bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishment, Long‐Term Maintenance, and Characterization of Primary Liver Cells from Astyanax mexicanus
Authors: Rajendran Naresh , Deng Fengyan , Wang Yan , Kenzior Olga , Krishnan Jaya , Biswas Tathagata , Parmely Tari , Rohner Nicolas , Zhao Chongbei 
Published: April 2023

AbstractThe tetra fish species Astyanax mexicanus comprises two morphotypes: cavefish that live in caves and surface fish that inhabit rivers and lakes. Because cavefish have adapted to the nutrient‐poor conditions in their habitat whereas the surface fish populations can be used as a proxy for the ancestral condition, this species has become a powerful model system for understanding genetic variation underlying metabolic adaptation. The liver plays a critical role in glucose and fat metabolism in the body and hence is an important tissue for studying altered metabolism in health and disease. Cavefish morphs of A. mexicanus have been shown to develop fatty livers and exhibit massive differences in gene expression and chromatin architecture. Primary cell lines from various tissues have become invaluable tools for biochemical, toxicology, and cell biology experiments, as well as genetic and genomic analyses. To enhance the utility of the model system by enabling an expanded set of biochemical and in vitro experiments, we developed protocols for the isolation and maintenance of primary liver cells from A. mexicanus surface fish and cavefish. We also describe methods that can be used for primary cell characterization, including cloning, characterization of cell growth pattern, and lentivirus transduction. © 2023 Wiley Periodicals LLC.Basic Protocol 1: Primary culture of liver cellsSupport Protocol 1: Maintenance of A. mexicanus primary liver cellsSupport Protocol 2: Banking of A. mexicanus primary liver cellsSupport Protocol 3: Recovery of A. mexicanus primary liver cellsSupport Protocol 4: Primary liver cell cloningSupport Protocol 5: Characterization of A. mexicanus primary liver cell growth patternBasic Protocol 2: Lentiviral transduction of A. mexicanus primary liver cells
Design, synthesis, and biological evaluation of thienopyrimidine derivatives as multifunctional agents against Alzheimer's disease
Authors: Eissa Kholoud I. , Kamel Mona M. , Mohamed Lamia W. , Doghish Ahmed S. , Alnajjar Radwan , Al‐Karmalawy Ahmed A. , Kassab Asmaa E. 
Published: April 2023

AbstractA series of 12 S‐substituted tetrahydrobenzothienopyrimidines were designed and synthesized based on the donepezil scaffold. All the newly synthesized compounds were evaluated for their acetylcholinesterase (AChE) inhibitory activity and the most active compounds were tested for their butyrylcholinesterase (BuChE) inhibitory activity. Moreover, all the synthesized compounds were evaluated for their inhibitory effects against Aβ aggregation and antioxidant activity using the oxygen radical absorbance capacity method. Compounds 4b, 6b, and 8b displayed the most prominent AChE inhibitory action comparable to donepezil. Compound 6b showed the greatest AChE inhibitory action (IC50 = 0.07 ± 0.003 µM) and the most potent BuChE inhibitory action (IC50 = 0.059 ± 0.004 µM). Furthermore, the three compounds exhibited significant antioxidant activity. Compounds 6b and 8b exerted more inhibitory action on Aβ aggregation than donepezil. The cytotoxic activity of compounds 4b, 6b, and 8b against the WI‐38 cell line in comparison with donepezil was examined using 3‐(4,5‐dimethylthiazolyl‐2)‐2,5‐diphenyltetrazolium bromide assay. The results revealed that compounds 6b and 8b were less cytotixic than donepezil, while compound 4b showed nonsignificant cytotoxicity compared to donepezil. For more insights about the binding patterns of the most promising compounds (4b, 6b, and 8b) with the AChE at molecular levels; molecular docking and molecular dynamics simulations were performed. The density functional theory calculations and absorption, distribution, metabolism, excretion and toxicity properties were described as well. The results highlighted compound 6b, which incorporates a phenylpiperazine moiety coupled to a thienopyrimidone scaffold via two‐atom spacer, to be a promising multifunctional therapeutic agent for the treatment of Alzheimer's disease. It is a potent dual AChE and BuChE inhibitor. Furthermore, it had stronger Aβ aggregation inhibitory action than donepezil. Additionally, compound 6b exerted significant antioxidant activity.
Dermal fillers: History 101
Authors: Andrews Laura , Shope Chelsea , Snyder Alan , Schlesinger Todd 
Published: April 2023

AbstractIntroductionDermal fillers are an efficacious option for treating age‐related volume deficiency, as well as scars and wrinkles. Additionally, they are useful for facial sculpting and contouring, and to augment anatomical structures such as the lips.DiscussionThe start of the search for an ideal dermal filler can be traced back to the late 1800s. Characteristics of this ideal filler product include nontoxic, nonmigratory, noncarcinogenic, easily applied, noninfectious, painless, and long‐lasting. It would also have predictable and consistent results, feel natural, and require no patient downtime. Over the past century and a half, numerous products have been used or developed in an attempt to achieve a filler possessing these characteristics. However, only in the past few decades have safe, injectable filler products approved by the US Food and Drug Administration (FDA), been developed. Herein, we discuss the various injectable agents used in the past, as well as the most commonly used agents of present day.ConclusionReflecting upon the history of dermal filler development serves as an important reminder to proceed with caution, as serious complications may occur with their use. Importantly, no single filler is ideal for all patients or indications, therefore optimal treatment requires awareness of the properties and characteristics of each available product, and discretionary use by providers.
Cementum is key to periodontal tissue regeneration: A review on apatite microstructures for creation of novel cementum‐based dental implants
Authors: Saito Mari M. , Onuma Kazuo , Yamakoshi Yasuo 
Published: April 2023

SummaryThe cementum is the outermost layer of hard tissue covering the dentin within the root portion of the teeth. It is the only hard tissue with a specialized structure and function that forms a part of both the teeth and periodontal tissue. As such, cementum is believed to be critical for periodontal tissue regeneration. In this review, we discuss the function and histological structure of the cementum to promote crystal engineering with a biochemical approach in cementum regenerative medicine. We review the microstructure of enamel and bone while discussing the mechanism underlying apatite crystal formation to infer the morphology of cementum apatite crystals and their complex structure with collagen fibers. Finally, the limitations of the current dental implant treatments in clinical practice are explored from the perspective of periodontal tissue regeneration. We anticipate the possibility of advancing periodontal tissue regenerative medicine via cementum regeneration using a combination of material science and biochemical methods.
Effect of intravenous iron replacement on recurrent heart failure hospitalizations and cardiovascular mortality in patients with heart failure and iron deficiency: A Bayesian meta‐analysis
Authors: Anker Stefan D. , Khan Muhammad Shahzeb , Butler Javed , von Haehling Stephan , Jankowska Ewa A. , Ponikowski Piotr , Friede Tim 
Published: April 2023

AbstractAimsIron deficiency is common in patients with heart failure (HF) and reduced ejection fraction (HFrEF) and is associated with a poor prognosis. Whether intravenous iron replacement improves recurrent HF hospitalizations and cardiovascular mortality of these patients is uncertain although several trials were conducted. Moreover, none of the trials were powered to assess the effect of intravenous iron in clinically important subgroups. Therefore, we conducted a Bayesian analysis to derive precise estimates of the effect of intravenous iron replacement on recurrent HF hospitalizations and cardiovascular mortality in iron‐deficient HFrEF patients using consistent subgroup definitions across trials.Methods and resultsIndividual participant data were used from the FAIR‐HF (n = 459), CONFIRM‐HF (n = 304) and AFFIRM‐AHF (n = 1108) trials. These data were re‐analysed following as closely as possible the approach taken in the analyses of IRONMAN (n = 1137), for which study level data were used. Definitions of outcomes and subgroups from the FAIR‐HF, CONFIRM‐HF and AFFIRM‐AHF were matched with those used in IRONMAN. The primary endpoint was recurrent HF hospitalizations and cardiovascular mortality. The analysis of recurrent events was based on rate ratios (RR) derived from the Lin‐Wei‐Yang‐Ying model, and the data were pooled using Bayesian random‐effects meta‐analysis. Compared with placebo, intravenous iron significantly reduced the rates of recurrent HF hospitalizations and cardiovascular mortality (RR 0.73, 95% credible interval [CI] 0.48–0.99; between‐trial heterogeneity tau = 0.16). The pooled treatment effects did not provide evidence for any differential effects for subgroups based on sex (ratio of rate ratios [RRR] 1.49 [95% CI 0.95–2.37], age <69.4 vs. ≥69.4 years) (RRR 0.68 [0.40–1.15]), ischaemic versus non‐ischaemic aetiology of HF (RRR 0.73 [0.42–1.33]), transferrin saturation <20% vs. ≥20% (RRR 0.75 [0.40–1.34]), estimated glomerular filtration rate ≤60 versus >60 ml/min/1.73 m2 (RRR 0.97 [0.56–1.68]), haemoglobin <11.8 versus ≥11.8 (RRR 0.95 [0.53–1.60]), ferritin <35 versus ≥35 μg/L (RRR 1.26 [0.72–2.48]) and New York Heart Association class II versus III/IV (RRR 0.91 [0.54–1.56]).ConclusionsTreatment of iron‐deficient HFrEF patients with intravenous iron – namely with ferric carboxymaltose or ferric derisomaltose – results in significant reduction in recurrent HF hospitalizations and cardiovascular mortality. Results were nominally consistent across the subgroups studied, but for several of these subgroups uncertainty remains present.
Cross-Species Extrapolation of Biological Data to Guide the Environmental Safety Assessment of Pharmaceuticals—The State of the Art and Future Priorities
Authors: Margiotta-Casaluci Luigi , Owen Stewart F. , Winter Matthew J. 
Published: April 2023

Abstract
The extrapolation of biological data across species is a key aspect of biomedical research and drug development. In this context, comparative biology considerations are applied with the goal of understanding human disease and guiding the development of effective and safe medicines. However, the widespread occurrence of pharmaceuticals in the environment and the need to assess the risk posed to wildlife have prompted a renewed interest in the extrapolation of pharmacological and toxicological data across the entire tree of life. To address this challenge, a biological “read-across” approach, based on the use of mammalian data to inform toxicity predictions in wildlife species, has been proposed as an effective way to streamline the environmental safety assessment of pharmaceuticals. Yet, how effective has this approach been, and are we any closer to being able to accurately predict environmental risk based on known human risk? We discuss the main theoretical and experimental advancements achieved in the last 10 years of research in this field. We propose that a better understanding of the functional conservation of drug targets across species and of the quantitative relationship between target modulation and adverse effects should be considered as future research priorities. This pharmacodynamic focus should be complemented with the application of higher-throughput experimental and computational approaches to accelerate the prediction of internal exposure dynamics. The translation of comparative (eco)toxicology research into real-world applications, however, relies on the (limited) availability of experts with the skill set needed to navigate the complexity of the problem; hence, we also call for synergistic multistakeholder efforts to support and strengthen comparative toxicology research and education at a global level. Environ Toxicol Chem 2024;43:513–525. © 2023 The Authors. Environmental Toxicology and Chemistry published by Wiley Periodicals LLC on behalf of SETAC.
Abstract
Enhancing chemical safety assessment with high-precision ecotoxicology predictions.
Clinical efficacy of ulinastatin in the treatment of unliquefied pyogenic liver abscess complicated by septic shock: A randomized controlled trial
Authors: Guo Mingfeng , Zhou Bing 
Published: April 2023

AbstractIntroductionThis study determined the therapeutic effect of ulinastatin (UTI) on unliquefied pyogenic liver abscesses complicated by septic shock (UPLA‐SS).MethodsThis was a randomized controlled trial involving patients with UPLA‐SS who underwent treatment at our hospital between March 2018 and March 2022. The patients were randomly divided into control (n = 51) and study groups (n = 48). Both groups received routine treatment, but the study group received UTI (200,000 units q8h for >3 days). Differences in liver function, inflammatory indices, and effectiveness between the two groups were recorded.ResultsFollowing treatment, the white blood cell count, and lactate, C‐reactive protein, procalcitonin, tumor necrosis factor‐α, and interleukin‐6 levels were significantly decreased in all patients compared to the admission values (p < .05). The study group had a faster decline with respect to the above indices compared to the control group (p < .05). The study group length of intensive care unit stay, fever duration, and vasoactive drug maintenance time were all significantly shorter than the control group (p < .05). The total bilirubin, alanine aminotransferase, and aspartate aminotransferase levels were significantly lower in the study and control groups after treatment compared to before treatment (p < .05); however, the study group had a faster recovery of liver function than the control group (p < .05). The overall mortality rate was 14.14% (14/99); 10.41% of the study group patients died and 17.65% of the control group patients died, but there was no statistically significant difference between the two groups (p > .05).ConclusionUTI combined with conventional treatment significantly controlled the infection symptoms, improved organ function, and shortened the treatment time in patients with UPLA‐SS.
Research integrity in randomized clinical trials: A scoping umbrella review
Authors: Núñez‐Núñez María , Maes‐Carballo Marta , Mignini Luciano E. , Chien Patrick F. W. , Khalaf Yacoub , Fawzy Mohamed , Zamora Javier , Khan Khalid S. , Bueno‐Cavanillas Aurora 
Published: April 2023

AbstractBackgroundRandomized clinical trials (RCTs) are experiencing a crisis of confidence in their trustworthiness. Although a comprehensive literature search yielded several reviews on RCT integrity, an overarching overview is lacking.ObjectivesThe authors undertook a scoping umbrella review of the research integrity literature concerning RCTs.Search strategy and selection criteriaFollowing prospective registration (https://osf.io/3ursn), two reviewers independently searched PubMed, Scopus, The Cochrane Library, and Google Scholar, without language or time restrictions, until November 2021. The authors included systematic reviews covering any aspect of research integrity throughout the RCT lifecycle.Data collection and analysisThe authors assessed methodological quality using a modified AMSTAR 2 (A Measurement Tool to Assess Systematic Reviews) tool and collated the main findings.Main resultsA total of 55 relevant reviews, summarizing 6001 studies (median per review, 63; range, 8–1106) from 1964 to 2021, had an overall critically low quality of 96% (53 reviews). Topics covered included general aspects (15%), design and approval (22%), conduct and monitoring (11%), reporting (38%), postpublication concerns (2%), and future research (13%). The most common integrity issues covered were ethics (18%) and transparency (18%).ConclusionsLow‐quality reviews identified various integrity issues across the RCT lifecycle, emphasizing the importance of high ethical standards and professionalism while highlighting gaps in the integrity landscape. Multistakeholder consensus is needed to develop specific RCT integrity standards.
Neonatal condition at birth of twins conceived by medically assisted reproductive technology compared to those conceived spontaneously: A retrospective study
Authors: Abu Nofal Mais , Abd Elgani Suzan , Zafran Noah , Garmi Gali , Romano Shabtai , Salim Raed 
Published: April 2023

AbstractObjectiveTo examine neonatal outcomes at birth among twins conceived spontaneously or by medically assisted reproduction (MAR).MethodsA retrospective study was conducted at a single university teaching hospital on data collected between January 1995 and September 2019. Live twin deliveries at more than 24 weeks of pregnancy were included. The study group consisted of women who conceived by MAR and the controls were spontaneously conceived twins. The study group was further divided into two groups: in vitro fertilization (IVF) and ovulation induction (OI) groups. The primary outcomes were umbilical artery pH less than 7.1 and/or Apgar score less than 7 of any twin 5 min after birth.ResultsOverall, 2235 eligible twin gestations were included, corresponding to a total of 4470 live neonates; 1009 (45.1%) conceived by MAR (762 [75.5%] IVF and 247 [24.5%] OI) and 1226 (54.9%) conceived spontaneously. Incidence of the primary outcome was 5.3% and 5.1% in the study and control groups, respectively (P = 0.71). The primary outcome was comparable among the IVF (5%), OI (6.2%), and control (5.1%) groups. The results did not change even after adjusting for demographic and obstetric variables, including mode of delivery, which differed between the groups.ConclusionNeonatal condition of twin pregnancies at birth among MAR subgroups is similar to spontaneously conceived twins.
Causal effects of COVID‐19 on cancer risk: A Mendelian randomization study
Authors: Li Jia , Bai Haocheng , Qiao Hao , Du Chong , Yao Peizhuo , Zhang Yu , Cai Yifan , Jia Yiwei , Wei Xinyu , Li Chaofan , Liu Xuanyu , Wang Weiwei , Sun Shiyu , Feng Cong , Hu Yijian , Zhou Zhangjian , Zhang Shuqun , Zhang Yinbin 
Published: April 2023

AbstractIn contemporary literature, little attention has been paid to the association between coronavirus disease‐2019 (COVID‐19) and cancer risk. We performed the Mendelian randomization (MR) to investigate the causal associations between the three types of COVID‐19 exposures (critically ill COVID‐19, hospitalized COVID‐19, and respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection) and 33 different types of cancers of the European population. The results of the inverse‐variance‐weighted model indicated that genetic liabilities to critically ill COVID‐19 had suggestive causal associations with the increased risk for HER2‐positive breast cancer (odds ratio [OR] = 1.0924; p‐value = 0.0116), esophageal cancer (OR = 1.0004; p‐value = 0.0226), colorectal cancer (OR = 1.0010; p‐value = 0.0242), stomach cancer (OR = 1.2394; p‐value = 0.0331), and colon cancer (OR = 1.0006; p‐value = 0.0453). The genetic liabilities to hospitalized COVID‐19 had suggestive causal associations with the increased risk for HER2‐positive breast cancer (OR = 1.1096; p‐value = 0.0458), esophageal cancer (OR = 1.0005; p‐value = 0.0440) as well as stomach cancer (OR = 1.3043; p‐value = 0.0476). The genetic liabilities to SARS‐CoV‐2 infection had suggestive causal associations with the increased risk for stomach cancer (OR = 2.8563; p‐value = 0.0019) but with the decreasing risk for head and neck cancer (OR = 0.9986, p‐value = 0.0426). The causal associations of the above combinations were robust through the test of heterogeneity and pleiotropy. Together, our study indicated that COVID‐19 had causal effects on cancer risk.
SARS‐CoV‐2 vaccine antibody response and breakthrough infections in transplant recipients
Authors: Vanlerberghe Benedict , Vrij Casper , Bogaerts Kris , Vermeersch Pieter , Lagrou Katrien , Molenberghs Geert , Rega Filip , Ceulemans Laurens J. , van Raemdonck Dirk , Jochmans Ina , Monbaliu Diethard , Pirenne Jacques , Vanuytsel Tim , Gillard Pieter , Schoemans Hélène , Cleemput Johan Van , Kuypers Dirk , Vos Robin , Nevens Frederik , Verbeek Jef 
Published: April 2023

AbstractRates and modulators of SARS‐CoV‐2 vaccine nonresponse and breakthrough infections remain unclear in serially vaccinated transplant recipients. In a prospective, mono‐centric, observational study, 1878 adult solid organ and hematopoietic cell transplant recipients, with prior SARS‐CoV‐2 vaccination, were included between March 2021 and February 2022. SARS‐CoV‐2 anti‐spike IgG antibodies were measured at inclusion and details on SARS‐CoV‐2 vaccine doses and infection were collected. No life‐threatening adverse events were reported after a total of 4039 vaccine doses. In transplant recipients without prior SARS‐CoV‐2 infection (n = 1636), antibody response rates ranged widely, from 47% in lung transplant to 90% in liver transplant and 91% in hematopoietic cell transplant recipients after third vaccine dose. Antibody positivity rate and levels increased after each vaccine dose in all types of transplant recipients. In multivariable analysis, older age, chronic kidney disease and daily dose of mycophenolate and corticosteroids were negatively associated with antibody response rate. Overall rate of breakthrough infections was 25.2% and mainly (90.2%) occurred after third and fourth vaccine dose. Lung transplant recipients had the highest rates of severe breakthrough infection (10.5%) and death (2.5%). In multivariable analysis, older age, daily dose of mycophenolate and corticosteroids were associated with severe breakthrough infection. Transplant recipients with infection before first vaccine dose (n = 160) had higher antibody response rates and levels after each vaccine dose, and a significantly lower overall rate of breakthrough infections compared to those without prior infection. Antibody response after SARS‐CoV‐2 vaccination and rate of severe breakthrough infections vary largely between different transplant types and are modulated by specific risk factors. The observed heterogeneity supports a tailored approach against COVID‐19 in transplant recipients.