bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of the adrenergic reserve associated with exercise intolerance in a murine model of heart failure with preserved ejection fraction
Authors: Semmler Lukas , Jeising Tobias , Huettemeister Judith , Bathe‐Peters Marc , Georgoula Konstantina , Roshanbin Rashin , Sander Paulina , Fu Shu , Bode David , Hohendanner Felix , Pieske Burkert , Annibale Paolo , Schiattarella Gabriele G. , Oeing Christian U. , Heinzel Frank R. 
Published: March 2024

AbstractAimExercise intolerance is the central symptom in patients with heart failure with preserved ejection fraction. In the present study, we investigated the adrenergic reserve both in vivo and in cardiomyocytes of a murine cardiometabolic HFpEF model.Methods12‐week‐old male C57BL/6J mice were fed regular chow (control) or a high‐fat diet and L‐NAME (HFpEF) for 15 weeks. At 27 weeks, we performed (stress) echocardiography and exercise testing and measured the adrenergic reserve and its modulation by nitric oxide and reactive oxygen species in left ventricular cardiomyocytes.ResultsHFpEF mice (preserved left ventricular ejection fraction, increased E/e', pulmonary congestion [wet lung weight/TL]) exhibited reduced exercise capacity and a reduction of stroke volume and cardiac output with adrenergic stress. In ventricular cardiomyocytes isolated from HFpEF mice, sarcomere shortening had a higher amplitude and faster relaxation compared to control animals. Increased shortening was caused by a shift of myofilament calcium sensitivity. With addition of isoproterenol, there were no differences in sarcomere function between HFpEF and control mice. This resulted in a reduced inotropic and lusitropic reserve in HFpEF cardiomyocytes. Preincubation with inhibitors of nitric oxide synthases or glutathione partially restored the adrenergic reserve in cardiomyocytes in HFpEF.ConclusionIn this murine HFpEF model, the cardiac output reserve on adrenergic stimulation is impaired. In ventricular cardiomyocytes, we found a congruent loss of the adrenergic inotropic and lusitropic reserve. This was caused by increased contractility and faster relaxation at rest, partially mediated by nitro‐oxidative signaling.
Systematic review: Defining, diagnosing and monitoring small bowel strictures in Crohn's disease on intestinal ultrasound
Authors: Lu Cathy , Rosentreter Ryan , Delisle Maxime , White Mattie , Parker Claire E. , Premji Zahra , Wilson Stephanie R. , Baker Mark E. , Bhatnagar Gauraang , Begun Jakob , Bruining David H. , Bryant Robert , Christensen Britt , Feagan Brian G. , Fletcher Joel G. , Jairath Vipul , Knudsen John , Kucharzik Torsten , Maaser Christian , Maconi Giovanni , Novak Kerri , Rimola Jordi , Taylor Stuart A. , Wilkens Rune , Rieder Florian ,   The Stenosis Therapy and Anti‐Fibrotic Research (STAR) consortium
Published: March 2024

SummaryBackgroundStricturing Crohn's disease (CD) occurs most commonly in the terminal ileum and poses a clinical problem. Cross‐sectional imaging modalities such as intestinal ultrasound (IUS), computed tomography enterography (CTE), and magnetic resonance enterography (MRE) allow for assessment of the entire bowel wall and associated peri‐enteric findings. Radiologic definitions of strictures have been developed for CTE and MRE; their reliability and responsiveness are being evaluated in index development programs. A comprehensive assessment strategy for strictures using IUS is needed.AimsTo provide a detailed summary of definitions, diagnosis and monitoring of strictures on IUS as well as technical aspects of image acquisition.MethodsWe searched four databases up to 6 January 2024. Two‐stage screening was done in duplicate. We assessed risk of bias using QUADAS‐2.ResultsThere were 56 studies eligible for inclusion. Definitions for strictures on IUS are heterogeneous, but the overall accuracy for diagnosis of strictures is high. The capability of IUS for characterising inflammation versus fibrosis in strictures is not accurate enough to be used in clinical practice or trials. We summarise definitions for improvement of strictures on IUS, and discuss parameters for image acquisition and standardisation.ConclusionsThis systematic review is the first step for a structured program to develop a stricture IUS index for CD.
Stem breaks as an indirect measure of megafaunal herbivory in tropical forests: An experimental study
Authors: Terborgh John , Solana Mena Alicia , Davenport Lisa , Pura Param Bin , A/L Din Husin Sudin , Tunil Charang Muhamad Tauhid Bin , Tan Wei Harn , Campos‐Arceiz Ahimsa 
Published: March 2024

AbstractTo simulate megafaunal (pig, tapir, and elephant) foraging, we cut 1228 saplings in a Sundaic rainforest. In total, 89%–94% of cut stems survived after 13.5 months. About 90% of naturally occurring break scars were at heights ≤1 m, implicating pigs, not elephants or tapirs, as the main source of stem damage in this forest.Abstract in Malay is available with online material.
Mitochondrial fission enhances IL‐6‐induced metastatic potential in ovarian cancer via ERK1/2 activation
Authors: Lee Juwon , Han Youngjin , Kim Soochi , Jo HyunA , Wang Wenyu , Cho Untack , Kim Se Ik , Kim Boyun , Song Yong Sang 
Published: March 2024

AbstractOvarian cancer is a lethal gynecologic cancer mostly diagnosed in an advanced stage with an accumulation of ascites. Interleukin‐6 (IL‐6), a pro‐inflammatory cytokine is highly elevated in malignant ascites and plays a pleiotropic role in cancer progression. Mitochondria are dynamic organelles that undergo fission and fusion in response to external stimuli and dysregulation in their dynamics has been implicated in cancer progression and metastasis. Here, we investigate the effect of IL‐6 on mitochondrial dynamics in ovarian cancer cells (OVCs) and its impact on metastatic potential. Treatment with IL‐6 on ovarian cancer cell lines (SKOV3 and PA‐1) led to an elevation in the metastatic potential of OVCs. Interestingly, a positive association was observed between dynamin‐related protein 1 (Drp1), a regulator of mitochondrial fission, and IL‐6R in metastatic ovarian cancer tissues. Additionally, IL‐6 treatment on OVCs was linked to the activation of Drp1, with a notable increase in the ratio of the inhibitory form p‐Drp1(S637) to the active form p‐Drp1(S616), indicating enhanced mitochondrial fission. Moreover, IL‐6 treatment triggered the activation of ERK1/2, and inhibiting ERK1/2 mitigated IL‐6‐induced mitochondrial fission. Suppressing mitochondrial fission through siRNA transfection and a pharmacological inhibitor reduced the IL‐6‐induced migration and invasion of OVCs. This was further supported by 3D invasion assays using patient‐derived spheroids. Altogether, our study suggests the role of mitochondrial fission in the metastatic potential of OVCs induced by IL‐6. The inhibition of mitochondrial fission could be a potential therapeutic approach to suppress the metastasis of ovarian cancer.
ILT4 facilitates angiogenesis in non‐small cell lung cancer
Authors: Wang Shuyun , Wang Jing , Gong Wenjing , Zhang Fang , Chen Xiaozheng , Xu Huijun , Han Yali , Fu Xuebing , Wang Leirong , Li Juan , Gao Aiqin , Sun Yuping 
Published: March 2024

AbstractAntiangiogenic therapy targeting VEGF‐A has become the standard of first‐line therapy for non‐small cell lung cancer (NSCLC). However, its clinical response rate is still less than 50%, and most patients eventually develop resistance, even when using combination therapy with chemotherapy. The major cause of resistance is the activation of complex bypass signals that induce angiogenesis and tumor progression. Therefore, exploring novel proangiogenic mechanisms and developing promising targets for combination therapy are crucial for improving the efficacy of antiangiogenic therapy. Immunoglobulin‐like transcript (ILT) 4 is a classic immunosuppressive molecule that inhibits myeloid cell activation. Recent studies have shown that tumor cell‐derived ILT4 drives tumor progression via the induction of malignant biologies and creation of an immunosuppressive microenvironment. However, whether and how ILT4 participates in NSCLC angiogenesis remain elusive. Herein, we found that enriched ILT4 in NSCLC is positively correlated with high microvessel density, advanced disease, and poor overall survival. Tumor cell‐derived ILT4 induced angiogenesis both in vitro and in vivo and tumor progression and metastasis in vivo. Mechanistically, ILT4 was upregulated by its ligand angiopoietin‐like protein 2 (ANGPTL2). Their interaction subsequently activated the ERK1/2 signaling pathway to increase the secretion of the proangiogenic factors VEGF‐A and MMP‐9, which are responsible for NSCLC angiogenesis. Our study explored a novel mechanism for ILT4‐induced tumor progression and provided a potential target for antiangiogenic therapy in NSCLC.
Is it more effective for anhedonia and avolition? A systematic review and meta‐analysis of non‐invasive brain stimulation interventions for negative symptoms in schizophrenia
Authors: Chen Yuying , Li Zhuofeng , Yan Chao , Zou Laiquan 
Published: March 2024

AbstractBackgroundNoninvasive brain stimulation (NIBS) techniques are a promising tool for treating the negative symptoms of schizophrenia. Growing evidence suggests that different dimensions of negative symptoms have partly distinct underlying pathophysiological mechanisms. Previous randomized controlled trials (RCTs) have shown inconsistent impacts of NIBS across dimensions.ObjectiveThis systematic review and meta‐analysis evaluated the effects of NIBS on general negative symptoms, and on specific domains, including blunted affect, alogia, asociality, anhedonia, and avolition.Data SourcesPubMed, Web of Science, Embase, Cochrane CENTRAL, PsycINFO, OpenGrey, and Clinicaltrials.gov from the first date available to October, 2023.ResultsAmong 1049 studies, we identified eight high‐quality RCTs. NIBS significantly affects general negative symptoms (SMD = −0.54, 95% CI [−0.88, −0.21]) and all five domains (SMD = −0.32 to −0.63). Among dimensions, better effects have been shown for improvement of avolition (SMD = −0.47, 95% CI [−0.81, −0.13]) and anhedonia (SMD = −0.63, 95% CI [−0.98, −0.28]). Subgroup analyses of studies that applied once daily stimulation or >10 sessions showed significantly reduced negative symptom severity.ConclusionNIBS exerts distinct effects across multiple dimensions of negative symptom, with treatment effects related to stimulation frequency and total sessions. These results need to be confirmed in dedicated studies.
Competition, over‐branching and bank failures during the Great Depression: New evidence from Italy
Authors: Molteni Marco 
Published: March 2024

AbstractThis paper employs quantitative and qualitative methods to examine the link between banking competition, branching and financial distress during the interwar period in Europe, focusing on Italy as a case study. Regression analysis and a systematic review of printed sources show that banks experiencing distress had opened scores of branches and operated in areas with harsher competition. Poor managerial choices led banks to have higher operational costs, pushing them to more remunerative but riskier activities. The 1920s saw a profound transformation of the Italian banking system, with extensive branch expansion and cut‐throat competition for deposits. This paper argues that these changes in the structure of the banking system rendered it more fragile when the international crisis hit. Available evidence on other European countries suggests that Italy was not an isolated case. The study contributes to the literature on banking crises during the Great Depression and the effects of banking competition on financial stability.
Du Châtelet, induction, and Newton's rules for reasoning
Authors: Wells Aaron 
Published: March 2024

AbstractI examine Du Châtelet's methodology for physics and metaphysics through the lens of her engagement with Newton's Rules for Reasoning in Natural Philosophy. I first show that her early manuscript writings discuss and endorse these Rules. Then, I argue that her famous published account of hypotheses continues to invoke close analogues of Rules 3 and 4, despite various developments in her position. Once relevant experimental evidence and some basic constraints are met, it is legitimate to inductively generalize from observations; general hypotheses can thereafter be assumed as true until contrary experiments show otherwise. I conclude by arguing that this account of induction plays an essential role in her metaphysics, both in an argument for simple substances—which has an inductive premise—and in her attempt to distinguish acceptable and unacceptable metaphysical commitments.
Cultivating empathy and compassion: Lived experiences of engagement with cognitively‐based compassion training in the US
Authors: McConnell Sara , Ozawa‐de Silva Brendan Richard , Ozawa‐de Silva Chikako 
Published: March 2024

AbstractThis qualitative study presents an analysis of data taken from 16 participants who were interviewed during and 1 year after they attended a course in Cognitively‐Based Compassion Training (CBCT), a meditation course that seeks to help participants cultivate empathy and compassion. The study sought to examine what benefits, if any, participants in a CBCT course reported with regard to their understanding and practice of empathy and compassion; and secondly, if their statements in the interviews exhibited understandings and practices consonant with emotional, social, and cognitive resilience as identified in the existing literature, and consonant with empathy and compassion as defined in CBCT and in existing literature on compassion. The study found that participant interviews provided significant evidence of the development of skills identified in the literature as components of emotional, cognitive, and social resilience, and that participant descriptions and definitions of compassion closely matched those existing in the literature.
Toward a culturally sensitive application of Emotionally Focused Couples Therapy: A qualitative study of therapists' experience using EFT in Spanish‐speaking countries/cultures
Authors: Sandberg Jonathan G. , Calatrava María , Andrade Dania , Lybbert Ragan , Mazo Sara , Rodríguez‐González Martiño 
Published: March 2024

AbstractThe purpose of the current study was to identify specific ways Emotionally Focused Couples Therapy (EFT; S. Johnson) could be adapted to better meet the needs of clients in Spanish‐speaking countries throughout Europe and the Americas. The results were drawn from responses to a qualitative questionnaire regarding the experiences of learning and applying EFT; 103 therapists in 12 different countries where Spanish is spoken responded to the survey. Overall, the results suggest that the therapists surveyed consider EFT to be a “good fit” for many Spanish‐speaking clients because of its focus on emotion, attachment theory, close interpersonal relationships, and model‐specific interventions that match cultural values. Participants suggested a few culture‐specific modifications regarding how to access and process emotion with men in therapy, translation of key EFT concepts and phrases into Spanish, and navigating the intersection of two cultural values (respeto and personalismo). Fewer modifications were suggested by therapists as they discussed application of the model than while learning it.
Plant–soil interactions alter nitrogen and phosphorus dynamics in an advancing subarctic treeline
Authors: Fetzer Jasmin , Moiseev Pavel , Frossard Emmanuel , Kaiser Klaus , Mayer Mathias , Gavazov Konstantin , Hagedorn Frank 
Published: March 2024

AbstractTreelines advance due to climate warming. The impacts of this vegetation shift on plant–soil nutrient cycling are still uncertain, yet highly relevant as nutrient availability stimulates tree growth. Here, we investigated nitrogen (N) and phosphorus (P) in plant and soil pools along two tundra–forest transects on Kola Peninsula, Russia, with a documented elevation shift of birch‐dominated treeline by 70 m during the last 50 years. Results show that although total N and P stocks in the soil–plant system did not change with elevation, their distribution was significantly altered. With the transition from high‐elevation tundra to low‐elevation forest, P stocks in stones decreased, possibly reflecting enhanced weathering. In contrast, N and P stocks in plant biomass approximately tripled and available P and N in the soil increased fivefold toward the forest. This was paralleled by decreasing carbon (C)‐to‐nutrient ratios in foliage and litter, smaller C:N:P ratios in microbial biomass, and lower enzymatic activities related to N and P acquisition in forest soils. An incubation experiment further demonstrated manifold higher N and P net mineralization rates in litter and soil in forest compared to tundra, likely due to smaller C:N:P ratios in decomposing organic matter. Overall, our results show that forest expansion increases the mobilization of available nutrients through enhanced weathering and positive plant–soil feedback, with nutrient‐rich forest litter releasing greater amounts of N and P upon decomposition. While the low N and P availability in tundra may retard treeline advances, its improvement toward the forest likely promotes tree growth and forest development.
Citizens' views on prices of medicines reimbursed by the National Health Service: Findings from Italian online focus groups
Authors: Colombo Cinzia , Caldara Daniele , Banzi Rita 
Published: March 2024

AbstractIntroductionAccess to medicines is one of the biggest challenges to health systems, affecting society and individuals. This study aims to explore citizens' opinions, perceptions and attitudes on the model of medicines' research and development (R&D) and price setting of medicines reimbursed by the Italian National Health Service.Materials and MethodsWe run four online focus groups, analysed through thematic analysis. Inclusion criteria: people aged 30–70 years, who had completed at least compulsory schooling (8–10 years), with no specialised knowledge about the subject. Exclusion criteria: healthcare workers, pharmaceutical and device industry employees, researchers and medicine policy board members. We aimed to include a purposive sample of 20 participants, variable in terms of age, educational level and place of residence.ResultsEleven women and six men participated. The mean age was 53 years (range: 28–73). Most (n = 15) had a university degree or attended secondary schools. Eight had a job, five were not employed, and four were retired. In general, participants supported the role of the public health service. Almost all had limited knowledge of medicines' R&D and price setting. Most asked for transparency on medicine prices and negotiation criteria. Participants considered revenues of pharmaceutical companies disproportionate and most called for containment measures of profits. Most were in favour of a stronger public intervention in R&D and prices' negotiations. Few were sceptical of the public sector's ability to play this role.DiscussionMedicines' prices were discussed as a health matter. Increasing citizens' awareness of these topics is needed by providing spaces and conditions to participate in the discussion, including different perspectives and interests.Patient or Public ContributionMembers of BEUC—the European consumer organisation—proposed the project. Altroconsumo, an independent consumer organisation and OCU, a Spanish consumer organisation, participated in developing the project and the main topics to discuss. The Mario Negri Institute and Aplica cooperative—the Spanish methodological team—were involved by BEUC and their national organisations to define the methodology, organisational aspects and contents and conducted the focus groups.
Enhancing heat dissipation in polyurethane sheets through the incorporation of freeze‐dried aluminum nitride nanofiber
Authors: Hossain Md. Shakhawat , Nakane Koji 
Published: March 2024

AbstractInspired by a three‐dimensional (3D) structure, we demonstrate 3D aluminum nitride (AlN) nanofibers fabricated by a freeze‐drying technique using polyvinyl alcohol (PVA)/boehmite precursor nanofibers. After applying hot pressing, a series of PVA/boehmite precursor nanofibers were prepared with varying PVA‐to‐boehmite ratios (30/70 wt%, 50/50 wt%, and 70/30 wt%). Our findings reveal that the thermal conductivity of the AlN composite nanofibers is significantly affected by the relative proportions of PVA and boehmite, where the ratio of PVA should be more significant than that of boehmite. We produced AlN nanofibers at a lower temperature (1500°C) than the theoretical formation temperature of AlN (1664°C). The minimum specific surface area and pore volumes were 8.39 m2/g and 0.0166 cm3/g, respectively, at 1500°C. X‐ray photoelectron spectroscopy spectra measured 38.27% aluminum and 23.55% nitrogen in AlN nanofibers. The aligned AlN nanofibers mat was impregnated with polyurethane (PU), which showed good thermal conductivity in the planar (4.1–13.6 W/(m·K)) and thickness (1.5–4.9 W/(m·K)) directions at 18–56 vol% AlN nanofibers content. The heat‐dissipating sheet also showed superior electrical insulating (1.2 × 1012 Ω/cm2) properties. In this study, the author sought to develop a heat‐spreading material made of thermally conductive, but electrically insulating PU/AlN nanofibers that could efficiently dissipate heat from electric devices.
A career in solving clinical‐pathological conundrums: Heyde syndrome, anti‐platelet factor 4 disorders, and microvascular limb ischemic necrosis
Authors: Warkentin Theodore E. 
Published: March 2024

AbstractHematology is a clinical specialty with strong roots in the laboratory; accordingly, the lab can help solve perplexing clinical problems. This review highlights clinical‐pathological conundrums addressed during my 35‐year hematology career at McMaster University. Heyde syndrome is the association between aortic stenosis and bleeding gastrointestinal (GI) angiodysplasia where the bleeding is usually cured by aortic valve replacement; the chance reading of a neonatal study showing reversible deficiency of high‐molecular‐weight (HMW) multimers of von Willebrand factor (vWF) following surgical correction of congenital heart disease provided the key insight that a subtle deficiency of HMW multimers of vWF explains Heyde syndrome. The unusual immunobiology of heparin‐induced thrombocytopenia (HIT)—a highly prothrombotic, antibody‐mediated, anti‐platelet factor 4 (PF4) disorder featuring rapid appearance and then disappearance (seroreversion) of the pathological heparin‐dependent platelet‐activating antibodies—permitted identification of key clinical features that informed development of a scoring system (4Ts) to aid in HIT diagnosis. Atypical clinical presentations of HIT prompted identification of heparin‐independent anti‐PF4 antibodies, now recognized as the explanation for vaccine‐induced immune thrombotic thrombocytopenia (VITT), as well as VITT‐like disorders triggered by adenovirus infection. Another unusual feature of HIT is its strong association with limb ischemia, including limb necrosis secondary to deep‐vein/microvascular thrombosis (venous limb gangrene). The remarkable observation that supratherapeutic warfarin anticoagulation predisposes to HIT‐ and cancer‐associated venous limb gangrene provided insight into disturbed procoagulant/anticoagulant balance; these concepts are relevant to microvascular thrombosis in critical illness (symmetrical peripheral gangrene), including a pathophysiological role for proximate “shock liver” (impaired hepatic synthesis of natural anticoagulants).