bluuebunny/crossref_metadata_2025_split huggingface dataset:
Thrombospondin 1 enhances systemic inflammation and disease severity in acute-on-chronic liver failure
Authors: Hassan Hozeifa Mohamed , Liang Xi , Xin Jiaojiao , Lu Yingyan , Cai Qun , Shi Dongyan , Ren Keke , Li Jun , Chen Qi , Li Jiang , Li Peng , Guo Beibei , Yang Hui , Luo Jinjin , Yao Heng , Zhou Xingping , Hu Wen , Jiang Jing , Li Jun 
Published: March 2024

Abstract
Background
The key role of thrombospondin 1 (THBS1) in the pathogenesis of acute-on-chronic liver failure (ACLF) is unclear. Here, we present a transcriptome approach to evaluate THBS1 as a potential biomarker in ACLF disease pathogenesis.

Methods
Biobanked peripheral blood mononuclear cells (PBMCs) from 330 subjects with hepatitis B virus (HBV)-related etiologies, including HBV-ACLF, liver cirrhosis (LC), and chronic hepatitis B (CHB), and normal controls (NC) randomly selected from the Chinese Group on the Study of Severe Hepatitis B (COSSH) prospective multicenter cohort underwent transcriptome analyses (ACLF = 20; LC = 10; CHB = 10; NC = 15); the findings were externally validated in participants from COSSH cohort, an ACLF rat model and hepatocyte-specific THBS1 knockout mice.

Results
THBS1 was the top significantly differentially expressed gene in the PBMC transcriptome, with the most significant upregulation in ACLF, and quantitative polymerase chain reaction (ACLF = 110; LC = 60; CHB = 60; NC = 45) was used to verify that THBS1 expression corresponded to ACLF disease severity outcome, including inflammation and hepatocellular apoptosis. THBS1 showed good predictive ability for ACLF short-term mortality, with an area under the receiver operating characteristic curve (AUROC) of 0.8438 and 0.7778 at 28 and 90 days, respectively. Enzyme-linked immunosorbent assay validation of the plasma THBS1 using an expanded COSSH cohort subjects (ACLF = 198; LC = 50; CHB = 50; NC = 50) showed significant correlation between THBS1 with ALT and γ-GT (P = 0.01), and offered a similarly good prognostication predictive ability (AUROC = 0.7445 and 0.7175) at 28 and 90 days, respectively. ACLF patients with high-risk short-term mortality were identified based on plasma THBS1 optimal cut-off value (< 28 µg/ml). External validation in ACLF rat serum and livers confirmed the functional association between THBS1, the immune response and hepatocellular apoptosis. Hepatocyte-specific THBS1 knockout improved mouse survival, significantly repressed major inflammatory cytokines, enhanced the expression of several anti-inflammatory mediators and impeded hepatocellular apoptosis.

Conclusions
THBS1 might be an ACLF disease development-related biomarker, promoting inflammatory responses and hepatocellular apoptosis, that could provide clinicians with a new molecular target for improving diagnostic and therapeutic strategies.

Graphical Abstract
Heterozygous truncating variant of TAOK1 in a boy with periventricular nodular heterotopia: a case report and literature review of TAOK1-related neurodevelopmental disorders
Authors: Cavalli Anna , Caraffi Stefano Giuseppe , Rizzi Susanna , Trimarchi Gabriele , Napoli Manuela , Frattini Daniele , Spagnoli Carlotta , Garavelli Livia , Fusco Carlo 
Published: March 2024

Abstract
Background
Thousand and one amino-acid kinase 1 (TAOK1) encodes the MAP3K protein kinase TAO1, which has recently been displayed to be essential for neuronal maturation and cortical differentiation during early brain development. Heterozygous variants in TAOK1 have been reported in children with neurodevelopmental disorders, with or without macrocephaly, hypotonia and mild dysmorphic traits. Literature reports lack evidence of neuronal migration disorders in TAOK1 patients, although studies in animal models suggest this possibility.

Case presentation
We provide a clinical description of a child with a neurodevelopmental disorder due to a novel TAOK1 truncating variant, whose brain magnetic resonance imaging displays periventricular nodular heterotopia.

Conclusions
To our knowledge, this is the first report of a neuronal migration disorder in a patient with a TAOK1-related neurodevelopmental disorder, thus supporting the hypothesized pathogenic mechanisms of TAOK1 defects.
The influence of transformations in supply on methamphetamine initiation among people injecting opioids in the United States
Authors: Mars Sarah , Ondocsin Jeff , Holm Nicole , Ciccarone Daniel 
Published: March 2024

Abstract
Background
Co-use of methamphetamine (MA) and opioids (pharmaceutical pills, heroin and fentanyls) has increased in the United States and is represented in rising mortality. Although coinciding with the import of low cost, high potency and purity methamphetamine, the relationship between supply and demand in propelling this polydrug use is not well understood. We consider the influence of macro changes in supply on the uptake of opioid and methamphetamine co-use by injection at the level of individual drug and injection initiation in West Virginia, a state which leads the US in drug overdose mortality.

Method
We recruited n = 30 people for semi-structured interviews who self-reported injecting heroin/fentanyl and using methamphetamine by any route at a West Virginia syringe service program and through snowball sampling. Interviews were recorded and transcripts analyzed using a thematic approach. Ethnographic observation was also conducted and recorded in fieldnotes. Sequence of substance and mode of use initiation and use trajectories for opioids and stimulants were charted for each participant.

Results
A clear pattern of individual drug initiation emerged that matched each successive supply wave of the US overdose epidemic: 25 participants had initiated opioid use with pills, followed by heroin, often mixed with/replaced by fentanyl, and subsequently added methamphetamine use. For participants, the supply and consumption of opioid analgesics had set in motion a series of steps leading to the addition of stimulant injection to existing opioid injecting repertoires. Unlike other studies that have found a birth cohort effect in patterns of initiation, participants showed the same sequence across age groups. Considerations of economy, availability, dependence, tolerance and the erosion of taboos that marked transitions from opioid pills to heroin injection influenced these subsequent trajectories in novel ways. The form, timing and extent of opioid and stimulant consumption was influenced by four stages of the changing drug supply, which in turn reflected back on demand.

Conclusion
Transformations in the social meaning and supply of methamphetamine enabled these transitions while other desired, non-injectable drugs were difficult to obtain. We discuss policy implications of injectable drugs’ market dominance at this location and possible interventions.
Assessment of artificial intelligence model and manual morphokinetic annotation system as embryo grading methods for successful live birth prediction: a retrospective monocentric study
Authors: Papamentzelopoulou Myrto-Sotiria , Prifti Ilectra-Niki , Mavrogianni Despoina , Tseva Thomais , Soyhan Ntilay , Athanasiou Aikaterini , Athanasiou Antonia , Athanasiou Adamantios , Vogiatzi Paraskevi , Konomos George , Loutradis Dimitrios , Sakellariou Maria 
Published: March 2024

Abstract
Purpose
The introduction of the time-lapse monitoring system (TMS) and the development of predictive algorithms could contribute to the optimal embryos selection for transfer. Therefore, the present study aims at investigating the efficiency of KIDScore and iDAScore systems for blastocyst stage embryos in predicting live birth events.

Methods
The present retrospective study was conducted in a private IVF Unit setting throughout a 10-month period from October 2021 to July 2022, and included the analysis of 429 embryos deriving from 91 IVF/ICSI cycles conducted due to infertility of various etiologies. Embryos incubated at the Embryoscope+ timelapse incubator were analyzed through the established scoring systems: KIDScore and iDAScore®. The main outcome measure was the comparison of the two scoring systems in terms of live birth prediction. Embryos with the higher scores at day 5 (KID5 score/iDA5 score) were transferred or cryopreserved for later use.

Results
Embryos with high KID5 and iDA5 scores positively correlated with the probability of successful live birth, with KID5 score yielding a higher efficiency in predicting a successful reproductive outcome compared to a proportionally high iDA5 score. KID5 demonstrated conservative performance in successfully predicting live birth compared to iDA5 score, indicating that an efficient prediction can be either provided by a relatively lower KID5 score or a relatively higher iDA5 score.

Conclusion
The developed artificial intelligence tools should be implemented in clinical practice in conjunction with the conventional morphological assessment for the conduction of optimized embryo transfer in terms of a successful live birth.
MORN2 regulates the morphology and energy metabolism of mitochondria and is required for male fertility in mice
Authors: Liu Yining , Li Tongtong , Shi Mingze , Wan Yanling , Li Hanzhen , Zhang Mingyu , Wang Ziqi , Wang Shiyu , Lv Yue , Lu Gang , Liu Hongbin , Zhang Haobo , Huang Tao 
Published: March 2024

Abstract
Background
Mitochondria produce adenosine triphosphate through respiratory activities to power sperm differentiation and motility, and decreased mitochondrial respiratory activity can result in poor sperm motility and asthenospermia. The mitochondrial sheath is a component of the mid-piece of the sperm flagellum, and dysfunction of the sheath can reduce sperm motility and cause male infertility. The membrane occupation and recognition nexus-motif protein 2 (MORN2) is testis enriched in mice, and the MORN motif was reported to play a role in the regulation of bioelectrical signal homeostasis in cardiomyocytes.

Methods
We generated Morn2–/– mice using CRISPR/Cas9 and evaluated the potential functions of MORN2 in spermiogenesis through histological analysis, fertility examination, RT-PCR, CASA, immunofluorescence, TUNEL, electron microscopy analysis, mitochondrial energy metabolism analysis, etc.

Results
The Morn2–/– mice were infertile, and their sperm showed severe motility defects. Morn2–/– sperm also had abnormal morphology characterized by bent heads, aberrant mitochondrial sheath formation, lower mitochondrial membrane potential, higher levels of reactive oxygen species, and decreased mitochondrial respiratory activity.

Conclusions
Our study demonstrates that MORN2 is essential for male fertility and indicates that MORN2 functions in mitochondrial sheath formation and regulates mitochondrial respiratory activity.
Meta-analysis of trigger timing in normal responders undergoing GnRH antagonist ovarian hyperstimulation protocol
Authors: Xie Qijun , Ni Danyu , Chen Sisi , Zhang Wenjie , Wang Jue , Ling Xiufeng , Shen Rong 
Published: March 2024

Abstract
Importance
The first meta-analysis focused only on gonadotropin-releasing hormone (GnRH) antagonists, which helped determine the effect of delay trigger on pregnancy outcomes.

Objective
To evaluate the impact of delay trigger compared with standard trigger in normal responders undergoing GnRH antagonist protocol in improving pregnancy outcomes.

Methods
Studies published before April 2023 in PubMed, EMBASE, Cochrane Library, Web of Science, CNKI, Wanfang, VIP and CBM databases were searched. Randomized controlled trials (RCTs) and cohort studies conducted in normal responders reporting the efficacy of delay trigger using GnRH antagonist protocol were included. Data were combined to calculate mean differences (MD) for continuous variables and odd ratios (OR) for categorical variables with their corresponding 95% confidence intervals (CIs). Heterogeneity was assessed using Cochran’s Q test.

Results
Endpoints, including clinical pregnancy rate (CPR), live birth rate (LBR), the number of oocyte retrievals and embryos, and fertilization rate, were analyzed. Six (6) clinical studies (4 RCTs and 2 cohort studies) with 1,360 subjects were included. The pooled results showed that the number of oocyte retrievals (MD: 1.20, 95% CI: 1.10, 1.30, p < 0.01), fertilization rate (MD: 0.64, 95% CI: 0.29, 0.99, p < 0.01) and days of stimulation (MD: 0.95; 95% CI: 0.54, 1.37; p < 0.01) in the delay trigger group was significantly higher than that in the standard trigger group. However, there was no significant difference in the number of embryos (MD: 0.19, 95% CI: -0.29, 0.67, p = 0.44), CPR (OR: 1.12; 95% CI: 0.72, 1.75; p = 0.062), and LBR (OR: 1.23; 95% CI: 0.90, 1.66; p = 0.19) between the two trigger groups.

Conclusion
Delaying trigger time in GnRH antagonist protocol increased the number of oocytes retrieved but not the number of embryos. Furthermore, delay trigger shot was not associated with a clinical benefit towards CPR and LBR in women who underwent fresh embryo transfer cycles.

Trial registration
The International Prospective Register of Systematic Reviews (PROSPERO), registration number: CRD42023413217.
Mesonephric-like adenocarcinoma of the ovary
Authors: Yang Yun , Zhao Mengru , Jia Qiuchen , Tang Huimin , Xing Tingwei , Li Yang , Tang Bin , Xu Lin , Wei Weiwei , Zheng Hong , Shi Ruxia , Xia Bairong , Chen Jiming 
Published: March 2024

AbstractMesonephric-like adenocarcinoma is a new class of rare subtypes of the female reproductive system. Its clinical symptoms are similar to other types of ovarian tumors. The diagnosis is based on pathological and immunohistochemical methods. The main treatment option is surgery combined with chemotherapy. Few cases have been reported at home and abroad. We reported a case of a 45-year-old woman with a cystic solid mass in the left adnexa. The postoperative pathological diagnosis was mesonephric-like adenocarcinoma of the left ovary and mature cystic teratoma (partial infiltration of the small intestine). This case had no specific clinical symptoms. Immunohistochemical findings showed positive results of GATA3, TTF1, CD10, ER, and PR. Paclitaxel and carboplatin chemotherapy were given after the operation. Currently, no specific criteria are available for diagnosis and treatment of the disease. This article aims to improve the understanding of clinicians in this disease and create a basis for clinical diagnosis and treatment.
Urinary prostanoids are elevated by anti-TNF and anti-IL6 receptor disease-modifying antirheumatic drugs but are not predictive of response to treatment in early rheumatoid arthritis
Authors: Liu Jianyang , Idborg Helena , Korotkova Marina , Lend Kristina , van Vollenhoven Ronald , Lampa Jon , Rudin Anna , Nordström Dan , Gudbjornsson Bjorn , Gröndal Gerdur , Uhlig Till , Hørslev-Petersen Kim , Lund Hetland Merete , Østergaard Mikkel , Nurmohamed Michael , Jakobsson Per-Johan 
Published: March 2024

Abstract
Background
Disease-modifying antirheumatic drugs (DMARDs) are widely used for treating rheumatoid arthritis (RA). However, there are no established biomarkers to predict a patient’s response to these therapies. Prostanoids, encompassing prostaglandins, prostacyclins, and thromboxanes, are potent lipid mediators implicated in RA progression. Nevertheless, the influence of DMARDs on prostanoid biosynthesis in RA patients remains poorly understood. This study aims to assess the impact of various DMARDs on urinary prostanoids levels and to explore whether urinary prostanoid profiles correlate with disease activity or response to therapy.

Methods
This study included 152 Swedish female patients with early RA, all rheumatoid factor (RF) positive, enrolled in the NORD-STAR trial (registration number: NCT01491815). Participants were randomized into four therapeutic regimes: methotrexate (MTX) combined with (i) prednisolone (arm ACT), (ii) TNF-α blocker certolizumab pegol (arm CZP), (iii) CTLA-4Ig abatacept (arm ABA), or (iv) IL-6R blocker tocilizumab (arm TCZ). Urine samples, collected before start of treatment and at 24 weeks post-treatment, were analyzed for tetranor-prostaglandin E metabolite (tPGEM), tetranor-prostaglandin D metabolite (tPGDM), 2,3-dinor thromboxane B2 (TXBM), 2,3-dinor-6-keto prostaglandin F1a (PGIM), leukotriene E4 (LTE4) and 12-hydroxyeicosatetraenoic acid (12-HETE) using liquid chromatography–mass spectrometry (LC–MS). Generalized estimating equation (GEE) models were used to analyze the change in urinary eicosanoids and their correlations to clinical outcomes.

Results
Patients receiving MTX combined with CZP or TCZ exhibited significant elevations in urinary tPGEM and TXBM levels after 24 weeks of treatment. Other eicosanoids did not show significant alterations in response to any treatment. Baseline urinary eicosanoid levels did not correlate with baseline clinical disease activity index (CDAI) levels, nor with changes in CDAI from baseline to week 24. Their levels were also similar between patients who achieved CDAI remission and those with active disease at week 24.

Conclusions
Treatment with anti-TNF or anti-IL6R agents in early RA patients leads to an increased systemic production of proinflammatory and prothrombotic prostanoids. However, urinary eicosanoid levels do not appear to be predictive of the response to DMARDs therapy.
Eosinophilic gastritis and gluten-sensitive enteropathy manifested as hypoproteinemia and treated with omalizumab: a case report
Authors: Du Zhirong , Wang Zixi , Zhou Weixun , Yin Jia , Zhi Yuxiang 
Published: March 2024

Abstract
Background
Eosinophilic gastritis (EoG) has rarely been reported in conjunction with gluten-sensitive enteropathy (GSE). When this does occur, patients typically present with gastrointestinal symptoms. To our knowledge, hypoproteinemia has not been reported as the primary manifestation. Anti-IgE therapy, such as omalizumab, lowers eosinophil counts in the blood, lungs, and gut. Its efficiency in treating active EoG remain unknown.

Case presentation
We report a 33-month-old boy with a history of food allergy and atopic dermatitis who developed recurrent edema, hypoproteinemia, and eosinophilia at the age of 14 months. The diagnoses of EoG and GSE were confirmed based on the clinical presentation and results of gastrointestinal biopsies and serological testing. Although prednisone and dietary intervention were initially effective, the boy developed prednisone-related facial swelling. After stopping prednisone, his symptoms relapsed. Subsequent treatment with omalizumab, combined with dietary intervention, showed good efficacy and safety.

Conclusions
To our knowledge, this is the first case of concurrent EoG and GSE that presented primarily with hypoproteinemia. We highlight the rare manifestations of these two diseases to raise clinical suspicion and prevent missed and delayed diagnoses. The pathogenesis of EoG is heterogeneous and complex. Omalizumab showed good efficacy, indicating that IgE-mediated processes may be involved in the pathogenesis of this patient’s diseases.
Digital skull anatomy of the Oligocene North American tortoise Stylemys nebrascensis with taxonomic comments on the species and comparisons with extant testudinids of the Gopherus–Manouria clade
Authors: Evers Serjoscha W. , Al Iawati Zahra 
Published: March 2024

AbstractThe anatomy of North American tortoises is poorly understood, despite a rich fossil record from the Eocene and younger strata. Stylemys nebrascensis is a particularly noteworthy turtle in this regard, as hundreds of specimens are known from Oligocene deposits, and as this species is one of the earliest fossil turtles to have been described in the scientific literature. Since its initial description based on a shell, many specimens with more complete material have been referred to Stylemys nebrascensis. Here, we review and confirm the referral of an important historic specimen to Stylemys nebrascensis, which includes shell, non-shell postcranial, and skull material. This allows us to document unique skull features of Stylemys nebrascensis (e.g., an unusual ‘poststapedial canal’ that connects the posterior skull surface with the cavum acustico-jugulare) and to refer another well-preserved skull to the species. Based on computed-tomography scanning of these two skulls, we provide a detailed description of the cranial and mandibular osteology of Stylemys nebrascensis. Stylemys nebrascensis has a combination of plesiomorphic skull characteristics (e.g., retention of a medial jugal process) and derived traits shared with extant gopher tortoises (e.g., median premaxillary ridge) that suggest it may be a stem-representative of the gopher tortoise lineage. This supports the hypothesis that extant and fossil tortoises from North America form a geographically restricted clade that split from Asian relatives during the Paleogene.
Low-cost and high-performance abnormal trajectory detection based on the GRU model with deep spatiotemporal sequence analysis in cloud computing
Authors: Tang Guohao , Zhao Huaying , Yu Baohua 
Published: March 2024

AbstractTrajectory anomalies serve as early indicators of potential issues and frequently provide valuable insights into event occurrence. Existing methods for detecting abnormal trajectories primarily focus on comparing the spatial characteristics of the trajectories. However, they fail to capture the temporal dimension’s pattern and evolution within the trajectory data, thereby inadequately identifying the behavioral inertia of the target group. A few detection methods that incorporate spatiotemporal features have also failed to adequately analyze the spatiotemporal sequence evolution information; consequently, detection methods that ignore temporal and spatial correlations are too one-sided. Recurrent neural networks (RNNs), especially gate recurrent unit (GRU) that design reset and update gate control units, process nonlinear sequence processing capabilities, enabling effective extraction and analysis of both temporal and spatial characteristics. However, the basic GRU network model has limited expressive power and may not be able to adequately capture complex sequence patterns and semantic information. To address the above issues, an abnormal trajectory detection method based on the improved GRU model is proposed in cloud computing in this paper. To enhance the anomaly detection ability and training efficiency of relevant models, strictly control the input of irrelevant features and improve the model fitting effect, an improved model combining the random forest algorithm and fully connected layer network is designed. The method deconstructs spatiotemporal semantics through reset and update gated units, while effectively capturing feature evolution information and target behavioral inertia by leveraging the integration of features and nonlinear mapping capabilities of the fully connected layer network. The experimental results based on the GeoLife GPS trajectory dataset indicate that the proposed approach improves both generalization ability by 1% and reduces training cost by 31.68%. This success do provides a practical solution for the task of anomaly trajectory detection.