bluuebunny/crossref_metadata_2025_split huggingface dataset:
Case Report: Identification of Two Variants of ALG13 in Families With or Without Seizure and Binocular Strabismus: Phenotypic Spectrum Analysis
Authors: Cai Tao , Huang Jieting , Ma Xiuwei , Hu Siqi , Zhu Lina , Zhu Jinwen , Feng Zhichun 
Published: July 2022

Background: Genetic causes in most affected children with intellectual disability and/or development delay remain unknown.Methods: To identify potential variants responsible for these disorders, we recruited 161 affected families and performed whole-exome sequencing and associated bioinformatics analysis.Results: In the present study, we report the identification of variants in the ALG13 gene in two of the families. In family 1, a known pathogenic missense variant (c.23T &gt; C; p.V8A) of ALG13 was identified in a boy and his mother. In family 2, a novel missense variant (c.862C &gt; G; p.L288V) of the same gene was identified in the affected boy and his phenotypically normal mother. Genotype–phenotype correlation analysis by comparing reported 28 different variants (HGMD) showed that three major phenotypes, including various seizures/epilepsy, intellectual disability, and development delay (such as growth, speech, motor, etc.), are present in most affected individuals. However, other phenotypes, such as strabismus and absence of seizure in our second patient, are not reported if any, which may represent a unique case of X-linked recessive nonsyndromic disorder caused by a mutation in ALG13.Conclusion: We identified two missense variants in ALG13 in a cohort of 161 families with affected individuals diagnosed as intellectual disability and/or development delay. A novel c.862C &gt; G mutation may represent a case of X-linked recessive.
A Novel Necroptosis-Related Gene Signature in Skin Cutaneous Melanoma Prognosis and Tumor Microenvironment
Authors: Song Binyu , Wu Pingfan , Liang Zhen , Wang Jianzhang , Zheng Yu , Wang Yuanyong , Chi Hao , Li Zichao , Song Yajuan , Yin Xisheng , Yu Zhou , Song Baoqiang 
Published: July 2022

Background: Necroptosis has been identified recently as a newly recognized programmed cell death that has an impact on tumor progression and prognosis, although the necroptosis-related gene (NRGs) potential prognostic value in skin cutaneous melanoma (SKCM) has not been identified. The aim of this study was to construct a prognostic model of SKCM through NRGs in order to help SKCM patients obtain precise clinical treatment strategies.Methods: RNA sequencing data collected from The Cancer Genome Atlas (TCGA) were used to identify differentially expressed and prognostic NRGs in SKCM. Depending on 10 NRGs via the univariate Cox regression analysis usage and LASSO algorithm, the prognostic risk model had been built. It was further validated by the Gene Expression Omnibus (GEO) database. The prognostic model performance had been assessed using receiver operating characteristic (ROC) curves. We evaluated the predictive power of the prognostic model for tumor microenvironment (TME) and immunotherapy response.Results: We constructed a prognostic model based on 10 NRGs (FASLG, TLR3, ZBP1, TNFRSF1B, USP22, PLK1, GATA3, EGFR, TARDBP, and TNFRSF21) and classified patients into two high- and low-risk groups based on risk scores. The risk score was considered a predictive factor in the two risk groups regarding the Cox regression analysis. A predictive nomogram had been built for providing a more beneficial prognostic indicator for the clinic. Functional enrichment analysis showed significant enrichment of immune-related signaling pathways, a higher degree of immune cell infiltration in the low-risk group than in the high-risk group, a negative correlation between risk scores and most immune checkpoint inhibitors (ICIs), anticancer immunity steps, and a more sensitive response to immunotherapy in the low-risk group.Conclusions: This risk score signature could be applied to assess the prognosis and classify low- and high-risk SKCM patients and help make the immunotherapeutic strategy decision.
Integrated Full-Length Transcriptome and MicroRNA Sequencing Approaches Provide Insights Into Salt Tolerance in Mangrove (Sonneratia apetala Buch.-Ham.)
Authors: Chen Beibei , Ding Zeyi , Zhou Xiang , Wang Yue , Huang Fei , Sun Jiaxin , Chen Jinhui , Han Weidong 
Published: July 2022

MicroRNAs (miRNAs) are small RNA molecules that serve as key players in plant stress responses. Although stress-regulated miRNAs have been explored in various plants, they are not well studied in mangroves. Herein, we combined PacBio isoform sequencing (Iso-Seq) with BGISEQ short-read RNA-seq to probe the role of miRNAs in the salt stress response of the mangrove plant, Sonneratia apetala Buch.-Ham. A total of 1,702,463 circular consensus sequencing reads were generated that produced 295,501 nonredundant full-length transcripts from the leaves of a 1-year-old S. apetala. After sequencing nine small RNA libraries constructed from control and 1- and 28-day 300 mM NaCl treatments, we identified 143 miRNAs (114 known and 29 novel) from a total of &gt;261 million short reads. With the criteria of |log2FC| ≥ 1 and q-value &lt; 0.05, 42 and 70 miRNAs were differentially accumulated after 1- and 28-day salt treatments, respectively. These differential accumulated miRNAs potentially targeted salt-responsive genes encoding transcription factors, ion homeostasis, osmotic protection, and detoxificant-related proteins, reminiscent of their responsibility for salinity adaptation in S. apetala. Particularly, 62 miRNAs were Sonneratia specific under salt stress, of which 34 were co-expressed with their 131 predicted targets, thus producing 140 miRNA–target interactions. Of these, 82 miRNA-target pairs exhibited negative correlations. Eighteen miRNA targets were categorized for the ‘environmental information processing’ during KEGG analysis and were related to plant hormone signal transduction (ko04075), MAPK signaling pathway–plant (ko04016), and ABC transporters (ko02010). These results underscored miRNAs as possible contributors to mangrove success in severe environments and offer insights into an miRNA-mediated regulatory mechanism of salt response in S. apetala.
Effect of Dysglycemia on Urinary Lipid Mediator Profiles in Persons With Pulmonary Tuberculosis
Authors: Arriaga María B. , Karim Farina , Queiroz Artur T.L. , Araújo-Pereira Mariana , Barreto-Duarte Beatriz , Sales Caio , Moosa Mahomed-Yunus S. , Mazibuko Matilda , Milne Ginger L. , Maruri Fernanda , Serezani Carlos Henrique , Koethe John R. , Figueiredo Marina C. , Kritski Afrânio L. , Cordeiro-Santos Marcelo , Rolla Valeria C. , Sterling Timothy R. , Leslie Alasdair , Andrade Bruno B. ,   the RePORT Brazil and South Africa consortia
Published: July 2022

BackgroundOxidized lipid mediators such as eicosanoids play a central role in the inflammatory response associated with tuberculosis (TB) pathogenesis. Diabetes mellitus (DM) leads to marked changes in lipid mediators in persons with TB. However, the associations between diabetes-related changes in lipid mediators and clearance of M. tuberculosis (Mtb) among persons on anti-TB treatment (ATT) are unknown. Quantification of urinary eicosanoid metabolites can provide insights into the circulating lipid mediators involved in Mtb immune responses.MethodsWe conducted a multi-site prospective observational study among adults with drug-sensitive pulmonary TB and controls without active TB; both groups had sub-groups with or without dysglycemia at baseline. Participants were enrolled from RePORT-Brazil (Salvador site) and RePORT-South Africa (Durban site) and stratified according to TB status and baseline glycated hemoglobin levels: a) TB-dysglycemia (n=69); b) TB-normoglycemia (n=64); c) non-TB/dysglycemia (n=31); d) non-TB/non-dysglycemia (n=29). We evaluated the following urinary eicosanoid metabolites: 11α-hydroxy-9,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (major urinary metabolite of prostaglandin E2, PGE-M), tetranor-PGE1 (metabolite of PGE2, TN-E), 9α-hydroxy-11,15-dioxo-2,3,4,5-tetranor-prostane-1,20-dioic acid (metabolite of PGD2, PGD-M), 11-dehydro-thromboxane B2 (11dTxB2), 2,3-dinor-6-keto-PGF1α (prostaglandin I metabolite, PGI-M), and leukotriene E4 (LTE4). Comparisons between the study groups were performed at three time points: before ATT and 2 and 6 months after initiating therapy.ResultsPGE-M and LTE4 values were consistently higher at all three time-points in the TB-dysglycemia group compared to the other groups (p&lt;0.001). In addition, there was a significant decrease in PGI-M and LTE4 levels from baseline to month 6 in the TB-dysglycemia and TB-normoglycemia groups. Finally, TB-dysglycemia was independently associated with increased concentrations of PGD-M, PGI-M, and LTE4 at baseline in a multivariable model adjusting for age, sex, BMI, and study site. These associations were not affected by HIV status.ConclusionThe urinary eicosanoid metabolite profile was associated with TB-dysglycemia before and during ATT. These observations can help identify the mechanisms involved in the pathogenesis of TB-dysglycemia, and potential biomarkers of TB treatment outcomes, including among persons with dysglycemia.
Cuproptosis-Related Risk Score Predicts Prognosis and Characterizes the Tumor Microenvironment in Hepatocellular Carcinoma
Authors: Zhang Zhen , Zeng Xiangyang , Wu Yinghua , Liu Yang , Zhang Xi , Song Zewen 
Published: July 2022

AimsCuproptosis is a recently identified form of programmed cell death; however, its role in hepatocellular carcinoma (HCC) remains unclear.MethodsA set of bioinformatic tools was integrated to analyze the expression and prognostic significance of ferredoxin 1 (FDX1), the key regulator of cuproptosis. A cuproptosis-related risk score (CRRS) was developed via correlation analyses, least absolute shrinkage and selection operator (LASSO) Cox regression, and multivariate Cox regression. The metabolic features, mutation signatures, and immune profile of CRRS-classified HCC patients were investigated, and the role of CRRS in therapy guidance was analyzed.ResultsFDX1 was significantly downregulated in HCC, and its high expression was associated with longer survival time. HCC patients in the high-CRRS group showed a significantly lower overall survival (OS) and enriched in cancer-related pathways. Mutation analyses revealed that the high-CRRS HCC patients had a high mutational frequency of some tumor suppressors such as tumor protein P53 (TP53) and Breast-cancer susceptibility gene 1 (BRCA1)-associated protein 1 (BAP1) and a low frequency of catenin beta 1 (CTNNB1). Besides, HCC patients with high CRRS showed an increase of protumor immune infiltrates and a high expression of immune checkpoints. Moreover, the area under the curve (AUC) values of CRRS in predicting the efficiency of sorafenib and the non-responsiveness to transcatheter arterial chemoembolization (TACE) in HCC patients reached 0.877 and 0.764, respectively.SignificanceThe cuproptosis-related signature is helpful in prognostic prediction and in guiding treatment for HCC patients.
Climate Change Will Fragment Florida Stone Crab Communities
Authors: Alaerts Lauranne , Dobbelaere Thomas , Gravinese Philip M. , Hanert Emmanuel 
Published: July 2022

Many marine species have been shown to be threatened by both ocean acidification and ocean warming which are reducing survival, altering behavior, and posing limits on physiology, especially during earlier life stages. The commercially important Florida stone crab, Menippe mercenaria, is one species that is affected by reduced seawater pH and elevated seawater temperatures. In this study, we determined the impacts of reduced pH and elevated temperature on the distribution of the stone crab larvae along the West Florida Shelf. To understand the dispersion of the larvae, we coupled the multi-scale ocean model SLIM with a larval dispersal model. We then conducted a connectivity study and evaluated the impacts of climate stressors by looking at four different scenarios which included models that represented the dispersion of stone crab larvae under: 1) present day conditions as modelled by SLIM for the temperature and NEMO-PISCES for the pH, 2) SSP1-2.6 scenario (-0.037 reduction in pH and +0.5°C compared to present-day conditions), 3) SSP2-4.5 scenario(-0.15 reduction in pH and +1.5°C) and 4) SSP5-8.5 scenario (-0.375 reduction in pH and +3.5°C). Our results show a clear impact of these climate change stressors on larval dispersal and on the subsequent stone crab distribution. Our results indicate that future climate change could result in stone crabs moving north or into deeper waters. We also observed an increase in the number of larvae settling in deeper waters (defined as the non-fishing zone in this study with depths exceeding 30 m) that are not typically part of the commercial fishing zone. The distance travelled by larvae, however, is likely to decrease, resulting in an increase of self-recruitment and decrease of the size of the sub-populations. A shift of the spawning period, to earlier in the spring, is also likely to occur. Our results suggest that habitats in the non-fishing zone cannot serve as a significant source of larvae for the habitats in the fishing zone (defined as water depth&lt; 30 m) since there is very little exchange (&lt; 5% of all exchanges) between the two zones. These results indicate that the stone crab populations in Florida may be susceptible to community fragmentation and that the management of the fishery should consider the potential impacts of future climate change scenarios.
Subcutaneous Enoxaparin for Systemic Anticoagulation of COVID-19 Patients During Extracorporeal Life Support
Authors: Wiegele Marion , Laxar Daniel , Schaden Eva , Baierl Andreas , Maleczek Mathias , Knöbl Paul , Hermann Martina , Hermann Alexander , Zauner Christian , Gratz Johannes 
Published: July 2022

BackgroundExtracorporeal membrane oxygenation, with an inherent requirement for anticoagulation to avoid circuit thrombosis, is a key element in the treatment of respiratory failure associated with COVID-19. Anticoagulation remains challenging, the standard of care being intravenous continuous administration of unfractionated heparin. Yet regimens vary. Some intensive care units in our center have successfully used enoxaparin subcutaneously in recent years and throughout the pandemic.MethodsWe retrospectively analyzed adult COVID-19 patients with respiratory failure who had been systemically anticoagulated using either enoxaparin or unfractionated heparin. The choice of anticoagulant therapy was based on the standard of the intensive care unit. Defined thromboembolic and hemorrhagic events were analyzed as study endpoints.ResultsOf 98 patients, 62 had received enoxaparin and 36 unfractionated heparin. All hazard ratios for the thromboembolic (3.43; 95% CI: 1.08–10.87; p = 0.04), hemorrhagic (2.58; 95% CI: 1.03–6.48; p = 0.04), and composite (2.86; 95% CI: 1.41–5.92; p = 0.007) endpoints favored enoxaparin, whose efficient administration was verified by peak levels of anti-factor Xa (median: 0.45 IU ml−1; IQR: 0.38; 0.56). Activated partial thromboplastin time as well as thrombin time differed significantly (both p&lt;0.001) between groups mirroring the effect of unfractionated heparin.ConclusionsThis study demonstrates the successful use of subcutaneous enoxaparin for systemic anticoagulation in patients with COVID-19 during extracorporeal membrane oxygenation. Our findings are to be confirmed by future prospective, randomized, controlled trials.
Diagnostic Utility of Non-invasive Tests for Inflammatory Bowel Disease: An Umbrella Review
Authors: Shi Jin-Tong , Zhang Yuexin , She Yuehan , Goyal Hemant , Wu Zhi-Qi , Xu Hua-Guo 
Published: July 2022

BackgroundThis study aims to consolidate evidence from published systematic reviews and meta-analyses evaluating the diagnostic performances of non-invasive tests for inflammatory bowel disease (IBD) in various clinical conditions and age groups.MethodsTwo independent reviewers systematically identified and appraised systematic reviews and meta-analyses assessing the diagnostic utility of non-invasive tests for IBD. Each association was categorized as adults, children, and mixed population, based on the age ranges of patients included in the primary studies. We classified clinical scenarios into diagnosis, activity assessment, and predicting recurrence.ResultsIn total, 106 assessments from 43 reviews were included, with 17 non-invasive tests. Fecal calprotectin (FC) and fecal lactoferrin (FL) were the most sensitive for distinguishing IBD from non-IBD. However, anti-neutrophil cytoplasmic antibodies (ANCA) and FL were the most specific for it. FC and FL were the most sensitive and specific tests, respectively, to distinguish IBD from irritable bowel syndrome (IBS). Anti-Saccharomyces cerevisiae antibodies (ASCA), IgA, were the best test to distinguish Crohn’s disease (CD) from ulcerative colitis (UC). Interferon-γ release assay was the best test to distinguish CD from intestinal tuberculosis (ITB). Ultrasound (US) and magnetic resonance enterography (MRE) were both sensitive and specific for disease activity, along with the high sensitivity of FC. Small intestine contrast ultrasonography (SICUS) had the highest sensitivity, and FC had the highest specificity for operative CD recurrence.ConclusionIn this umbrella review, we summarized the diagnostic performance of non-invasive tests for IBD in various clinical conditions and age groups. Clinicians can use the suggested non-invasive test depending on the appropriate clinical situation in IBD patients.
Course of Preexisting Migraine Following Spontaneous Subarachnoid Hemorrhage
Authors: Valdueza José Manuel , Dreier Jens Peter , Woitzik Johannes , Dohmen Christian , Sakowitz Oliver , Platz Johannes , Leistner-Glaess Stefanie , Witt Victoria Dorothea 
Published: July 2022

BackgroundOur objective was to observe the course of preexisting migraine following subarachnoid hemorrhage (SAH) in patients with and without craniotomy.MethodsWe designed an exploratory analysis and hypothesis-generating study of prospectively collected data starting by recruiting patients suffering from SAH with the Hunt and Hess scale score of ≤ 4. Out of 994 cases, we identified 46 patients with preexisting active migraine defined by at least four attacks in the year before SAH. According to the treatment, we subdivided the patients into two groups: the first group included patients with surgical aneurysm clipping with transection of the middle meningeal artery (MMA) and accompanying trigeminal nerve branches and the second group included patients with endovascular aneurysm coiling or without any interventional treatment. During the follow-up, we recorded the course of migraine frequency, duration, intensity, and character.ResultsFor both groups (craniotomy n = 31, without craniotomy n = 15), a significant improvement regarding the preexisting migraine during a mean follow-up of 46 months (min. 12 months, max. 114 months) was seen regarding complete remission or at least &gt;50% reduction in migraine attacks (p &lt; 0.001 and p = 0.01). On comparing the groups, this effect was significantly more pronounced in patients with craniotomy (for no recurrence of migraine: p = 0.049). After craniotomy, 77.4% of the patients had no further attacks of migraine headache and 19.4% showed a reduction of &gt;50% while only 2.2% did not report any relevant change. In the non-surgical group, 46.7% had no further migraine attacks, 20% had a reduction of &gt;50%, while no change was noted in 33.3%.ConclusionsOur study provides evidence that the dura mater might be related to migraine headaches and that transection of the MMA and accompanying trigeminal dural nerve branches might disrupt the pathway leading to a reduction of migraine attacks. However, coiling alone ameliorated migraine complaints.
The Role of Bioelectrical Impedance Analysis in Predicting COVID-19 Outcome
Authors: Stevanovic Djordje , Zdravkovic Vladimir , Poskurica Mina , Petrovic Marina , Cekerevac Ivan , Zdravkovic Nemanja , Mijailovic Sara , Todorovic Dusan , Divjak Ana , Bozic Dunja , Marinkovic Milos , Jestrovic Aleksandra , Azanjac Anja , Miloradovic Vladimir 
Published: July 2022

BackgroundPublished data regarding the impact of obesity on COVID-19 outcomes are inconsistent. However, in most studies, body composition was assessed using body mass index (BMI) alone, thus neglecting the presence and distribution of adipose tissue. Therefore, we aimed to investigate the impact of body and visceral fat on COVID-19 outcomes.MethodsObservational, prospective cohort study included 216 consecutive COVID-19 patients hospitalized at University Clinical Center Kragujevac (Serbia) from October to December 2021. Body composition was assessed using the BMI, body fat percentage (%BF), and visceral fat (VF) via bioelectrical impedance analysis (BIA). In addition to anthropometric measurements, variables in the research were socio-demographic and medical history data, as well as admission inflammatory biomarkers. Primary end-points were fatal outcomes and intensive care unit (ICU) admission.ResultsThe overall prevalence of obesity was 39.3% according to BMI and 50.9% according to % BF, while 38.4% of patients had very high VF levels. After adjusting odds ratio values for cofounding variables and obesity-related conditions, all three anthropometric parameters were significant predictors of primary end-points. However, we note that % BF and VF, compared to BMI, were stronger predictors of both mortality (aOR 3.353, aOR 3.05, and aOR 2.387, respectively) and ICU admission [adjusted odds ratio (aOR) 7.141, aOR 3.424, and aOR 3.133, respectively].ConclusionObesity is linked with COVID-19 mortality and ICU admission, with BIA measurements being stronger predictors of outcome compared to BMI use alone.
Deciphering Prognostic Value of TTN and Its Correlation With Immune Infiltration in Lung Adenocarcinoma
Authors: Chen Jianing , Wen Yaokai , Su Hang , Yu Xin , Hong Ruisheng , Chen Chang , Su Chunxia 
Published: July 2022

BackgroundLung adenocarcinoma (LUAD) is the most common type of lung cancer, accounting for around 40%. Despite achievements in the treatment approach, the prognosis is still dismal, with overall survival of fewer than five years. Thus, novel prognostic biomarkers are needed to predict the clinical outcomes of individual patients better. TTN has a high mutation rate in the LUAD, which encodes a large abundant protein of striated muscle. However, the value of TTN in prognosis and the immune environment are poorly understood.MethodsWe investigated the clinicopathological characteristics, transcriptional and protein level, prognostic value, biological function, and its relationship with immune infiltration of TTN gene in LUAD patients through bioinformatics analysis.ResultsTTN expression was significantly lower in LUAD than that in normal lung tissue. Lower TTN expression was associated with worse survival. Besides, TTN is highly expressed in alveolar type 2 cells which were surmised as the origin of LUAD.ConclusionOur findings indicated the potential prognostic value of TTN and its role as a biomarker for determining the immune infiltration levels in patients with LUAD.