bluuebunny/crossref_metadata_2025_split huggingface dataset:
Momordica charantia L.-derived exosome-like nanovesicles stabilize p62 expression to ameliorate doxorubicin cardiotoxicity
Authors: Ye Cong , Yan Chen , Bian Si-Jia , Li Xin-Ran , Li Yu , Wang Kai-Xuan , Zhu Yu-Hua , Wang Liang , Wang Ying-Chao , Wang Yi-Yuan , Li Tao-Sheng , Qi Su-Hua , Luo Lan 
Published: August 2024

Abstract
Background
Doxorubicin (DOX) is a first-line chemotherapeutic drug for various malignancies that causes cardiotoxicity. Plant-derived exosome-like nanovesicles (P-ELNs) are growing as novel therapeutic agents. Here, we investigated the protective effects in DOX cardiotoxicity of ELNs from Momordica charantia L. (MC-ELNs), a medicinal plant with antioxidant activity.

Results
We isolated MC-ELNs using ultracentrifugation and characterized them with canonical mammalian extracellular vesicles features. In vivo studies proved that MC-ELNs ameliorated DOX cardiotoxicity with enhanced cardiac function and myocardial structure. In vitro assays revealed that MC-ELNs promoted cell survival, diminished reactive oxygen species, and protected mitochondrial integrity in DOX-treated H9c2 cells. We found that DOX treatment decreased the protein level of p62 through ubiquitin-dependent degradation pathway in H9c2 and NRVM cells. However, MC-ELNs suppressed DOX-induced p62 ubiquitination degradation, and the recovered p62 bound with Keap1 promoting Nrf2 nuclear translocation and the expressions of downstream gene HO-1. Furthermore, both the knockdown of Nrf2 and the inhibition of p62-Keap1 interaction abrogated the cardioprotective effect of MC-ELNs.

Conclusions
Our findings demonstrated the therapeutic beneficials of MC-ELNs via increasing p62 protein stability, shedding light on preventive approaches for DOX cardiotoxicity.
Frontline use of rituximab may prevent ADAMTS13 inhibitor boosting during caplacizumab treatment in patients with iTTP: post hoc analysis of a phase 2/3 study in Japan
Authors: Imada Kazunori , Miyakawa Yoshitaka , Ichikawa Satoshi , Uchiyama Hitoji , Ueda Yasunori , Hashimoto Yasuhiro , Nishimi Masashi , Tsukamoto Masako , Tahara Sayaka , Matsumoto Masanori 
Published: August 2024

Abstract
Background
A recent Phase 2/3 study in Japanese patients showed that caplacizumab was effective in treating immune-mediated thrombotic thrombocytopenic purpura (iTTP), with a low rate of iTTP recurrence. ADAMTS13 activity is monitored weekly during caplacizumab treatment to guide discontinuation of caplacizumab and consequently avoid exacerbations or relapse. The aim of this study was to assess changes in ADAMTS13 activity/inhibitor levels during caplacizumab treatment in this patient population.

Methods
A post hoc analysis of the Phase 2/3 study in Japanese patients was conducted. Patients ≥ 18 years old with confirmed iTTP received 10 mg of caplacizumab daily in conjunction with therapeutic plasma exchange (TPE) and immunosuppression for 30 days post-TPE. Outcomes included time to recovery of ADAMTS13 activity, ADAMTS13 activity level at treatment end, incidence of ADAMTS13 inhibitor re-elevation (ie, inhibitor boosting) during treatment, time to platelet count recovery, number of days of TPE, and safety. Outcomes according to presence of inhibitor boosting were also assessed.

Results
Nineteen patients had confirmed iTTP and were included in this analysis. Median (95% confidence interval) time to recovery of ADAMTS13 activity to ≥ 10%, ≥ 20%, and ≥ 60% was 14.6 (5.9–24.8), 18.5 (5.9–31.8), and 47.5 (18.5–60.9) days, respectively. Median (range) ADAMTS13 activity level at caplacizumab treatment end was 62.0% (29.0–101.0). Nine patients had ADAMTS13 inhibitor boosting. Delayed response of ADAMTS13 activity was observed in patients with inhibitor boosting. The median time to platelet count response and median number of TPE days were shorter in patients with inhibitor boosting compared with patients without inhibitor boosting. Rituximab was administered to almost all patients with inhibitor boosting (88.9%), after completion of TPE. Patients without inhibitor boosting who were treated with rituximab received it prior to completion of TPE. Only one patient experienced a recurrence, which occurred shortly after caplacizumab discontinuation due to an adverse event.

Conclusions
In patients with iTTP, caplacizumab with TPE and immunosuppression may reduce the risk of ADAMTS13 inhibitor boosting if rituximab is administered early in the iTTP treatment period. Early administration of rituximab in addition to caplacizumab may prevent iTTP recurrence with inhibitor boosting.

Trial registration
NCT04074187.
Expert consensus on multilevel implementation hypotheses to promote the uptake of youth care guidelines: a Delphi study
Authors: Dubbeldeman Eveline M. , van der Kleij Rianne M. J. J. , Brakema Evelyn A. , Crone Mathilde R. 
Published: August 2024

Abstract
Background
The implementation of youth care guidelines remains a complex process. Several evidence–based frameworks aid the identification and specification of implementation determinants and strategies. However, the influence of specific strategies on certain determinants remains unclear. Therefore, we need to clarify which active ingredients of strategies, known as behaviour change techniques (BCTs), elicit behaviour change and improve implementation outcomes. With this knowledge, we are able to formulate evidence–based implementation hypotheses. An implementation hypothesis details how determinants and in turn, implementation outcomes might be influenced by specific implementation strategies and their BCTs. We aimed to identify (1) determinants relevant to the implementation of youth care guidelines and (2) feasible and potentially effective implementation hypotheses.

Methods
A four–round online modified Delphi study was conducted. In the first round, experts rated the implementation determinants based on their relevance. Next, experts formulated implementation hypotheses by connecting BCTs and implementation strategies to determinants and were asked to provide a rationale for their choices. In round three, the experts reconsidered and finalised their hypotheses based on an anonymous overview of all formulated hypotheses, including rationales. Finally, the experts rated the implementation hypotheses based on their potential effectiveness and feasibility.

Results
Fourteen experts completed the first, second, and third rounds, with 11 completed the final round. Guideline promotion, mandatory education, presence of an implementation leader, poor management support, knowledge regarding guideline use, and a lack of communication skills were reported as most relevant determinants. In total, 46 hypotheses were formulated, ranging from 6 to 9 per determinant. For each determinant, we provide an overview of the implementation hypotheses that were most commonly deemed feasible and potentially effective.

Conclusion
This study offers valuable insights into youth care guideline implementation by systematically identifying relevant determinants and formulating hypotheses based on expert input. Determinants related to engagement and to knowledge and skills were found to be relevant to youth care guideline implementation. This study offers a set of hypotheses that could help organisations, policymakers, and professionals guide the implementation process of youth care guidelines to ultimately improve implementation outcomes. The effectiveness of these hypotheses in practice remains to be assessed.
CD44 signaling in Müller cells impacts photoreceptor function and survival in healthy and diseased retinas
Authors: Ayten Monika , Straub Tobias , Kaplan Lew , Hauck Stefanie M. , Grosche Antje , Koch Susanne F. 
Published: August 2024

AbstractRetinitis pigmentosa (RP), an inherited retinal disease, affects 1,5 million people worldwide. The initial mutation-driven photoreceptor degeneration leads to chronic inflammation, characterized by Müller cell activation and upregulation of CD44. CD44 is a cell surface transmembrane glycoprotein and the primary receptor for hyaluronic acid. It is involved in many pathological processes, but little is known about CD44’s retinal functions. CD44 expression is also increased in Müller cells from our Pde6bSTOP/STOP RP mouse model. To gain a more detailed understanding of CD44’s role in healthy and diseased retinas, we analyzed Cd44−/− and Cd44−/−Pde6bSTOP/STOP mice, respectively. The loss of CD44 led to enhanced photoreceptor degeneration, reduced retinal function, and increased inflammatory response. To understand the underlying mechanism, we performed proteomic analysis on isolated Müller cells from Cd44−/− and Cd44−/−Pde6bSTOP/STOP retinas and identified a significant downregulation of glutamate transporter 1 (SLC1A2). This downregulation was accompanied by higher glutamate levels, suggesting impaired glutamate homeostasis. These novel findings indicate that CD44 stimulates glutamate uptake via SLC1A2 in Müller cells, which in turn, supports photoreceptor survival and function.
The immunology of B-1 cells: from development to aging
Authors: Mattos Matheus Silvério , Vandendriessche Sofie , Waisman Ari , Marques Pedro Elias 
Published: August 2024

AbstractB-1 cells have intricate biology, with distinct function, phenotype and developmental origin from conventional B cells. They generate a B cell receptor with conserved germline characteristics and biased V(D)J recombination, allowing this innate-like lymphocyte to spontaneously produce self-reactive natural antibodies (NAbs) and become activated by immune stimuli in a T cell-independent manner. NAbs were suggested as “rheostats” for the chronic diseases in advanced age. In fact, age-dependent loss of function of NAbs has been associated with clinically-relevant diseases in the elderly, such as atherosclerosis and neurodegenerative disorders. Here, we analyzed comprehensively the ontogeny, phenotypic characteristics, functional properties and emerging roles of B-1 cells and NAbs in health and disease. Additionally, after navigating through the complexities of B-1 cell biology from development to aging, therapeutic opportunities in the field are discussed.
Ethnozoological study of medicinal animals used by the inhabitants of the Kucha District, Gamo Zone, Southern Ethiopia
Authors: Mengistu Meselech , Kebebew Mulugeta , Meyer-Rochow Victor Benno 
Published: August 2024

Abstract
Background
An ethnozoological study of medicinal animals in the Kucha district, Gamo zone, Southern Ethiopia, was conducted to investigate and document the use of traditional medicinal animals and the associated indigenous knowledge. Tribal people still make abundant use of animals and their parts to manage diseases in humans and even livestock.

Method
A cross sectional study design and purposively sampling techniques were used. Data were collected from 132 respondents based on semi structured questionnaires. Focus group discussions (FGD) and Key informant interviews (KII) were conducted; Fidelity level (FL), Relative frequency of citation (RFC) and Informants’ consensus factor (ICF) were used to analyze species preference and importance.

Results
A total of 24 medicinal animals were identified with 13 species (54.2%) being mammals of which 5 species (20.8%) dominated. They were followed by arthropods, reptiles and fishes. Seven out of the total were domestic species (29%) and 17 (70%) were wild animals. The majority of these animals, i.e. 22 (91.7%), were used to treat human ailments; whereas 2 (8.3%) were used to treat livestock ailments. The ICF values varied from 0.8 to 1.The highest FL value (98%) was linked to the cow (cattle), the lowest (1.5%) to the scorpion. The RFC value (1.0) was highest for the cow and lowest (0.02) for the scorpion. Honey, milk, and butter were the most commonly used therapeutic animal products, but regarding direct uses, fresh/raw meat dominated. Out of ten ailment categories, headaches had the lowest ICF value (0.8). All others scored at least 0.9.

Conclusions
In rural areas, sick people often do not only have limited access to modern medical facilities, they actually prefer traditional treatments considering them to be more reliable and effective. It is therefore important to focus on documenting, conserving, and safeguarding the indigenous knowledge so that strategies to manage the traditional wisdom can be implemented in the future. To achieve these goals, it is important to make sure that medicinal animal species are available in sufficient numbers and neither threatened by habitat changes or overexploitation.
Bartonella quintana detection among arthropods and their hosts: a systematic review and meta-analysis
Authors: Boodman Carl , Gupta Nitin , van Griensven Johan , Van Bortel Wim 
Published: August 2024

Abstract
Background
Bartonella quintana is a body louse-borne bacterium causing bacteremia and infective endocarditis. We aimed to describe B. quintana detection among arthropods and their hosts.

Methods
We searched databases in PubMed Central/MEDLINE, Scopus, Embase, and Web of Science from January 1, 1915 (the year of B. quintana discovery) to January 1, 2024, to identify publications containing specific search terms relating to B. quintana detection among arthropods. Descriptive statistics and meta-analysis of pooled prevalence using random-effects models were performed for all arthropods and body and head lice.

Results
Of 1265 records, 62 articles were included, describing 8839 body lice, 4962 head lice, and 1692 other arthropods, such as different species of fleas, bedbugs, mites, and ticks. Arthropods were collected from 37 countries, of which 28 had arthropods with B. quintana DNA. Among articles that reported B. quintana detection among individual arthropods, 1445 of 14,088 (0.1026, 95% CI [0.0976; 0.1077]) arthropods tested positive for B. quintana DNA, generating a random-effects model global prevalence of 0.0666 (95% CI [0.0426; 0.1026]). Fifty-six studies tested 8839 body lice, of which 1679 had B. quintana DNA (0.1899, 95% CI [0.1818; 0.1983]), generating a random-effects model pooled prevalence of 0.2312 (95% CI [0.1784; 0.2843]). Forty-two studies tested 4962 head lice, of which 390 head lice from 20 studies originating from 11 different countries had B. quintana DNA (0.0786, 95% CI [0.0713; 0.0864]). Eight studies detected B. quintana DNA exclusively on head lice. Five studies reported greater B. quintana detection on head lice than body lice; all originated from low-resource environments.

Conclusions
Bartonella quintana is a vector-borne bacterium with a global distribution, disproportionately affecting marginalized populations. Bartonella quintana DNA has been detected in many different arthropod species, though not all of these arthropods meet criteria to be considered vectors for B. quintana transmission. Body lice have long been known to transmit B. quintana. A limited number of studies suggest that head lice may also act as possible vectors for B. quintana in specific low-resource contexts.

Graphical Abstract
A novel multitask learning algorithm for tasks with distinct chemical space: zebrafish toxicity prediction as an example
Authors: Lin Run-Hsin , Lin Pinpin , Wang Chia-Chi , Tung Chun-Wei 
Published: August 2024

AbstractData scarcity is one of the most critical issues impeding the development of prediction models for chemical effects. Multitask learning algorithms leveraging knowledge from relevant tasks showed potential for dealing with tasks with limited data. However, current multitask methods mainly focus on learning from datasets whose task labels are available for most of the training samples. Since datasets were generated for different purposes with distinct chemical spaces, the conventional multitask learning methods may not be suitable. This study presents a novel multitask learning method MTForestNet that can deal with data scarcity problems and learn from tasks with distinct chemical space. The MTForestNet consists of nodes of random forest classifiers organized in the form of a progressive network, where each node represents a random forest model learned from a specific task. To demonstrate the effectiveness of the MTForestNet, 48 zebrafish toxicity datasets were collected and utilized as an example. Among them, two tasks are very different from other tasks with only 1.3% common chemicals shared with other tasks. In an independent test, MTForestNet with a high area under the receiver operating characteristic curve (AUC) value of 0.911 provided superior performance over compared single-task and multitask methods. The overall toxicity derived from the developed models of zebrafish toxicity is well correlated with the experimentally determined overall toxicity. In addition, the outputs from the developed models of zebrafish toxicity can be utilized as features to boost the prediction of developmental toxicity. The developed models are effective for predicting zebrafish toxicity and the proposed MTForestNet is expected to be useful for tasks with distinct chemical space that can be applied in other tasks.Scieific contributionA novel multitask learning algorithm MTForestNet was proposed to address the challenges of developing models using datasets with distinct chemical space that is a common issue of cheminformatics tasks. As an example, zebrafish toxicity prediction models were developed using the proposed MTForestNet which provide superior performance over conventional single-task and multitask learning methods. In addition, the developed zebrafish toxicity prediction models can reduce animal testing.
Risk stratification of new-onset psychiatric disorders using clinically distinct traumatic brain injury phenotypes
Authors: Kureshi Nelofar , Nunes Abraham , Feng Cindy , Clarke David B. , Abidi Syed Sibte Raza 
Published: August 2024

Abstract
Background
Patients with traumatic brain injury (TBI) constitute a highly heterogeneous population, with varying risks for New-onset Psychiatric Disorders (NPDs). The objectives of this study were to identify TBI phenotypes and determine how NPDs differ among these phenotypes.

Methods
Hospitalized TBI patients from 2003 to 2019 were obtained from the provincial trauma registry. Propensity score matching was conducted to balance covariates among patients with TBI and controls. To uncover heterogeneity in TBI, latent class analysis (LCA)-based clustering was applied. LCA was conducted separately for two TBI cohorts: those with and without pre-injury psychiatric conditions The effect of classes on NPDs was assessed using log binomial regression models.

Results
A total of 3,453 patients with TBI and 13,112 controls were included in the analysis. In a conditional regression involving propensity matched patients with TBI and controls, TBI was significantly associated with the development of NPD-A (OR: 2.78; 95% CI: 2.49–3.09), as well as NPD-P (OR: 2.36; 95% CI: 2.07–2.70). Eight distinct latent classes were identified which differed in the incidence of NPDs. Four classes displayed a 53% (RR:1.53; 95% CI: 1.31–1.78), 48% (RR:1.48; 95% CI: 1.26–1.74), 28% (RR:1.28; 95% CI: 1.08–1.54), and 20% (RR: 1.20, 95%CI: 1.03–1.39), increased NPD risk.

Conclusion
TBI is a significant predictor of NPDs. There are clinically distinguishable phenotypes with different patterns of NPD risk among patients with TBI. Identifying individuals with respect to their phenotype may improve risk stratification of patients with TBI and promote early intervention for psychiatric care in this vulnerable population.
Exploring perceptions of genetic risk and the transmission of substance use disorders
Authors: Keller Amanda , Bosk Emily A. , Mendez Alicia , Greenfield Brett , Flynn Carolynn , Everett Gina , Julien Fabrys , Michael MacKenzie 
Published: August 2024

Abstract
Background
Substance use disorders (SUDs) have been consistently shown to exhibit moderate intergenerational continuity (1–3). While much research has examined genetic and social influences on addiction, less attention has been paid to clients’ and lay persons’ perceptions of genetic influences on the heritability of SUD (4) and implications for treatment.

Methods
For this qualitative study, twenty-six structured Working Model of the Child Interviews (WMCI) were conducted with mothers receiving inpatient SUD treatment. These interviews were thematically analyzed for themes related to maternal perceptions around intergenerational transmission of substance use behaviours.

Results
Findings show that over half of the mothers in this sample were preoccupied with their children’s risk factors for addictions. Among this group, 29% spontaneously expressed concerns about their children’s genetic risk for addiction, 54% shared worries about their children’s propensity for addiction without mentioning the word gene or genetic. Additionally, 37% had challenges in even discussing their children’s future when prompted. These concerns mapped onto internal working models of attachment in unexpected ways, with parents who were coded with balanced working models being more likely to discuss intergenerational risk factors and parents with disengaged working models displaying difficulties in discussing their child’s future.

Conclusion
This research suggests that the dominant discourse around the brain-disease model of addictions, in its effort to reduce stigma and self-blame, may have unintended downstream consequences for parents’ mental models about their children’s risks for future addiction. Parents receiving SUD treatment, and the staff who deliver it, may benefit from psychoeducation about the intergenerational transmission of SUD as part of treatment.
A scoping review of Enhanced Recovery After Surgery (ERAS), protocol implementation, and its impact on surgical outcomes and healthcare systems in Africa
Authors: Kifle Fitsum , Kenna Peniel , Daniel Selam , Maswime Salome , Biccard Bruce 
Published: August 2024

Abstract
Background
Enhanced Recovery After Surgery (ERAS) is a patient-centered approach to surgery designed to reduce stress responses and facilitate faster recovery. ERAS protocols have been widely adopted in high-income countries, supported by robust research demonstrating improved patient outcomes. However, in Africa, there is limited evidence regarding its implementation. This review aims to identify the existing literature on the implementation of ERAS principles in Africa, the reported clinical outcomes, and the challenges and recommendations for successful implementation.

Methods
We conducted a librarian-assisted literature search of electronic research databases between October and November 2023. Titles and abstracts were screened for eligibility, and duplicates were then removed, followed by full-text assessment of potentially eligible studies. We utilized the summative content analysis method to synthesize and group the data into fewer categories based on agreed-upon criteria. Descriptive statistics were used to describe the results.

Results
The search identified 342 potential studies resulting in 15 eligible studies for inclusion in the review. The publication years ranged from 2016 to 2023. The studies originated from three countries: Egypt (n = 10), South Africa (n = 4), and Uganda (n = 1). Successful implementation was associated with reduced hospital length of stay (n = 12), lower mortality rates (n = 3), and improved pain outcomes (n = 7). Challenges included protocol adherence (n = 5) and limitations of the research design to generate strong evidence (n = 3). Recommendations included formal adoption of ERAS principles (n = 5), the need for sustained research commitment, and exploration of the applicability of ERAS in diverse surgical contexts (n = 8). Large-scale implementation beyond individual institutions was encouraged to further validate its impact on patient outcomes and healthcare costs (n = 1).

Conclusions
Despite the limited number of studies on ERAS implementation in Africa, the available evidence suggests that it reduces the length of hospital stays and mortality rates. This is crucial for the region, given its higher mortality rates, necessitating more collaborative, methodically well-designed studies to establish stronger evidence for ERAS in lower-resource environments.