bluuebunny/crossref_metadata_2025_split huggingface dataset:
Struct2Graph: a graph attention network for structure based predictions of protein–protein interactions
Authors: Baranwal Mayank , Magner Abram , Saldinger Jacob , Turali-Emre Emine S. , Elvati Paolo , Kozarekar Shivani , VanEpps J. Scott , Kotov Nicholas A. , Violi Angela , Hero Alfred O. 
Published: September 2022

AbstractBackgroundDevelopment of new methods for analysis of protein–protein interactions (PPIs) at molecular and nanometer scales gives insights into intracellular signaling pathways and will improve understanding of protein functions, as well as other nanoscale structures of biological and abiological origins. Recent advances in computational tools, particularly the ones involving modern deep learning algorithms, have been shown to complement experimental approaches for describing and rationalizing PPIs. However, most of the existing works on PPI predictions use protein-sequence information, and thus have difficulties in accounting for the three-dimensional organization of the protein chains.ResultsIn this study, we address this problem and describe a PPI analysis based on a graph attention network, namedStruct2Graph, for identifying PPIs directly from the structural data of folded protein globules. Our method is capable of predicting the PPI with an accuracy of 98.89% on the balanced set consisting of an equal number of positive and negative pairs. On the unbalanced set with the ratio of 1:10 between positive and negative pairs, Struct2Graph achieves a fivefold cross validation average accuracy of 99.42%. Moreover, Struct2Graph can potentially identify residues that likely contribute to the formation of the protein–protein complex. The identification of important residues is tested for two different interaction types: (a) Proteins with multiple ligands competing for the same binding area, (b) Dynamic protein–protein adhesion interaction. Struct2Graph identifies interacting residues with 30% sensitivity, 89% specificity, and 87% accuracy.ConclusionsIn this manuscript, we address the problem of prediction of PPIs using a first of its kind, 3D-structure-based graph attention network (code available athttps://github.com/baranwa2/Struct2Graph). Furthermore, the novel mutual attention mechanism provides insights into likely interaction sites through its unsupervised knowledge selection process. This study demonstrates that a relatively low-dimensional feature embedding learned from graph structures of individual proteins outperforms other modern machine learning classifiers based on global protein features. In addition, through the analysis of single amino acid variations, the attention mechanism shows preference for disease-causing residue variations over benign polymorphisms, demonstrating that it is not limited to interface residues.
A heat shock 70kDa protein MaltHSP70-2 contributes to thermal resistance in Monochamus alternatus (Coleoptera: Cerambycidae): quantification, localization, and functional analysis
Authors: Li Hui , Li Shouyin , Chen Jin , Dai Lulu , Chen Ruixu , Ye Jianren , Hao Dejun 
Published: September 2022

Abstract
Background
Heat Shock Proteins 70 (HSP70s) in insects act on a diverse range of substrates to assist with overcoming extreme high temperatures. MaltHSP70-2, a member of HSP70s, has been characterized to involve in the thermotolerance of Monochamus alternatus in vitro, while quantification and localization of MaltHSP70-2 in various tissues and its functional analysis in vivo remain unclear.

Results
In this study, temporal expression of MaltHSP70-2 indicated a long-last inductive effect on MaltHSP70-2 expression maintained 48 hours after heat shock. MaltHSP70-2 showed a global response to heat exposure which occurring in various tissues of both males and females. Particularly in the reproductive tissues, we further performed the quantification and localization of MaltHSP70-2 protein using Western Blot and Immunohistochemistry, suggesting that enriched MaltHSP70-2 in the testis (specifically in the primary spermatocyte) must be indispensable to protect the reproductive activities (e.g., spermatogenesis) against high temperatures. Furthermore, silencing MaltHSP70-2 markedly influenced the expression of other HSP genes and thermotolerance of adults in bioassays, which implied a possible interaction of MaltHSP70-2 with other HSP genes and its role in thermal resistance of M. alternatus adults.

Conclusions
These findings shed new insights into thermo-resistant mechanism of M. alternatus to cope with global warming from the perspective of HSP70s functions.
Comparative analysis of two genomes of Chlamydia pecorum isolates from an Alpine chamois and a water buffalo
Authors: Rigamonti Sara , Floriano Anna Maria , Scaltriti Erika , Longbottom David , Livingstone Morag , Comandatore Francesco , Pongolini Stefano , Capucci Lorenzo , Mandola Maria Lucia , Bazzucchi Moira , Prati Paola , Vicari Nadia 
Published: September 2022

AbstractBackgroundTo date, whole genome sequencing has been performed mainly for isolates ofChlamydia trachomatis,C. pneumoniae,C. psittaciandC. abortus, but only a few isolates ofC. pecorumhave been entirely sequenced and this makes it difficult to understand its diversity and population structure. In this study the genome of twoC. pecorumstrains isolated from the lung of an Alpine chamois affected with pneumonia (isolate PV7855) and the brain of a water buffalo affected with meningoencephalomyelitis (isolate PV6959), were completely sequenced with MiSeq system (Illumina) and analyzed in their most polymorphic regions.ResultsThe genome length and GC content of the two isolates were found to be consistent with otherC. pecorumisolates and the gene content of polymorphic membrane proteins and plasticity zone was found to be very similar. Some differences were observed in the phospholipase genes for both isolates and in the number of genes in the plasticity zone, such as the presence of some hypothetical proteins in PV6959, not present in any other genomes analyzed in this study. Interestingly, PV6959 possesses an extrapmpand has an incomplete tryptophan biosynthesis operon. Plasmids were detected in both isolates.ConclusionsGenome sequencing of the twoC. pecorumstrains did not reveal differences in length and GC content despite the origin from different animal species with different clinical disease. In the plasticity zone, the differences in the genes pattern might be related to the onset of specific symptoms or infection of specific hosts. The absence of a tryptophan biosynthesis pathway in PV6959 may suggest a strict relationship betweenC. pecorumand its host.
The potential pathogenic roles of S100A8/A9 and S100A12 in patients with MPO-ANCA-positive vasculitis
Authors: Bai Xue , Xu Peng-Cheng , Chen Tong , Zhang Hao-Miao , Wu Si-Jing , Yang Xia , Gao Shan , Jia Jun-Ya , Jiang Jian-Qing , Yan Tie-Kun 
Published: September 2022

Abstract
Background
The significance of S100A8/A9 and S100A12 in anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) has not been clarified. This study was dedicated to exploring the potential pathogenic roles of S100A8/A9 and S100A12 in patients with myeloperoxidase (MPO)-ANCA-positive vasculitis.

Methods
Serum and urine concentrations of S100A8/A9 and S100A12 of forty-two AAV patients were evaluated. The influence of S100A8/A9 and S100A12 on the chemotaxis, the apoptosis, the release of IL-1β, the complement activation, the respiratory burst, as well as the neutrophil extracellular traps (NETs) formation of MPO-ANCA-activated neutrophils was investigated.

Results
The serum and urine S100A8/A9 and S100A12 of active MPO-AAV significantly increased (compared with inactive AAV and healthy controls, p < 0.001) and were correlated with the severity of the disease. In vitro study showed that S100A8/A9 and S100A12 activated the p38 MAPK/NF-κB p65 pathway, increased the chemotaxis index (CI) and the release of IL-1β, extended the life span, and enhanced the complement activation ability of MPO-ANCA-activated neutrophils. The Blockade of TLR4 and RAGE inhibited the effects of S100A8/A9 and S100A12. All above-mentioned effects of S100A8/A9 and S100A12 were ROS-independent because neither S100A8/A9 nor S100A12 enhanced the ROS formation and NETs formation of MPO-ANCA-activated neutrophils.

Conclusion
S100A8/A9 and S100A12 serve as markers for assessing the disease severity, and they may also play a role in MPO-AAV pathogenesis.
A chloroplast-localized pentatricopeptide repeat protein involved in RNA editing and splicing and its effects on chloroplast development in rice
Authors: Wang Yanwei , Yang Zhimin , Zhang Meng , Ai Pengfei 
Published: September 2022

Abstract
Background
The chloroplast is the organelle responsible for photosynthesis in higher plants. The generation of functional chloroplasts depends on the precise coordination of gene expression in the nucleus and chloroplasts and is essential for the development of plants. However, little is known about nuclear-plastid regulatory mechanisms at the early stage of chloroplast generation in rice.

Results
In this study, we identified a rice (Oryza sativa) mutant that exhibited albino and seedling-lethal phenotypes and named it ssa1(seedling stage albino1). Transmission electron microscopy (TEM) analysis indicated that the chloroplasts of ssa1 did not have organized thylakoid lamellae and that the chloroplast structure was destroyed. Genetic analysis revealed that the albino phenotypes of ssa1 were controlled by a pair of recessive nuclear genes. Map-based cloning experiments found that SSA1 encoded a pentapeptide repeat (PPR) protein that was allelic to OSOTP51,which was previously reported to participate in Photosystem I (PSI) assembly. The albino phenotype was reversed to the wild type (WT) phenotype when the normal SSA1 sequence was expressed in ssa1 under the drive of the actin promoter. Knockout experiments further created mutants ssa1–2/1–9, which had a phenotype similar to that of ssa1. SSA1 consisted of 7 pentatricopeptide repeat domains and two C-terminal LAGLIDADG tandem sequence motifs and was located in the chloroplast. GUS staining and qRT–PCR analysis showed that SSA1 was mainly expressed in young leaves and stems. In the ssa1 mutants, plastid genes transcribed by plastid-encoded RNA polymerase decreased, while those transcribed by nuclear-encoded RNA polymerase increased at the mRNA level. Loss-of-function SSA1 destroys RNA editing of ndhB-737 and intron splicing of atpF and ycf3–2 in the plastid genome. Yeast two-hybrid and BiFC assays revealed that SSA1 physically interacted with two new RNA editing partners, OsMORF8 and OsTRXz, which have potential functions in RNA editing and chloroplast biogenesis.

Conclusions
Rice SSA1 encodes a pentatricopeptide repeat protein, which is targeted to the chloroplast. SSA1 regulates early chloroplast development and plays a critical role in RNA editing and intron splicing in rice. These data will facilitate efforts to further elucidate the molecular mechanism of chloroplast biogenesis.
Incidence and risk factors of intraoperative hyperglycemia in non-diabetic patients: a prospective observational study
Authors: Sermkasemsin Varunya , Rungreungvanich Mali , Apinyachon Worapot , Sangasilpa Inthuon , Srichot Wanlee , Pisitsak Chawika 
Published: September 2022

Abstract
Background
Intraoperative hyperglycemia has been associated with multiple postoperative complications such as surgical site infection, myocardial infarction, stroke, and death. These complications are not confined to only diabetic patients. However, the incidence of intraoperative hyperglycemia in non-diabetic patients has not been fully elucidated. Additionally, these patients’ risk factors were not well established in previous studies.

Methods
Four hundred forty non-diabetic patients who underwent intermediate- to high-risk surgery were included in the study. We prospectively measured the capillary blood glucose level in all patients during surgery. The incidence of intraoperative hyperglycemia was defined as at least one episode of blood glucose level of more than 180 mg/dL. Risk factors for hyperglycemia were assessed using multivariable logistic regression analysis.

Results
Sixty-five (14.7%) patients developed hyperglycemia during surgery. The independent risk factors for intraoperative hyperglycemia were an American Society of Anesthesiologists status ≥ 3 (odds ratio [OR] 6.09, 95% confidence interval [CI]: 2.67–13.89, p < 0.001), preoperative impaired fasting blood sugar (OR 2.28, 95%CI:1.13–4.61, p = 0.021), duration of anesthesia ≥ 3 h (OR 4.06, 95%CI: 1.23–13.45, p = 0.021), intraoperative hypotension (OR 5.37, 95%CI: 2.35–12.29, p < 0.001), intraoperative blood transfusion (OR 4.35, 95%CI: 2.15–8.79, p < 0.001), and steroid use (OR 2.39, 95%CI: 1.20–4.76, p = 0.013). Surgical site infection was higher in patients with intraoperative hyperglycemia compared with patients without intraoperative hyperglycemia (4 [6.1%] vs. 6 [1.6%], respectively, p = 0.035).

Conclusion
The incidence of intraoperative hyperglycemia was significant in non-diabetic patients during intermediate- to high-risk surgery. Risk factors should be identified to prevent intraoperative hyperglycemia.

Trial registration
The study was prospectively registered at https://www.thaiclinicaltrials.org (TCTR20191114001).
Impact of lactate dehydrogenase on prognosis of patients undergoing cardiac surgery
Authors: Zeng Yu , Zhao Yuhe , Dai Shuren , Liu Yanyan , Zhang Ruoyu , Yan Hong , Zhao Min , Wang Yong 
Published: September 2022

Abstract
Background
Lactate dehydrogenase (LDH) has been reported in multiple heart diseases. Herein, we explored the prognostic effects of preoperative LDH on adverse outcomes in cardiac surgery patients.

Methods
Retrospective data analysis was conducted from two large medical databases: Medical Information Mart for Intensive Care (MIMIC) III and MIMIC IV databases. The primary outcome was in-hospital mortality, whereas the secondary outcomes were 1-year mortality, continuous renal replacement therapy, prolonged ventilation, and prolonged length of intensive care unit and hospital stay.

Results
Patients with a primary endpoint had significantly higher levels of LDH (p < 0.001). Multivariate regression analysis presented that elevated LDH was independently correlated with increased risk of primary and secondary endpoints (all p < 0.001). Subgroup analyses showed that high LDH was consistently associated with primary endpoint. Moreover, LDH exhibited the highest area under the curve (0.768) for the prediction of primary endpoint compared to the other indicators, including neutrophil–lymphocyte ratio (NLR), lymphocyte-monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), lactate, and simplified acute physiology score (SAPS) II. The above results were further confirmed in the MIMIC IV dataset.

Conclusions
Elevated preoperative LDH may be a robust predictor of poor prognosis in cardiac surgery patients, and its predictive ability is superior to NLR, LMR, PLR, lactate, and SAPS II.
Informed Bayesian survival analysis
Authors: Bartoš František , Aust Frederik , Haaf Julia M. 
Published: September 2022

AbstractBackgroundWe provide an overview of Bayesian estimation, hypothesis testing, and model-averaging and illustrate how they benefit parametric survival analysis. We contrast the Bayesian framework to the currently dominant frequentist approach and highlight advantages, such as seamless incorporation of historical data, continuous monitoring of evidence, and incorporating uncertainty about the true data generating process.MethodsWe illustrate the application of the outlined Bayesian approaches on an example data set, retrospective re-analyzing a colon cancer trial. We assess the performance of Bayesian parametric survival analysis and maximum likelihood survival models with AIC/BIC model selection in fixed-n and sequential designs with a simulation study.ResultsIn the retrospective re-analysis of the example data set, the Bayesian framework provided evidence for the absence of a positive treatment effect of adding Cetuximab to FOLFOX6 regimen on disease-free survival in patients with resected stage III colon cancer. Furthermore, the Bayesian sequential analysis would have terminated the trial 10.3 months earlier than the standard frequentist analysis. In a simulation study with sequential designs, the Bayesian framework on average reached a decision in almost half the time required by the frequentist counterparts, while maintaining the same power, and an appropriate false-positive rate. Under model misspecification, the Bayesian framework resulted in higher false-negative rate compared to the frequentist counterparts, which resulted in a higher proportion of undecided trials. In fixed-n designs, the Bayesian framework showed slightly higher power, slightly elevated error rates, and lower bias and RMSE when estimating treatment effects in small samples. We found no noticeable differences for survival predictions. We have made the analytic approach readily available to other researchers in the RoBSA R package.ConclusionsThe outlined Bayesian framework provides several benefits when applied to parametric survival analyses. It uses data more efficiently, is capable of considerably shortening the length of clinical trials, and provides a richer set of inferences.
A pilot and ex-vivo study of examination of endometrium tissue by catheter based optical coherence tomography
Authors: Ding Bo , Jinyuan Tao , Tao Kuiyuan , Ding Zhenyang , Yang Shen 
Published: September 2022

Abstract
Objective
This study aimed to distinguish ex-vivo normal and abnormal endometrium tissue samples histologically by catheter based optical coherence tomography (OCT).

Methods
A total of 72 ex-vivo endometrium specimens were obtained from June 2018 to March 2021 and were imaged fresh after hysterectomy. The scanned region of endometrium was excised for histological examination and endometrium OCT images were precisely compared to corresponding histological images. Meanwhile endometrium OCT images were analyzed quantitatively with intensity of backscattered light in region of interest (ROI) and maximum penetration depth of the OCT signal. Blinded qualitative analysis on endometrium OCT images was performed by 2 assessors to determine accuracy rate and inter-rating reliability on the histopathological diagnosis.

Results
OCT images were performed successfully in 72 endometrium specimens. Five endometrium specimens developed OCT interpretation criteria and the rest 67 endometrium specimens validated qualitatively and analyzed quantitatively. We defined an OCT criteria to distinguish normal endometrium and five different abnormal endometrium phases including proliferative endometrium, secretory phase endometrium, atrophic endometrium, endometrial hyperplasia with atypia and endometrial carcinoma based on OCT imaging features. The overall diagnosis accuracy achieved by the two assessors was 72.4% based on the OCT criteria. The inter-rater reliability between assessors on overall OCT images was substantial (Kendall τb of 0.720, p < 0.05). The changes in ROI minimum intensity, ROI maximum intensity, ROI average intensity and OCT signal maximum penetration depth of five different abnormal endometrium phases were significantly different (all p < 0.001). These parameters of endometrium carcinomas were significantly different from the other four endometrium phases (all p < 0.001).

Conclusion
OCT has the advantage of noninvasive and rapid diagnosis, which can contribute to the diagnosis of endometrial cancer and will be an indispensable complement to traditional biopsy. Future studies in vivo with larger samples are needed to confirm this conclusion.
The value of whole-lesion histogram analysis based on field‑of‑view optimized and constrained undistorted single shot (FOCUS) DWI for predicting axillary lymph node status in early-stage breast cancer
Authors: Fang Shu , Zhu Jun , Wang Yafeng , Zhou Jie , Wang Guiqian , Xu Weiwei , Zhang Wei 
Published: September 2022

Abstract
Background
This study aims to estimate the amount of axillary lymph node (ALN) involvement in early-stage breast cancer utilizing a field of view (FOV) optimized and constrained undistorted single-shot (FOCUS) diffusion-weighted imaging (DWI) approach, as well as a whole-lesion histogram analysis.

Methods
This retrospective analysis involved 81 individuals with invasive breast cancer. The patients were divided into three groups: N0 (negative ALN metastasis), N1–2 (low metastatic burden with 1–2 ALNs), and N≥3 (heavy metastatic burden with ≥ 3 ALNs) based on their sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND). Histogram parameters of apparent diffusion coefficient (ADC) depending basically on FOCUS DWI were performed using 3D-Slicer software for whole lesions. The typical histogram characteristics for N0, N1–2, and N≥ 3 were compared to identify the significantly different parameters. To determine the diagnostic efficacy of significantly different factors, the area under their receiver operating characteristic (ROC) curves was examined.

Results
There were significant differences in the energy, maximum, 90 percentile, range, and lesion size among N0, N1–2, and N≥ 3 groups (P < 0.05). The energy differed significantly between N0 and N1–2 groups (P < 0.05), and some certain ADC histogram parameters and lesion sizes differed significantly between N0 and N≥3, or N1–2 and N≥3 groups. For ROC analysis, the energy yielded the best diagnostic performance in distinguishing N0 and N1–2 groups from N≥3 group with an AUC value of0.853. All parameters revealed excellent inter-observer agreement with inter-reader consistencies data ranging from0.919 to 0.982.

Conclusion
By employing FOCUS DWI method, the analysis of whole-lesion ADC histogram quantitatively provides a non-invasive way to evaluate the degree of ALN metastatic spread in early-stage breast cancer.