bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling the intriguing interplay: Exploring the role of lncRNAs in caspase‐independent cell death
Authors: Ciftci Yusuf Cem , Vatansever İpek Erdoğan , Akgül Bünyamin 
Published: June 2024

AbstractCell death plays a crucial role in various physiological and pathological processes. Until recently, programmed cell death was mainly attributed to caspase‐dependent apoptosis. However, emerging evidence suggests that caspase‐independent cell death (CICD) mechanisms also contribute significantly to cellular demise. We and others have reported and functionally characterized numerous long noncoding RNAs (lncRNAs) that modulate caspase‐dependent apoptotic pathways potentially in a pathway‐dependent manner. However, the interplay between lncRNAs and CICD pathways has not been comprehensively documented. One major reason for this is that most CICD pathways have been recently discovered with some being partially characterized at the molecular level. In this review, we discuss the emerging evidence that implicates specific lncRNAs in the regulation and execution of CICD. We summarize the diverse mechanisms through which lncRNAs modulate different forms of CICD, including ferroptosis, necroptosis, cuproptosis, and others. Furthermore, we highlight the intricate regulatory networks involving lncRNAs, protein‐coding genes, and signaling pathways that orchestrate CICD in health and disease. Understanding the molecular mechanisms and functional implications of lncRNAs in CICD may unravel novel therapeutic targets and diagnostic tools for various diseases, paving the way for innovative strategies in disease management and personalized medicine.This article is categorized under:
RNA in Disease and Development > RNA in Disease
Thirty years of conservation breeding: Assessing the genetic diversity of captive Livingstone's fruit bats
Authors: Richdon Sarah , Menchaca Rodriguez Angelica , Price Eluned , Wormell Dominic , McCabe Grainne , Jones Gareth 
Published: June 2024

AbstractFruit bats (genus Pteropus) are typically island‐endemic species important in seed dispersal and reforestation that are vulnerable to increased extinction risk. An effective method of reducing extinction risk in vulnerable species that cannot be conserved in their native habitat is establishing an ex‐situ captive breeding programme. Due to anthropogenic threats and low population numbers, in the early 1990s, a captive breeding programme was established at Jersey Zoo, British Isles, for Critically Endangered Livingstone's fruit bats (Pteropus livingstonii). Here we use six polymorphic microsatellite loci to assess genetic diversity in the captive breeding population of Livingstone's fruit bats (P. livingstonii), 30 years after the programme's establishment, investigating change over generations and comparing our findings with published data from the wild population. We found no significant difference between the genetic diversity in the captive and wild populations of Livingstone's fruit bats (P. livingstonii), in both expected heterozygosity and allelic richness. The captive population has retained a comparable level of genetic diversity to that documented in the wild, and there has been no significant decline in genetic diversity over the last 30 years. We advise that a full pedigree of the paternal lineage is created to improve the management of the captive breeding programme and further reduce the possibility of inbreeding. However, it appears that the captive breeding programme is currently effective at maintaining genetic diversity at levels comparable to those seen in the wild population, which suggests reintroductions could be viable if genetic diversity remains stable in captivity.
Safety and effectiveness of SGLT2 inhibitors in a UK population with type 2 diabetes and aged over 70 years: an instrumental variable approach
Authors: Güdemann Laura M. , Young Katie G. , Thomas Nicholas J. M. , Hopkins Rhian , Challen Robert , Jones Angus G. , Hattersley Andrew T. , Pearson Ewan R. , Shields Beverley M. , Bowden Jack , Dennis John M. , McGovern Andrew P. ,   on behalf of the MASTERMIND consortium
Published: June 2024

Abstract
Aims/hypothesis
Older adults are under-represented in trials, meaning the benefits and risks of glucose-lowering agents in this age group are unclear. The aim of this study was to assess the safety and effectiveness of sodium–glucose cotransporter 2 inhibitors (SGLT2i) in people with type 2 diabetes aged over 70 years using causal analysis.

Methods
Hospital-linked UK primary care data (Clinical Practice Research Datalink, 2013–2020) were used to compare adverse events and effectiveness in individuals initiating SGLT2i compared with dipeptidyl peptidase-4 inhibitors (DPP4i). Analysis was age-stratified: <70 years (SGLT2i n=66,810, DPP4i n=76,172), ≥70 years (SGLT2i n=10,419, DPP4i n=33,434). Outcomes were assessed using the instrumental variable causal inference method and prescriber preference as the instrument.

Results
Risk of diabetic ketoacidosis was increased with SGLT2i in those aged ≥70 (incidence rate ratio compared with DPP4i: 3.82 [95% CI 1.12, 13.03]), but not in those aged <70 (1.12 [0.41, 3.04]). However, incidence rates with SGLT2i in those ≥70 was low (29.6 [29.5, 29.7]) per 10,000 person-years. SGLT2i were associated with similarly increased risk of genital infection in both age groups (incidence rate ratio in those <70: 2.27 [2.03, 2.53]; ≥70: 2.16 [1.77, 2.63]). There was no evidence of an increased risk of volume depletion, poor micturition control, urinary frequency, falls or amputation with SGLT2i in either age group. In those ≥70, HbA1c reduction was similar between SGLT2i and DPP4i (−0.3 mmol/mol [−1.6, 1.1], −0.02% [0.1, 0.1]), but in those <70, SGLT2i were more effective (−4 mmol/mol [4.8, −3.1], −0.4% [−0.4, −0.3]).

Conclusions/interpretation
Causal analysis suggests SGLT2i are effective in adults aged ≥70 years, but increase risk for genital infections and diabetic ketoacidosis. Our study extends RCT evidence to older adults with type 2 diabetes.

Graphical Abstract
What Goes Around Comes Around: Covering Tours and Cycle Covers with Turn Costs
Authors: Fekete Sándor P. , Krupke Dominik 
Published: June 2024

AbstractWe investigate several geometric problems of finding tours and cycle covers with minimum turn cost, which have been studied in the past, with complexity, approximation results, and open problems dating back to work by Arkin et al. in 2001. Many new practical applications have spawned variants: For full coverage, all points have to be covered, for subset coverage, specific points have to be covered, and for penalty coverage, points may be left uncovered by incurring a penalty. We show that finding a minimum-turn (full) cycle cover is NP-hard even in 2-dimensional grid graphs, solving the long-standing open Problem 53 in The Open Problems Project edited by Demaine, Mitchell and O’Rourke. We also prove NP-hardness of finding a subset cycle cover of minimum turn cost in thin grid graphs, for which Arkin et al. gave a polynomial-time algorithm for full coverage; this shows that their boundary techniques cannot be applied to compute exact solutions for subset and penalty variants. We also provide a number of positive results. In particular, we establish the first constant-factor approximation algorithms for all considered subset and penalty problem variants for grid-based instances, based on LP/IP techniques. These geometric versions allow many possible edge directions (and thus, turn angles, such as in hexagonal grids or higher-dimensional variants); our approximation factors improve the combinatorial ones of Arkin et al.
DSC-PWI presurgical differentiation of grade 4 astrocytoma and glioblastoma in young adults: rCBV percentile analysis across enhancing and non-enhancing regions
Authors: Pons-Escoda Albert , Naval-Baudin Pablo , Viveros Mildred , Flores-Casaperalta Susanie , Martinez-Zalacaín Ignacio , Plans Gerard , Vidal Noemi , Cos Monica , Majos Carles 
Published: June 2024

Abstract
Purpose
The presurgical discrimination of IDH-mutant astrocytoma grade 4 from IDH-wildtype glioblastoma is crucial for patient management, especially in younger adults, aiding in prognostic assessment, guiding molecular diagnostics and surgical planning, and identifying candidates for IDH-targeted trials. Despite its potential, the full capabilities of DSC-PWI remain underexplored. This research evaluates the differentiation ability of relative-cerebral-blood-volume (rCBV) percentile values for the enhancing and non-enhancing tumor regions compared to the more commonly used mean or maximum preselected rCBV values.

Methods
This retrospective study, spanning 2016–2023, included patients under 55 years (age threshold based on World Health Organization recommendations) with grade 4 astrocytic tumors and known IDH status, who underwent presurgical MR with DSC-PWI. Enhancing and non-enhancing regions were 3D-segmented to calculate voxel-level rCBV, deriving mean, maximum, and percentile values. Statistical analyses were conducted using the Mann-Whitney U test and AUC-ROC.

Results
The cohort consisted of 59 patients (mean age 46; 34 male): 11 astrocytoma-4 and 48 glioblastoma. While glioblastoma showed higher rCBV in enhancing regions, the differences were not significant. However, non-enhancing astrocytoma-4 regions displayed notably higher rCBV, particularly in lower percentiles. The 30th rCBV percentile for non-enhancing regions was 0.705 in astrocytoma-4, compared to 0.458 in glioblastoma (p = 0.001, AUC-ROC = 0.811), outperforming standard mean and maximum values.

Conclusion
Employing an automated percentile-based approach for rCBV selection enhances differentiation capabilities, with non-enhancing regions providing more insightful data. Elevated rCBV in lower percentiles of non-enhancing astrocytoma-4 is the most distinguishable characteristic and may indicate lowly vascularized infiltrated edema, contrasting with glioblastoma’s pure edema.
Congenital Heart Defects in Patients with Anorectal Malformations: A Retrospective Cohort Study of 281 Patients
Authors: de Beaufort Cunera M. C. , Mackay Tara M. , Stevens Markus F. , Polderman Jorinde A. W. , de Jong Justin R. , van der Hulst Annelies E. , Straver Bart , Gorter Ramon R. 
Published: June 2024

AbstractIn patients born with anorectal malformations (ARM), additional congenital heart defects (CHD) can occur. We aimed to provide an overview on disease and treatment details of CHD identified in patients born with ARM, from a unique large cohort of a very rare disease. We performed a retrospective single-center cohort study between January 2000 and July 2023. All consecutive patients with ARM were included. Outcomes were the number of patients with CHD, and screening percentage and percentage of patients diagnosed with CHD over 3 time periods (2000–2006, 2007–2014, 2015–2023). We used uni- and multi-variable logistic regression analyses to search for associations between CHD present and baseline characteristics. In total, 281 patients were included. Some 241 (85.8%) underwent echocardiography, of whom 80 (33.2%) had CHD. Screening percentage with echocardiography increased (74.1% vs. 85.7% vs. 95.9%, p < 0.001) and percentage of patients diagnosed with CHD remained similar over time (30.2% vs. 34.5% vs. 34.0%, p = 0.836). Atrial and ventricular septal defects (n = 36, n = 29), and persistent left superior vena cava (n = 17) were most identified. The presence of VACTERL-association or a genetic syndrome was independently associated with the presence of CHD. CHD were present in 33% of patients with ARM that underwent echocardiography. Over time, the number of CHD identified through screening remained similar. Patients with the presence of VACTERL-association or a genetic syndrome had a higher risk of having CHD. Therefore, acknowledging the potential presence of CHD in patients with ARM remains important.
Mechanistic study of the differences in lactic acid bacteria resistance to freeze- or spray-drying and storage
Authors: Gagneten Maite , Passot Stéphanie , Cenard Stéphanie , Ghorbal Sarrah , Schebor Carolina , Fonseca Fernanda 
Published: June 2024

Abstract
Lactobacillus delbrueckii subsp. bulgaricus and Lactiplantibacillus plantarum are two lactic acid bacteria (LAB) widely used in the food industry. The objective of this work was to assess the resistance of these bacteria to freeze- and spray-drying and study the mechanisms involved in their loss of activity. The culturability and acidifying activity were measured to determine the specific acidifying activity, while membrane integrity was studied by flow cytometry. The glass transitions temperature and the water activity of the dried bacterial suspensions were also determined. Fourier transform infrared (FTIR) micro-spectroscopy was used to study the biochemical composition of cells in an aqueous environment. All experiments were performed after freezing, drying and storage at 4, 23 and 37 °C. The results showed that Lb. bulgaricus CFL1 was sensitive to osmotic, mechanical, and thermal stresses, while Lpb. plantarum WCFS1 tolerated better the first two types of stress but was more sensitive to thermal stress. Moreover, FTIR results suggested that the sensitivity of Lb. bulgaricus CFL1 to freeze-drying could be attributed to membrane and cell wall degradation, whereas changes in nucleic acids and proteins would be responsible of heat inactivation of both strains associated with spray-drying. According to the activation energy values (47–85 kJ/mol), the functionality loss during storage is a chemically limited reaction. Still, the physical properties of the glassy matrix played a fundamental role in the rates of loss of activity and showed that a glass transition temperature 40 °C above the storage temperature is needed to reach good preservation during storage.

Key points
• Specific FTIR bands are proposed as markers of osmotic, mechanic and thermal stress
• Lb. bulgaricus CFL1 was sensitive to all three stresses, Lpb. plantarum WCFS1 to thermal stress only
• Activation energy revealed chemically limited reactions ruled the activity loss in storage

Graphical abstract
Unraveling the efficacy of verbascoside in thwarting MRSA pathogenicity by targeting sortase A
Authors: Li Xingchen , Hou Yingying , Zou Haoyan , Wang Yueying , Xu Yueshan , Wang Li , Wang Bingmei , Yan Ming , Leng Xiangyang 
Published: June 2024

Abstract
In the fight against hospital-acquired infections, the challenge posed by methicillin-resistant Staphylococcus aureus (MRSA) necessitates the development of novel treatment methods. This study focused on undermining the virulence of S. aureus, especially by targeting surface proteins crucial for bacterial adherence and evasion of the immune system. A primary aspect of our approach involves inhibiting sortase A (SrtA), a vital enzyme for attaching microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) to the bacterial cell wall, thereby reducing the pathogenicity of S. aureus. Verbascoside, a phenylethanoid glycoside, was found to be an effective SrtA inhibitor in our research. Advanced fluorescence quenching and molecular docking studies revealed a specific interaction between verbascoside and SrtA, pinpointing the critical active sites involved in this interaction. This molecular interaction significantly impedes the SrtA-mediated attachment of MSCRAMMs, resulting in a substantial reduction in bacterial adhesion, invasion, and biofilm formation. The effectiveness of verbascoside has also been demonstrated in vivo, as shown by its considerable protective effects on pneumonia and Galleria mellonella (wax moth) infection models. These findings underscore the potential of verbascoside as a promising component in new antivirulence therapies for S. aureus infections. By targeting crucial virulence factors such as SrtA, agents such as verbascoside constitute a strategic and potent approach for tackling antibiotic resistance worldwide.

Key points
• Verbascoside inhibits SrtA, reducing S. aureus adhesion and biofilm formation.
• In vivo studies demonstrated the efficacy of verbascoside against S. aureus infections.
• Targeting virulence factors such as SrtA offers new avenues against antibiotic resistance.

Graphical abstract
Evaluation of the Effect of Botulinum Toxin A on the Lymphatic Endothelial Cells
Authors: Vasella Mauro , Wolf Stefan , Grünherz Lisanne , Kim Bong-Sung , Lindenblatt Nicole , Giovanoli Pietro , Gousopoulos Epameinondas 
Published: June 2024

Abstract
Introduction
Botulinum toxin A (BoTA) is a neurotoxin formed by Clostridium botulinum, with a broad medical application spectrum. While the primary effect of BoTA is on the muscles, the effects of BoTA in other systems including the blood vasculature have already been examined, revealing unexpected actions. However, no studies exist to the best of our knowledge regarding the potential effects of BoTA on the lymphatic vascular system, possessing a critical role in health and disease. Isolated human lymphatic endothelial cells (LECs) were cultured in dedicated in vitro culture systems. The analysis including imaging and cell culture approaches as well as molecular biology techniques is performed to examine the LEC alterations occurring upon exposure to different concentrations of BoTA.

Materials and Methods
Human LECs were cultured and expanded on collagen-coated petri dishes using endothelial basal medium and the commercial product Botox from Allergan as used for all our experiments. Harvested cells were used in various in vitro functional tests to assess the morphologic and functional properties of the BoTA-treated LECs. Gene expression analysis was performed to assess the most important lymphatic system-related genes and pathways.

Results
Concentrations of 1, 5 or 10 U of BoTA did not demonstrate a significant effect regarding the proliferation and migration capacity of the LECs versus untreated controls. Interestingly, even the smallest BoTA dose was found to significantly decrease the cord-like-structure formation capacity of the seeded LECs. Gene expression analysis was used to underpin possible molecular alterations, suggesting no significant effect of BoTA in the modification of gene expression versus the starvation medium control.

Conclusion
LECs appear largely unaffected to BoTA treatment, with an isolated effect on the cord-like-structure formation capacity. Further work needs to assess the effect of BoTA on the smooth-muscle-cell-covered collecting lymphatic vessels and the possible aesthetic implications of such an effect, due to edema formation.

Level of Evidence V
This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
Multi-Center Two-Year Patency Outcomes of Endovascular Arteriovenous Fistulas (endoAVF) Created with a 4 French System
Authors: Klein Erez , Repko Brandon , Alvarez Alejandro , Inston Nicholas , Jones Robert , Rajan Dheeraj K. 
Published: June 2024

Abstract
Purpose
To assess multicenter two-year patency outcomes of endovascular arteriovenous fistulas (endoAVF) created with the WavelinQ device.

Materials and Methods
Patients who had fistulas created at three centers from January 2018 to December 2020 were included in this retrospective study. In total, 112 patients underwent endoAVF creation [40 females, 72 males; mean age 60 years (range 18–88)]. Data collected included patient demographics, location of fistula creation, interventions performed, and brachial artery flows pre- and post-creation. Two-year cumulative patency, functional patency, and primary patency were assessed with Kaplan–Meier methodology. Factors affecting patency and maturation were examined using the Cox proportional hazards model.

Results
Technical success defined as angiographically successful endoAVF creation was 97.3% (109/112). In 11 patients the fistula did not mature for dialysis use. For 98 patients (87%) with endoAVF maturation, 12- and 24-month cumulative patency was 94.3% and 91.7%. Functional patency (two-needle cannulation) at 12 and 24 months was 95.7% and 92.7%, respectively. Median maturation time is 95 days (IQR 51–231 days). Male gender and brachial vein coiling at the time of endoAVF creation were predictive of maturation. There were 34 censored events (four patients undergoing renal transplantation; 30 patients deceased). Number of reinterventions per patient year was 0.73 where 43 were maturation procedures and 101 were maintenance procedures. One Grade 3 complication occurred of arterial access puncture site pseudoaneurysm.

Conclusion
A high two-year functional and cumulative patency following endoAVF creation with the WavelinQ device was observed in this multicenter real-world experience Level of Evidence: 3
Level of Evidence III

Graphical Abstract
Fruits and vegetables intake and bladder cancer risk: a pooled analysis from 11 case–control studies in the BLadder cancer Epidemiology and Nutritional Determinants (BLEND) consortium
Authors: Boot Iris W. A. , Wesselius Anke , Jochems Sylvia H. J. , Yu Evan Y. W. , Bosetti Cristina , Taborelli Martina , Porru Stefano , Carta Angela , Golka Klaus , Jiang Xuejuan , Stern Mariana C. , Kellen Eliane , Pohlabeln Hermann , Tang Li , Karagas Margaret R. , Zhang Zuo-Feng , Taylor Jack A. , La Vecchia Carlo , Zeegers Maurice P. 
Published: June 2024

Abstract
Purpose
High consumption of fruits and vegetables decrease the risk of bladder cancer (BC). The evidence of specific fruits and vegetables and the BC risk is still limited.

Methods
Fruit and vegetable consumptions in relation to BC risk was examined by pooling individual participant data from case–control studies. Unconditional logistic regression was used to estimate study-specific odds ratio’s (ORs) with 95% confidence intervals (CIs) and combined using a random-effects model for intakes of total fruits, total vegetables, and subgroups of fruits and vegetables.

Results
A total of 11 case–control studies were included, comprising 5637 BC cases and 10,504 controls. Overall, participants with the highest intakes versus the lowest intakes of fruits in total (OR 0.79; 95% CI 0.68–0.91), citrus fruits (OR 0.81; 95% CI 0.65–0.98), pome fruits (OR 0.76; 95% CI 0.65–0.87), and tropical fruits (OR 0.84; 95% CI 0.73–0.94) reduced the BC risk. Greater consumption of vegetables in total, and specifically shoot vegetables, was associated with decreased BC risk (OR 0.82; 95% CI 0.68–0.96 and OR 0.87; 95% CI 0.78–0.96, respectively). Substantial heterogeneity was observed for the associations between citrus fruits and total vegetables and BC risk.

Conclusion
This comprehensive study provides compelling evidence that the consumption of fruits overall, citrus fruits, pome fruits and tropical fruits reduce the BC risk. Besides, evidence was found for an inverse association between total vegetables and shoot vegetables intake.