bluuebunny/crossref_metadata_2025_split huggingface dataset:
End‐organ protective effect of serelaxin in patients hospitalized for heart failure: Results of the biomarker substudy of Relaxin in Acute Heart Failure‐2 (RELAX‐AHF‐2)
Authors: Voors Adriaan A. , Metra Marco , Postmus Douwe , Greenberg Barry H. , Cotter Gadi , Davison Beth A. , Beldhuis Iris E. , Felker G. Michael , Filippatos Gerasimos , Pang Peter S. , Ponikowski Piotr , Gimpelewicz Claudio , Teerlink John R. 
Published: December 2024

AbstractAimsSerelaxin is recombinant human relaxin‐2, a hormone responsible for haemodynamic adaptations and organ protection in pregnancy. In the RELAX‐AHF trial, serelaxin demonstrated reductions in cardiac, renal and hepatic damage. In RELAX‐AHF‐2, organ damage‐related biomarkers were assessed in a biomarker substudy.Methods and resultsPatients enrolled within 16 h of presentation for heart failure hospitalization were randomized to 48‐h infusions of either serelaxin (30 μg/kg/day) or placebo, and plasma samples were obtained at baseline, 2, 5, and 14 days in patients participating in the biomarker substudy. Of the 6545 patients analysed in RELAX‐AHF‐2, 1020 (15.6%) patients (mean age 72 ± 12 years; 61% male) were enrolled in the biomarker substudy. Compared to placebo, serelaxin decreased percentage change from baseline in troponin T through day 14 (serelaxin +0.2% vs. placebo +40.3%; p = 0.042), as well as creatinine (−0.8% vs. +5.8%; p = 0.002), cystatin C (+3.8% vs. +8.3%; p = 0.016), and uric acid (+0.8% vs. +7.2%; p = 0.0014) at day 2. The decrease of N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) from baseline to day 2 was greater in serelaxin‐treated patients (−39.8% vs. −27.6%; p = 0.002). Early changes in NT‐proBNP and troponin, but not creatinine, cystatin C and uric acid, were associated with 180‐day mortality. In this substudy population, serelaxin did not reduce 180‐day cardiovascular death (hazard ratio [HR] 0.78; 95% confidence interval [CI] 0.49–1.25; p = 0.30), but significantly reduced worsening heart failure through day 5 (HR 0.55; 95% CI 0.33–0.93; p = 0.027).ConclusionIn this substudy, serelaxin decreased plasma concentrations of cardiac, renal and hepatic injury markers. Changes of most of these markers were associated with cardiovascular mortality. In this pre‐specified biomarker subgroup, serelaxin did not reduce 180‐day cardiovascular mortality but significantly reduced worsening heart failure through day 5.
A Switch Protein Adapter for Anti‐LILRB4 CAR‐T Cells
Authors: Huang Ryan , Chen Heyu , Xie Jingjing , Lou Qi , Tan Lingxiao , Zhang Ningyan , An Zhiqiang , John Samuel , Zhang Cheng Cheng 
Published: December 2024

ABSTRACTChimeric antigen receptor‐T cell (CAR‐T) immunotherapy has shown remarkable results for the treatment of certain hematologic malignancies. A redirection strategy that utilizes clinically relevant CAR‐T cells in combination with adapter proteins may be an effective strategy to target other hematologic and solid cancers. We established a fusion antibody‐based strategy with flexibility to target multiple tumor types in combination with a novel anti‐leukocyte immunoglobulin‐like receptor‐B 4 (LILRB4) CAR‐T cell. Specifically, we engineered switch protein (SwP) adapters containing the LILRB4 extracellular domain fused to either an anti‐CD19 or anti‐CD20 single‐chain variable fragment (scFv). These SwPs were sufficient to stimulate anti‐LILRB4 CAR‐T cells against SwP‐tagged LILRB4‐CD19+ and LILRB4‐CD20+ cancers in vitro and in vivo. This strategy may allow CAR‐T cells to be redirected against a variety of tumor antigens and cancer types and become a valuable approach to expand the impact of cellular immunotherapy.
Subglacial hydrology insights from eskers developed atop soft beds of the Laurentide ice sheet
Authors: Núñez Ferreira Francisca A. , Zoet Lucas K. , Rawling J. Elmo , Haseloff Marianne , Rehwald Matt , Ullman David J. 
Published: December 2024

AbstractGlacial landforms provide a valuable record from which to study the history and dynamics of past ice sheets. Eskers record paleo subglacial hydrologic and sediment transport conditions because they are composed of sediment deposited by water flowing through subglacial channels. Despite decades of study, there is still debate about their formation mechanisms and little investigation of the differences between eskers formed over soft and hard beds. To address this complexity, we analysed eskers formed over soft beds along the southern margin of the Laurentide Ice Sheet (LIS) in the Lake Superior region. This included developing a new method to calculate the basal effective pressure gradient during esker formation along the subglacial channel using grain size estimates from a 20 m tall esker exposure.The morphometry and distribution of eskers were mapped with GIS to quantify their sinuosity and lateral spacing, and to compare those to the underlying bedrock elevation and sediment thickness. Lateral spacing decreased over time as the ice margin retreated, suggesting that melt rates increased during the LIS deglaciation. Furthermore, the relation between esker distribution and sediment thickness showed that eskers formed preferentially over thinner layers of sediment, irrespective of whether erosion occurred before their formation. The sedimentology of the Cable Esker exhibits a non‐monotonic pattern in channel boundary shear stress ranging from 10 to 300 Pa, alongside a basal effective pressure gradient fluctuating between −9 to −70 Pa m−1. Negative basal effective pressure gradients are consistent with esker formation in channels close to the glacier terminus, which suggests lower water pressure than normally assumed. This, combined with dynamic water level fluctuations within the esker channel, supports the theory of the formation of eskers near the ice margin.
Mechanism of Action and Beneficial Effects of Probiotics in Amateur and Professional Athletes
Authors: Nami Yousef , Barghi Anahita , Shahgolzari Mehdi , Salehian Melika , Haghshenas Babak 
Published: December 2024

ABSTRACTProbiotics are live microorganisms that, when administered in adequate amounts, provide health benefits to the host. According to the International Society of Sports Nutrition (ISSN), probiotic supplementation can optimize the health, performance, and recovery of athletes at all stages of their careers. Recent research suggests that probiotics can improve immune system functions, reduce gastrointestinal distress, and increase gut permeability in athletes. Additionally, probiotics may provide athletes with secondary health benefits that could positively affect athletic performance through enhanced recovery from fatigue, improved immune function, and maintenance of healthy gastrointestinal tract function. The integration of some probiotic strains into athletes' diets and the consumption of multi‐strain compounds may lead to an improvement in performance and can positively affect performance‐related aspects such as fatigue, muscle pain, body composition, and cardiorespiratory fitness. In summary, probiotics can be beneficial for athletes at all stages of their careers, from amateur to professional. This paper reviews the progress of research on the role of probiotic supplementation in improving energy metabolism and immune system functions, reducing gastrointestinal distress, and enhancing recovery from fatigue in athletes at different levels.
Public Health Insurance and Healthcare Utilisation Decisions of Young Adults
Authors: Rizal Muhammad Fikru 
Published: December 2024

ABSTRACTThis paper investigates the impact of a dependent coverage age‐eligibility rule on young adults' health and healthcare utilisation under Indonesia's National Health Insurance (NHI) program. Employing a regression discontinuity design, analysis of the NHI administrative data documents a significant 14.6 to 20.9 percentage points drop in coverage among young adults at age 21, the age cut‐off imposed by the rule. Using a large nationally representative household survey, this paper shows that the loss of insurance coverage does not change young adults' health status but markedly decreases the utilisation of outpatient care among those who are ill. Specifically, there is an abrupt 5.3 to 8.4 percentage points reduction in the probability of young adults having any outpatient visit in the past month, primarily driven by lower utilisation of primary care services. The study also finds an increased likelihood of self‐treatment and the use of traditional healers, indicating a substitution effect. Further analysis shows a larger impact on those who are poor, less educated, and live in regions with higher healthcare costs.
Memory Development, Configurations, Conjunctions, and the Hippocampal Index
Authors: Rudy Jerry W. 
Published: December 2024

ABSTRACTWhen I began my career, I had no idea that much of it would center around the hippocampus. Here I discuss some of the history of how this happened. I briefly mention my early undergraduate life and the problems it posed for getting into graduate school. I describe the unique circumstances that led me to Allan Wagner's laboratory and changed my career trajectory. My path to the hippocampus began with a decision to study memory development. This led to a collaboration with Rob Sutherland that produced the configural theory of the hippocampus. The idea was that the hippocampus facilitated the construction of representations of the co‐occurring stimulus elements currently experienced by the organism. Thus, if two elements, A and B, occurred together, a representation, AB, could be constructed that could be discriminated from its elements, A and B. This idea was partially correct, but we missed an important property of the hippocampal system that was recognized by O'Keefe and Nadel, 1978 that is, that the hippocampus is an unmotivated, rapid learning system. Randy O'Reilly and I addressed this issue in what we called conjunctive representation theory and put forth a detailed cortical‐hippocampus computational theory to explain how this could work I later realized that our ideas were remarkably like Tim Teyler's indexing theory of how the hippocampal system supports memory. At a Park City meeting, a chance encounter with Tim (whom I had never met) resulted in the opportunity to write a paper with Tim updating the indexing theory, It is my favorite theoretical paper.
Agomelatine as Antidepressant Treatment in Elderly Patients With Previous Hyponatremia Due To SSRI Use: Case Series
Authors: Barquera José Alfonso. Ontiveros‐Sánchez de la , García Luis Alberto De la Garza , Sánchez‐Torres Guillermo , Gogeascoechea‐Hernández Andoni , Martinez Sofia Jezzini , Porras‐Garza Guillermo A. , Garza Pablo Patricio Zarate 
Published: December 2024

ABSTRACTObjectiveTo evaluate agomelatine treatment in elderly patients with major depressive disorder (MDD) who developed hyponatremia while using selective serotonin receptor inhibitors (SSRIs).MethodsPatients (60 years or older) with hyponatremia after SSRI treatment for MDD were changed to agomelatine 50 mg/day during one month to observe sodium levels during the treatment and change in depressive symptoms. Montgomery‐Asberg Depression Rating Scale (MADRS) and the Clinical Global Impression Scale (CGI) of severity were used before and after treatment with agomelatine.ResultsThe mean age of our sample (five patients) was 75.3 (SD ± 7.8) years. Sodium levels while using SSRIs were reported with a mean of 122.54 (SD ± 10.8) mEq/L. Mean MADRS and CGI scores on SSRIs before treatment with agomelatine were 27.8 (SD ± 3.90) and 5 (SD ± 0.71) respectively. After 4 weeks of treatment with agomelatine 50 mg/day, mean scores of sodium were reported at 135.48 (SD ± 1.6) mEq/L, and mean MADRS and CGI scores were 13.6 (SD ± 8.35) and 2.4 (SD ± 1.5). The difference in means of the MADRS scale before and after treatment with agomelatine was found to be statistically significant (27.8 [3.89] versus 13.6 [8.35], p = < 0.01).ConclusionOur open observational study suggests that agomelatine represents a safe and effective treatment option for elderly patients with major depressive disorder and previous SSRIs‐induced hyponatremia.
Reproductive outcomes after surgical resection of isthmocele in secondary infertility
Authors: Piróg Magdalena , Pulka Anna , Kacalska‐Janssen Olga , Zmaczyński Andrzej , Jach Robert 
Published: December 2024

AbstractObjectivesTo evaluate the reproductive outcomes after different approaches of surgical isthmocele excision in women with secondary infertility.MethodsThe present study was conducted between November 2017 and February 2023 in the Department of Gynecological Endocrinology and Gynecology at Jagiellonian University Medical College, Krakow, Poland. Women with large isthmocele with residual myometrial thickness (RMT) <3 mm and secondary infertility were included in this retrospective study. Surgical removal of the uterine defect was performed either by the laparoscopic or laparotomic approach. Pregnancy outcomes were measured.ResultsFifty‐eight women aged 32.3 ± 3.5 years with a body mass index 22.9 ± 3.4 kg/m2 were included. Pregnancy was confirmed in 62.1% of women after surgical repair of isthmocele either via laparoscopy (n = 19) or laparotomy (n = 17) and 36 women (44.8%) women delivered healthy babies. There were no differences in the type of surgical approach used for isthmocele removal regarding pregnancy outcomes. Women in the laparotomic group had a higher number of abdominal surgeries (2.8 times) and longer postsurgical hospitalization (+85.7%). There were no differences between the laparoscopy and laparotomy groups regarding the duration of infertility, number of pregnancies, performed cesarean sections, and the type of cesarean sections (urgent vs planned).ConclusionSurgical treatment should be offered to symptomatic women with isthmocele and secondary infertility. Given the absence of comparative studies, laparoscopic niche resection is the method of choice for a large uterine niche with an RMT <3 mm. Nonetheless, it offers comparable pregnancy outcomes to the laparotomic approach.
Chimeric Antigen Receptor (CAR)‐T Cells: A New Era for Hepatocellular Carcinoma Treatment
Authors: Xu Ming , Pan Yang 
Published: December 2024

ABSTRACTHepatocellular carcinoma (HCC) is one of the most common cancers and a worldwide health concern that requires novel treatment approaches. Tyrosine kinase inhibitors (TKIs) and immune checkpoint blockades (ICBs) are the current standard of care; however, their clinical benefits are limited in some advanced and metastatic patients. With the help of gene engineering techniques, a novel adoptive cellular therapy (ACT) called chimeric antigen receptor (CAR)‐T cells was recently introduced for treating HCC. A plethora of current clinical and preclinical studies are attempting to improve the efficacy of CAR‐T cells by dominating the immunosuppressive environment of HCC and finding the best tumor‐specific antigens (TSAs). The future of care for HCC patients might be drastically improved due to the convergence of novel therapeutic methods and the continuous progress in ACT research. However, the clinical application of CAR‐T cells in solid tumors is still facing several challenges. In this study, we provide an overview of the advancement and prospects of CAR‐T cell immunotherapy in HCC, as well as an investigation of how cutting‐edge engineering could improve CAR‐T cell efficacy and safety profile.
Pharmacokinetics, Pharmacodynamics and Bioavailability of ACM‐001.1 (S‐Pindolol Benzoate) in Healthy Volunteers
Authors: Misselwitz Frank , Henderson Dennis , Menakuru Somasekhara R. , Morten Elaine , Roe Chris , Whitaker Gareth , Wohlfeil Stefan , McDermott John 
Published: December 2024

ABSTRACTBackgroundS‐pindolol has metabolic effects of potential benefit in cancer cachexia: reduced catabolism through nonselective β‐blockade; increased anabolism through partial β2 receptor agonism; and increased appetite and reduced fatigue through central 5‐hydroxytryptamine/serotonin receptor activity. A Phase 2a clinical trial demonstrated that S‐pindolol can reverse weight loss and improve fat‐free mass in patients with cancer‐related weight loss. A comparative phase I bioavailability study of S‐pindolol and racemic pindolol was performed to support the development of S‐pindolol in cancer cachexia.MethodsThis two‐part study assessed the comparative bioavailability and pharmacokinetics of single doses of S‐pindolol benzoate (ACM‐001.1) or pindolol (Part 1) and the steady‐state pharmacokinetics and pharmacodynamics of multiple doses of ACM‐001.1 and pindolol (Part 2) in healthy volunteers (NCT06028321). ACM‐001.1 5, 10 and 15 mg and pindolol 15, 20 and 30 mg were tested. In Part 1, subjects were randomised to ACM‐001.1 15 mg followed after a 48‐h washout period by pindolol 30 mg, or the reverse sequence; another group received pindolol 15 mg. Subjects in Part 2 were randomised to pindolol 20 mg twice‐daily or ACM‐001.1 5, 10 or 15 mg twice‐daily for 4 days. Bioavailability, pharmacokinetics, pharmacodynamics, potential for and extent of stereoconversion, and tolerability were assessed.ResultsParts 1 and 2 included 24 and 27 healthy volunteers, respectively. ACM‐001.1 had predictable pharmacokinetics up to a dose of 15 mg twice daily, with low intersubject variability, after single and multiple doses (Tmax 1 vs. 1.5 h; Cmax 74 vs. 73.6 ng/mL; AUC(0−t) 440 vs. 414 ng·h/mL; t1/2 4.042 vs. 3.566 h). The bioavailability of S‐pindolol after equivalent doses of pindolol (20 mg) and ACM‐001.1 (10 mg) was comparable, and formal bioequivalence margins were met (90% CI for Cmax, AUC(0−t) and AUC(0–inf) within 80%–125% bioequivalence acceptance criteria). No evidence of stereoconversion of the S‐enantiomer into the R‐enantiomer, no accumulation, dose linearity and dose proportionality of S‐pindolol over a range of doses were demonstrated; we also show indirectly that there was no food effect. ACM‐001.1 was generally well tolerated, with no apparent relationship of side effects to dose, no serious adverse events, severe treatment‐emergent adverse events (TEAEs) or deaths, and similar incidences of TEAEs (fatigue, dizziness, somnolence, nausea and headache) with ACM‐001.1 10 and 15 mg and pindolol 20 mg.ConclusionsData from this bridging study of enantiomerically pure ACM‐001.1 and its parent racemic drug, pindolol, support clinical trials of ACM‐001.1 for the treatment of cancer cachexia.
Beyond the Organization: Implications of Geographic Flexibility for Workers
Authors: Merriman Kimberly K. 
Published: December 2024

ABSTRACTGeographic flexibility among workers to choose where they live rather than remain tethered to a specific physical office has emerged as a valued workplace benefit. Even before the prevalence of remote and distributed work, in‐demand skilled workers were known to weigh desirable aspects of locales over pay. However, the COVID‐19 pandemic elevated geographic choice to a broader role in workers' lives and the future of work. This study examines how workers derive utility from geographic flexibility and corresponding implications for organizations. I consider both instrumental and symbolic manifestations of utility, including but going beyond pragmatic motives for relocating, such as economic benefits and proximity to family, to encompass the less understood function of place as a target of identification. Findings are derived through an abductive qualitative analysis of 1300 personal narratives on chosen or desired moves at a time of geographic flexibility. Overall this work substantiates four distinct forms of personal utility offered by geographic flexibility—wanderlust, economic, affiliation, and self‐fulfillment—and clarifies identity mechanisms that underlie the place (dis)identification process to advance theorizing. Implications for organizational research and practice are discussed.
Clinical and Multimodal Imaging Features of Hepatic Inflammatory Pseudotumors
Authors: Chen Keke , Luo Minhua , He Yuhong , Huang Danqing , Tang Min , Shi Jiong , Qin Hong , Deng Minying , Wang Wenping , Kong Wentao 
Published: December 2024

ObjectivesCurrent literature on imaging characteristics of hepatic inflammatory pseudotumor (HIPT) is limited. This study aimed to analyze the contrast‐enhanced ultrasound (CEUS) features in HIPT and compare them with contrast‐enhanced computed tomography (CECT) and contrast‐enhanced magnetic resonance imaging (CEMRI).MethodsA total of 83 patients with histologically proven HIPT from two medical institutions were included in this study. All patients underwent CEUS within 1 week before surgery or biopsy. Some patients received additional CECT or CEMRI. B‐mode ultrasound (BMUS) features, enhancement parameters of CEUS, CECT and CEMRI were analyzed. Chi‐square test was used to compare the enhancement patterns and diagnostic sensitivity between CEUS and CECT/CEMRI.ResultsOn the BMUS, HIPT mainly appeared hypoechoic (83.5%, 66/79), irregular shapes (62.0%, 49/79), heterogeneous echogenicity (72.2%, 57/79), and unclear boundary (65.8%, 52/79). A total of 61.5% (51/83) lesions exhibited mild hyper‐ or iso‐enhancement in the arterial phase (AP), 59.0% (49/83) lesions had internal nonenhanced areas, and most lesions (71.1%, 59/83) showed early wash‐out (<60 seconds) on the CEUS. There were significant differences between CEUS and CECT/CEMRI in enhancement intensity of AP and wash‐out pattern (P < .05). The sensitivity in the diagnosis of HIPT among the three had no statistical difference (P>.05).ConclusionsThe CEUS features of HIPT lesions typically include mildly hyper‐enhanced or iso‐enhanced in AP, rapid wash‐out in PVP, and often small nonenhanced areas within the mass. Furthermore, the wash‐out pattern of CEUS and CECT/CEMRI are inconsistent, more akin to cholangiocarcinoma. The diagnostic efficacy of the three modalities is similar.
Short and proximalized interference screw fixation leads to tibial tunnel bone re‐growth and better hamstring graft integration in ACL reconstruction
Authors: Simon‐Sanchez Francisco J. , Perelli Simone , Pizza Nicola , Delmedico Michelangelo , Morales‐Avalos Rodolfo , Torres Claramunt Raúl , Monllau Joan C. 
Published: December 2024

AbstractPurposeThe stability of the graft in the bony tunnels is of utmost importance in the anterior cruciate ligament reconstruction (ACLR) since it ensures safe healing at the tendon‐bone interface. The hypothesis was that when a double tibial fixation was used in ACLR with a short graft of autologous hamstrings, tibial tunnel bone re‐growth and better graft integration would be observed at short‐term follow‐up.MethodsThe analysis included a cohort of 112 patients after a primary ACLR with hamstring tendons who underwent postoperative magnetic resonance imaging (MRI) 3.0‐Tesla (3.0‐T) 6 months after the surgery. The patients were divided into three groups based on the tibial fixation technique: 40 had a screw (group S), 35 had a screw and cortical button (group S + B) and 37 had a screw and anchor (group S + A). Two orthopaedic specialists independently evaluated the images, who measured the screw‐free tunnel space, and assessed the presence of bone filling in the free tunnel. Furthermore, Ge's protocol was used to determine the graft healing in the tunnel.ResultsIn 94 patients a screw‐free tunnel space was detected, and a filling of the tunnel was reported in 80.85% of the cases (76 patients), being partial in 15.79% (12 patients) and complete in 84.21% (64 patients). Patients who presented better graft integration (Ge1) had significantly higher values of screw‐free tunnel length compared to the other ones who had lower graft integration (Ge3)(p < 0.05).ConclusionsAt 6 months postoperative MRI, tibial tunnel bone re‐growth and graft‐tunnel tibial integration after hamstring ACLR is significantly associated with the presence of free space between the anterior tibial cortex and the most distal portion of the interference screw, hence the use of a short and proximalized interference screw is suggested to restore bone stock after hamstring ACLR.Level of EvidenceLevel IV retrospective comparative cohort study.