bluuebunny/crossref_metadata_2025_split huggingface dataset:
An expectation–maximization framework for comprehensive prediction of isoform-specific functions
Authors: Karlebach Guy , Carmody Leigh , Sundaramurthi Jagadish Chandrabose , Casiraghi Elena , Hansen Peter , Reese Justin , Mungall Christopher J , Valentini Giorgio , Robinson Peter N 
Published: March 2023

AbstractMotivationAdvances in RNA sequencing technologies have achieved an unprecedented accuracy in the quantification of mRNA isoforms, but our knowledge of isoform-specific functions has lagged behind. There is a need to understand the functional consequences of differential splicing, which could be supported by the generation of accurate and comprehensive isoform-specific gene ontology annotations.ResultsWe present isoform interpretation, a method that uses expectation–maximization to infer isoform-specific functions based on the relationship between sequence and functional isoform similarity. We predicted isoform-specific functional annotations for 85 617 isoforms of 17 900 protein-coding human genes spanning a range of 17 430 distinct gene ontology terms. Comparison with a gold-standard corpus of manually annotated human isoform functions showed that isoform interpretation significantly outperforms state-of-the-art competing methods. We provide experimental evidence that functionally related isoforms predicted by isoform interpretation show a higher degree of domain sharing and expression correlation than functionally related genes. We also show that isoform sequence similarity correlates better with inferred isoform function than with gene-level function.Availability and implementationSource code, documentation, and resource files are freely available under a GNU3 license at https://github.com/TheJacksonLaboratory/isopretEM and https://zenodo.org/record/7594321.
IntestLine: a shiny-based application to map the rolled intestinal tissue onto a line
Authors: Yuzeir Altay , Bejarano David Alejandro , Grein Stephan , Hasenauer Jan , Schlitzer Andreas , Yu Jiangyan 
Published: March 2023

AbstractSummaryTo allow the comprehensive histological analysis of the whole intestine, it is often rolled to a spiral before imaging. This Swiss-rolling technique facilitates robust experimental procedures, but it limits the possibilities to comprehend changes along the intestine. Here, we present IntestLine, a Shiny-based open-source application for processing imaging data of (rolled) intestinal tissues and subsequent mapping onto a line. The visualization of the mapped data facilitates the assessment of the whole intestine in both proximal–distal and serosa-luminal axis, and enables the observation of location-specific cell types and markers. Accordingly, IntestLine can serve as a tool to characterize the intestine in multi-modal imaging studies.Availability and implementationSource code can be found at Zenodo (https://doi.org/10.5281/zenodo.7081864) and GitHub (https://github.com/SchlitzerLab/IntestLine).
A potential protective role of the nuclear receptor-related factor 1 (Nurr1) in multiple sclerosis motor cortex: a neuropathological study
Authors: Pansieri Jonathan , Pisa Marco , Yates Richard L , Esiri Margaret M , DeLuca Gabriele C 
Published: March 2023

AbstractCerebral cortical inflammation and neurodegeneration are hallmark pathological features of multiple sclerosis that contribute to irreversible neurological disability. While the reason for nerve cell death is unknown, the pathogenic inflammatory role of infiltrating lymphocytes is likely an important contributor. The nuclear receptor-related factor 1 counteracts inflammation in animal models of multiple sclerosis, and protects against neuronal loss in other neurodegenerative disorders, but its expression in post-mortem multiple sclerosis tissue is not known. This study aims to investigate the nuclear receptor-related factor 1 expression in multiple sclerosis motor cortex and evaluate its relationship with motor cortical pathology. To accomplish this, an autopsy cohort of pathologically confirmed multiple sclerosis (n = 46), and control (n = 11) cases was used, where the nuclear receptor-related factor 1 expression was related to neuronal and lymphocytic densities. Motor cortical nuclear receptor-related factor 1 was overexpressed in multiple sclerosis compared to control cases. Increased nuclear receptor-related factor 1 expression positively associated with neuronal densities, especially when present in nucleus of neurons, and associated with decreased CD8+ cytotoxic lymphocyte density. Our findings expand the current knowledge on nuclear receptor-related factor 1 in neurological diseases, and support the hypothesis that nuclear receptor-related factor 1 may play a dual neuroprotective role in multiple sclerosis by influencing inflammatory and neurodegenerative processes. Future studies elucidating the influence of nuclear receptor-related factor 1 on these processes in multiple sclerosis may cast light onto novel targets that may be modulated to alter clinical outcome.
Comprehensive and Validated Chromatographic Techniques for the Estimation of Lercanidipine Hydrochloride and Atenolol in Bulk and Combined Dosage Form in the Presence of Lercanidipine Degradation Products with LC/MS Characterization
Authors: Boltia Shereen A , Fattah Taghreed A , Saad Marwa T , Zaazaa Hala E 
Published: March 2023

Abstract
Two rapid, smart and validated stability indicating HPLC and TLC techniques were developed to determine atenolol (ATE) and lercanidipine HCl (LER) simultaneously in their pharmaceutical formulation. HPLC chromatographic separation was implemented by using Microsorb C18 (250 × 4.6 mm, 5 μm) column, with mobile phase of acetonitrile and 20 mM potassium dihydrogen phosphate buffer pH 3.5 adjusted by orthophosphoric acid in the ratio of (65:35, v/v) at a flow rate of 1.2 mL/min at 240 nm also the injection volume adjusted to be 30 μL. These selected conditions effectively separated ATE and LER at a retention time of 2 and 6.7 min, respectively, by isocratic elution mode without any interference from the obtained degradation products of LER. The densitometric determination was performed by using precoated silica gel 60F254 aluminum plates and chloroform, methanol and triethylamine (11.3:1.3: 0.3, by volume) as a developing system. The detection wavelength for simultaneous estimation of both drugs was 240 nm in the presence of the oxidative product of LER. The RF values for ATE and LER were 0.22 and 0.78, respectively. The calibration curves of both techniques were constructed with linearity ranges of (5–55) μg.mL−1 and (1–55) μg.mL−1 for both ATE and LER, respectively, for HPLC determination. While for TLC, the linearity ranges were (1–4) μg/band and (0.2–1.4) μg/band for ATE and LER, respectively. LER degradation products were characterized using UPLC/MS and the suggested mechanisms and degradation pathways were introduced.
Capillary-Mitochondrial Oxygen Transport in Muscle: Paradigm Shifts
Authors: Poole David C , Musch Timothy I 
Published: March 2023

AbstractWhen exercising humans increase their oxygen uptake (V̇O2) 20-fold above rest the numbers are staggering: Each minute the O2 transport system - lungs, cardiovascular, active muscles – transports and utilizes 161 sextillion (10 21) O2 molecules. Leg extension exercise increases the quadriceps muscles’ blood flow 100-times; transporting 17 sextillion O2 molecules per kilogram per minute from microcirculation (capillaries) to mitochondria powering their cellular energetics. Within these muscles, the capillary network constitutes a prodigious blood-tissue interface essential to exchange O2 and carbon dioxide requisite for muscle function. In disease, microcirculatory dysfunction underlies the pathophysiology of heart failure, diabetes, hypertension, pulmonary disease, sepsis, stroke and senile dementia. Effective therapeutic countermeasure design demands knowledge of microvascular/capillary function in health to recognize and combat pathological dysfunction. Dated concepts of skeletal muscle capillary (from the Latin capillus meaning ‘hair’) function prevail despite rigorous data-supported contemporary models; hindering progress in the field for future and current students, researchers and clinicians. Following closely the 100th anniversary of August Krogh’s 1920 Nobel Prize for capillary function this Evidence Review presents an anatomical and physiological development of this dynamic field: Constructing a scientifically defensible platform for our current understanding of microcirculatory physiological function in supporting blood-mitochondrial O2 transport. New developments include: 1. Putative roles of red blood cell aquaporin and rhesus channels in determining tissue O2 diffusion. 2. Recent discoveries regarding intramyocyte O2 transport. 3. Developing a comprehensive capillary functional model for muscle O2 delivery-to-V̇O2 matching. 4. Use of kinetics analysis to discriminate control mechanisms from collateral or pathological phenomena.
Introducción: Los entes autónomos en el derecho constitucional latinoamericano
Authors: García-Huidobro Luis Eugenio , Guidi Sebastián 
Published: March 2023

Abstract
This introduction provides an overview of the concept and role of independent authorities in comparative public law, with a particular emphasis on Latin America. First, we outline an idea of these institutions and examine how they have assumed critical responsibilities traditionally allocated to one of the three branches of government. We also explore their role in protecting constitutional democracy and discuss some problems associated with their democratic legitimacy. Second, we outline these entities’ situation in Latin America, stressing how little academic attention they have received in contrast with their growing importance. Finally, we provide a critical review of each of the contributions to the symposium.
On Density of Modular Points in Pseudo-Deformation Rings
Authors: Deo Shaunak V 
Published: March 2023

Abstract
Given a continuous, odd, reducible, and semi-simple $2$-dimensional representation $\bar \rho _{0}$ of $G_{{\mathbb{Q}},Np}$ over a finite field of odd characteristic $p$, we study the relation between the universal deformation ring of the pseudo-representation corresponding to $\bar \rho _{0}$ (pseudo-deformation ring) and the big $p$-adic Hecke algebra to prove that the maximal reduced quotient of the pseudo-deformation ring is isomorphic to the local component of the big $p$-adic Hecke algebra corresponding to $\bar \rho _{0}$ if a certain global Galois cohomology group has dimension $1$. This partially extends the results of Böckle to the case of residually reducible representations. We give an application of our main theorem to the structure of Hecke algebras modulo $p$. As another application of our methods and results, we prove a result about non-optimal levels of newforms lifting $\bar \rho _{0}$ in the spirit of Diamond–Taylor. This also gives a partial answer to a conjecture of Billerey–Menares.
Endothelial damage occurs early after inhalation injury as measured by increased syndecan-1 levels
Authors: Kelly Edward J , Carney Bonnie C , Oliver Mary A , Keyloun John W , Prindeze Nicholas J , Nisar Saira , Moffatt Lauren T , Shupp Jeffrey W 
Published: March 2023

Abstract
Inhalation injury is a significant cause of morbidity and mortality in the burn patient population. However, the pathogenesis of inhalation injury and its potential involvement in burn shock is not well understood. Preclinical studies have shown endothelial injury, as measured by syndecan-1 (SDC-1) levels, to be involved in the increased vascular permeability seen in shock states. Furthermore, the lung has been identified as a site of significant SDC-1 shedding. Here we aim to characterize the contribution of endotheliopathy caused by inhalation alone in a swine model. When comparing injured animals, the fold change of circulating SDC-1 levels from preinjury was significantly higher at 2, 4, and 6 hours postinjury (P = .0045, P = .0017, and P &lt; .001, respectively). When comparing control animals, the fold change of SDC-1 from preinjury was not significant at any timepoint. When comparing injured animals versus controls, the fold change of SDC-1 injured animals was significantly greater at 2, 4, 6, and 18 hours (P = .004, P = .03, P &lt; .001, and P = .03, respectively). Histological sections showed higher lung injury severity compared to control uninjured lungs (0.56 vs 0.38, P &lt; .001). This novel animal model shows significant increases in SDC-1 levels that provide evidence for the connection between smoke inhalation injury and endothelial injury. Further understanding of the mechanisms underlying inhalation injury and its contribution to shock physiology may aid in development of early, more targeted therapies.
Using ChatGPT to evaluate cancer myths and misconceptions: artificial intelligence and cancer information
Authors: Johnson Skyler B , King Andy J , Warner Echo L , Aneja Sanjay , Kann Benjamin H , Bylund Carma L 
Published: March 2023

AbstractData about the quality of cancer information that chatbots and other artificial intelligence systems provide are limited. Here, we evaluate the accuracy of cancer information on ChatGPT compared with the National Cancer Institute’s (NCI’s) answers by using the questions on the “Common Cancer Myths and Misconceptions” web page. The NCI’s answers and ChatGPT answers to each question were blinded, and then evaluated for accuracy (accurate: yes vs no). Ratings were evaluated independently for each question, and then compared between the blinded NCI and ChatGPT answers. Additionally, word count and Flesch-Kincaid readability grade level for each individual response were evaluated. Following expert review, the percentage of overall agreement for accuracy was 100% for NCI answers and 96.9% for ChatGPT outputs for questions 1 through 13 (ĸ = ‒0.03, standard error = 0.08). There were few noticeable differences in the number of words or the readability of the answers from NCI or ChatGPT. Overall, the results suggest that ChatGPT provides accurate information about common cancer myths and misconceptions.
Radiofrequency thermocoagulation of haemorrhoids: learning curve of a novel approach
Authors: Butnari Valentin , Mansuri Ahmer , Kaul Sandeep , Shatkar Veeranna , Boulton Richard 
Published: March 2023

AbstractHaemorrhoidal disease (HD) is a common condition that often requires surgical treatment. In comparison with other traditional techniques, radiofrequency thermocoagulation (RFTC) has multiple advantages to traditional repairs and can be a good alternative in surgical management of HD. We retrospectively analysed 20 patients with Grades 2 (n = 6, 30%) and 3 (n = 12, 70%) haemorrhoids undergoing RFTC from 1 September 2019 to 31 December 2021. Outcomes including post-operative (PO) pain, immediate/late PO complications, recurrence and patient satisfaction were assessed. Twenty cases were included in this case series. All pathological symptoms showed significant improvement in PO period. Eight complications were noted, including minor bleeding (n = 2), bleeding that required admissions (n = 3), pain (n = 2) and recurrence (n = 1). The mean time off work is 7 days and all patients were satisfied or very satisfied PO as per telephone questionnaire. RFTC is a safe and effective solution in the management of HD and is a good alternative to conventional procedures.
Time-consciousness in computational phenomenology: a temporal analysis of active inference
Authors: Bogotá Juan Diego , Djebbara Zakaria 
Published: March 2023

AbstractTime plays a significant role in science and everyday life. Despite being experienced as a continuous flow, computational models of consciousness are typically restricted to a sequential temporal structure. This difference poses a serious challenge for computational phenomenology—a novel field combining phenomenology and computational modelling. By analysing the temporal structure of the active inference framework, we show that an integrated continuity of time can be achieved by merging Husserlian temporality with a sequential order of time. We also show that a Markov blanket of the present moment integrates past and future moments of both subjective temporality and objective time in an asynchronous manner. By applying the integrated continuity, it is clear that active inference makes use of both subjective temporality and objective time in an integrated fashion. We conclude that active inference, on a temporal note, qualifies as a computational model for phenomenological investigations.
Silencing of STE20-type kinase TAOK1 confers protection against hepatocellular lipotoxicity through metabolic rewiring
Authors: Xia Ying , Andersson Emma , Anand Sumit K. , Cansby Emmelie , Caputo Mara , Kumari Sima , Porosk Rando , Kilk Kalle , Nair Syam , Marschall Hanns-Ulrich , Blüher Matthias , Mahlapuu Margit 
Published: March 2023

Background:
NAFLD has become the leading cause of chronic liver disease worldwide afflicting about one quarter of the adult population. NASH is a severe subtype of NAFLD, which in addition to hepatic steatosis connotes liver inflammation and hepatocyte ballooning. In light of the exponentially increasing prevalence of NAFLD, it is imperative to gain a better understanding of its molecular pathogenesis. The aim of this study was to examine the potential role of STE20-type kinase TAOK1 —a hepatocellular lipid droplet-associated protein—in the regulation of liver lipotoxicity and NAFLD etiology.

Methods:
The correlation between TAOK1 mRNA expression in liver biopsies and the severity of NAFLD was evaluated in a cohort of 62 participants. Immunofluorescence microscopy was applied to describe the subcellular localization of TAOK1 in human and mouse hepatocytes. Metabolic reprogramming and oxidative/endoplasmic reticulum stress were investigated in immortalized human hepatocytes, where TAOK1 was overexpressed or silenced by small interfering RNA, using functional assays, immunofluorescence microscopy, and colorimetric analysis. Migration, invasion, and epithelial-mesenchymal transition were examined in TAOK1-deficient human hepatoma-derived cells. Alterations in hepatocellular metabolic and pro-oncogenic signaling pathways were assessed by immunoblotting.

Results:
We observed a positive correlation between the TAOK1 mRNA abundance in human liver biopsies and key hallmarks of NAFLD (i.e., hepatic steatosis, inflammation, and ballooning). Furthermore, we found that TAOK1 protein fully colocalized with intracellular lipid droplets in human and mouse hepatocytes. The silencing of TAOK1 alleviated lipotoxicity in cultured human hepatocytes by accelerating lipid catabolism (mitochondrial β-oxidation and triacylglycerol secretion), suppressing lipid anabolism (fatty acid influx and lipogenesis), and mitigating oxidative/endoplasmic reticulum stress, and the opposite changes were detected in TAOK1-overexpressing cells. We also found decreased proliferative, migratory, and invasive capacity, as well as lower epithelial-mesenchymal transition in TAOK1-deficient human hepatoma-derived cells. Mechanistic studies revealed that TAOK1 knockdown inhibited ERK and JNK activation and repressed acetyl-CoA carboxylase (ACC) protein abundance in human hepatocytes.

Conclusions:
Together, we provide the first experimental evidence supporting the role of hepatic lipid droplet-decorating kinase TAOK1 in NAFLD development through mediating fatty acid partitioning between anabolic and catabolic pathways, regulating oxidative/endoplasmic reticulum stress, and modulating metabolic and pro-oncogenic signaling.
P2X7-NLRP3-Caspase-1 signaling mediates activity-induced muscle pain in male but not female mice
Authors: Hayashi Kazuhiro , Lesnak Joseph B. , Plumb Ashley N. , Rasmussen Lynn A. , Sluka Kathleen A. 
Published: March 2023

Abstract
We developed an animal model of activity-induced muscle pain that is dependent on local macrophage activation and release of interleukin-1β (IL-1β). Activation of purinergic type 2X (P2X) 7 receptors recruits the NOD-like receptor protein (NLRP) 3 and activates Caspase-1 to release IL-1β. We hypothesized that pharmacological blockade of P2X7, NLRP3, and Caspase-1 would prevent development of activity-induced muscle pain in vivo and release of IL-1β from macrophages in vitro. The decrease in muscle withdrawal thresholds in male, but not female, mice was prevented by the administration of P2X7, NLRP3, and Caspase-1 inhibitors before induction of the model, whereas blockade of IL-1β before induction prevented muscle hyperalgesia in both male and female mice. Blockade of P2X7, NLRP3, Capsase-1, or IL-1β 24 hours, but not 1 week, after induction of the model alleviated muscle hyperalgesia in male, but not female, mice. mRNA expression of P2X7, NLRP3, Caspase-1, and IL-1β from muscle was increased 24 hours after induction of the model in both male and female mice. Using multiplex, increases in IL-1β induced by combining adenosine triphosphate with pH 6.5 in lipopolysaccharide-primed male and female macrophages were significantly lower with the presence of inhibitors of P2X7 (A740003), NLRP3 (MCC950), and Caspase-1 (Z-WEHD-FMK) when compared with the vehicle. The current data suggest the P2X7/NLRP3/Caspase-1 pathway contributed to activity-induced muscle pain initiation and early maintenance phases in male but not female, and not in late maintenance phases in male mice.
Shoutai pills for threatened abortion: A protocol for systematic review and meta-analysis
Authors: Song Chuangxiu , Zhang Shan , Gao Xiaojing , Zhang Haidi , Zuo Songbo , Qin Yuxuan , Bi Xiaotao , Chen Huijuan 
Published: March 2023

Background:
Threatened abortions are a serious health risk for women. Deferiprone tablets are commonly used in the treatment of clinical delivery. Traditional Chinese medicine, a characteristic medical system inherited for thousands of years, often applies Shoutai pills in the treatment of Threatened abortion and has achieved good results. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Shoutai pills combined with dedrogesterone tablets for the treatment of early preterm abortion.

Methods:
Electronic searches of clinical randomized controlled trials in PubMed, Web of Science, MEDLINE, EMBASE, China National Knowledge Infrastructure, Wanfang database, and China Scientific Journal Database (VIP) were conducted. References to the included literature, gray literature in Open Grey, and other relevant literature such as clinical studies registered in ClinicalTrials.gov, were also manually searched. Relevant data were extracted, and a meta-analysis was performed using Reviewer Manager 5.4.

Results:
The results of this study will be submitted to peer-reviewed journals.

Conclusion:
This study provides high-quality evidence on the efficacy and safety of Shoutai pills in combination with dedrogesterone tablets for the treatment of preterm abortion.