrodeposition leading to low-capacity retention and potential short‑circuit. Challenges persist in ensuring close electrode/SSE contact, enhancing ionic conductivities, electrochemical stability at operating temperatures, cycle life and fast charging capabilities. Here, a composite SSE composed of a dispersion of ionic conductive ceramic particles in a polymer electrolyte matrix is studied to leverage different SSE types. Li+ ions dynamics are investigated at 60 °C with Li isotopic tracing after applying an electrical field. High‑resolution solid-state NMR and orthogonal time‑of‑flight secondary ion mass spectrometry are employed for characterizing Li isotopic relative abundance in SSE at global and local levels, respectively. By differentiating Li in the polymer phase from ceramic particles, both techniques reveal that Li+ ions preferentially diffuse through the ceramic dispersion. Surprisingly, electrochemical impedance spectroscopy analysis shows no enhancement in ionic conductivity between polymer and composite electrolytes, highlighting the impact of other parameters such as percolation or polymer/ceramic interface properties.

Chinese hamster ovary (CHO) bioprocesses, the dominant platform for therapeutic protein production, are increasingly used to produce complex multispecific proteins. Product quantity and quality are affected by intracellular conditions, but these are challenging to measure and often overlooked during process optimization studies. pH is known to impact quality attributes like protein aggregation across upstream and downstream processes, yet the effects of intracellular pH on cell culture performance are largely unknown. Recently, advances in protein biosensors have enabled investigations of intracellular environments with high spatiotemporal resolution. In this study, we integrated a fluorescent pH-sensitive biosensor into a bispecifc (bisAb)-producing cell line to investigate changes in endoplasmic reticulum pH (pH ER). We then investigated how changes in lactate metabolism impacted pH ER, cellular redox, and product quality in fed-batch and perfusion bioreactors. Our data show pH ER rapidly increased during exponential growth to a maximum of pH 7.7, followed by a sharp drop in stationary phase in all perfusion and fed-batch conditions. pH ER decline in stationary phase was driven by an apparent loss of cellular pH regulation that occurred despite differences in redox profiles. Protein aggregate levels correlated positively with pH ER, indicating that aggregation is not solely driven by oxidative stress and cellular protein load. Improved characterization of intracellular changes in bioprocesses can help guide media optimizations, improve bioprocess control strategies or provide new targets for cell engineering.

Geographical distribution and diversity patterns of bird species are influenced by climate change. The Rouget’s rail (Rougetius rougetii) is a ground-dwelling endemic bird species distributed in Ethiopia and Eritrea. It is a near-threatened species menaced by habitat loss, one of the main causes of population declines for bird species. The increasing effects of climate change may further threaten the species’ survival. So far, the spatial distribution of this species is not fully documented. With this study, we develop current potential suitable habitat and predict the future habitat shift of R. rougetii based on environmental data such as bioclimatic variables, population density, vegetation cover, and elevation using ten algorithms. We evaluated the importance of environmental factors in shaping the bird’s distribution and how it shifts under climate change scenarios. We used 182 records of R. rougetii from Ethiopia and nine bioclimatic, population density, vegetation cover, and elevation variables to run the 10 model algorithms. Among 10 algorithms, eight were selected for ensembling models according to their predictive abilities. The current suitable habitats for R. rougetii were predicted to cover an area of about 82,000 km² despite being highly fragmented. The model suggested that temperature seasonality (bio4), elevation, and mean daily air temperatures of the driest quarter (bio9) contributed the most to delimiting suitable areas for this species. R. rougetii is sensitive to climate change associated with elevation, leading to a large, shrinking distribution of suitable areas. The projected spatial and temporal pattern of habitat loss of R. rougetii suggests the importance of climate change mitigation and implementing long-term conservation and management strategies for this threatened endemic bird species.

The development of sophisticated artificial intelligence systems has rapidly transformed various industries, creating an increased demand for models capable of advanced linguistic processing and comprehensive knowledge integration. Addressing this demand, the presented evaluation explores the capabilities of ChatGPT and Google Gemini through a dual lens of linguistic skill and world knowledge, offering a unique perspective that goes beyond traditional assessments focused solely on language generation or factual recall. Through a carefully structured methodology, which incorporates a range of tasks designed to test syntax, grammar, vocabulary, and logical reasoning, the study provides a comparative analysis of how well each model can manage both linguistic complexity and the retrieval and application of factual information. Results indicate that ChatGPT excels in maintaining grammatical accuracy and consistency, making it particularly suitable for applications requiring rigorous language precision, while Google Gemini demonstrates superior contextual comprehension and logical reasoning abilities, suggesting its efficacy in scenarios where complex understanding and the ability to integrate diverse knowledge are crucial. The insights derived from this evaluation not only highlight the current capabilities and limitations of both models but also provide a foundational understanding that can inform future developments in enhancing language processing and knowledge management within AI systems.