Introduction Co-infection with tuberculosis (TB) is the leading cause of death in individuals infected with human immunodeficiency virus (HIV)-1. Dolutegravir and lamivudine (DTG+3TC) has recently been recommended as the preferred first-line regimen for the treatment of new and treatment-experienced HIV-infected patients. The primary objective of this study was to determine the efficacy and safety of DTG 50 mg + 3TC 300 mg in HIV-positive antiretroviral therapy (ART)-naïve patients with TB who were receiving a rifampicin- or rifabutin-based treatment regimen, and to characterize viral suppression rates at week 48. Methods A single-center retrospective observational case series, spanning January 1, 2021 to March 1, 2023, was conducted in Guiyang Public Health Treatment Center. The outcomes of interest were successful TB treatment, viral load suppression, and immunological and biochemical indexes. Results All PWH had at least 48 weeks of follow-up, and all TB treatments were successful. A total of seven PWH (100%) achieved viral suppression (VL <50 copies/mL) from a baseline VL greater than 500,000 copies/mL. Among the PWH who started DTG+3TC after the initiation of the rifabutin-based anti-TB regimen, all achieved viral suppression by week 24, except for the non-suppressed PWH. CD4+ T-cell counts were greatly improved after antiretroviral treatment. The CD4+/CD8+ ratio increased by 0.38 (P < 0.001). Serum creatinine, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol levels significantly increased (P = 0.054, P = 0.015, P < 0.001, and P < 0.05, respectively). There were no significant changes in body weight, alanine aminotransferase, aspartate aminotransferase, chronic kidney disease epidemiology collaboration-based serum creatinine, or triglyceride levels from baseline to week 48 (P > 0.05). No serious adverse events were observed. Conclusion This case series preliminarily validated the efficacy of DTG+3TC when combined with rifabutin-based anti-TB regimens in patients with TB and HIV.

This article explores the issues involved in developing personalized medicine as part of the KidneySign project, which aim is to mobilize translational Big Data to validate a proteomic biomarker of renal fibrosis. This research offers hope for the management of chronic kidney disease in terms of early diagnosis and treatment. This article looks at how the human and social sciences can be mobilized within the project to study the adjoining ethical, legal and social issues. By highlighting these aspects, this point of view defends a multidisciplinary approach to personalized medicine and artificial intelligence in medicine. The presentation of theoretical and methodological contributions of social sciences in the case of KidneySign offers an opportunity to better understand the integration of these disciplines into biomedical research. It allows to question the study protocol itself and to frame it through legal contributions (considering the legal aspects, consequences and challenges). Moreover, by carrying out a sociological study, one may identify key points and highlight the limits of the technophile fantasy in the representations of patients and healthcare professionals. The introduction of new technologies into medical research and practice requires particular attention to ethics.

Objective: This systematic review and network meta-analysis aimed to compare and evaluate the efficacy and safety of five medications, Dupilumab, Tralokinumab, Upadacitinib, Baricitinib, and Abrocitinib, for the treatment of adolescent atopic dermatitis, in order to provide decision support to support clinical decision-making by developing more scientifically-grounded and effective treatment strategies. Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science (WoS), and the Cochrane database to collect randomized controlled trials (RCTs) and Phase 3 clinical trials up to April 13, 2024. Supplementary data were retrieved from trial registries, and researchers contacted study authors and pharmaceutical companies when necessary to obtain complete data. Inclusion criteria comprised treatment studies for moderate to severe atopic dermatitis in adolescents aged 12 and above, with outcome measures including efficacy and safety assessments. Data extraction and risk bias assessment were independently performed by two researchers, using Excel for data extraction and the netmeta package in R software for network meta-analysis. Sensitivity analysis and bias risk assessment were conducted to validate the robustness and credibility of the results. Our research protocol was registered in PROSPERO (CRD42023480597) and did not require approval from an institutional review board or written informed consent. Results: In the primary efficacy outcome measures, Upadacitinib 30mg/d, Upadacitinib 15mg/d, and Dupilumab 300mg/2w demonstrated excellent efficacy in EASI75 compared to placebo, significantly outperforming other medications and placebo. Dupilumab 300 mg/2w, Upadacitinib 30 mg/d, and Upadacitinib 15mg/d showed excellent treatment effects in IGA0/1. Among the outcome measures for improvement in itch severity rating PP-NRS4, Dupilumab 300mg/2w and Tralokinumab 300mg/2w showed the highest efficacy values. Compared to these medications, Baricitinib 1mg/d exhibited weaker performance across all three indicators, particularly in EASI75 and IGA0/1, with effects approaching no significant difference. Due to limited sample sizes, estimates for treatment-emergent adverse events (TEAEs), serious adverse events (SAEs), and drug-induced adverse events (DIAEs) safety indicators were unstable, preventing strong conclusions on safety outcomes. Further studies with long-term follow-up and larger sample sizes are required to explore the safety of these five medications in the adolescent population. Conclusion: Upadacitinib and Dupilumab demonstrate strong efficacy and symptom improvement in the treatment of moderate to severe atopic dermatitis in adolescents, particularly in reducing the severity of skin lesions and itchiness. Therefore, these medications should be considered as primary treatment options for adolescents with atopic dermatitis.

Service-learning is one way to engage students in health professions and promote health literacy in the community. This paper describes developing and delivering a service-learning course designed to improve diabetes literacy and diabetes outcomes among a medically underserved population. The didactic component of the course introduced topics such as health literacy, health education techniques, and diabetes pathophysiology, prevention, and treatment. Later, students designed and delivered community diabetes education classes at a local free clinic. After the classes were offered, diabetes knowledge and self-efficacy scores improved for community members and students leading the classes. A subset of community members also had lower body mass index at a 6-month follow-up. Though COVID-19 interfered with student's ability to offer in-person education sessions in the last semester this course was offered, it provided an opportunity to examine differences in diabetes knowledge and self-efficacy scores between students who offered in-person courses versus those who were unable to go out to the community and developed an online class instead. Self-efficacy was significantly higher at the end of the semester compared to at the end of the didactic component of the class for only those students who delivered in-person community education and not for those who developed the online class, providing further evidence of the benefit of engaging with community members on student outcomes. Community members and students alike were delighted with the program. Student-led community classes can be a financially sustainable solution to improving health literacy that benefits community members and students alike.

As software artifacts continuously evolve and increase in number, the need for automated traceability increases due to the complexity of trace links. Besides tracing components across different artifacts, the need for tracing to application domains is critical to understand the classification of semantics and the coverage (i.e., which application domain is present in each artifact?). In this paper, we propose the notion of using NLP to map concepts emerging from software artifacts to application domains, and tracing these between artifacts. We extracted the corpus keywords from source code, documentation, and tests. We ran an optimised Latent Dirichlet Allocation (LDA) to generate the concepts emerging from each artifact. We then calculated the similarity scores of each concept against each application domain, and ranked the difference of these scores between pairwise artifacts. Results show that the ranking of the inverse of the difference represents the strength of tracing in semantics, and different embeddings show varying results. We observed the strong applicability of our method and its replicability by other researchers and practitioners, particularly in detecting synchronised application domains that are traced between artifacts.

In Pakistan, pneumonia is a leading cause of death among children less than five years. Antibiotics’ limited efficacy in reducing pneumonia-related pediatric deaths may be due to viral respiratory infections. This study aimed to determine the incidence of eight viruses and their subtypes associated with severe pneumonia in under five children in a community in Karachi, Pakistan. It was conducted from November 2011 to July 2013 in a community in Bin Qasim Town Karachi, Pakistan. Under five children, who met the criteria for Lower Respiratory Tract Infection (LRTI) were enrolled. Nasal and throat swabs of confirmed pneumonia cases were performed for viral diagnosis. The incidence of all LRTI episodes and viral-specific LRTI episodes was determined. A total of 646 study participants were enrolled, out of which 53% were male. The overall incidence of pneumonia in this cohort was 26.4 (21.98-30.82) episodes per 100 child-year of follow-up. The most frequently detected viruses were enterovirus/rhinovirus at 62.6% (n=57), followed by RSV at 14.2% (n=13) and Para influenza virus type III at 6.5% (n=6.). 17.5% (n=24) of the nasopharyngeal swabs that were positive revealed co-infection. This study could be useful in exploring prevention strategies in community settings to reduce respiratory infections among children.

Objective: To evaluate the effectiveness of the COVID-19 Stringency Index (SI) during the pre-vaccination (PVACC) and vaccination (VACC) periods in five English speaking countries: Bahamas (BHS), Barbados (BRB), Guyana (GUY), Jamaica (JAM) and Trinidad and Tobago (TT). Methods: Timeseries data on the 2019 Novel Coronavirus were obtained, manipulated, and cleaned from March 2020 to March 2021 the (PVACC period) and April 2021 to June 2022 (VACC period). Analysis of Variance (ANOVA) and Fishers HSD test, along with Welch’s ANOVA and the Games-Howell test where necessary, were conducted on SI by country for each period. A canonical correlation analysis (CCA) was used to investigate the intercorrelation between dependent (COVID-19 indicators: cases and deaths) and independent variables for both periods. Results: During the PVACC period, BRB showed the lowest SI (mean=57.48, Standard Deviation (SD)=18.04; deaths=42) while JAM had the highest SI (mean=73.37, SD=6.66; deaths=596). In the VACC period, TT had the highest SI (Mean=63.14, SD=21.37; deaths=159071) and BHS had the lowest SI (mean=51.16, SD=8.07; deaths=629). The correlation between SI with cases and deaths were as follows: PVACC: r = 0.024 (p >0.01) and r=0.206 (p<0.01) and VACC: r=0.085 (p<0.01) and r=0.332 (p<0.01). The first pair of canonical variates’ correlation coefficients were PVACC: R c =0.504 ( R C 2 =25.4%) and VACC: R c =0.775 ( R C 2 = 60%). Canonical loadings between the SI are PVACC: r s =0.313 ( r s 2 =9.8%) and VACC: r s =-0.049 ( r s 2 =23.8%), and the cross loadings between SI and canonical covariate of COVID-19 indicators are PVACC: r=0.157 ( r 2=0.025) and VACC: r=0.038 ( r 2=0.001). Conclusion: The SI appears to have no significant impact during the pandemic. This suggests that there is no association between the stringency index and the deaths due to Covid-19.

Title: Addressing Potential Biases in the BEEP Trial’s Cow’s Milk Allergy Overdiagnosis StudyChia-Tsu Kao MD MBA123, I-Han Cheng MD4, Su-Boon Yong567 Chin-Yuan Yii8 Yu-Tsun Su 9,101Department of Rehabilitation, Kaohsiung Municipal United Hospital2Department of Rehabilitation, E-Da Dachang Hospital3Jiahua Health Co., Ltd.4Chung Shan Medical University5 Department of Allergy and Immunology, China Medical University Children’s Hospital, Taichung, Taiwan6Department of Medicine, College of Medicine, China Medical University, Taichung, Taiwan7 Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan8 Division of Gastroenterology and Hepatology, Department of Internal Medicine, LandseedInternational Hospital, Taoyuan, Taiwan9 Department of Pediatrics, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan10 School of Medicine for International Students, I-Shou University, Kaohsiung, Taiwan

not-yet-known not-yet-known not-yet-known unknown Unexpected Guillain-Barré Syndrome After Hysterectomy: A Clinical Case Report

Successful Management of Severe Unknown Snake Bite with Coagulopathy in an Intensive Care Unit (ICU) of a peripheral district hospital: A Case Report S Bijukchhe1, S Adhikari21.      Department of Anesthesia and Critical CareHetauda Hospital, Madan Bhandari Academy of Health Sciences2. Pharmacy Officer, Health Logistic Management Center, Hetauda.

IntroductionDepressive disorders are characterized by recurrent episodes and a substantial disease burden, often leading to chronic functional impairment and reduced quality of life [1, 2]. Approximately one-third of patients fail to achieve satisfactory remission despite appropriate treatment, including antidepressant medications, electroconvulsive therapy(ECT), and psychotherapy[3-5]. This results in TRD, a severely disabling psychiatric disorder that is often refractory to conventional treatments. Patients face increased treatment costs, complications, and the heightened risk of recurrent hospitalizations. TRD poses a major clinical challenge within psychiatric practice due to delayed onset of action and low remission rates following multiple antidepressant doses[6, 7].Treatment options remain limited due to the prevalence of adverse effects tied to pharmacological therapies, low accessibility to psychotherapy, and high tolerance levels for electroconvulsive therapy. New neuromodulation techniques, such as rTMS, may offer potential solutions to these limitations[8, 9]. The U.S. Food and Drug Administration (FDA) approved rTMS for TRD in 2008, and it is recognized in the latest Canadian Network for Mood and Anxiety Treatments (CANMAT) guidelines [10, 11]. However, not all patients benefit from standard rTMS regimens[10], with meta-analytic evidence indicating an average effectiveness of 29.3% for the left dorsal lateral prefrontal cortex (lDLPFC) using high-frequency rTMS [10]. The FDA-approved rTMS regimen for TRD operates at 10 Hz, with a minimum of 60,000 total pulses; higher doses of 15 Hz or 20 Hz may achieve more favorable outcomes[12].Various classes of antidepressants, including tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), and serotonin-norepinephrine reuptake inhibitors (SNRIs) have been utilized in the treatment of depression [13]. However, the estimated rate of TRD persists above 30% after treatment with multiple antidepressant classes [4]. Currently available antidepressants are effective for treating depression; however, they are often accompanied by notable limitations. These include delayed onset of action, limited therapeutic efficacy (yielding moderate effectiveness ranging from 50% to 70%), and a lack of cognitive improvement. Consequently, there is a growing clinical need for safer and more effective antidepressant options [14, 15]. In recent years, the triple monoamine reuptake inhibition hypothesis has gained significant recognition as a potentially effective strategy for treating depression. Toludesvenlafaxine, also known as Ansofaxine, LY03005, or LPM570065, is a triple reuptake inhibitor (TRI) that has been integrated into clinical settings. It functions by inhibiting the reuptake of serotonin, dopamine, and norepinephrine in the central nervous system. The simultaneous activation of all three monoamine systems is believed to have a favorable impact on mood by alleviating symptoms such as loss of pleasure, irritability, and depressive symptoms. It also supports cognitive improvement, including better attention span, learning abilities, and memory, and addresses somatic symptoms by reducing fatigue, increasing energy, and addressing insomnia in individuals with depressive disorders. Preclinical studies suggest that toludesvenlafaxine exhibits superior efficacy and a favorable safety profile compared to traditional monoamine reuptake inhibitors. It shows promise for addressing the unmet needs in the treatment of TRD by alleviating symptoms that are resistant to current standard therapies. Toludesvenlafaxine is noted for its rapid antidepressant-like effects and is considered a promising treatment option[15-18].On the other hand, previous studies have demonstrated that DTMS demonstrates beneficial therapeutic outcomes on depressed patients who are already on medication[19, 20]. Additionally, there is an urgent need for a safe and effective treatment for TRD. Therefore, this study aims to utilize a newer rTMS regimen, such as DTMS, in combination with a novel triple monoaminergic reuptake inhibitor (toludesvenlafaxine) to augment efficacy and achieve the therapeutic remission of TRD patients. By focusing on novel treatment combinations and techniques, this approach seeks to provide a safe and effective treatment strategy for managing patients with TRD who have experienced limited success with traditional treatment trials.

A document by Yuhui Luo. Click on the document to view its contents.

The analysis of natural abundance isotopes in biogenic N 2O molecules can give precious information such as the nature of their precursor. However, many uncertainties exist and further validations are necessary to confirm this method as a reliable tracer of biogeochemical cycles. In particular, current methodologies (such as the isotopocule map approach) can only estimate the combined contributions of several processes at once. In this study, we aimed to develop a new methodology capable of individually discriminating the main sources of N 2O production in soil by combining natural abundance isotopes with the use of a 15N tracer ( 15N Gas Flux method). To achieve this, we conducted parallel laboratory incubations of an agricultural soil, during which we optimized the denitrification conditions through increase of moisture and amendment of nitrate; where this nitrate was either labelled or unlabeled with 15N atoms. A new linear system combined with Monte Carlo simulation enabled the determination of N 2O source partitioning, where bacterial denitrification was identified as the dominant process (87.6%), compared to fungal denitrification (9.4%), nitrification (1.5%) and nitrifier denitrification (1.6%). This new system has been compared to a recently developed stable isotope modelling tool applying Bayesian statistics (FRAME). The results agreed generally well at the exception of lower bacterial denitrification (80%) and higher nitrifier-denitrification (9%) contributions found with the FRAME model. This new approach provides a perspective for a wider application, potentially enabling the source partitioning of nitrous oxide emissions in agroecosystems.

Over the past decade, the extensive consumption of finite energy resources has caused severe environmental pollution. Meanwhile, the promotion of renewable energy sources is limited by their intermittent and regional nature. Thus, developing effective energy storage and conversion technologies and devices holds considerable importance. Zinc-ion hybrid supercapacitors (ZISCs) merge the beneficial aspects of both supercapacitors and batteries, rendering them an exceptionally promising energy storage method. As an important cathode material for ZISCs, the tunnel structure MnO 2 has poor conductivity and structural stability. Herein, the Zn xMnO 2/PPy (ZMOP) electrode materials are prepared by hydrothermal method. Doping with Zn 2+ is used to enhance its structural stability, while adding polypyrrole to improve its conductivity. Therefore, the fabricated ZMOP cathode presents superb specific capacity (0.1 A g -1, 156.4 mAh g -1) and remarkable cycle performance (82.6%, 5000 cycles, 0.2 A g -1). Furthermore, the assembled aqueous ZISCs with ZMOP cathode and PPy-derived porous carbon nanotubes anode obtain a superb capacity of 109 F g -1 at 0.1 A g -1. Meanwhile, at a power density of 867 W kg -1, the corresponding energy density can achieve 20 Wh kg -1. And over 5000 cycles at 0.2 A g -1, the ZISCs can exhibit excellent cycle stability (86.4%). This suggests that ZMOP nanowires are potential cathode materials for superior-performance aqueous ZISCs.

Protein farming, or molecular farming, is an innovative approach that utilizes plants/animals/microorganisms as biofactories to produce valuable pharmaceutical proteins, antibodies, vaccines, and other high-value bio-active molecules. This emerging field has gained significant attention due to its potential to address the growing demand for affordable and scalable biopharmaceutical production platform. Correspondingly, plants offer several advantages over traditional expression systems, including low production costs, scalability, ease of manipulation, and reduced risk of contamination by pathogens. This review provides an overview of principles underlying protein farming in plants (P-farm), including the identification and selection of host, optimization of transgene expression, and downstream processing techniques for protein purification. It also discusses recent advancements in plant biotechnology and the development of transient expression systems to use genetically modified plants (transgenic plants) in the enhancement of protein production. Additionally, the potential applications and challenges associated with molecular farming in plants are considered, including prospects of commercialization and novel opportunities to meet the growing demands of global healthcare markets.

In this paper, we conduct a thorough analysis for a group of stochastic Hilfer fractional delay differential equations (SHFDDEs) with Lipschitz parameters. By introducing innovative theoretical conditions, we successfully establish the existence and uniqueness solutions using the Carath e ̵́ odory approximation approach. Furthermore, we deduce the average principle for accordingly system by employing H o ̵̈ lder’s inequality, Jensen’s inequality, It o ˆ isometric distance, and Gronwall’s inequality. Ultimately, two demonstrative examples are undertaken to substantiate the efficacy and practical applicability of our findings.

The objective of the study is to investigate and solve the model equations for an unsteady magnetohydrodynamic Carreau fluid flow using the overlapping grid spectral simple iteration method (O-SSIM). The study centres on the behavior of Carreau fluid flow over surfaces subjected to certain external forces and environmental factors. Numerical solutions are conducted to analyze the effects of inclined stretching/shrinking surfaces, and an inclined magnetic field on flow characteristics. The O-SSIM algorithm was implemented in MATLAB and tested for its convergence and accuracy. This research highlights the importance of the O-SSIM as a robust and accurate numerical technique for solving nonlinear differential equations. The R programming language was utilized to generate insightful plots and visualizations of the results to identify patterns and relationships between the local Nusselt number and skin friction coefficient. The results indicate several important trends and patterns, including a positive correlation between the small surface angle and magnetic field with the skin friction coefficient. Additionally, there is a positive relationship between increasing the thermal buoyancy parameter and a negative relationship between a higher Eckert number and the local Nusselt number. The paper provides valuable insights into the flow behavior of Carreau fluid and highlights the impact of an inclined magnetic field on the thermal and mechanical properties of the fluid.

not-yet-known not-yet-known not-yet-known unknown Case report Title: Cornerstones as treatment of brown tumour and low turnover in peritoneal dialysis patient: Case Report. Authors: Hernandez P, Mariel1; Enos, Daniel1.

Objective To determine whether home cervical ripening is associated with acceptable safety margins compared to in-hospital cervical ripening during induction of labour. Design A prospective multicentre observational cohort study using routinely collected data. Setting Twenty-six UK maternity units; 18 offering only in-hospital cervical ripening and 8 offering both in-hospital and home cervical ripening. Population Women with singleton pregnancies, no previous caesarean section, at or beyond 37 weeks gestation having induction with details of cervical ripening method and location recorded. Methods Home cervical ripening using a balloon catheter was compared to in-hospital cervical ripening using prostaglandin. Multivariable logistic regression was performed for the primary outcome. Exposure: Cervical ripening at home using balloon catheter. Main outcome measures Primary outcome: neonatal unit admission within 48 hours of birth for 48 hours or more. Additional neonatal, maternal, labour progress and process outcomes were reported. Results Of 17,530 eligible women, 515 had balloon cervical ripening at home and 4332 had prostaglandin cervical ripening in a hospital that did not offer home cervical ripening. The primary outcome following home cervical ripening with balloon was not higher {16/515 (3.1%) vs 208/4332 (4.8%)}, but with substantial uncertainty on adjusted analysis consistent with a 64% lower risk through to an 81% higher risk. Conclusions Home cervical ripening using balloon catheter may be as safe for babies as using prostaglandin in hospital in low and moderate-risk groups, but further safety data are required.

Aim: This study assesses the efficacy and safety of IL-1-targeted biological agents(BAs) in pediatric juvenile idiopathic arthritis (JIA), a condition characterized by chronic inflammation from excessive proinflammatory cytokine production, especially IL-1. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted through May 2024 for randomized controlled trials (RCTs) comparing IL-1-targeted BAs (anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab) with placebo in JIA. Efficacy was assessed using ACR 30 response. Safety was evaluated using serious adverse events (SAEs).Pairwise and network meta-analyses (NMA) were performed, analyzing parallel and withdrawal RCTs separately. Results: Six RCTs (four parallel and two withdrawal) were identified, involving anakinra, canakinumab, and rilonacept. In parallel RCTs, IL-1-targeted BAs significantly improved ACR 30 response compared with placebo [OR = 7.03, 95% CI (1.54, 32.30), I² = 74%, P = 0.008]. In withdrawal RCTs, fewer patients in the IL-1 group reported disease flare [OR = 0.27, 95% CI (0.13, 0.55), I² = 0.00%, P = 0.909]. SAEs did not differ from placebo in either trial type. The NMA showed canakinumab was more effective than rilonacept [OR = 14.05, 95% CI (2.93, 67.45)], with similar SAE risks among BAs. The SUCRA of ACR 30 response shows that canakinumab ranked first. Conclusion: IL-1-targeted BAs were more effective than placebo in treating JIA without increasing SAEs, with canakinumab being particularly effective. However, differences in ACR 30 criteria and trial heterogeneity should be considered.

Transient numerical flow models were developed and calibrated in Processing MODFLOW to quantitatively examine the groundwater-surface water interaction in a floodplain hyporheic zone. Although understanding of groundwater–surface water flux exchange in a hyporheic zone is crucial for effective water management and a variety of scientific purposes, it is a difficult place to study. Our numerical modelling of Danube River and Surány aquifers interaction revealed that there was a strong relationship between the response time lag (of river level change and groundwater level change) and the distance of wells from the river; the response time between a river rise (flooding) and GW level rise increased with increasing distance from the river and vice versa. Further, there were bigger depressions due to pumping in production wells located farther away from the river as a result of decreasing recharge from the river. The water budget from the models showed that the river seepage was the biggest contributor of inflow into the aquifer with over 70% contribution. The analysis of bank filtrate demonstrated that the level of river stage influenced the length of particle travel time; higher river stages led to shorter particle travel times. For the wells closer to the Danube River, the calculated travel times were shorter and increased with wells located farther away from the river. The numerical modelling results imply a strong hydraulic and hydrogeological connection between the permanent river and the adjacent alluvial aquifer. This investigation directly contributes to the implementation of the Danube River basin-wide water resources management and Flood Risk Management Plan developed in 2015 and the European Union Floods Directive requirements. Our models may be used in advancing understanding of the groundwater-surface water hydrogeological and hydraulic connectivity processes and mechanisms in floodplain environments.

The study was conducted to investigate the botanical pesticides or phytopesticides used by the ethnic farmers to control insect pests in the Dimapur district of Nagaland and their phytochemical analysis. This study broadly aimed to contribute to modern biopesticide formulation. Thirty-five locally grown phytopesticidal species belonging to 31 genera and 21 families were recorded. Asteraceae and Zingiberaceae possessed the highest number of species with 4 each followed by Solanaceae and Lamiaceae (3 species each). Among the species, 14 herbs, 10 trees, 9 shrubs, 1 climber and 1 creeper were present. Twenty types of insect pests including termites stem borers, nematodes, jassids, aphids, grasshoppers, semiloopers, whiteflies, cutworms, armyworms, gundhi bugs, ants, caterpillars, thrips, leaf miners, leaf webbers, beetles, etc., were reported. Eight different plant parts were used as phytopesticides. The highest used plant part was the leaf with 80% use reports. The lowest used part was the stem (2.85%). Twelve modes of traditional pesticide formulation were recorded from the study. Quantitative indices like use value (UV) and family use value (FUV) of the botanical pesticides were calculated. Azadirachta indica has shown the highest use value. The lowest use value was 0.06, recorded for Tamarindus indica and Cucumis sativus. Similarly, Caricaceae showed Cucurbitaceae and Fabaceae showed the highest FUV of 0.52, and the lowest FUV with the FUV of 0.06 each. Out of 35 species, 32 species possessed alkaloids; flavonoids and tannins were present in 30 species each, saponins were present in 28 species, terpenoids were found in 21 species, and glycosides were detected in 20 species. Five different botanical pesticide preparation methods were recorded. Shortly, such plants would contribute to formulating modern biopesticides with better outcomes.

not-yet-known not-yet-known not-yet-known unknown In 2015, the United States Food and Drug Administration (FDA) approved uridine triacetate to treat overdose and severe toxicity of the fluoropyrimidine chemotherapy agents 5-fluorouracil (5-FU) and its oral prodrug capecitabine. Uridine triacetate is as an oral prodrug of uridine which competes with cytotoxic fluoropyrimidine metabolites for incorporation into nucleotides. Two million people worldwide start fluoropyrimidine chemotherapy each year with 20-30% developing severe or life-threatening adverse effects, often attributable to a genetic predisposition such as dihydropyrimidine dehydrogenase deficiency. Whilst genetic pre-screening is recommended prior to starting fluoropyrimidine agents, this only prevents 20-30% of early-onset life-threatening toxicity and so does not obviate the need for an antidote. Initial in-human studies established that uridine triacetate more than doubles the maximum tolerated weekly 5-FU bolus dose . A lack of clinical equipoise meant a placebo-controlled phase-III trial was not ethical and so the phase-III trials used historical controls. These found that uridine triacetate improved survival in those with fluoropyrimidine overdose and severe toxicity from 16% to 94%, with 34% able to resume chemotherapy within 30days. Five case reports of delayed fluoropyrimidine toxicity demonstrate improvement following uridine triacetate treatment 120-504 hours after last fluoropyrimidine administration suggesting efficacy beyond the FDA licensing indications. Mechanistically uridine triacetate would be expected to be effective for overdose and severe toxicity of Tegafur (a 5-FU prodrug), but there are no published case reports describing this. Uridine triacetate is available internationally through an expanded access scheme and has been available in the UK since 2019 on a named patient basis.

not-yet-known not-yet-known not-yet-known unknown In this paper, an innovative torsional fatigue model is investigated based on the concept of M-integral in DD6 nickel based alloy. It is demonstrated that the Δ M/ AP as the driving force of fatigue damage can well describe the kinetics of fatigue damage evolution of the DD6 nickel based alloy under torsional fatigue loading. The new form of fatigue damage evolution rate ( dVD/dN) and fatigue driving force (Δ M/AP) are introduced. For the experimental study, the change of the total potential energy ( CTPE) is introduced to measure the value of M-integral. The fatigue tests show that the torsional fatigue damage evolution can be divided into three stages from the initiation and aggregation of microcracks to the growth of macrocracks. During stage I, the relationship between VD and fatigue number N satisfies a quadratic function, and the relationship between dVD/dN and ∆M/ AP is logarithmically linear independent of the load size. During stage II, VD and fatigue number N satisfy a linear relationship. During stage III, macroscopic cracks/pores appear, and the damage evolution rate begins to increase until fracture. It is concluded that the proposed fatigue model based on M-integral can accurately predict the torsional fatigue lifetime of the DD6 nickel based alloy.