Biopsychosocial approaches to treat female chronic pelvic painJim Thornton, Emeritus professor obstetrics & gynaecology, university of Nottingham, UKNick Brown, Department of Psychology, Linnaeus University, Växjö, SwedenCorresponding author: jim.thornton@nottingham.ac.ukDear Dr. Aris Papageorghiou,We read the recent systematic review of biopsychosocial approaches to treat female chronic pelvic pain (October 2024) [1] with interest. The fact that three included studies had been conducted by the same research group, and differed only in the type and focus of goal setting [2, 3, 4], inspired us to read them carefully.All three studies contain multiple reported mean values, for variables which are normally reported as integers, which appear to be impossible: so-called GRIM inconsistencies [5]. We have posted our concerns on the peer review website PubPeer.com,https://pubpeer.com/publications/A182FA06122C1D2C38E819415EC155\#1, https://pubpeer.com/publications/16A4EA3222C67B2E38AD0790F38E43 and https://pubpeer.com/publications/7B0A50B193748DEF5196E10529FC76\#1 and asked the editors of Maturitas and Archives of Physical Medicine and Rehabilitation to investigate.Although such inconsistencies can be due to typos, or other minor data errors, the occurrence of so many, in three different randomised controlled trials by the same investigator group, raises serious questions about the integrity of the data and, hence, the validity of the results in these articles.We suggest that readers interpret the reliability of these three studies, and hence also the systematic review, which is partly based on them, with caution unless the respective journal investigations indicate no cause for concern. We also think it essential that the authors should provide their data for reanalysis, to determine the origin of these inconsistencies.Jim Thornton, Emeritus professor obstetrics & gynaecology, iniversity of Nottingham, UKNick Brown, Department of Psychology, Linnaeus University, Växjö, SwedenJohnson, S., Bradshaw, A., Bresnahan, R., Evans, E., Herron, K. and Hapangama, D. (2024), Biopsychosocial Approaches for the Management of Female Chronic Pelvic Pain: A Systematic Review. BJOG. https://doi.org/10.1111/1471-0528.17987Ariza-Mateos MJ, Cabrera-Martos I, Ortiz-Rubio A, Torres-Sánchez I, Rodríguez-Torres J, Valenza MC. Effects of a Patient-Centered Graded Exposure Intervention Added to Manual Therapy for Women With Chronic Pelvic Pain: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2019 Jan;100(1):9-16. doi: 10.1016/j.apmr.2018.08.188. Epub 2018 Oct 9. PMID: 30312595.Rodríguez-Torres J, López-López L, Cabrera-Martos I, Prados-Román E, Granados-Santiago M, Valenza MC. Effects of an Individualized Comprehensive Rehabilitation Program on Impaired Postural Control in Women With Chronic Pelvic Pain: A Randomized Controlled Trial. Arch Phys Med Rehabil. 2020 Aug;101(8):1304-1312. doi: 10.1016/j.apmr.2020.02.019. Epub 2020 Apr 20. PMID: 32325162.Ariza-Mateos MJ, Cabrera-Martos I, López-López L, Rodríguez-Torres J, Torres-Sánchez I, Valenza MC. Effects of a patient-centered program including the cumulative-complexity model in women with chronic pelvic pain: a randomized controlled trial. Maturitas. 2020 Jul;137:18-23. doi: 10.1016/j.maturitas.2020.04.005. Epub 2020 Apr 25. PMID: 32498932.Brown, N. J. L., & Heathers, J. A. J. (2017). The GRIM Test: A Simple Technique Detects Numerous Anomalies in the Reporting of Results in Psychology. Social Psychological and Personality Science, 8(4), 363-369. https://doi.org/10.1177/1948550616673876

The Adaptive Semantic Framework introduces a modular architecture for large language models, enabling dynamic integration of semantic components to enhance scalability and adaptability across diverse natural language processing tasks. By employing modular semantic units, the framework facilitates efficient knowledge incorporation, resulting in improved performance metrics such as accuracy and inference speed. Empirical evaluations demonstrate the framework's resilience to noisy inputs, maintaining high accuracy levels and showing its robustness for real-world applications. Additionally, the framework's capacity for domain adaptation without extensive retraining highlights its versatility and practical utility. The mathematical foundations of the framework provide a formal basis for modeling semantic modularity and integration, contributing to the theoretical understanding of large language model architectures. Comparative analyses with existing models establish the framework's superiority, setting a new benchmark in the field. The scalability assessment reveals that the framework effectively manages computational demands, making it suitable for deployment in resource-constrained environments. Furthermore, the energy efficiency evaluation indicates a favorable balance between performance and power consumption, aligning with sustainable computing practices. Collectively, these contributions mark a substantial progression in the development of large language models, offering a robust foundation for future innovations in the field.

A document by Kemal Odev. Click on the document to view its contents.

Background: Fish is a leading trigger of food anaphylaxis. Co-sensitisation to various bony fish species is common due to similar beta-parvalbumin allergens, leading many fish-allergic individuals avoiding all types of fish. Cartilaginous fish, like sharks and rays, predominantly contain alpha-parvalbumin as the major allergen. This unique allergen profile suggests that cartilaginous fish could be a safe alternative for bony fish allergic individuals. We aimed to determine the rate of oral tolerance to gummy shark ( Mustelus antarcticus) among children with IgE-mediated bony fish allergy and evaluate the predictive value of raw gummy shark skin prick testing (SPT). Methods: Children aged 1-18 years with an IgE-mediated bony fish allergic reaction within the past 3 years underwent medical evaluation and SPTs to cartilaginous and bony fish species. All participants underwent an open challenge with 100g cooked gummy shark. Follow-up at 2 weeks and 6 months assessed ongoing tolerance and dietary incorporation. Results: All 21 children with bony fish allergy tolerated gummy shark during the challenge, despite seven (33%) children having a positive SPT (>3mm) to gummy shark (median 5mm). Six months post-challenge, 7 out of the 21 children (33%) did not incorporate gummy shark in their diet, citing taste aversion and difficulties finding a reliable source. There was one reported reaction in the community to gummy shark following the OFC. Conclusion: Bony-fish allergic children demonstrated tolerance to gummy shark. SPT to gummy shark showed limited predictive value in this cohort. Gummy shark may be a safe alternative in children with bony fish allergy.

Background: Patients with sickle cell disease (SCD) experience painful vaso-occlusive episodes that increase with age; a subset develop chronic pain (CP). CP is usually managed with acute pain management guidelines despite evidence of ineffectiveness. Buprenorphine, a partial opioid agonist, a potent analgesic with less liking and has a respiratory ‘ceiling effect’. Buprenorphine therefore provides an alternative ‘harms reduction’ approach for CP management in pediatric SCD patients. Methods: This single urban center retrospective study assessed the feasibility of inpatient transition to buprenorphine-containing analgesics in adolescents with SCD and CP. Patients aged 12-20 years transitioned from FOA to buprenorphine between December 2020 and September 2022 were included. Acute care utilization, hospital length of stay, and FOA use in both inpatient and outpatient settings were compared pre- and post-buprenorphine induction for at least 6 months. Results: Fourteen adolescents with SCD underwent inpatient buprenorphine induction and maintenance therapy. Inpatient transition using a micro-induction approach was feasible and well tolerated in this population. There were low rates of adverse events such as opioid withdrawal signs. Maintenance on buprenorphine products was sustainable over the one-year post-induction period. Three patients (21.4%) discontinued buprenorphine during maintenance therapy. There was a significant reduction (p<0.05) in acute care utilization, length of stay, and FOA use (both inpatient and outpatient). Conclusion: Inpatient micro-induction to buprenorphine from FOA in adolescent SCD patients with CP is feasible with minimal signs of opioid withdrawals. This study suggests decreased acute care utilization with buprenorphine.

Purpose: This study aims to provide a comprehensive evaluation of the current state of pediatric radiation therapy (RT) in China, identifying key challenges in infrastructure, workforce, and access to advanced technologies while exploring opportunities for improving care delivery. Methods and Materials: A 29-item online questionnaire was distributed to radiation oncologists and clinical teams across China, with 123 responses from 103 hospitals. The survey explored six domains: hospital characteristics, radiotherapy equipment and techniques, pediatric oncology staffing, patient admission and treatment status, treatment and follow-up, and social work support and charitable partnerships. Results: Among the 103 hospitals, 66.0% provide pediatric RT, but only 7.4% have dedicated pediatric RT departments, and 57% lack pediatric radiation oncologist. Advanced techniques like Intensity Modulated Radiation Therapy (IMRT) and Volume Intensity Modulated Radiotherapy (VMAT) are widely used (95.1%), but only 11.7% of hospitals offer proton therapy, and just 8.7% have pediatric-specific radiotherapy machines. Anesthesia resources are inadequate, with only 27.2% of hospitals equipped for sedation. Furthermore, 78% of hospitals have not participated in clinical research, and only 33% adhere to standardized treatment protocols. Social work support and charitable partnerships are present in just 44% of facilities. Conclusions: Significant gaps in pediatric RT services, including shortages in workforce, advanced technologies, and holistic support systems, hinder equitable care. Addressing these deficiencies through workforce development, increased access to advanced RT modalities, and enhanced support systems is essential to improving outcomes for pediatric cancer patients in China.

FPIES after umbilical cord blood transplantation: a case series.All authors disclose any potential conflict of interest. They received no specific funding for this work.Keywords: Food Protein–Induced Enterocolitis Syndrome I FPIES I umbilical cord blood transplantation I recurrent vomitingTo the Editor,Acute Food Protein–Induced Enterocolitis Syndrome (FPIES) is a potentially severe non-IgE-mediated food allergy.1FPIES is a clinical diagnosis defined by repeated vomiting 1 to 4 hours after food ingestion, often accompanied with pallor, lethargy and (bloody) diarrhea, which in severe cases can lead to hypotension and shock. Unlike IgE-mediated anaphylaxis, FPIES does not involve respiratory or cutaneous symptoms and has a delayed onset.2 To diagnose FPIES, a patient must meet the major criterion and at least three minor criteria as described in table 1. An oral food challenge (OFC) can help confirm the diagnosis, see table 2, in case of unclear history in combination with a favorable risk/benefit ratio. Common triggers include cow’s milk, soy, and grains, with geographical variation in prevalence. FPIES typically presents in infancy (solid food-induced FPIES between 5-7 months), and children usually outgrow it by 35-42 months.We observed two patients in our pediatric transplantation ward (combined University Medical Center Utrecht and Princess Máxima Center, the Netherlands) with documented FPIES after an umbilical cord blood transplantation (UCBT). There is institutional biobank approval for the use of data within retrospective studies, for which both patients gave informed consent.UCBT is an important treatment option for patients in need of an allogeneic hematopoietic stem cell transplantation where there is no fully matched donor available.3 While IgE-mediated hypersensitivity can sometimes be transferred after allogeneic bone marrow transplantation, FPIES following UCBT is a newly identified phenomenon.4, 5, 6 A recently published case report detailed an 8-month-old girl diagnosed with FPIES six months following UCBT.7 The onset of FPIES typically coincides with dietary expansion during infancy; however, it remains uncertain whether the condition would have developed in the absence of UCBT. In contrast, our cases involve two patients who were not diagnosed with FPIES prior to transplantation but exhibited atypical onset of the syndrome during adolescence following UCBT.Our best documented case is a 15-year-old girl with late juvenile metachromatic leukodystrophy for which she had a 6/6 UCBT without complications or graft versus host disease (GvHD). She first presented four months post-transplant with repeated vomiting, bloody diarrhea, reduced alertness and eventually hypovolemic shock. Treatment included IV fluid resuscitation, blood transfusions, broad-spectrum antibiotics, and increased hydrocortisone to address potential adrenal insufficiency. There were no signs of classical IgE-mediated symptoms. Blood culture, viral and bacterial feces test were all negative. Her symptoms improved within hours.In total she had five episodes of repeated vomiting, (bloody) diarrhea and in several cases hypotension. The initial presentation was the most critical, the clinical presentation was less severe in subsequent episodes. The suspicion rose that these episodes were correlated with eating fish, shellfish or crustaceans for which she was referred to a pediatric allergist. Table 1 shows the clinical symptoms in our patient during five episodes consistent with a diagnosis of FPIES. In addition to FPIES, she developed a symptomatic IgE-mediated allergy for cow’s milk and macadamia nuts with elevated serum IgE levels. Before the UCBT, she had no history of allergic reactions or FPIES-like symptoms. Clinical OFCs with whitefish and crustaceans both resulted in repeated vomiting and diarrhea, for which she needed ondansetron and IV resuscitation, in combination with a more than 1.5x109/L increase in neutrophil count. In table 2 can be seen that the OFC also confirms the diagnosis of FPIES. Whitefish, shellfish and crustaceans were eliminated from her diet and the patient had no further episodes of repeated vomiting.Our second case is a 16-year-old girl with myelodysplastic syndrome, subtype refractory cytopenia in childhood (MDS-RCC), who underwent a 5/6 UCBT. Her post-UCBT course was complicated with intestinal GvHD. She presented in our center eight months after the UCBT with symptoms of repeated vomiting, bloody diarrhea (six times), pallor and hypotension. There were no signs of IgE-mediated symptoms. She was started on IV rehydration and anti-emetics. After six hours, the symptoms of vomiting and diarrhea disappeared. The symptoms started several hours after eating hazelnut, in hindsight she had two earlier mild reactions of vomiting and diarrhea without need for a visit to the emergency department after eating hazelnut. Feces PCR was since three months after the UCBT still positive for adeno- and norovirus, a recent endoscopy showed no signs of active GvHD. The patient was referred to a pediatric allergist who diagnosed FPIES based on a clear clinical history (1 major and 6 minor criteria). There was therefore no indication for an OFC to confirm the diagnosis. After a year, another more minor reaction to hazelnut ingestion occurred.The exact pathophysiology of FPIES remains unclear which makes it difficult to explain why some patients develop FPIES after a stem cell transplant and if the phenomenon is specific to UCBT. The hypothesis is that naïve T cells are exposed to the trigger food proteins and mistakenly recognize these food proteins as dangerous which leads to the activation and differentiation of naïve T cells into antigen specific T cells. Antigen-specific T-cells produce proinflammatory cytokines (TNF-α and IL-6) which lead to inflammation of the intestinal lining increasing permeability and fluid secretion, causing symptoms like vomiting and diarrhea.8After an UCBT, naive T cell counts are higher than after bone marrow or peripheral blood stem cell transplantation.9Furthermore, the neonatal naïve T cell compartment differs from that of adults, which may explain why FPIES has only been observed in UCBT patients and not in those receiving stem cells from other sources.10 The time of onset post-UCBT mirrors that in infants, hinting at a common mechanism involving the developing immune system. With one of our two patients also diagnosed with gastro-intestinal GVHD it is unclear if this correlates with FPIES, but the activation of T cells seen in GVHD might increase the risk.Of note, last decade we have observed four additional cases of potential FPIES in post-UCBT patients, though the data were insufficient for a definitive diagnosis. These two cases identify FPIES as a crucial consideration in the differential diagnosis alongside gastrointestinal GvHD for patients experiencing recurrent vomiting and diarrhea post-UCBT, even at an age older than infancy. Food as a culprit and the rapid recovery without treatment besides IV rehydration are the main clinical discriminators. Therefore, (pediatric) oncologists and transplant specialists should be familiar with FPIES diagnostic criteria and a thorough (food intake) history in patients with acute self-limiting vomiting and diarrhea is essential.Further research is imperative to comprehend FPIES pathophysiology, enabling the identification of at-risk individuals and GvHD as a possible risk factor. More follow-up is needed to determine whether these patients develop natural tolerance just as infants do, and after how long this tolerance evolves.Ludo Cuppen, MD, Princess Máxima Center for pediatric oncology, Utrecht, The Netherlands.Annemieke Schuurhof, MD, PhD Pediatric Allergology, Wilhelmina Children’s Hospital, UMC Utrecht, UU, Utrecht, The NetherlandsBirgitta Versluijs, MD, PhD, Princess Máxima Center for pediatric oncology, Utrecht, The NetherlandsDorine Bresters, MD, PhD, Princess Máxima Center for pediatric oncology, Utrecht, The NetherlandsMarike Staderman MD, PhD, Pediatric Allergology, Wilhelmina Children’s Hospital, UMC Utrecht, UU, Utrecht, The Netherlands & Allergy center Diakonessenhuis, Utrecht, The NetherlandsCaroline Lindemans, MD, PhD, Dept of Pediatrics, UMC Utrecht, & Princess Máxima Center for pediatric oncology, Utrecht, The Netherlands, Utrecht, The Netherlands

A document by Mohanaraj Ramachandran. Click on the document to view its contents.

Alginate, known for its unique properties such as biocompatibility, biodegradability, and gel forming capability, has emerged as a corrosion-resistant material in aqueous environments for sustainable and environmentally friendly solutions. Further, alginate-based composites possess self-healing features through their distinctive molecular structure, encapsulating unprotected metal surfaces and preventing additional corrosion. As a result, alginate-based coatings on metals provide extended corrosion protection while requiring less frequent maintenance, which is highly attractive for long-term use in hostile settings. In this review, we comprehensively explore the diverse applications of alginate-based coatings, with a focus on their roles in corrosion inhibition, antifouling, and biocidal activities. After a brief introduction to the fundamental principles of corrosion-resistance behaviors, we will examine the interfacial and surface properties that make alginate-based coatings effective for these protective functions. This includes an analysis of their molecular structure, amphiphilic nature, and specific attributes that contribute to their effectiveness in various industrial applications such as ship hulls, undersea structures, and maritime equipment. We also review the current state of research, evaluation methods, and comparative analyses with traditional coatings in each segment. Last, the review highlights the advantages of alginate-based coatings, along with the challenges and future perspectives.

Africa faces a growing mental health crisis, characterized by limited resources, pervasive stigma, and restricted access to mental health services. Cultural beliefs often hinder individuals from seeking help, exacerbating the situation. Mental Health First Aid (MHFA) programmes present a culturally sensitive approach to addressing these issues, highlighting the urgent need for action. Integrating MHFA into existing mental health frameworks across African communities has shown promise in enhancing public understanding and the ability to provide timely support to those experiencing mental health challenges. This integration improves access to mental health services, reduces stigma, fosters inclusivity in healthcare, and encourages greater tolerance and compassion for individuals facing mental health issues. To achieve these outcomes, advocacy efforts must focus on widespread MHFA training within communities, government partnerships to fund primary healthcare systems incorporating MHFA, and media campaigns aimed at de-stigmatizing mental health conditions. By embedding MHFA into mental health strategies, Africa can address its mental health crisis more effectively, creating a more inclusive, community-driven, and sustainable framework for improved mental health outcomes.

Nigeria's organ donation and transplantation systems remain underdeveloped, yet they hold great potential to address the nation's escalating healthcare challenges. This commentary provides a comprehensive overview of the current state of organ donation and transplantation in Nigeria, highlighting historical milestones, legal frameworks, and the pressing issues that hinder progress, including organ trafficking, cultural barriers, and inadequate healthcare infrastructure. Additionally, it reviews the disparities in access to transplantation services and the critical role of socioeconomic factors in this divide. The commentary offers a forward-looking approach, presenting key recommendations for policy reform, infrastructure development, and public education. Implementing these strategies would be pivotal in ensuring equitable access to organ donation services while setting a precedent for medical innovation in West Africa. Ultimately, this paper underscores the need for government action, international collaboration, and community engagement to create a robust and ethical organ donation framework in Nigeria.

Objective: In response to the urgent need for COVID-19 vaccination clinics for vulnerable populations in Kentucky (12.2% live in poverty; 5.6% lack healthcare coverage), nurse leaders received training through a standardized training program to prevent COVID-19 vaccine administration errors (VAE). This project aimed to evaluate the process effectiveness of the training program as perceived by the trainees (Team Leaders) and to assess the number and types of vaccination errors that occurred during mobile vaccination clinics during the mobile clinics in Kentucky. Design: A program evaluation. Sample: A total of 12 Nurse Team Leaders underwent the standardized training program. Measurement: The Logic-Model-based, 7-item, 4-point Likert scale (α=. 84) was used to evaluate training effectiveness. VAE rates were calculated. Intervention: The Kentucky Nurses Association (KNA) developed a standardized COVID-19 vaccination training program for Team Leaders to prevent VAE during the mobile clinics. Components of the training program (program development, training protocols, and error monitoring) were based on the CDC’s (2022) recommendation that all healthcare providers need to know how to store, handle, prepare, and administer each COVID-19 vaccine product. Results: Team Leaders strongly agreed on the effectiveness of the training (e.g., the importance of training, staying updated, and feeling prepared). VAE was 0.001% (9/8086 administrations over 16 months). Conclusion: Findings suggest that the training program successfully prevented vaccination errors, and that Nurse Team Leaders collectively perceived the training program as effective. Widespread adoption of similar programs is recommended to prevent VAE during public health emergencies, including future pandemics.

The Urgent Need to Address Neonatal Mortality in NigeriaKehinde Precious Fadelea Igwe Stephen Chukwuemekab Deborah Shomuyiwac Don Eliseo Lucero-Prisno IIId,e,fAffiliationsa. Department of Medicine and Surgery, Faculty of Medical Sciences, College of Medicine, University of Nigeria, Enugu Campus, Enugu. 0000-0002-0464-4167b. Department of Medicine and Surgery, University of Ilorin, Ilorin, Nigeria. 0000-0001-6443-261Xc. Faculty of Pharmacy, University of Lagos, Nigeria 0000-0001-6665-9439d. Department of Global Health and Development, London School of Hygiene and Tropical Medicine, London, United Kingdom.0000-0002-2179-6365e. Office for Research, Innovation and Extension Services, Southern Leyte State University, Sogod, Southern Leyte, Philippinesf. Research and Innovation Office, Biliran Province State University, Naval, Biliran Province, Philippines

The conventional Frequency Diverse Array (FDA) system, using linear frequency offsets, forms periodic grating lobes and coupling, which may increase interference for potential users and difficulty in controlling parameters. To mitigate these issues and generate a dot-shaped beampattern, nonlinear frequency offsets are introduced to decouple the interdependence of parameters in the range and angle dimensions. Furthermore, to obtain the optimal nonlinear frequency offsets, we propose an algorithm based on the FDA Multiple-Input Multiple-output (FDA-MIMO) structure that integrates the Revised Dingo Optimization Algorithm (RDOA) with a Kaiser window function (referred to as the RDOAK algorithm) to form a dot-shaped beampattern. Specifically, the RDOA is used to optimize the nonlinear frequency offset coefficients, and the Kaiser window function is applied to adjust the waveform. Simulation results demonstrate the superior performance of our proposed RDOAK approach in preventing the mainlobe shift of the beampattern, eliminating grating lobes, suppressing jammings, and achieving narrower mainlobe width in the range dimension compared to other widely used algorithms.

Introduction: The Sri Lankan leopard (Panthera pardus kotiya) is a sub species of the Panthera pardus family. It inhabits a variety of island’s habitats ranging from tropical rainforests to arid zone scrublands. This report documents the rare sighting of a newborn Sri Lankan leopard cub observed with its mother in a tree hole within Yala National Park, Sri Lanka. Results: On April 7, 2023, a female leopard and a newborn cub, estimated to be less than 10 days old, were sighted in a tree hole located approximately 15 feet above ground level. The mother leopard was observed nursing and grooming the cub, exhibiting relaxed yet vigilant behavior. The interaction was captured through high-resolution photography, capturing this rare display of maternal care and habitat use. Subsequent observations, including a follow-up sighting in 2024, indicated that the cub has continued to thrive, highlighting successful mother-cub bonding and survival. Discussion: This sighting marks the youngest leopard cub ever documented in the Yala National Park, Sri Lanka and highlights the suitability for leopard breeding within the ecosystem. These observations contribute to understanding critical aspects of leopard maternal care and habitat requirements, which impact the cub survival during early life. Continued conservation and research in Sri Lanka’s protected areas are essential to ensure the survival of this vulnerable species and its future within the island’s ecosystems.

Aim: Polypharmacy, defined as the concurrent use of multiple medications, poses significant health risks, particularly among aging populations. While polypharmacy is a recognized concern, limited research has investigated its spatial distribution or the demographic and socioeconomic factors influencing its prevalence. This study aimed to examine the spatial patterns of polypharmacy across Japan and identify regional characteristics associated with higher polypharmacy rates. Methods: An ecological study was conducted across 335 local health units in Japan using data from national health, demographic, and geographic databases. Polypharmacy was defined as prescriptions containing seven or more drugs, and the standardized polypharmacy ratio (SPR) was calculated by age-group population. Spatial autocorrelation of SPR was assessed using Moran’s I statistic. Clustering analysis incorporating SPR and regional variables identified distinct high-risk areas. Results: The prediction model for polypharmacy prescriptions achieved an R² of 0.98, indicating high accuracy, though SPR remained heterogeneous. Significant spatial autocorrelation was observed for both polypharmacy prescriptions (Moran’s I = 0.4; P < 0.001) and SPR (Moran’s I = 0.24; P < 0.001), highlighting regional clustering. Clustering analysis identified four groups by polypharmacy risk (Critical, High, Moderate, and Low). High-SPR areas were associated with higher population density, a greater proportion of younger adults (ages 20–60), and increased levels of education, income, and tertiary industry workers. Conclusion: Polypharmacy in Japan exhibits significant spatial clustering, with higher rates in urbanized regions driven by demographic and socioeconomic factors. Region-specific interventions addressing these unique characteristics are essential for improving polypharmacy management.

Thiopurines are a class of immunosuppressant and anti-neoplastic agents. They are widely used in the treatment of inflammatory bowel disease, hematological malignancies, and autoimmune diseases, but can cause significant toxicity. Inherited gene mutations are now recognized as independent risk factors for severe adverse drug reactions to thiopurines even at tenfold dose reductions. We present a case of thiopurine toxicity resulting in severe myelosuppression, hepatotoxicity, and alopecia in an individual with homozygous *3/*3 loss-of-function alleles in the NUDT15 gene. Our case highlights important differences in gene mutation frequencies between races that can help guide pharmacogenomic testing.

The role of notch geometry and stress levels on fatigue crack initiation and small crack propagation behavior in the FGH96 superalloy was investigated using groove and bolt hole simulation specimens at 500 °C. The findings indicate that the fatigue crack initiation mechanisms and the number of cracks significantly affected by stress levels. The fatigue crack initiation life and its contribution to the total fatigue lives were analyzed for both specimen types. Notch geometry was found to have a more pronounced effect on crack propagation life than on initiation life under high applied stress. The smaller notch root radius could accelerate the occurrence of crack coalescence, thereby shortening the propagation life. These results are valuable for optimizing the fatigue damage tolerance design of FGH96 turbine discs.

Water is the basic need of life. Chlorination is a well-known disinfection technique for potable water due to its cheap availability. Yet, some aspects are harmful to human health and found carcinogenic. An attempt has been made to quantify the occurrence of two prominent Chlorination Disinfectant byproducts (DBPs), i.e., Trihalomethanes (THMs) and Trihalo acetic acids (THAAs) in the water distribution network of galvanized iron Pipes Medium using GC-Mass Spectrometry equipped with Electron Capture Detector (ECD). Two filtration setups, i.e., Granular Activated Carbon (GAC) and a pack of sand, were evaluated as abatement techniques were introduced for removing these chlorination disinfectants by products according to the water source and pipe medium used. The chromatogram with mass spectrometry hints at the occurrence of these two DBPs and the filtration media’s characterization and removal capacity. A combination of granulated activated carbon accompanied with sand media and based on gravel was found to be the more feasible and efficient setup to remove DBPs for the galvanized iron pipes distribution network medium.

This book is dedicated to Yahowah the living one Allaha, who is Yeshua ben Joseph ben David. Thank you for letting me write this book.

On October 7, 2024 the Nobel Assembly of the Karolinska Institute awarded this year’s Nobel Prize in Physiology or Medicine to Victor Ambrose and Gary Ruvkun “for the discovery of microRNA and its role in post-transcriptional gene regulation” (https://www.nobelprize.org/prizes/medicine/2024/press-release/). The prize-winning research was published in back-to-back 1993 papers in Cell demonstrating in the nematode worm C. elegans that the lin-4 microRNA regulates the translation and degradation of lin-14 mRNA post-transcriptionally in the cytoplasm during transition from the first to the second stage of larval developments by base-pairing to the target mRNA. When Ruvkun and colleagues later identified and characterized the more evolutionarily conserved let-7 microRNA to play a similar post-transcriptional regulatory role during the transition from late larval to adult stages in animals from mollusks to vertebrates (but not in plants, yeast, bacteria, jellyfish or sponges), the scientific community began to accept microRNAs as part of the canonical developmental regulatory machinery of multicellular organisms [1].

The proliferation of sophisticated encryption techniques has meant the development of advanced detection mechanisms capable of distinguishing between legitimate and malicious activities. Traditional methods often struggle to keep pace with the rapid evolution of ransomware, leading to significant challenges in timely identification and mitigation. The Dynamic Encryption Signal Profiling (DESP) framework offers a novel approach to this issue, focusing on the real-time analysis of encryption patterns to detect ransomware activities. By capturing and analyzing encryption-related signals within data streams, DESP constructs dynamic profiles that effectively differentiate between benign and malicious behaviors. Comprehensive evaluations demonstrate that DESP achieves high detection accuracy across various ransomware strains, including CryptoLocker, TeslaCrypt, and Jigsaw, with minimal false positive rates. The framework's low detection latency and efficient resource utilization further demonstrate its suitability for deployment in diverse operational environments. Comparative analyses reveal that DESP outperforms existing detection methods, particularly in adapting to new ransomware variants employing advanced evasion techniques. These findings highlight the potential of DESP to enhance current cybersecurity defenses, providing a proactive and effective solution to the growing threat of ransomware attacks.

A document by Ngoc Truc Ngan Ho. Click on the document to view its contents.

In the current situation, social policy in many countries is aimed at supporting various categories of families in vulnerable situations. The article examines government support for large families in 15 post-soviet countries. In the 20th century in the Soviet Union most families were large ones. Nowdays families with small and medium number of children became a common family model. Post-Soviet states have been forming their own systems of state support for large families over the past 30 years. The article analyses approaches to establishing the consequences of large families in post-communist countries. A comparative analysis of government support measures for large families, which include monthly payments and social benefits, is provided. As a result of the comparative analysis, groups of countries were identified depending on whether special payments and benefits were established for large families, and they were differentiated by the number of children