bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics of JNJ‐73763989 and JNJ‐56136379 (Bersacapavir) in Participants With Moderate Hepatic Impairment
Authors: Kakuda Thomas N. , Halabi Atef , Klein Gernot , Sanga Madhu , Guinard‐Azadian Carine , Kowalik Monika , Nedoschinsky Katja , Nangosyah Julius , Ediage Emmanuel Njumbe , Hillewaert Vera , Verboven Peter , Goris Ivo , Snoeys Jan , Palmer Martyn , Biermer Michael 
Published: February 2023

AbstractJNJ‐73763989 is comprised of 2 short interfering RNAs (siRNAs), JNJ‐73763976 and JNJ‐73763924, that target hepatitis B virus (HBV) mRNAs for degradation, thereby inhibiting HBV replication. JNJ‐56136379 is a capsid assembly modulator that inhibits HBV replication by inducing the formation of empty capsids (CAM‐E). In 2 phase 1, open‐label, non‐randomized, single‐center studies, the single‐dose pharmacokinetics, safety, and tolerability of JNJ‐73763989 or JNJ‐56136379 were assessed in participants with moderate hepatic impairment (Child–Pugh Class B) versus participants with normal liver function. Participants in both studies received a single subcutaneous dose of JNJ‐73763989 200 mg or oral JNJ‐56136379 250 mg, followed by an evaluation of plasma pharmacokinetic parameters and safety assessments. Plasma exposure to JNJ‐73763976, JNJ‐73763924, and JNJ‐56136379 was 1.3‐ to 1.4‐, 1.8‐ to 2.2‐, and 1.1‐ to 1.3‐fold higher in participants with moderate hepatic impairment versus participants with normal liver function; however, these increases were not considered clinically relevant. Both drugs were well tolerated and safe, with 7 (21.9%) participants experiencing 1 or more treatment‐emergent adverse events, 3 of which were related to JNJ‐56136379. Overall, the plasma exposures of JNJ‐73763989 and JNJ‐56136379 were higher in participants with moderate hepatic impairment, but both were well tolerated. Further studies are needed to evaluate the effect of hepatic impairment under multiple‐dose administration.
Second trimester fetal MRI of the brain: Through the ground glass
Authors: Fileva Nevena , Severino Mariasavina , Tortora Domenico , Ramaglia Antonia , Paladini Dario , Rossi Andrea 
Published: February 2023

AbstractFetal MRI is an important tool for the prenatal diagnosis of brain malformations and is often requested after second‐trimester ultrasonography reveals a possible abnormality. Despite the immature state of the fetal brain at this early stage, early suggestive signs of the presence of brain malformations can be recognized. To differentiate between the normal dynamics of the growing brain and the developing pathological conditions can be challenging and requires extensive knowledge of normal central nervous system developmental stages and their neuroradiological counterparts at those different stages. This article reviews the second‐trimester appearances of some commonly encountered brain malformations, focusing on helpful tricks and subtle signs to aid in the diagnosis of such conditions as rhombencephalosynapsis, various causes of vermian rotation, molar tooth spectrum anomalies, diencephalic‐mesencephalic junction dysplasia, ganglionic eminence anomalies, and the most common malformations of cortical development.
Efficacy and safety of endosonography‐guided transvascular needle aspiration of thoracic and abdominal lesions: A systematic review and meta‐analysis
Authors: Giri Suprabhat , Harindranath Sidharth , Angadi Sumaswi , Afzalpurkar Shivaraj , Sundaram Sridhar 
Published: February 2023

AbstractBackgroundThe diagnosis of intrathoracic and abdominal masses is challenging when lesions are located behind major vessels. Endoscopic ultrasound (EUS) or endobronchial ultrasound (EBUS)‐guided transvascular needle aspiration (TVNA) provides a potentially useful diagnostic tool for such lesions. Data with respect to the safety and outcome of E‐TVNA are scarce. Hence, this meta‐analysis was conducted to assess the critical role of E‐TVNA for diagnosis of various lesions.Methods and MaterialA meta‐analysis was performed by pooling the data from studies obtained from comprehensive search of Medline, Embase, and Scopus from January 2000 to September 2022. The outcomes analyzed included sample adequacy, diagnostic accuracy and adverse events including bleeding.ResultsA total of 17 studies (n = 411) were included in the final analysis. The pooled rate of sample adequacy was 91.5% [95% confidence interval (CI): 86.8–96.2], while the pooled rate of diagnostic accuracy was 85.0% (95% CI: 78.9–91.2). The pooled rate of bleeding with E‐TVNA was 1.4% (95% CI 0.0–3.1%). All the episodes of bleeding were mild and resolved without any further intervention. There was no significant heterogeneity with respect to various outcomes and results were comparable on sensitivity analysis.ConclusionsE‐TVNA offers a safe and accurate diagnostic modality for the diagnosis of mediastinal and abdominal lesions located on the other side of major vessels. Selection of potential candidates and close periprocedural observation are essential to improve the outcome.
An in vitro approach to understand contribution of kidney cells to human urinary extracellular vesicles
Authors: Barreiro Karina , Lay Abigail C. , Leparc German , Tran Van Du T. , Rosler Marcel , Dayalan Lusyan , Burdet Frederic , Ibberson Mark , Coward Richard J. M. , Huber Tobias B. , Krämer Bernhard K. , Delic Denis , Holthofer Harry 
Published: February 2023

AbstractExtracellular vesicles (EV) are membranous particles secreted by all cells and found in body fluids. Established EV contents include a variety of RNA species, proteins, lipids and metabolites that are considered to reflect the physiological status of their parental cells. However, to date, little is known about cell‐type enriched EV cargo in complex EV mixtures, especially in urine. To test whether EV secretion from distinct human kidney cells in culture differ and can recapitulate findings in normal urine, we comprehensively analysed EV components, (particularly miRNAs, long RNAs and protein) from conditionally immortalised human kidney cell lines (podocyte, glomerular endothelial, mesangial and proximal tubular cells) and compared to EV secreted in human urine. EV from cell culture media derived from immortalised kidney cells were isolated by hydrostatic filtration dialysis (HFD) and characterised by electron microscopy (EM), nanoparticle tracking analysis (NTA) and Western blotting (WB). RNA was isolated from EV and subjected to miRNA and RNA sequencing and proteins were profiled by tandem mass tag proteomics. Representative sets of EV miRNAs, RNAs and proteins were detected in each cell type and compared to human urinary EV isolates (uEV), EV cargo database, kidney biopsy bulk RNA sequencing and proteomics, and single‐cell transcriptomics. This revealed that a high proportion of the in vitro EV signatures were also found in in vivo datasets. Thus, highlighting the robustness of our in vitro model and showing that this approach enables the dissection of cell type specific EV cargo in biofluids and the potential identification of cell‐type specific EV biomarkers of kidney disease.
Discriminating alkylbenzene isomers with tandem mass spectrometry using a dielectric barrier discharge ionization source
Authors: Begley Alina , Zenobi Renato 
Published: February 2023

AbstractSoft ambient ionization sources generate reactive species that interact with analyte molecules to form intact molecular ions, which allows rapid, sensitive, and direct identification of the molecular mass. We used a dielectric barrier discharge ionization (DBDI) source with nitrogen at atmospheric pressure to detect alkylated aromatic hydrocarbon isomers (C8H10 or C9H12). Intact molecular ions [M]•+ were detected at 2.4 kVpp, but at increased voltage (3.4 kVpp), [M + N]+ ions were formed, which could be used to differentiate regioisomers by collision‐induced dissociation (CID). At 2.4 kVpp, alkylbenzene isomers with different alkyl‐substituents could be identified by additional product ions: ethylbenzene and ‐toluene formed [M‐2H]+, isopropylbenzene formed abundant [M‐H]+, and propylbenzene formed abundant C7H7+. At an operating voltage of 3.4 kVpp, fragmentation of [M + N]+ by CID led to neutral loss of HCN and CH3CN, which corresponded to steric hindrance for excited state N‐atoms approaching the aromatic ring (C‐H). The ratio of HCN to CH3N loss (interday relative standard deviation [RSD] < 20%) was distinct for ethylbenzene and ethyltoluene isomers. The greater the number of alkyl‐substituents (C‐CH3) and the more sterically hindered (meta > para > ortho) the aromatic core, the greater the loss of CH3CN relative to HCN was.
Fungi‐mediated synthesis of nanoparticles: characterization process and agricultural applications
Authors: Anjum Shahnaz , Vyas Ashish , Sofi Tariq 
Published: February 2023

AbstractIn the field of nanotechnology, the use of biologically active products from fungi for the reduction and synthesis of nanoparticles as an alternative to toxic chemicals has received extensive attention, due to their production of large quantities of proteins, high yields, easy handling, and the low toxicity of the residues. Fungi have become valuable tools for the manufacture of nanoparticles in comparison with other biological systems because of their enhanced growth control and diversity of metabolites, including enzymes, proteins, peptides, polysaccharides, and other macro‐molecules. The ability to use different species of fungi and to perform the synthesis under different conditions enables the production of nanoparticles with different physicochemical characteristics. Fungal nanotechnology has been used to develop and offer products and services in the agricultural, medicinal, and industrial sectors. Agriculturally, it has found applications in plant disease management, crop improvement, biosensing, and the production of environmentally friendly, non‐toxic pesticides and fertilizers to enhance agricultural production in general. The subject of this review is the application of fungi in the synthesis of inorganic nanoparticles, characterization, and possible applications of fungal nanoparticles in the diverse agricultural sector. The literature shows potential uses of fungi in biogenic synthesis, enabling the production of nanoparticles with different physiognomies. © 2023 Society of Chemical Industry.
Contribution of process‐induced molten‐globule state formation in duck liver protein to the enhanced binding ability of (E,E)‐2,4‐heptadienal
Authors: Han Chuanhu , Zheng Yuanrong , Wang Libin , Zhou Changyu , Wang Jianhui , He Jun , Sun Yangying , Cao Jinxuan , Pan Daodong , Xia Qiang 
Published: February 2023

AbstractBACKGROUNDExtracted proteins of alternative animal origin tend to present strong off‐flavor perception due to physicochemical interactions of coextracted off‐flavor compounds with proteins. To investigate the relationship between absorption behaviors of volatile aromas and the processes‐induced variations in protein microstructures and molecular conformations, duck liver protein isolate (DLp) was subjected to heating (65/100 °C, 15 min) and ultra‐high pressure (UHP, 100–500 MPa/10 min, 28 °C) treatments to obtain differential unfolded protein states.RESULTSHeat and UHP treatments induced the unfolding of DLp to varied degrees, as revealed by fluorescence spectroscopy, ultraviolet–visible absorption, circular dichroism spectra and surface hydrophobicity measurements. Two types of heating‐denatured states with varied unfolding degrees were obtained, while UHP at both levels of 100/500 MPa caused partial unfolding of DLp and the presence of a molten‐globule state, which significantly enhanced the binding affinity between DLp and (E,E)‐2,4‐heptadienal. In particular, significantly modified secondary structures of DLp were observed in heating‐denatured samples. Excessive denaturing and unfolding degrees resulted in no significant changes in the absorption behavior of the volatile ligand, as characterized by observations of fluorescence quenching and analysis of headspace concentrations.CONCLUSIONDefining process‐induced conformational transition behavior of matrix proteins could be a promising strategy to regulate food flavor attributes and, particularly, to produce DLp coextracted with limited off‐flavor components by modifying their interaction during extraction processes. © 2023 Society of Chemical Industry.
Discontinuation and nonpublication of clinical trials for the pharmacologic treatment of posttraumatic stress disorder among military veterans
Authors: Weygandt Jonas , Moody Morgan , Sajjadi Nicholas B. , Greiner Benjamin , Ford Alicia Ito , Mazur Anna , Hartwell Micah 
Published: February 2023

AbstractFailures by researchers and clinicians to overcome barriers in veteran health–related research may result in clinical trial (CT) discontinuation and nonpublication. Such outcomes are a waste of limited academic resources. To determine rates of discontinuation and nonpublication among CTs for posttraumatic stress disorder (PTSD) with pharmaceutical interventions specific to the veteran population, we performed a systematic search of registered trials in ClinicalTrials.gov for pharmaceutical interventions for the treatment of PTSD. Extracted study characteristics included sample size, study design, trial status, phase, and funding source. Studies were classified as completed or discontinued based on the status listed in ClinicalTrials.gov. Descriptive statistics of trials were reported, and associations of trial termination and nonpublication were assessed using logistic regression. The final sample included 54 CTs, 15 of which (27.8%) had not been published within the FDA's required timeframe, and 11 (20.4%) were discontinued. The total number of trial participants was 3,463, with a median of 37 (interquartile range: 15–92). Of the 54 trials, 12 (22.2%) were nonrandomized, and 42 (77.8%) were randomized. There were 25 (46.3%) trials that were in either Phase 3 or Phase 4, and 39 (72.2%) were government‐funded. We found high rates of CT discontinuation and nonpublication among PTSD pharmaceutical intervention studies in veterans, as has been shown in other fields of research.
Predictors of treatment completion in group psychotherapy for male veterans with posttraumatic stress disorder
Authors: Stoycos Sarah A. , Berzenski Sara R. , Beck J. Gayle , Unger William , Cappellano Jessica M. , Spofford Christopher M. , Sloan Denise M. 
Published: February 2023

AbstractGroup therapy is a frequently used therapy format for posttraumatic stress disorder (PTSD). However, factors contributing to treatment completion remain understudied. The current study examined predictors of treatment completion, defined as having completed 10 out of 14 sessions within 16 weeks, in veterans with PTSD who engaged in a hybrid efficacy–effectiveness randomized controlled trial of group psychotherapy for PTSD. Veterans (N = 198) were randomly assigned to 14 sessions of either group cognitive behavioral treatment (GBCT; n = 98) or group present‐centered treatment (GPCT; n = 100). Four primary domains of predictors were examined, encompassing sociodemographic factors, the severity of PTSD and comorbid conditions, modifiable predictors, and treatment condition. Multilevel binomial logistic regression models following the Fournier analysis approach were used to examine significant predictors within domains, which were then included in a final model. Overall, 70.7% of participants completed treatment (GCBT = 61.6%, GPCT = 79.8%). Participants in the GPCT condition were 2.389 times, 95% CI [1.394, 4.092], more likely to complete treatment than those in the GCBT condition. Older age, a higher income and level of educational attainment, more lifetime and current mental health diagnoses, and higher use of positive reappraisal ER skills predicted treatment completion. Higher levels of depressive symptoms, cumulative trauma burden, and use of positive refocusing ER skills predicted treatment noncompletion. These findings are discussed in the context of current clinical and research practices for examining treatment noncompletion, with attention to the inclusion of translational predictors.
Ethyl Cellulose‐Based Thermoreversible Organogel Photoresist for Sedimentation‐Free Volumetric Additive Manufacturing
Authors: Toombs Joseph T. , Shan Ingrid K. , Taylor Hayden K. 
Published: February 2023

AbstractLiquid photoresists are abundant in the field of light‐based additive manufacturing (AM). However, printing unsupported directly into a vat of material in emerging volumetric AM technologies―typically a benefit due to fewer geometric constraints and less material waste―can be a limitation when printing low‐viscosity liquid monomers and multimaterial constructs due to part drift or sedimentation. With ethyl cellulose (EC), a thermoplastic soluble in organic liquids, a simple three‐component transparent thermoreversible gel photoresist with melting temperature of ≈64 °C is formulated. The physically crosslinked network of the gel leads to storage moduli in the range of 0.1−10 kPa and maximum yield stress of 2.7 kPa for a 10 wt% EC gel photoresist. Nonzero yield stress enables sedimentation‐free tomographic volumetric patterning in low‐viscosity monomer without additional hardware or modification of apparatus. In addition, objects inserted into the print container can be suspended in the gel material which enables overprinting of multimaterial devices without anchors connecting the object to the printing container. Flexural strength is also improved by 100% compared to the neat monomer for a formulation with 7 wt% EC.
Impact of Parkinson's Disease on Caregiver Quality of Life in Japan
Authors: Nagaki Koichi , Nakagawa Ryoko , Ishido Miwako , Yoshinaga Yoko , Watanabe Jun , Kurihara Kanako , Hayashi Yuka , Ogura Hiromu , Mishima Takayasu , Fujioka Shinsuke , Tsuboi Yoshio 
Published: February 2023

AbstractBackgroundParkinson's disease (PD) adversely affects the quality of life (QoL) of not only patients but also their caregivers.ObjectiveTo determine the factors that most impact the QoL of family caregivers of patients with PD in a large Japanese population using data from the Japanese Quality‐of‐Life Survey of Parkinson's Disease (JAQPAD) study.MethodsQuestionnaires, including the Parkinson's Disease Questionnaire‐Carer (PDQ‐Carer), were distributed to patients and their caregivers. Univariate and multivariate regression analyses were performed with the PDQ‐Carer Summary Index (SI) score as the dependent variable to determine the factors that impact caregiver QoL.ResultsOverall, 1,346 caregivers were included in the analysis. Female sex, unemployment, caring for a patient with a high‐level need for nursing care, and a high Nonmotor Symptoms Questionnaire score were factors with a significant negative impact on caregiver QoL.ConclusionResults from this study identified several factors that affect caregiver QoL in Japan.
The current benefit of genome sequencing compared to exome sequencing in patients with developmental or epileptic encephalopathies
Authors: Grether Anna , Ivanovski Ivan , Russo Martina , Begemann Anaïs , Steindl Katharina , Abela Lucia , Papik Michael , Zweier Markus , Oneda Beatrice , Joset Pascal , Rauch Anita 
Published: February 2023

AbstractBackgroundAs the technology of next generation sequencing rapidly develops and costs are constantly reduced, the clinical availability of whole genome sequencing (WGS) increases. Thereby, it remains unclear what exact advantage WGS offers in comparison to whole exome sequencing (WES) for the diagnosis of genetic diseases using current technologies.MethodsTrio‐WGS was conducted for 20 patients with developmental or epileptic encephalopathies who remained undiagnosed after WES and chromosomal microarray analysis.ResultsA diagnosis was reached for four patients (20%). However, retrospectively all pathogenic variants could have been detected in a WES analysis conducted with today's methods and knowledge.ConclusionThe additional diagnostic yield of WGS versus WES is currently largely explained by new scientific insights and the general technological progress. Nevertheless, it is noteworthy that whole genome sequencing has greater potential for the analysis of small copy number and copy number neutral variants not seen with WES as well as variants in noncoding regions, especially as potentially more knowledge of the function of noncoding regions arises. We, therefore, conclude that even though today the added value of WGS versus WES seems to be limited, it may increase substantially in the future.
Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High‐Fat Diet
Authors: Neto Jessika Geisebel Oliveira , Woyames Juliana , Andrade Cherley Borba Vieira , de Almeida Mariana Macedo , Fassarella Larissa Brito , Atella Georgia Correia , Takyia Christina Maeda , Trevenzoli Isis Hara , Pazos‐Moura Carmen Cabanelas 
Published: February 2023

ScopePerinatal maternal moderately high‐fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n‐3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning.Methods and resultsFemale Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high‐fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics.ConclusionsGestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long‐term outcomes.