bluuebunny/crossref_metadata_2025_split huggingface dataset:
Selective genetic inactivation of Caspase 8 in hepatocytes ameliorates progression of MASH following Jnk deficiency
Authors: Volkert Ines , Grube Julia , Woitok Marius Maximilian , Mohamed Mohamed Ramadan , Edlund Karolina , Duda Julia Christin , Dietrich Jana , Schneider Ursula , Yin Guo , Lin Cheng , Erschfeld Stephanie , Berger Hilmar , Candels Lena , Davis Roger J. , Bartneck Matthias , Kühnel Mark Phillip , Guillot Adrien , Schneider Kai Markus , Schneider Carolin Victoria , Jonigk Danny , Rahnenführer Jörg , Tacke Frank , Hengstler Jan , Trautwein Christian 
Published: February 2025

Background and Aims:
Metabolic dysfunction-associated steatohepatitis (MASH) is associated with c-Jun N-terminal kinases (JNK) activation across various cell types, but its hepatocyte-specific function in steatotic liver disease remains unclear. Our study investigates the role of JNK1/JNK2 during MASH progression and dissect its hepatocyte-specific function.

Approach and Results:
We showed that UK biobank patients with a predicted-loss-of-function (pLOF) variant of JNK1 presented an increased prevalence of MASLD and liver damage. Analysis of a pathology cohort of patients with steatotic liver disease revealed increased oxidative stress response and apoptosis. After subjecting mice deficient for Jnk1 and Jnk2 in hepatocytes (Jnk1/2
Δhepa) to two different MASH models, we observed enhanced liver injury, fibrosis and oxidative stress. RNA sequencing revealed highly up-regulated pathways in Jnk1/2
Δhepa livers, including inflammatory signals and apoptotic pathways. Additional blocking of Caspase 8 signaling improved HFD-induced liver damage, fibrogenesis and oxidative stress. Ultimately, a therapeutic approach using lipid nanoparticles containing small interfering RNA (siRNA) targeting Caspase 8 during MASH progression attenuated liver injury and cell death in mice.

Conclusions:
Our findings define a protective role of JNK1/JNK2 in hepatocytes during the oxidative stress response driving progression of MASH. This process is mainly mediated by Caspase 8-dependent apoptosis, thereby discovering that Caspase 8 is a downstream target of JNK1/2. Caspase 8 directed therapy in hepatocytes might be a promising treatment for patients with an increased oxidative stress response and MASH.
Discrete Bayesian Dose-response Analysis under Dose Uncertainty
Authors: Hofer Eduard 
Published: February 2025

Abstract
Establishing a relationship between disease and dose requires each individual in the population under investigation to be known by disease status and by the value of the dose received. Frequently, the dose values are reconstructed using a dose assessment model containing imprecisely known parameter values, model formulations, and input data (epistemic uncertainties). As a consequence, the state of knowledge of the assessed dose values needs to be expressed by a joint subjective probability distribution thereby accounting for state of knowledge dependence due to uncertainties shared by the assessed dose values of several individuals. Dose-response analysis must apply this joint state of knowledge in obtaining a subjective probability distribution for the parameters of the dose-response model. This is achieved by drawing a random sample of dose vectors according to the joint distribution, by applying Bayes’ theorem for each vector, and by averaging the posterior parameter distributions (Bayesian model averaging). If the dose response is quantified by a binary variable, a logistic regression model is embedded in the likelihood function. This paper presents a new, computationally efficient Bayesian model averaging method that operates over the discretized parameter space and thereby does away with the computational complexities of Bayesian methods. It corrects for the attenuation effect that is due to the application of dose vectors other than the true vector. Results obtained for a sample of dose vectors are compared to those obtained with the standard discrete Bayesian method using the true dose vector.
Application of ultrawide-field ss-OCTA in the precise diagnosis of diabetic retinopathy
Authors: Zou Chen , Liu Wei , Chang Qing , Xuan Yi , Zhou Yao , Tang Nuo , Wang Min 
Published: February 2025

Purpose:
To study the imaging findings of ultrawide-field swept source optical coherence tomography angiography (ss-OCTA) and its advantages with respect to ultrawide-field fundus photography (FP) in the precise diagnosis of diabetic retinopathy (DR), and to reveal its applications in DR.

Methods:
The imaging findings of microangiopathy in ultrawide-field ss-OCTA and ultrawide-field FP from DR patients were retrospectively analyzed, and the differences between the two methods were assessed. In addition, the grade of DR based on the imaging findings of the two modalities was determined and compared.

Results:
Ultra-widefield ss-OCTA clearly revealed various occult retinal microvascular lesions in DR patients over a detection range which was similar to ultrawide-field FP. Significantly more retinal microangiopathy were detected and more eyes were given a worse DR grade with ultrawide-field ss-OCTA than those with ultrawide-field FP.

Conclusion:
Ultrawide-field ss-OCTA is more able to detect retinal microangiopathy compared with ultrawide-field FP and is contributive in the precise diagnosis of DR. Ultrawide-field ss-OCTA has substantial applicability in the precise diagnosis of DR, especially when ultrawide-field fundus fluorescence angiography (FFA) is unavailable.
Epstein-Barr Virus Associated Frosted Branch Angiitis
Authors: Xia Julia L. , Lai Jennifer M. , Palestine Alan G. , Reddy Amit K. 
Published: February 2025

Purpose:
To describe two cases of frosted branch angiitis (FBA) in the setting of Epstein-Barr virus (EBV) infection.

Methods:
Retrospective case series of two patients at the University of Colorado Sue Anschutz-Rodgers Eye Center.

Results:
Case 1 is a 17-year-old female who presented with bilateral floaters and blurry vision two weeks after a diagnosis of mononucleosis. Visual acuity was 20/20 in both eyes and exam was significant for vitreous cell and FBA appearance to the retinal vasculature in both eyes. Treatment with oral prednisone and valacyclovir was initiated with improvement in vitritis and vascular sheathing. One month after all treatment was discontinued, there was a recurrence of vitritis that was treated with bilateral sub-Tenon’s triamcinolone acetonide injections. Final visual acuity was 20/20 in both eyes with resolved vitritis. Case 2 is a 20-year-old male who presented with headache and acute bilateral vision loss. He was found to have a meningoencephalitis with cerebrospinal fluid positive for EBV that was treated with intravenous methylprednisolone and acyclovir. Visual acuity was count fingers in both eyes. Exam was significant for diffuse bilateral frosted branch angiitis which the subsequent development of bilateral bacillary detachments and neuroretinitis that required treatment with oral prednisone, oral acyclovir, and bilateral intravitreal dexamethasone implants, which resolved all ocular inflammation. Final visual acuity was 20/30 right eye and 20/25 left eye.

Conclusion:
Bilateral FBA may present following EBV infection and responds well to corticosteroids and antiviral therapy.
The Interaction of Shock Waves With Biological Tissue - Momentum Transfer, the Key for Tissue Stimulation and Fragmentation
Authors: Wess Othmar , Mayer Juergen 
Published: February 2025

Background:
Shock waves in medicine have gained enormous importance and have spread since 1980, and the first kidney stone was successfully fragmented in a patient in Munich. Meanwhile, the spectrum of medical applications of shock waves ranges from powerful fragmentation of kidney stones to diverse indications such as wound healing, chronic pelvic pain, spasticity, erectile dysfunction, and others, to neuro-stimulation in the context of Alzheimer’s disease. A comprehensive working mechanism for this diverse field of medical indications are still missing.

Objective:
Investigation of the physical basis of the working mechanism of shock waves in medical applications.

Methods:
We developed a model based on the mechanical forces generated by the momentum transfer at the acoustic interfaces of different layers of biological tissue. The generated forces are strong enough to crash brittle material and provide an adequate mechanical stimulus to activate mechano-transduction and mechano-sensory-transduction with nerve stimulation, thereby affecting the neural memory function of the central nervous system.

Results:
The key to generating appropriate forces in the millisecond range is the mechanism of momentum transfer at the interfaces between tissue layers with different acoustic impedances. According to Newton´s laws of motion, a change in momentum (momentum transfer) generates force F = dP/dt. The inherent shear forces can stretch biological membranes to release biomolecules such as VEGF and NO. A most favourable feature of this mechanism is the selective effect on soft tissue interfaces and small tissue inhomogeneities to generate small forces in the range of few (≤ 10) Newton to stimulate tissue and nerve cells, while the same shock wave can generate forces ≥ 200 Newton and more on hard tissue interfaces such as bones or stones.

Conclusion:
The mechanism of momentum transfer is the basis for mechano-transduction and mechano-sensory transduction. It offers the opportunity to stimulate peripheral nerves and modify the motor reflex patterns of “pathologic” reflexes by hyper stimulation. The new technique of transcranial pulse stimulation (TPS) may be based on direct stimulation and reactivation of neurons in the brain. Momentum transfer is the basic physical mechanism and the initiator for successive biological processes in medical shock wave therapy.
Intracorporeal versus extracorporeal anastomosis in laparoscopic total gastrectomy: a systematic review and meta-analysis
Authors: Zaman Shafquat , Hussain Mohammad Iqbal , Kausar Maria , Mostafa Omar E.S. , Mohamedahmed Ali Yasen , Hajibandeh Shahab , Hajibandeh Shahin , Camprodon Ricardo , Sellahewa Chaminda 
Published: February 2025

Background:
To evaluate outcomes of intracorporeal (IOJ) versus extracorporeal (EOJ) oesophagojejunostomy following laparoscopic total gastrectomy (LTG) for the treatment of gastric cancer.

Methods:
A comprehensive search of various electronic databases was conducted. Comparative studies of IOJ versus EOJ following LTG in patients with gastric malignancy were included. Primary outcomes were anastomotic leak, anastomotic bleeding, and anastomotic stricture formation. Secondary outcomes included operative time, length of hospital stay (LOS), volume of intra-operative haemorrhage, number of harvested lymph nodes, time to flatus, time to soft diet, intra-abdominal infection, pulmonary infection, surgical site infection (SSI), duodenal stump leak, pancreatic fistula occurrence, postoperative ileus, re-operation, and mortality. Combined overall effect sizes were calculated using the random-effects model, and the Newcastle-Ottawa Scale was used to assess risk of bias.

Results:
Seventeen non-randomised studies enrolling 2,960 patients divided between an IOJ (n = 1430) and EOJ (n = 1530) group were included. IOJ was associated with significantly lower risk of anastomotic stricture (P = 0.01), volume of intra-operative bleeding (P = < 0.001), and SSI (P = 0.04) compared to EOJ. No difference was found in anastomotic leak (P = 0.93); anastomotic bleeding (P = 0.35); operative time (P = 0.63); LOS (P = 0.30); lymph node yield (P = 0.17); time to first flatus (P = 0.77); time to resumption of soft diet (P = 0.32); intra-abdominal infection (P = 0.22); pulmonary infection (P = 0.45); duodenal stump leak (P = 0.46); pancreatic fistula occurrence (P = 0.16); and paralytic ileus (P = 0.59), re-operation (P = 0.50), and mortality (P = 0.23) between the two groups.

Conclusions:
LTG for gastric malignancy with IOJ may be associated with lower risk of anastomotic stricture and SSI compared to the extracorporeal approach. However, future adequately powered randomized studies are needed to compare the two techniques.
Wild honey grayanotoxin intoxication in rural Himalayan region of Nepal: a case report
Authors: Adhikari Aayush , Aryal Roshan , Baral Pratik , Acharya Baburam , Neupane Peter , Paudel Aadesh , Yadav Sushil Kumar 
Published: February 2025

Introduction and importance:
Wild honey from Nepal’s Himalayas contains grayanotoxin, derived from rhododendron flowers, and is used in alternative medicine. However, it can cause severe side effects like vomiting, hypotension, and bradycardia.

Case presentation:
A 52-year-old baker from Chame, Manang, Nepal experienced dizziness, vomiting, sweating, and hypersalivation 30 minutes after consuming a teaspoon of wild honey for mild abdominal pain. In the emergency department, he had severe dizziness, low blood pressure of 48/32 mm Hg, heart rate of 49 beats per minute, and oxygen saturation of 90%. Electrocardiogram showed sinus bradycardia. He received IV fluids, oxygen, ondansetron, and atropine, with low-dose vasopressor support. His condition gradually improved, and he was discharged with stable vitals follow-up showed stable vitals and no symptoms.

Clinical discussion:
Consumption of honey containing grayanotoxins, derived from rhododendron plants, can lead to wild honey intoxication, prevalent in regions such as Turkey, South Korea, and Nepal. Symptoms include dizziness, hypotension, bradycardia, and cardiac disturbances. Diagnosis is clinical with use of laboratory tests to rule out other differentials if available and treatment involves symptomatic care with fluids, atropine, and monitoring. Distinguishing mad honey intoxication from conditions like acute coronary syndromes and organophosphate poisoning is crucial.

Conclusion:
Wild honey intoxication from rhododendron grayanotoxins causes symptoms such as dizziness, hypotension, and bradycardia, requiring clinical diagnosis and management with symptomatic care, fluids, and atropine, along with close monitoring for recovery.
Exploring the evolution of evidence synthesis: a bibliographic analysis of umbrella reviews
Authors: Nayak Sandeep Samethadka , Amini-Salehi Ehsan , Ulrich Michael T. , Sahli Yasmin , Fleischman Micah , Patel Masum , Naeiji Mahdi , Maghsoodifar Hasan , Sadeghi Douki Seyed Amir Hossein , Alroqi Hadi , Faraji Niloofar , Hassanipour Soheil , Hashemi Mohammad , Keivanlou Mohammad-Hossein 
Published: February 2025

Background:
Umbrella review studies have become increasingly vital in evidence synthesis, offering a comprehensive overview by analyzing multiple systematic reviews and meta-analyses. This bibliometric study aimed to delineate the growth and thematic evolution of umbrella reviews within evidence-based medicine, illuminating their integral role in synthesizing high-level evidence.

Methods:
Utilizing the Web of Science Core Collection, we performed a search for publications on umbrella reviews, identifying relevant articles through a refined strategy. Analytical tools including VOS Viewer and CiteSpace were employed to visualize connections and trends among the gathered data, converting intricate bibliometric information into comprehensible visual maps.

Results:
Our search yielded 2965 pertinent publications, highlighting a marked growth in research output, particularly from 2010 to 2023. The United States, United Kingdom, and China were predominant in this field, with leading institutions like King’s College London and the University of Toronto at the forefront. The analysis identified major journals such as BMJ Open and PLOS One as key publishers. Co-citation and keyword analysis revealed current research focuses, with recent trends emphasizing COVID-19 and mental health. The study also uncovered a robust international collaboration network, underscoring the global impact of umbrella reviews.

Conclusion:
This bibliometric analysis confirms the expanding influence and utility of umbrella reviews in medical research and decision-making. By charting the evolution and current trends in this field, our study not only showcases the geographical and institutional distribution of research but also guides future scholarly efforts to advance evidence synthesis methodologies.
Effectiveness of virtual reality-based cognitive behavioral group therapy on reducing anxiety and depression in Parkinson’s patients: a randomized controlled trial
Authors: Asadiof Farnaz , Gharehtapeh Zhaleh Hasanpour , Naeim Mahdi , Mirzai Fatemeh , Mohammadi Yasaman 
Published: February 2025

Introduction/objective:
This study aimed to evaluate the impact of virtual reality-based cognitive behavioral group therapy (VR-CBGT) on reducing anxiety and depression in patients with Parkinson’s disease.

Methods:
A randomized clinical trial with a pretest and posttest design was conducted involving 90 Parkinson’s patients, from Roozbeh Hospital, Tehran in 2023. Participants were randomly assigned to an experimental group receiving 12 sessions of VR-CBGT over 3 months or a control group with no psychological intervention. Both groups completed the Beck Depression Inventory and Beck Anxiety Inventory before and after the intervention. Data were analyzed using multivariate analysis of covariance in SPSS-25.

Results:
The experimental group showed significant reductions in depression and anxiety compared to the control group. VR-CBGT explained 15% of the variance in depression (F = 6.148, P < 0.0005) and 31% in anxiety (F = 17.800, P < 0.0005).

Conclusion:
VR-CBGT effectively alleviates depression and anxiety in Parkinson’s patients, offering a promising therapeutic approach. Integrating VR into CBT enhances engagement and real-life skill application, supporting its use as a complementary intervention.
Hemodynamically stable despite ruptured cesarean scar ectopic pregnancy: a case report and literature review
Authors: Gurjar Bhakti , Wankhede Sachin , Saha Indrakshi , Narayan Gaurang , Rusho Maher Ali , Budair Mayar Moustafa , Wei Calvin R. , Mousa Hazem Mohamed , Naaz Farheen , Rizvi Syeda Vilay Zehra , Rizvi Syeda Umme Abiha , Fatima Sabika , Akilimali Aymar 
Published: February 2025

Introduction and importance:
The increasing prevalence of cesarean sections has raised concerns regarding associated risks such as ectopic pregnancy, placenta previa, and placenta accreta. Cesarean scar ectopic pregnancy (CSEP), although uncommon, has become more frequent with the rising rate of cesarean deliveries. This condition involves implantation of an embryo within the myometrial defect of a previous cesarean uterine incision. It requires early detection to mitigate life-threatening complications due to its potential rupture.

Clinical presentation:
A 27-year-old G5P3L3A1 female was referred to our facility presenting with vaginal bleeding post-medical termination of pregnancy at 16 weeks of gestation. Ultrasound and MRI findings indicated an adherent placenta at the previous C-section scar site, suggestive of placenta accreta complex and scar site ectopic gestation. To navigate the diagnostic dilemma, a laparoscopy was planned. The omentum was found covering a ruptured area. Once it was removed, the patient began bleeding profusely at the rupture site. Thus, the omentum had sealed the ruptured CSEP, preventing massive blood loss and keeping the patient hemodynamically stable.

Clinical discussion:
Transabdominal ultrasound is currently the primary method of CSEP diagnosis. Other methods include color Doppler, transvaginal ultrasound, and MRI. Due to the rarity of the diagnosis, there are no established treatment guidelines, and case reports and small case series make up the majority of management evidence. CSEP can be treated by methotrexate or surgery. Our patient was treated through a laparoscopic procedure as the complex nature of the case required intervention. Forty percent of ectopic pregnancies found on cesarean scars are asymptomatic while some patients present with abdominal pain or vaginal bleeding. Our patient had clinical manifestations of severe bleeding, pointing toward rupture of the ectopic pregnancy. The omentum however covered the ruptured uterine area in a rare occurence, limiting blood loss.

Conclusion:
CSEP cases always pose a diagnostic dilemma that could lead to severe maternal morbidity if not managed accurately. The diagnostic methods for CSEP need to be reviewed based on accuracy and efficiency. From this case, we can also conclude that the existence of a rupture should not be eliminated based on clinical findings as the patient was hemodynamically stable. This highlights the varied complex presentations that patients with ruptured CSEP may have.
From pregnancy to beyond: renewed emphasis on comprehensive HIV prevention in South Africa
Authors: Babalola Chibuzor M. , Peters Remco P.H. , Muzny Christina A. , Davey Dvora Joseph , Taylor Christopher M. , Mdingi Mandisa M. , Mukomana Freedom , de Vos Lindsey , Medina-Marino Andrew , Klausner Jeffrey D. 
Published: February 2025

South Africa continues to document high HIV prevalence, particularly among pregnant women, highlighting significant prevention gaps. This viewpoint triangulates findings from the Sixth South African HIV Prevalence Survey, the 2022 Antenatal HIV Sentinel Survey, and our ongoing “Philani Ndiphile” trial, which is evaluating STI screening algorithms to improve pregnancy outcomes. Despite a recent national decline in antenatal HIV prevalence, the Philani trial recorded an HIV prevalence of 28.6% among pregnant women, mirroring high rates across the Eastern Cape Province. The trial cohort also revealed a significant increasing trend in HIV prevalence with age, from 6% at 18 years to 63% at 43 years, highlighting the need for age-targeted interventions in young women of childbearing age.
National progress toward UNAIDS’ targets for HIV status knowledge and ART initiation is evident; however, viral suppression remains a challenge, reflected in the 20% of Philani participants newly initiated or reinitiated on ART at their first antenatal visit. Efforts to reduce new HIV infections require strengthening, as high incidence rates persist among young women and during pregnancy and postpartum.
Expanding access to oral and long-acting PrEP for pregnant and postpartum women is critical. Current coverage is low, and while new options show promise, implementation guidance remains limited. Socioeconomic factors, such as poverty and intimate partner violence, exacerbate HIV risk. Comprehensive interventions, including educational and vocational support, engaging male partners, and addressing STIs are essential. Continued support from global health partnerships and innovation in prevention strategies are vital to ending the epidemic and ensuring equitable outcomes.