bluuebunny/crossref_metadata_2025_split huggingface dataset:
Coral Sr/Ca records provide realistic representation of eastern Indian Ocean cooling during extreme positive Indian Ocean Dipole events
Authors: Pfeiffer Miriam , Watanabe Takaaki Konabe , Takayanagi Hideko , Cahyarini Sri Yudawati , Garbe-Schönberg Dieter , Watanabe Tsuyoshi 
Published: June 2022

AbstractExtreme positive Indian Ocean Dipole (pIOD) events are amplified by non-linear ocean–atmosphere interactions and are characterized by pronounced cooling in the eastern equatorial Indian Ocean. These non-linear feedbacks are not adequately represented in historical products of sea surface temperatures that underestimate the magnitude of extreme pIOD events. Here, we present a sea surface temperature (SST) reconstruction based on monthly coral Sr/Ca ratios measured in two coral cores from Enggano Island (Indonesia), that lies in the eastern pole of the IOD. The coral SST reconstruction extends from 1930 to 2008 and captures the magnitude of cooling during extreme pIOD events as shown in recent satellite and reanalysis data of SST that include ocean dynamics. The corals indicate that the 1961 pIOD event was at least as severe as the 1997 event, while the 1963 pIOD was more comparable to the 2006 event. The magnitude 1967 pIOD is difficult to assess at present due to poor replication between coral cores, and may be comparable to either 1997 or 2006. Cooling during the 1972 pIOD was short-lived and followed by pronounced warming, as seen in the moderate pIOD event of 1982. A combination of coral SST reconstructions and an extension of new reanalysis products of SST to historical time scales could help to better assess the severity and impact of past pIOD events such as the ones seen in the 1960s.
Cancer immunohistogram representing cancer-immunity cycle by immunohistochemistry predicts the efficacy of immune checkpoint inhibitors in urological cancer patients
Authors: Kijima Toshiki , Kubo Terufumi , Nishihara Daisaku , Nukui Akinori , Hirohashi Yoshihiko , Torigoe Toshihiko , Kamai Takao 
Published: June 2022

AbstractWe developed an immunohistogram representing an individual cancer-immunity cycle based on immunohistochemical analyses. We evaluated its ability to predict the efficacy of immune checkpoint inhibitors (ICI) in 11 patients with urothelial carcinoma and 7 patients with renal cell carcinoma who underwent surgery and received ICIs for disease recurrence. Immunohistochemical analyses for CD8, TIA-1, HLA class I, HLA-DR, and PD-L1 were performed and scored 0–3. T-cell infiltration pattern was classified into desert, excluded, partially inflamed, and inflamed. Tumors with an inflamed or partially inflamed pattern and positive scores (score ≥ 1) for all five immune markers were classified as “immune-hot” and others as “immune-cold.” Association between the immunohistogram and ICI treatment efficacy was evaluated with objective response rate, disease control rate (DCR), progression-free survival (PFS), and cancer-specific survival (CSS). Eight (44%) and 10 (56%) patients had immune-hot and immune-cold tumors, respectively. Immune-hot tumors showed a higher DCR (100% vs. 40%, p < 0.01), longer PFS (median unreached for hot, 1.3 months for cold, p < 0.01), and longer CSS (median unreached for hot, 3.3 months for cold, p < 0.01) than immune-cold tumors. The immunohistogram could be clinically useful as an accessible biomarker for precision cancer immunotherapy in urological cancer.
Construction of a four-mRNA prognostic signature with its ceRNA network in CESC
Authors: Li Lang , Guo Qiusheng , Lan Gaochen , Liu Fei , Wang Wenwu , Lv Xianmei 
Published: June 2022

AbstractCervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tumorigenesis involves a combination of multiple genetic alteration processes. Constructing a survival-associated competing endogenous RNA (ceRNA) network and a multi-mRNA-based prognostic signature model can help us better understand the complexity and genetic characteristics of CESC. In this study, the RNA-seq data and clinical information of CESC patients were downloaded from The Cancer Genome Atlas. Differentially expressed mRNAs, lncRNAs and miRNAs were identified with the edgeR R package. A four-mRNA prognostic signature was developed by multivariate Cox regression analysis. Kaplan–Meier survival with the log-rank tests was performed to assess survival rates. The relationships between overall survival (OS) and clinical parameters were evaluated by Cox regression analysis. A survival-associated ceRNA network was constructed with the multiMiR package and miRcode database. Kyoto encyclopedia of genes and genomes (KEGG) analysis and gene ontology analyses were used to identify the functional role of the ceRNA network in the prognosis of CESC. A total of 298 differentially expressed mRNAs, 8 miRNAs, and 29 lncRNAs were significantly associated with the prognosis of CESC. A prognostic signature model based on 4 mRNAs (OPN3, DAAM2, HENMT1, and CAVIN3) was developed, and the prognostic ability of this signature was indicated by the AUC of 0.726. Patients in the high-risk group exhibited significantly worse OS. The KEGG pathways, TGF-β and Cell adhesion molecules, were significantly enriched. In this study, a CESC-associated ceRNA network was constructed, and a multi-mRNA-based prognostic model for CESC was developed based on the ceRNA network, providing a new perspective for cancer pathogenesis research.
Disentangling the relationship of gut microbiota, functional gastrointestinal disorders and autism: a case–control study on prepubertal Chinese boys
Authors: Wong Oscar W. H. , Lam Angela M. W. , Or Brian P. N. , Mo Flora Y. M. , Shea Caroline K. S. , Lai Kelly Y. C. , Ma Suk Ling , Hung Se Fong , Chan Sandra , Kwong Thomas N. Y. , Wong Sunny , Leung Patrick W. L. 
Published: June 2022

AbstractEmerging evidence of an altered gut microbiome in autism spectrum disorder (ASD) suggests a pathomechanism through the gut–brain axis despite the inconsistent microbiome profile reported across studies. One of the knowledge gaps in the existing ASD microbiota studies is the lack of systematic exploration of the role of comorbid functional gastrointestinal disorder (FGID) in the association of ASD and altered gut microbiome. Consequently, 92 ASD and 112 age-matched typically developing (TD) boys were profiled on general psychopathology, FGID status by Rome IV classification, and gut microbiota using 16S ribosomal RNA amplicon sequencing at the V4 hypervariable region. Compared to TD, a significant decrease in the within-sample abundance of taxa was observed in ASD, regardless of FGID status. The microbiota of ASD FGID+ and ASD FGID− clustered apart from the TD groups. The microbiota of ASD FGID+ also showed qualitative differences from that of ASD FGID− and had the highest-level Firmicutes: Bacteroidetes ratio, which was paralleled by elevated levels of anxiety and overall psychopathology. The altered gastrointestinal microbiota composition in ASD appeared to be independent of comorbid FGID. Further studies should address how FGID may mediate neuropsychiatric symptoms in ASD through inflammation along the microbiota–gut–brain axis.
Fixed complex electrograms during sinus rhythm and local pacing: potential ablation targets for persistent atrial fibrillation
Authors: Xu Buyun , Xu Chao , Sun Yong , Peng Jiahao , Peng Fang , Tang Weiliang , Zhou Yan , Wang Shengkai , Pan Jie , Xing Yangbo 
Published: June 2022

AbstractIn atrial fibrillation (AF) patients, complex electrograms during sinus rhythm (C-EGMs) could be pathological or not. We aimed to demonstrate whether local pacing was helpful to discern pathological C-EGMs. 126 persistent AF patients and 27 patients with left-side accessory pathway (LAP) underwent left atrial mapping during sinus rhythm. If C-EGMs were detected, local pacing was performed. If the electrograms turned normal, we defined them as non-fixed C-EGMs, otherwise as fixed C-EGMs. No difference was detected in the incidence and proportion of non-fixed C-EGMs between AF patients and LAP patients (101/126 vs. 19/27, P = 0.26; 9.1 ± 6.0% vs. 7.7 ± 5.7%, P = 0.28). However, the incidence and proportion of fixed C-EGMs were higher in persistent AF patients (87/126 vs. 1/27, P < 0.01; 4.3 ± 3.4% vs. 0.1 ± 0.5%, P < 0.01). Compared with non-fixed C-EGMs, fixed C-EGMs had lower amplitudes, longer electrogram durations and longer Stimuli-P wave internals. All AF patients received circumferential pulmonary vein isolation. Among AF patients with fixed C-EGMs, 45 patients received fixed C-EGMs ablation and 42 patients underwent linear ablation. Compared with linear ablation, fixed C-EGMs ablation reduced recurrence (HR: 0.43; 95% CI 0.21‐0.81; P = 0.011). Among patients without fixed C-EGMs ablation, the proportion of fixed C-EGMs was an independent predictor of ablation outcomes (HR for per percent: 1.13, 95% CI 1.01–1.28, P = 0.038). C-EGMs could be classified into fixed and non-fixed C-EGMs through local pacing. Fixed rather than non-fixed C-EGMs might indicate abnormal atrial substrates and fixed C-EGMs ablation improve outcomes of persistent AF ablation.
Impact of previous cardiac function status assessed by echocardiography on the outcome of COVID-19
Authors: Carrión Irene , Olmos Carmen , Luaces María , Cortés Ana Isabel , Real Carlos , de Agustín Alberto , Bottino Roberta , Pozo Eduardo , de Isla Leopoldo Pérez , Islas Fabián 
Published: June 2022

AbstractMore than 91,000 fatalities due to Coronavirus Disease 2019 (COVID-19) have occurred in Spain. Several factors are associated with increased mortality in this disease, including cardiovascular risk factors (CVRF). However, information on the cardiac function of patients prior to the onset of COVID-19 is scarce and the potential impact it may have is uncertain. The aim of the EchoVID study was to describe the potential association between CVRF and cardiac function status prior to SARS-CoV-2 infection and in-hospital mortality. We studied clinical characteristics and cardiac function of patients admitted during the first wave of COVID-19. All patients had a transthoracic echocardiogram performed in the previous 12 months prior to diagnosis; conventional systolic and diastolic function parameters were analyzed. Logistic regression analysis was performed to identify predictors of in-hospital mortality. We included 296 individuals. Median age was higher in the group of patients who died (81.0 vs 76.1 years; p = 0.007). No significant differences were found in CVRF. Survivors were more frequently receiving anticoagulation therapy (52.9% vs 70.8%; p = 0.003). LVEF, although preserved on average in both groups, was significantly lower in the group of deceased patients (56.9% vs 61.1%; p = 0.017). Average E/e′ ratio was higher in the deceased group (11.1 vs 10.1; p = 0.049). Five variables were found to be independently associated with in-hospital mortality due to COVID-19: Age, male gender, LVEF, E/e′ ratio and anticoagulation therapy. A model including these variables had an area under the ROC curve of 0.756 (CI 0.669–0.843). The echocardiographic variables included in the model significantly improved the discriminative power, compared to a model including only demographic data. Left ventricular ejection fraction and E/e′ ratio prior to SARS-CoV-2 infection are two easily-obtained echocardiographic parameters that provide additional prognostic information over clinical factors when assessing patients admitted for SARS-CoV-2 infection.
A deep learning method for miRNA/isomiR target detection
Authors: Talukder Amlan , Zhang Wencai , Li Xiaoman , Hu Haiyan 
Published: June 2022

AbstractAccurate identification of microRNA (miRNA) targets at base-pair resolution has been an open problem for over a decade. The recent discovery of miRNA isoforms (isomiRs) adds more complexity to this problem. Despite the existence of many methods, none considers isomiRs, and their performance is still suboptimal. We hypothesize that by taking the isomiR–mRNA interactions into account and applying a deep learning model to study miRNA–mRNA interaction features, we may improve the accuracy of miRNA target predictions. We developed a deep learning tool called DMISO to capture the intricate features of miRNA/isomiR–mRNA interactions. Based on tenfold cross-validation, DMISO showed high precision (95%) and recall (90%). Evaluated on three independent datasets, DMISO had superior performance to five tools, including three popular conventional tools and two recently developed deep learning-based tools. By applying two popular feature interpretation strategies, we demonstrated the importance of the miRNA regions other than their seeds and the potential contribution of the RNA-binding motifs within miRNAs/isomiRs and mRNAs to the miRNA/isomiR–mRNA interactions.
Association between mental health and duty hours of postgraduate residents in Japan: a nationwide cross-sectional study
Authors: Nagasaki Kazuya , Nishizaki Yuji , Shinozaki Tomohiro , Shimizu Taro , Yamamoto Yu , Shikino Kiyoshi , Fukui Sho , Nishiguchi Sho , Kurihara Masaru , Kataoka Koshi , Tokuda Yasuharu , Kobayashi Hiroyuki 
Published: June 2022

AbstractThe new duty hour (DH) limit for doctors in Japan will begin in 2024, setting the maximum DHs for postgraduate residents at approximately 80 h weekly. To set appropriate limits, understanding the association between DHs and psychological health is necessary. Thus, we assessed the relationship between residents’ psychological health and DHs. We conducted a cross-sectional study involving examinees of the General Medicine In-training Examination 2020. Mental health outcomes were measured dichotomously using the Patient Health Questionnaire-2 for depression and Mini-Z 2.0, for burnout, stress, and satisfaction. Weekly DHs were measured in seven categories at 10-h intervals. The prevalence ratios (PRs) between the DH categories were estimated for each outcome. Of the 6045 residents who provided data on DHs and psychological outcomes, 37.3% showed signs of depression, 21.6% experienced burn out, and 39.2% were highly stressed. In contrast, 62.3% were highly satisfied with their training. Proportions of burnout were higher among residents in Category 6 (≥ 90 and < 100 h; PR 1.36; 95% CI 1.11–1.66) and Category 7 (≥ 100 h; PR 1.36; 95% CI 1.10–1.68) compared with residents in Category 3 (≥ 60 and < 70 h; reference). The results partially support the weekly 80-h DH limit in terms of resident well-being.
Evidence for a mixed-age group in a pterosaur footprint assemblage from the early Upper Cretaceous of Korea
Authors: Jung Jongyun , Huh Min , Unwin David M. , Smyth Robert S. H. , Hwang Koo-Geun , Kim Hyun-Joo , Choi Byung-Do , Xing Lida 
Published: June 2022

AbstractHere we describe a new pterosaur footprint assemblage from the Hwasun Seoyuri tracksite in the Upper Cretaceous Jangdong Formation of the Neungju Basin in Korea. The assemblage consists of many randomly oriented prints in remarkably high densities but represents a single ichnotaxon, Pteraichnus. Individuals exhibit a large but continuous size range, some of which, with a wingspan estimated at 0.5 m, are among the smallest pterosaurs yet reported from the Upper Cretaceous, adding to other recent finds which contradict the idea that large and giant forms entirely dominated this interval. Unusual features of the tracks, including relatively long, slender pedal digit impressions, do not match the pes of any known Cretaceous pterosaur, suggesting that the trackmakers are as yet unknown from the body fossil record. The Hwasun pterosaur footprints appear to record gregarious behavior at the exact location by individuals of different ages, hinting at the possibility that pterosaurs gathered in mixed-age groups.
Terminalia catappa aqueous leaf extract reverses insulin resistance, improves glucose transport and activates PI3K/AKT signalling in high fat/streptozotocin-induced diabetic rats
Authors: Iheagwam Franklyn Nonso , Iheagwam Olawumi Toyin , Onuoha Michael Kemjika , Ogunlana Olubanke Olujoke , Chinedu Shalom Nwodo 
Published: June 2022

AbstractRising prevalence of type 2 diabetes mellitus (T2DM) in sub-Saharan Africa has necessitated surveys of antidiabetic medicinal plants. This study assessed the antidiabetic mechanism of Terminalia catappa aqueous leaf extract (TCA) in high fat/low dose streptozotocin-induced type 2 diabetic rats. T2DM was induced by a combination of high-fat diet and low dose STZ (30 mg/kg bw) and the animals were administered with TCA (400 and 800 mg/kg bw) orally daily for 28 days. Biochemical parameters and indices for diabetes including renal function tests and pancreatic histology were evaluated. Relative expression of hepatic insulin resistance, signalling and glucose transport genes were also assessed. Induction of T2DM resulted in significant (p < 0.05) weight loss, dysregulated glucose level and clearance, electrolyte imbalance and disrupted diabetic biochemical parameters. Diabetes onset also perturbed β-cell function and insulin resistance indices, damaged pancreas microanatomy, while disrupting the expression of insulin receptor substrate 1 (IRS-1), phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and glucose transporter isoform 4 (GLUT-4) mRNA. Oral treatment of diabetic animals with TCA significantly (p < 0.05) ameliorated alterations due to T2DM induction in a manner comparable with glibenclamide. These results suggest TCA exerts its antidiabetic action by reversing insulin resistance, improving glucose transport and activating PI3K/AKT signalling.
Hummingbird plumage color diversity exceeds the known gamut of all other birds
Authors: Venable Gabriela X. , Gahm Kaija , Prum Richard O. 
Published: June 2022

AbstractA color gamut quantitatively describes the diversity of a taxon’s integumentary coloration as seen by a specific organismal visual system. We estimated the plumage color gamut of hummingbirds (Trochilidae), a family known for its diverse barbule structural coloration, using a tetrahedral avian color stimulus space and spectra from a taxonomically diverse sample of 114 species. The spectra sampled occupied 34.2% of the total diversity of colors perceivable by hummingbirds, which suggests constraints on their plumage color production. However, the size of the hummingbird color gamut is equivalent to, or greater than, the previous estimate of the gamut for all birds. Using the violet cone type visual system, our new data for hummingbirds increases the avian color gamut by 56%. Our results demonstrate that barbule structural color is the most evolvable plumage coloration mechanism, achieving unique, highly saturated colors with multi-reflectance peaks.
Serine hydroxymethyltransferase as a potential target of antibacterial agents acting synergistically with one-carbon metabolism-related inhibitors
Authors: Makino Yuko , Oe Chihiro , Iwama Kazuya , Suzuki Satoshi , Nishiyama Akie , Hasegawa Kazuya , Okuda Haruka , Hirata Kazushige , Ueno Mariko , Kawaji Kumi , Sasano Mina , Usui Emiko , Hosaka Toshiaki , Yabuki Yukako , Shirouzu Mikako , Katsumi Makoto , Murayama Kazutaka , Hayashi Hironori , Kodama Eiichi N. 
Published: June 2022

AbstractSerine hydroxymethyltransferase (SHMT) produces 5,10-methylenetetrahydrofolate (CH2-THF) from tetrahydrofolate with serine to glycine conversion. SHMT is a potential drug target in parasites, viruses and cancer. (+)-SHIN-1 was developed as a human SHMT inhibitor for cancer therapy. However, the potential of SHMT as an antibacterial target is unknown. Here, we show that (+)-SHIN-1 bacteriostatically inhibits the growth of Enterococcus faecium at a 50% effective concentration of 10–11 M and synergistically enhances the antibacterial activities of several nucleoside analogues. Our results, including crystal structure analysis, indicate that (+)-SHIN-1 binds tightly to E. faecium SHMT (efmSHMT). Two variable loops in SHMT are crucial for inhibitor binding, and serine binding to efmSHMT enhances the affinity of (+)-SHIN-1 by stabilising the loop structure of efmSHMT. The findings highlight the potency of SHMT as an antibacterial target and the possibility of developing SHMT inhibitors for treating bacterial, viral and parasitic infections and cancer.
Century-long column ozone records show that chemical and dynamical influences counteract each other
Authors: Brönnimann Stefan 
Published: June 2022

AbstractThe recovery of the ozone layer, which is expected as stratospheric chlorine levels have decreased over the past 25 years, remains difficult to detect. Column ozone has been monitored from 1924 to 1975 in Oxford, UK. Here, I present a century-long Oxford column ozone record, extended to the present based on re-discovered material and neighbouring series, and analyse it together with a record from Arosa, Switzerland that starts in 1926. Neither series shows a clear increase over the past 25 years but suggest stratospheric circulation. I separate chemical and dynamical effects using a regression approach and find that chemical recovery amounts to +8 DU between peak stratospheric chlorine concentrations in 1997 to 2021, consistent with model simulations. However, this trend is counteracted by a −5 DU dynamical trend. Century-long ozone records provide a window to the past dynamical, chemical and radiative state of the stratosphere and help better constrain circulation effects on ozone recovery.
Possible regulation of Toll-like receptor 4 by lysine acetylation through LPCAT2 activity in RAW264.7 cells
Authors: Poloamina Victory Ibigo , Abate Wondwossen , Fejer Gyorgy , Jackson Simon K. 
Published: June 2022

Abstract
Inflammation is central to several diseases. TLR4 mediates inflammation by recognising and binding to bacterial lipopolysaccharides and interacting with other proteins in the TLR4 signalling pathway. Although there is extensive research on TLR4-mediated inflammation, there are gaps in understanding its mechanisms. Recently, TLR4 co-localised with LPCAT2, a lysophospholipid acetyltransferase. LPCAT2 is already known to influence lipopolysaccharide-induced inflammation; however, the mechanism of LPCAT2 influencing lipopolysaccharide-mediated inflammation is not understood.
The present study combined computational analysis with biochemical analysis to investigate the influence of LPCAT2 on lysine acetylation in LPS-treated RAW264.7 cells.
The results suggest for the first time that LPCAT2 influences lysine acetylation in LPS-treated RAW264.7 cells. Moreover, we detected acetylated lysine residues on TLR4. The present study lays a foundation for further research on the role of lysine acetylation on TLR4 signalling. Moreover, further research is required to characterise LPCAT2 as a protein acetyltransferase.