bluuebunny/crossref_metadata_2025 huggingface dataset:
High efficacy and safety of direct‐acting antivirals for the treatment of chronic hepatitis C: A cohort study conducted in Vietnam
Authors: Vo Thong Duy , Bui Van Thi Thu , Lam Huong Tu , Bui Quynh Thi Huong
Published: September 2024

Direct‐acting antivirals (DAAs) have revolutionized hepatitis C virus (HCV) treatment through their high cure rates and improved safety profiles. We aimed to evaluate the efficacy and safety, and identify the optimal combination, of DAAs for the treatment of chronic HCV. A retrospective study was conducted of 613 patients with chronic HCV who were treated with DAAs. Demographic, HCV genotype, treatment regimen, virological response, and adverse drug event (ADE) data were collected at the initial visit and 4, 8, 12, and 24 weeks later. The rapid virologic response (RVR) and sustained virologic response (SVR) rates were 90.4% and 97.8% for HCV genotype 1, 89.2% and 98.7% for genotype 6, 92.8% and 99% for genotype 2, and 90.9% and 100% for mixed genotype 2/6 or unspecified genotypes, respectively. There were no significant differences in the RVR and SVR rates for the various DAA regimens. The mean ALT, AST, and GGT activities decreased, and the PLT count increased during the treatments. ADEs occurred in 8% of the patients. The commonest ADEs were itching (3.1%), fatigue (1.8%), and dizziness (1.1%). None of the patients discontinued treatment because of an ADE. Posttreatment disease progression occurred in 7.7% of the patients, including liver fibrosis (3.6%), cirrhosis (1.1%), hepatocellular carcinoma (1.1%), and high alpha‐fetoprotein (AFP) (1%). The factors associated with the achievement of RVR were low viral load, the use of sofosbuvir/ledipasvir or sofosbuvir/daclatasvir regimens, and a treatment duration of 12 weeks. No specific factors were found to be associated with the achievement of SVR. Posttreatment disease progression was associated with a high AFP and the use of sofosbuvir/ledipasvir. Thus, DAAs are highly effective and well‐tolerated means of treating chronic HCV, and significantly improve patient outcomes. Their high efficacy and favorable safety profiles highlight the importance of early diagnosis and the use of personalized treatment strategies.
Regulating the dynamic wetting behavior of pesticide on banana leaves at different growth stages with surfactants
Authors: Jiang Tingting , Yang Zhou , Jiang Yinlong , Xie Bowei , Huang Chaowei , Yu Jiaxiang , Yuan Haotian , Duan Jieli
Published: September 2024

BACKGROUND

Pesticide spraying constitutes an essential component of the production and management regimen within banana orchards, extending throughout the entire growth cycle of the banana plants. Exploring the intricate interplay between surfactants, pesticide formulations, and the evolving surface properties of banana leaves throughout their growth stages is critical to the enhancement of pesticide application methods and the elevation of agricultural productivity.

RESULTS

Through investigating the regulatory impact of surfactants on the physicochemical properties of medicinal solutions, this study elucidates the interaction mechanism between the physicochemical properties of pesticides and the surface characteristics of banana leaves. The findings reveal that the energy dissipation rate of pesticide droplets exhibits a natural exponential rise in correlation with the increase in both the We number and the concentration of surfactant present. Comparatively, the adaxial surface of banana leaves demonstrates superior spreading and adhesion properties for droplets than the abaxial surface. Specifically, droplets containing the anionic surfactant sodium dodecyl sulfate on the adaxial surface of banana leaves are found to spread well with a reduced retraction effect. Conversely, the application of the non‐ionic surfactant fatty acid polyoxyethylene ether (AEO‐3) on the abaxial surface of banana leaves is more beneficial for the wetting and retention of droplets. As banana leaves grow, there is a noted decline in the spreading and retraction properties of droplets. However, droplets have a higher propensity to wet and adhere to the surfaces of mature banana leaves.

CONCLUSION

To bolster the adherence of pesticide droplets to leaf surfaces, it is imperative to ensure they possess superior spreading properties and a controlled retraction pace. This facilitates an extended period of contact and enhanced stability, thereby optimizing the spray's deposition efficacy. © 2024 Society of Chemical Industry.
A tutorial on physiologically based pharmacokinetic approaches in lactation research
Authors: Pansari Amita , Pan Xian , Almond Lisa M. , Rowland‐Yeo Karen
Published: September 2024

In breastfeeding mothers, managing medical conditions presents unique challenges, particularly concerning medication use and breastfeeding practices. The transfer of drugs into breast milk and subsequent exposure to nursing infants raises important considerations for drug safety and efficacy. Modeling approaches are increasingly employed to predict infant exposure levels, crucial for assessing drug safety during breastfeeding. Physiologically‐based pharmacokinetic (PBPK) modeling provides a valuable tool for predicting drug exposure in lactating individuals and their infants. This tutorial offers an overview of PBPK modeling in lactation research, covering key concepts, prediction approaches, and best practices for model development and application. We delve into milk composition dynamics and its influence on drug transfer into breast milk, addressing modeling considerations, knowledge gaps, and future research directions. Practical examples and case studies illustrate PBPK modeling application in lactation studies. We demonstrate how prediction algorithms for Milk‐to‐Plasma (M/P) ratios within a PBPK framework can support scenarios lacking clinical lactation data or extend the utility of available lactation clinical data to support further untested clinical scenarios. This tutorial aims to assist researchers and clinicians in understanding and applying PBPK modeling to understand and support clinical scenarios in breastfeeding mothers. Advances in PBPK modeling techniques, along with ongoing research on lactation physiology and drug disposition, promise further insights into drug transfer during lactation.
Poly(N‐2‐Aminoethylacrylamide)‐Cu(I) Chelate Grafted from Fe3O4@SiO2 Core‐Shells for the Selective Monoarylation of Anilines via the Ullmann Reaction
Authors: Pourshahi Mohammad Ali , Mansoori Yagoub , Ghahramani Fatemeh , Bezaatpour Abolfazl , John Michael
Published: September 2024

The present work describes the grafting of a polymer‐metal chelate (PMC) from Fe3O4@SiO2 core‐shells via the Surface Initiated‐Atom Transfer Radical Polymerization (SI‐ATRP). The magnetic core‐shells were silylated by 2‐bromo‐2‐methyl‐N‐(3‐(trimethoxysilyl)propanamide (BTPAm) to give the surface‐anchored ATRP initiator. Acrylamide was polymerized from the Fe3O4@SiO2 surface via the ATRP approach. The grafted magnetic nanoparticles were trans‐amidated with ethylenediamine to give poly(N‐2‐aminoethylacrylamide) grafted magnetic core‐shells, Fe3O4@SiO2‐g‐PAE‐AAm. The grafted chelating polymer ligand (CPL) was treated with an acetonitrile solution of CuI to afford the Fe3O4@SiO2‐g‐PAE‐AAm−Cu(I). The grafted PMC was characterized by FT‐IR, CP/MAS 13C NMR, and thermo‐gravimetric analysis (TGA). The grafted PMC catalyzed the N−C bond formation via the Ullmann‐type N‐arylation reaction of haloarenes and anilines under optimal reaction conditions. Mono N‐arylation product was obtained as the major product with excellent selectivity. The excellent recyclability of the catalyst was shown by negligible deactivation over six runs.
The Anticholinesterase Perspective of Dimethoxyindole Based Benzenesulfonamides: Synthesis, Biological Investigation and Molecular Docking Applications
Authors: Bingul Murat , Ercan Selami , Boga Mehmet , Arslan Zehra , Tuneğ Muhammet , Akocak Suleyman , Bingul Alev Arslanturk , Sengul İbrahim F. , Sahin Hasan
Published: September 2024

Due to the well‐known biological potential of benzenesulfonamides for the inhibition of specific enzymes, here in, we propose to investigate anticholinesterase efficiencies of five newly synthesized benzenesulfonamides incorporating dimethoxyindole tails. The targeted compounds were synthesized through the C7 position of the methyl 4,6‐dimethoxy‐1H‐indole‐2‐carboxylate via Schiff‐base reaction. The biological study was directed to identify the acetylcholinesterase (ACh) and butyrylcholinesterase (BCh) enzyme inhibitions. The molecular docking studies were also carried out to determine the possible poses of ligands 8 a–e in binding sites of enzymes and ligand‐residue interactions. Molecular dynamics simulations, RMSD and RMSF plots, hydrogen bond analysis, per‐residue energy decomposition and MM‐PB(GB)/SA calculations were carried out investigate the potentials of the compounds towards the designated enzymes. It is important to note that all the synthesized compounds were found to be selective towards the BChE inhibition with a range of efficiencies. In addition to that the compound 8 a exhibited more potency than the standard Galanthamine with the value of 87.75 % for the same enzyme. The results could be valuable for the determination of new targets which are highly selective for BChE inhibition. The formation of hydrogen bonds and hydrophobic interactions with the residues located on the compounds were responsible for the binding free energy scores. The stability of all the compounds proved by molecular dynamics simulations were also promising for the further directions of the study.
Multi‐Functional AIE Phototheranostic Agent Enhancing αPD‐L1 Response for Oral Squamous Cell Carcinoma Immunotherapy
Authors: Yu Yuewen , Ni Zihui , Xu Yanbin , Zhang Le , Liu Yucheng , Zeng Fanrui , Zhang Ming , Liu Laikui , Feng Guangxue , Tang Ben Zhong
Published: September 2024

Oral squamous cell carcinoma (OSCC) represents a prevalent head and neck malignancy with surgical intervention as the primary clinical option. Immunotherapy, particularly immune checkpoint blockade (ICB) targeting PD‐1/PD‐L1 shows great promise but is impeded by the immunosuppressive tumor microenvironment and low PD‐L1 expression in OSCC. Herein, the “all‐in‐one” phototherapeutic nanoparticles (TSD NPs) are reported with balanced reactive oxygen species and photothermal conversion capacity for combined photoimmunotherapy and ICB immunotherapy against OSCC. A novel electron acceptor, 3‐(dicyanomethylene)‐2,3‐dihydrobenzothiophene‐1,1‐dioxide (DTM), is introduced to develop the phototherapeutic agent with aggregation‐induced emission (AIE) feature and NIR‐II fluorescence centered at 1000 nm. Benefiting from the AIE feature and the DTM acceptor, the resultant TSD NPs also exhibit strong type I reactive oxygen species (ROS) generation and high photothermal conversion efficiency (45.3%), which can profoundly induce immunogenic cell death (ICD), activate cytotoxic T lymphocytes, and convert the immunosuppressive tumor microenvironment into an immune‐supportive one. Additionally, TSD NPs upregulate the PD‐L1 expression on OSCC cells, thus enhancing the efficacy of combined treatment with αPD‐L1 ICB immunotherapy. This results show that the synergistic treatment of TSD NPs and αPD‐L1 effectively eradicates solid OSCC tumors without adverse effects on normal tissues, proving a novel and promising strategy for OSCC management.
Large‐Scale Atomic Strain Defects on Palladium Surfaces for Enhanced Oxygen Reduction and Zinc–Air Batteries
Authors: Shi Jianqiao , Qi Defeng , Zhang Hao , Zeng Xuemei , Li Yanshuai , He Kun , Li Wenqiang , Zhang Hao , Luo Jun , Xu Jie , Wang Shun , Yuan Yifei
Published: September 2024

Designing nano‐electrocatalysts rich in surface defects is critical to improve their catalytic performance. However, prevailing synthesis techniques rely heavily on complex procedures that compromise defect extensiveness and uniformity, casting a high demand for methods capable of synthesizing large‐scale crystalline defects. An innovative design strategy is herein proposed that induces ample strain/dislocation defects during the growth of palladium (Pd), which is well‐known as a good oxygen reduction reaction (ORR) catalyst. The controlled defect engineering on Pd core is achieved by the tensile stress exerted from an intentionally applied Fe3O4 skin layer during synthesis, which changes the surface free energy of Pd to stabilize the defect presence. With such large‐scale crystalline defects, this Pd catalyst exhibits significantly higher ORR activity than commercial Pt/C, enabling its promising future in zinc–air battery catalysis. Additionally, the protective Fe3O4 skin covering the catalyst also enhances its catalytic stability. Theoretical calculations show that the superior catalytic property of such defect‐engineered Pd is associated with the correspondingly modified adsorption energy of *O intermediates onto its surface, which further improves the reaction rate and thus boosts ORR kinetics. Findings here are expected to provide a paradigm for designing efficient and stable metal catalysts with plentiful large‐scale strain defects.
Enhanced Buried Interface Engineering for Efficient Inverted Perovskite Solar Cells Fabricated via Vapor–Solid Reaction
Authors: Dou Yichen , Lv Pin , Yuan Zhangwei , Xiong Wenjuan , Liang Jiace , Peng Yong , Liang Guijie , Ku Zhiliang
Published: September 2024

Vapor‐deposited inverted perovskite solar cells utilizing self‐assembled monolayer (SAM) as hole transport material have gained significant attention for their high efficiencies and compatibility with silicon/perovskite monolithic tandem devices. However, as a small molecule, the SAM layer suffers low thermal tolerance in comparison with other metal oxide or polymers, rendering poor efficiency in solar device with high‐temperature (> 160 °C) fabricating procedures. In this study, a dual modification approach involving AlOx and F‐doped phenyltrimethylammonium bromide (F‐PTABr) layers is introduced to enhance the buried interface. The AlOx dielectric layer improves the interface contact and prevents the upward diffusion of SAM molecules during the vapor–solid reaction at 170 °C, while the F‐PTABr layer regulates crystal growth and reduces the interfacial defects. As a result, the AlOx/F‐PTABr‐treated perovskite film exhibits a homogeneous, pinhole‐free morphology with improved crystal quality compared to the control films. This leads to a champion power conversion efficiency of 21.53% for the inverted perovskite solar cells. Moreover, the encapsulated devices maintained 90% of the initial efficiency after 600 h of ageing at 85 °C in air, demonstrating promising potential for silicon/perovskite tandem application.
What Mamá Gallina Can Teach Literacy Educators about Healing Biliteracies
Authors: Muñoz Kimberly , Babino Alexandra (Ale)
Published: September 2024

In this Action & Learning article, we describe the connections between the popular Spanish nursery song “Los pollitos dicen” (The Little Chicks Say) and Aesop's fable's “The Fox and Hen” with the literacy teaching of bilingual Latinx students. In this metaphor, the bilingual teachers represent the Mamá Gallina (Mother Hen) and their students represent the pollitos (little chicks) in their care. Then, we detail the teaching context from three elementary classrooms with bilingual Latinx students that spurred the metaphor for Mamá Gallina taking care of her pollitos in the classroom. These classrooms suggest how teachers could act as the “Fox” and perpetuate white English hegemony and the “Mother Hen” who mobilized their biliteracies to metaphorically feed and clothe their “baby chicks” with cariño (often translated as “care”). The rest of the article centers on how the metaphor of Mamá Gallina serves as a compelling vision for the healing practices of bilingual teachers themselves, before detailing principles for healing biliteracies in the classroom. These tools include: personal connections, cultural practices, linguistic relevance, and bilingual/biliterate pride. Ultimately, this metaphor illustrates how emancipatory pro‐Latinx teaching must attend to dual purposes: responding to the harm to bilingual teachers and students' biliteracies while also nurturing their dynamic beauty.
Sociopolitical, clinical, and ethical challenges of sustainable fracture care in Haiti
Authors: Charles Antoinette J. , Bethell Mikhail A. , Pean Marc‐Alain , Ochoa Brielle , Nau Bernard , Pean Christian A.
Published: September 2024

Introduction

In low‐ and middle‐income countries such as Haiti, musculoskeletal injuries are the leading cause of morbidity and mortality. Untreated injuries can contribute to decreased mobility, leading to disability and reduced productivity for individuals. The accessibility of timely fracture care poses a substantial challenge in Haiti, where socioeconomic instability and recent surges in gang violence exacerbate an already strained healthcare infrastructure. This manuscript delves into the intricate barriers to sustainable fracture care in Haiti, shedding light on the sociopolitical landscape and clinical challenges that influence the delivery of orthopedic services.

Ethical Discussion

The ethical considerations in providing fracture care in Haiti are multifaceted, including classic medical principles, self‐preservation in the face of violence, issues of justice in resource and service allocation, and concerns of nonmaleficence in the context of international volunteers. These ethical dilemmas arise from the complex interplay of limited resources, the dangers posed by the current sociopolitical climate, and the involvement of international aid in a vulnerable healthcare system.

Conclusion

To address the clinical and ethical conflicts of providing fracture care in Haiti, solutions include education and training of Haitian orthopedic surgeons, capacity building of healthcare facilities, and establishing ethical standards for international volunteers. This comprehensive approach is vital for advancing sustainable fracture care in Haiti and other resource‐limited settings.
Risk factor analysis of postoperative pancreatic fistula after distal pancreatectomy with a focus on the peritoneum to portal vein distance on computed tomography
Authors: Uemura Sho , Ban Daisuke , Esaki Minoru , Nara Satoshi , Takamoto Takeshi , Mizui Takahiro , Shimada Kazuaki
Published: September 2024

Background

Postoperative pancreatic fistula (POPF) is a major complication of distal pancreatectomy (DP). Although the visceral fat area (VFA) is a risk factor for POPF in DP, its measurement is complicated. This study aimed to identify a simple marker as a predictive indicator of POPF.

Methods

We included 210 patients who underwent resection at our institution between 2020 and 2023. The patients' characteristics, preoperative laboratory data, and radiographic findings (e.g., portal vein distance and VFA) and their association with pancreatic fistula after DP were analyzed. POPF was defined as Grade B or C pancreatic fistula on the basis of the International Study Group of Pancreatic Surgery 2016 consensus.

Results

POPF developed in 82 (39.0%) patients. Univariate analysis showed that female sex, pancreatic thickness of the cutting line, operative time, blood loss, C‐reactive protein (CRP) level on postoperative day (POD) 3, drain amylase level on POD 3, VFA, and the peritoneum to portal vein distance (PPD) were associated with POPF. Receiver operating characteristic curve analysis of PPD showed a higher area under the curve than VFA (cutoff for PPD: 68 mm). Multivariate analysis showed that CRP (odds ratio [OR]: 2.214), drain amylase (OR: 2.875), and PPD (OR: 15.538) were independent risk factors. When we compared the DP fistula risk score and PPD, receiver operating characteristic analysis showed areas under the curve of 0.650 and 0.803, respectively.

Conclusions

A PPD of ≥68 mm is a useful risk predictor of POPF. Determining this distance is simple and easily applicable in the clinical setting.
Social connection as a critical factor for mental and physical health: evidence, trends, challenges, and future implications
Authors: Holt‐Lunstad Julianne
Published: September 2024

Rising concerns about social isolation and loneliness globally have highlighted the need for a greater understanding of their mental and physical health implications. Robust evidence documents social connection factors as independent predictors of mental and physical health, with some of the strongest evidence on mortality. Although most data are observational, evidence points to directionality of effects, plausible pathways, and in some cases a causal link between social connection and later health outcomes. Societal trends across several indicators reveal increasing rates of those who lack social connection, and a significant portion of the population reporting loneliness. The scientific study on social isolation and loneliness has substantially extended over the past two decades, particularly since 2020; however, its relevance to health and mortality remains underappreciated by the public. Despite the breadth of evidence, several challenges remain, including the need for a common language to reconcile the diverse relevant terms across scientific disciplines, consistent multi‐factorial measurement to assess risk, and effective solutions to prevent and mitigate risk. The urgency for future health is underscored by the potentially longer‐term consequences of the COVID‐19 pandemic, and the role of digital technologies in societal shifts, that could contribute to further declines in social, mental and physical health. To reverse these trends and meet these challenges, recommendations are offered to more comprehensively address gaps in our understanding, and to foster social connection and address social isolation and loneliness.
Ethical challenges in contemporary psychiatry: an overview and an appraisal of possible strategies and research needs
Authors: Galderisi Silvana , Appelbaum Paul S. , Gill Neeraj , Gooding Piers , Herrman Helen , Melillo Antonio , Myrick Keris , Pathare Soumitra , Savage Martha , Szmukler George , Torous John
Published: September 2024

Psychiatry shares most ethical issues with other branches of medicine, but also faces special challenges. The Code of Ethics of the World Psychiatric Association offers guidance, but many mental health care professionals are unaware of it and the principles it supports. Furthermore, following codes of ethics is not always sufficient to address ethical dilemmas arising from possible clashes among their principles, and from continuing changes in knowledge, culture, attitudes, and socio‐economic context. In this paper, we identify topics that pose difficult ethical challenges in contemporary psychiatry; that may have a significant impact on clinical practice, education and research activities; and that may require revision of the profession's codes of ethics. These include: the relationships between human rights and mental health care, research and training; human rights and mental health legislation; digital psychiatry; early intervention in psychiatry; end‐of‐life decisions by people with mental health conditions; conflicts of interests in clinical practice, training and research; and the role of people with lived experience and family/informal supporters in shaping the agenda of mental health care, policy, research and training. For each topic, we highlight the ethical concerns, suggest strategies to address them, call attention to the risks that these strategies entail, and highlight the gaps to be narrowed by further research. We conclude that, in order to effectively address current ethical challenges in psychiatry, we need to rethink policies, services, training, attitudes, research methods and codes of ethics, with the concurrent input of a range of stakeholders, open minded discussions, new models of care, and an adequate organizational capacity to roll‐out the implementation across routine clinical care contexts, training and research.
An Analysis of Welfare Standards Within Tiger (Panthera tigris) Facilities in Thailand
Authors: Erzinçlioğlu Tanya S. , Groves Georgina , Ward Samantha
Published: September 2024

In Thailand, tigers are more numerous in captivity than they are in the wild, with 51 facilities housing approximately 1962 tigers. As charismatic fauna, tigers are popular with tourists, and the majority of facilities offer a variety of entertainment activities with controversial reports towards the animals' welfare. The aim of this research was to investigate tiger welfare in Thai zoos to identify specific welfare issues. We assessed 34 tourism facilities holding tigers in Thailand in 2019 using a 25‐point welfare assessment that utilizes the Five Domain model (incorporating all five domains: nutrition, physical environment, health, behavioural interactions and mental state). The mental domain score was derived from the scores of the other four domains. Additional data were collected from each facility, including the number of tigers, any colour variants, types of human interaction and admission cost. Welfare scores for each domain were calculated by totalling the scores per domain and dividing by the number of points allocated to that domain. A multiple regression was used to identify any significant predictors of mental domain score. The results revealed that the provision of a suitable physical environment scored the lowest, while nutrition scored the highest though this was still a low score overall. The multiple regression showed that 45.4% of the variance for the mental domain score was significantly affected by the number of colour variants housed and the types of human interaction available with facilities, with more of both these factors contributing to a more negative score. Our results demonstrate the need for urgent, comprehensive infrastructural, species‐appropriate environment and design and animal management improvements to increase animal welfare. Informed institutional change toward the breeding and use of tigers for public interactions is also required. This is the first assessment completed of captive tiger welfare of tiger facilities in Thailand and shows that the welfare concerns encountered are within a high proportion (67%) of Thailand's facilities. This supports the need for the creation and enforcement of effective and clear captive wildlife operational standards to provide a sustained solution for captive tiger welfare and can provide a considered approach to ex‐situ tiger management that, in conjunction with in‐situ efforts, can improve much needed conservation efforts of this species.
Diversity Accommodation and Fiscal Federalism: Comparative Remarks from a Constitutional Law Perspective
Authors: Valdesalici Alice , Romero Caro Francisco Javier
Published: September 2024

The chapter attempts to highlight the challenges that arise in the chapters of this book when examining the interaction between diversity accommodation and fiscal federalism within the selected federal systems. It explores how the need to address diversities influences financial relations and their evolution, focusing on which types of diversity drive these dynamics, potentially leading to integrative or disintegrative effects for the federal system. To accomplish this, the chapter delves into three major critical areas: the cause-effect relationship between diversity and fiscal arrangements, the balance between financial autonomy and solidarity, and the participation of subnational governments in decision-making processes. Examples from the case studies analyzed in this book are used to illustrate the complexities of accommodating diversities through fiscal federalism.
Unity and Diversity: A Turbulent Journey Through Italian Fiscal Federalism
Authors: Baraggia Antonia , Vimercati Benedetta
Published: September 2024

This chapter aims to analyze, from a diachronic perspective, the relationship between Italian regionalism and Italian fiscal federalism. Within a journey that will touch upon the main stages that have outlined the “incomplete Italian fiscal federalism”, an attempt will be made to highlight how—in the peculiarity of the Italian vertical division of powers—efforts have been made to reconcile key elements of any decentralized system, namely differentiation, autonomy, equality, and solidarity. The analysis will also highlight the most recent challenge posed to this reconciliation, namely the process of implementation of the so-called differentiated regionalism as provided for in Article 116.3 of the Italian Constitution.
Accommodating Diversity or Imposing Uniformity? The Hollowing Out of Provincial Governments in South Africa
Authors: Ajam Tania
Published: September 2024

The creation of the nine South African provincial governments was a concession by the African National Congress (ANC) to the National Party (NP) regime during the negotiated transition to democracy. The ANC favored a strong national government and strong local government, while the NP saw provinces as a vehicle for protection of White minority rights and privileges. While playing an important peace building function, provinces were endowed by the 1996 Constitution with few exclusive functions and negligible own revenue raising powers, therefore largely reliant on intergovernmental grants from national government. These already limited provincial powers have been further attenuated over the last two decades by the relocation of functions (e.g., social security and training and vocational colleges to national government, housing and public transport to large metropolitan governments, the proposed National Health Insurance system which will centralize current provincial health functions). This is exacerbated by centralized wage bargaining resulting in provincial wage bill escalation outstripping increases in intergovernmental grants and crowded out other non-wage expenditures. Provincial governments have little control over their largest cost driver which introduces budgetary rigidities. The highly centralized application of intergovernmental relations has limited scope for provincial experimentation and innovation.
Implementing stereotactic arrhythmia radioablation with STOPSTORM.eu consortium support: intermediate results of a prospective Israeli single-institutional trial
Authors: Borzov Egor , Efraim Roi , Suleiman Mahmoud , Bar-Deroma Raquel , Billan Salem , Xie Jingyang , Hohmann Stephan , Blanck Oliver , Charas Tomer
Published: September 2024

Background

Ventricular tachycardia (VT) is a life-threatening arrhythmia originating from the heart’s ventricles. Traditional treatments include antiarrhythmic medications, implantable cardioverter-defibrillators (ICDs), and catheter ablation. Stereotactic body radiation therapy (SBRT) targeting the arrhythmogenic focus in the left ventricle—stereotactic arrhythmia radioablation (STAR)—is an emerging treatment and may offer a potential solution for patients with refractory VT.

Objective

We designed an interventional prospective clinical trial in Israel aligned with the STOPSTORM.eu consortium’s benchmarks, recommendations, and directives to assess the safety and efficacy of STAR in patients with refractory VT.

Methods

Our phase I/II single-institutional trial was approved by the Ministry of Health of Israel for 10 patients, initially assessing safety in the first 3 patients. We included patients with ICDs experiencing symptomatic monomorphic VT after an inadequate response to previous therapies. The primary endpoints were treatment-related serious adverse events and a reduction in VT burden as assessed by ICD interrogation. Secondary outcomes included a reduction in antiarrhythmic medications and changes in quality of life.

Results

From August 2023 to August 2024, 3 patients underwent STAR treatment. The prescription dose was a single fraction of 25 Gy. Planning target volumes were 47.8, 49.7, and 91.8 cc, and treatment was successfully delivered with no grade 3 or higher adverse events reported. Over a follow-up period of 12 months for the first patient and 8 months for the second one, no VT events were recorded after treatment. The third patient died from progressive heart failure 3 months after treatment. Left ventricular ejection fraction remained stable, and no significant radiation-induced inflammatory changes were noted.

Conclusion

The initial results of this trial suggest that STAR can reduce VT episodes in patients with refractory VT without severe adverse effects. The study highlights the importance of international collaboration and standardization in pioneering new treatments. Further follow-up and additional patient data will be necessary to confirm these findings and evaluate long-term outcomes, including potential adjustments to antiarrhythmic medication regimens.
Obstetric Perineal Tears, Birth Characteristics and the Association with Urinary Incontinence Among Primiparous Women 12 Months Postpartum: A Prospective Cohort Study
Authors: Gommesen Ditte , Hjorth Sarah , Nohr Ellen A. , Qvist Niels , Rasch Vibeke
Published: September 2024

Introduction and Hypothesis

Postpartum urinary incontinence (UI) is common and a concern for many women, as UI leads to a lower quality of life and self-esteem. Perineal tears may be a risk factor for UI, yet few studies have investigated the association between the degree of perineal tear and risk of developing UI postpartum. The objective was to examine how the degree of perineal tear and selected obstetric risk factors were associated with any UI and stress ultrasound (SUI) 12 months postpartum among primiparous women.

Methods

A prospective cohort study was conducted at four Danish hospitals. Baseline data were obtained at a clinical examination 2 weeks postpartum. Symptoms of UI were evaluated 12 months postpartum by the International Consultation on Incontinence Questionnaire-Urinary Incontinence Short Form questionnaire (web-based). Multivariate regression analyses were performed to investigate the risk factors for UI.

Results

A total of 603 primiparous women (203 with none/labia/first-degree tears, 200 with second-degree tears and 200 with third-/fourth-degree tears) were included between July 2015 and January 2018. Women with tears involving the perineal muscles reported any UI more often than women with no/labia or first-degree tears (spontaneous second-degree tear: RR 2.04, 95% CI 0.92–4.50; episiotomy: RR 2.22, 95% CI 0.99–4.96; third- or fourth-degree tear: RR 2.73, 95% CI 1.18–6.28). The same was found for SUI, but with wider confidence intervals.

Conclusions

A higher prevalence of any UI and SUI was found among women with perineal tears involving any perineal muscles, compared with women with no, labia, or first-degree tears.
Logarithmic Corrections to the Alexander–Orbach Conjecture for the Four-Dimensional Uniform Spanning Tree
Authors: Halberstam Noah , Hutchcroft Tom
Published: September 2024

We compute the precise logarithmic corrections to Alexander–Orbach behaviour for various quantities describing the geometric and spectral properties of the four-dimensional uniform spanning tree. In particular, we prove that the volume of an intrinsic n-ball in the tree is $$n^2 (\log n)^{-1/3+o(1)}$$

n
2

(
log
n
)

-
1
/
3
+
o
(
1
)

, that the typical intrinsic displacement of an n-step random walk is $$n^{1/3} (\log n)^{1/9-o(1)}$$

n

1
/
3

(
log
n
)

1
/
9
-
o
(
1
)

, and that the n-step return probability of the walk decays as $$n^{-2/3}(\log n)^{1/9-o(1)}$$

n

-
2
/
3

(
log
n
)

1
/
9
-
o
(
1
)

.
A Boundary-Local Mass Cocycle and the Mass of Asymptotically Hyperbolic Manifolds
Authors: Čap Andreas , Gover A. Rod
Published: September 2024

We construct a cocycle that, for a given n-manifold, maps a pair of asymptotically locally hyperbolic (ALH) metrics to a tractor-valued $$(n-1)$$

(
n
-
1
)

-form field on the conformal infinity. This requires the metrics to be asymptotically related to a given order that depends on the dimension. It then provides a local geometric quantity on the boundary that is naturally associated to the pair and can be interpreted as a relative energy-momentum density. It is distinguished as a geometric object by its property of being invariant under suitable diffeomorphisms fixing the boundary, and that act on (either) one of the argument metrics. Specialising to the case of an ALH metric h that is suitably asymptotically related to a locally hyperbolic conformally compact metric, we show that the cocycle determines an absolute invariant c(h), which still is local in nature. This tractor-valued $$(n-1)$$

(
n
-
1
)

-form field on the conformal infinity is canonically associated to h (i.e. is not dependent on other choices) and is equivariant under the appropriate diffeomorphisms. Finally specialising further to the case that the boundary is a sphere and that a metric h is asymptotically related to a hyperbolic metric on the interior, we show that the invariant c(h) can be integrated over the boundary. The result pairs with solutions of the KID (Killing initial data) equation to recover the known description of hyperbolic mass integrals of Wang, and Chruściel–Herzlich.
Universality in the 2d Quasi-periodic Ising Model and Harris–Luck Irrelevance
Authors: Gallone Matteo , Mastropietro Vieri
Published: September 2024

We prove that in the 2D Ising model with a weak bidimensional quasi-periodic disorder in the interaction, the critical behavior is the same as in the non-disordered case; that is, the critical exponents for the specific heat and energy-energy correlations are identical, and no logarithmic corrections are present. The disorder produces a quasi-periodic modulation of the amplitude of the correlations and a renormalization of the velocities, that is, the coefficients of the rescaling of positions, and of the critical temperature. The result establishes the validity of the prediction based on the Harris–Luck criterion, and it provides the first rigorous proof of universality in the Ising model in the presence of quasi-periodic disorder in both directions and for any angle. Small divisors are controlled assuming a Diophantine condition on the frequencies, and the convergence of the series is proved by Renormalization Group analysis.
Cluster analysis of 100 Marfan patients based on aortic 4D flow MRI and Z-score: insights into disease heterogeneity and stratification of subgroups
Authors: Lenz Alexander , Bahr Flora , Riedel Christoph , Wright Felicia , Sinn Martin , Zhang Shuo , Schuett Marion , Well Lennart , Adam Gerhard , von Kodolitsch Yskert , Schoennagel Bjoern P. , Bannas Peter
Published: September 2024

Objectives

4D flow MRI-derived variables from Marfan patients are highly heterogeneous. Our aim was to identify distinct Marfan patient subgroups based on aortic 4D flow MRI and Z-score for stratification of distinct hemodynamic profiles and clinical features by means of hierarchical cluster analysis.

Materials and methods

One hundred Marfan patients underwent baseline aortic 4D flow MRI at 3 T. Z-scores, degree of helical and vortical flow, wall shear stress, flow displacement, and peak velocity were determined in the ascending aorta. Sex, age, BMI, antihypertensive medication, and dural ectasia were recorded. Hierarchical cluster analysis was performed using 4D flow MRI variables and Z-scores as input.

Results

Cluster analysis resulted in three distinct clusters characterized by different Z-scores (mean ± SD); cluster 1: 0.4 ± 1.1 vs. cluster 2: 3.1 ± 1.1 vs. cluster 3: 3.6 ± 1.9. The three clusters delivered differences in helical and vortical flow patterns (global p = 0.003 and p < 0.001, respectively), wall shear stress (0.49 ± 0.11 vs. 0.44 ± 0.12 vs. 0.37 ± 0.09 N/m2, global p < 0.001), flow displacement (0.11 ± 0.05 vs. 0.16 ± 0.08 vs. 0.15 ± 0.07, global p = 0.006), and peak velocity (76.3 ± 9.0 vs. 60.1 ± 7.3 vs. 56.0 ± 7.8 cm/s, global p < 0.001). Patients in cluster 1 and 2 were relevantly younger than in cluster 3 (32.3 ± 13.8 vs. 32.8 ± 12.6 vs. 40.2 ± 15.0 years, all pairwise ∆p < 0.0297).

Conclusion

Hierarchical cluster analysis based on aortic 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients, each characterized by specific hemodynamic profiles and clinical features. Follow-up of our patients is warranted to assess if 4D flow MRI- and Z-score-based stratification can predict future aortic diameter growth and ultimately improve outcomes.

Clinical relevance statement

A combination of Z-score and 4D flow MRI-derived parameters may help identify subgroups of Marfan patients representing different stages or phenotypes of aortic disease, which require specific management strategies.

Key Points

Four-dimensional (4D) flow MRI-derived variables of Marfan patients are highly heterogeneous across varying Z-scores.

Cluster analysis based on 4D flow MRI and Z-score revealed three distinct subgroups of Marfan patients.

A combination of Z-score and 4D flow MRI-derived parameters may identify different stages of aortic disease in Marfan patients.

Graphical Abstract
Effects of Azithromycin on Blood Inflammatory Gene Expression and Cytokine Production in Sarcoidosis
Authors: Fraser Simon D. , Thackray-Nocera Susannah , Wright Caroline , Flockton Rachel , James Sally R. , Crooks Michael G. , Kaye Paul M. , Hart Simon P.
Published: September 2024

Introduction

In sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis.

Methods

Blood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP.

Results

Differential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers.

Conclusion

Blood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood.

Trial registration: EudraCT 2019-000580-24 (17 May 2019)
Heart rate to identify non-febrile children with dehydration and acute kidney injury in emergency department: a prospective validation study
Authors: Marzuillo Pierluigi , Rivetti Giulio , Galeone Antonietta , Capasso Giusy , Tirelli Paola , Di Sessa Anna , Miraglia del Giudice Emanuele , Guarino Stefano , Nunziata Felice
Published: September 2024

We previously developed and retrospectively validated the estimated percentage of heart rate variation (EHRV) as a predictor of the composite outcome of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile children. The current study aimed to prospectively validate EHRV as a predictor for dehydration or AKI in a different cohort of children attending the Pediatric Emergency Department. From July 2022 to August 2023, 256 pediatric patients aged 0–18 years attending the Pediatric Emergency Department were enrolled. EHRV was calculated as follows: [(HR at admission − 50th percentile of HR for age and sex)/HR at admission] × 100. Dehydration was categorized as < 5% or ≥ 5% fluid deficit. AKI was defined according to KDIGO creatinine criteria. Statistical analyses included receiver-operating characteristic (ROC) curves and logistic regression analysis. Among enrolled patients, 52 had ≥ 5% dehydration, 50 had AKI, and 16 had both conditions. EHRV demonstrated significant predictive ability for both ≥ 5% dehydration (AUROC = 0.71; 95% confidence interval (CI), 0.63–0.78; p < 0.001) and AKI (AUROC = 0.78; 95% CI, 0.71–0.84; p < 0.001). An EHRV > 24.5% was associated with an increased odds ratio (OR), adjusted for confounders, of ≥ 5% dehydration (OR = 3.5; 95% CI, 1.6–8.0; p = 0.003) and AKI (OR = 3.4; 95% CI, 1.6–7.3; p = 0.002). The sensitivity and specificity of this cut-off were 34% and 83% for ≥ 5% dehydration and 36% and 84% for AKI, respectively.

Conclusions: This study prospectively validates the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting. An EHRV > 24.5% could serve as a marker for suspecting dehydration or AKI. Further validation across diverse patient populations and settings is needed.

What is Known:• An increased heart rate (HR) is a readily detectable sign of dehydration in children.• In a retrospective validation cohort, an estimated HR variation (EHRV) greater than 24.5% compared to the 50th percentile of HR was predictive of ≥ 5% dehydration and/or acute kidney injury (AKI) in non-febrile patients.

What is New:• We prospectively validated the clinical utility of EHRV in predicting dehydration and AKI in a pediatric emergency care setting.• We confirmed that an EHRV greater than 24.5% is associated with increased odds of ≥ 5% dehydration and AKI.
National trends in pediatric drowning — insights from the Israeli Ministry of Health registry-based cohort
Authors: Applbaum Yael , Cohen-Cymberknoh Malena , Avniel-Aran Adi , Yahav Ayala , Weinblatt Ezra , Brooks Rebecca , Reiter Joel , Gordon Shulamit , Haklai Ziona , Pollak Uri
Published: September 2024

This study analyzes the epidemiology of pediatric drowning in Israel from 2010 to 2022, focusing on differences across age groups, sex, and regions. We conducted a retrospective cohort study using data from the Ministry of Health’s administrative databases, covering all children aged 0–17 years who were seen in the emergency department, discharged after hospitalization, or died at the scene due to drowning, excluding cases of intentional harm or suicide. The primary outcome was the annual drowning rate per 100,000 children, categorized by age, sex, and region, along with hospitalization duration, intensive care unit admissions, and mortality rates. A total of 2101 drowning incidents were identified, with 9% resulting in death. Higher drowning rates were found in younger children (1–4 years) and teenagers (15–17 years), with notable differences by sex. Drowning rates were higher in coastal regions and more frequent during winter and spring. An increase in drowning rates was observed over the last 3 years of the study (2020–2022). Children hospitalized for more than 3 days had significantly higher mortality rates, both in general wards and intensive care units.

Conclusions: Pediatric drowning is a persistent public health concern in Israel, with distinct seasonal, regional, age-specific, and sex-specific patterns in incidence and mortality. This study underscores the need for a comprehensive prevention strategy that includes year-round public education, environmental safety measures, and targeted interventions for high-risk groups to reduce drowning incidents and fatalities among children effectively.

What is Known:• Pediatric drowning represents a significant public health challenge globally, with varying rates.• In Israel, pediatric drowning is the second leading cause of death from all injury-related deaths. Thus far, the measures and interventions to reduce fatalities were not proven effective enough.

What is New:• Pediatric drowning in Israel, with a 9% mortality rate, revealed a biphasic rate varied by sex and is higher in coastal regions and during winter and spring.• There was a notable increase in drowning incidents during the last 3 years of the study period (2020–2022), coinciding with the COVID-19 pandemic.