bluuebunny/crossref_metadata_2025_split huggingface dataset:
Management of presumed candida endophthalmitis during the COVID-19 pandemic: Case report and review of the literature
Authors: Fossataro Federica , Martines Francesco , Neri Piergiorgio , Allegri Pia , Pece Alfredo 
Published: April 2022

Purpose To report the management of a case of candida endophthalmitis following intubation for SARS-CoV-2 ARDS, during the first lockdown, underlining consequently the limited access to the gold standard of care. Methods Case report. Results We have described the case of a 56-year-old Hispanic man who developed bilateral Candida endophthalmitis after one month of hospitalization in the intensive care unit for severe SARS-CoV-2 pneumonia. Multimodal imaging was obtained. Full serological screening for infection was done resulting negative. A diagnostic vitrectomy was impossible due to the limited access at the surgery room. Diagnosis of presumed candida endophthalmitis was made, according to a highly qualified center, and therapy with intravenous liposomal amphotericin B was administered. At three months, we observed lack of vitreous opacities and atrophic scars with no active lesions. Conclusions Diagnosis of candida endophthalmitis was a challenge in this pandemic scenario, given the impossibility of performing a diagnostic vitrectomy. Therefore, it was mainly based on patient's clinical manifestations, multimodal imaging and on unanimity of collegiality between our hospital and the highly specialized center.
ABO O blood group as a risk factor for platelet reactivity in heparin-induced thrombocytopenia
Authors: Karnes Jason H. , Rollin Jerome , Giles Jason B. , Martinez Kiana L. , Steiner Heidi E. , Shaffer Christian M. , Momozawa Yukihide , Inai Chihiro , Bombin Andrei , Shi Mingjian , Mosley Jonathan D. , Stanaway Ian , Selleng Kathleen , Thiele Thomas , Mushiroda Taisei , Pouplard Claire , Heddle Nancy M. , Kubo Michiaki , Phillips Elizabeth J. , Warkentin Theodore E. , Gruel Yves , Greinacher Andreas , Roden Dan M. 
Published: April 2022

Abstract
Heparin-induced thrombocytopenia (HIT) is an unpredictable, potentially catastrophic adverse effect resulting from an immune response to platelet factor 4 (PF4)/heparin complexes. We performed a genome-wide association study (GWAS) with positive functional assay as the outcome in a large discovery cohort of patients divided into 3 groups: (1) functional assay-positive cases (n = 1269), (2) antibody-positive (functional assay-negative) controls (n = 1131), and (3) antibody-negative controls (n = 1766). Significant associations (α = 5 × 10−8) were investigated in a replication cohort (α = 0.05) of functional assay-confirmed HIT cases (n = 177), antibody-positive (function assay-negative) controls (n = 258), and antibody-negative controls (n = 351). We observed a strong association for positive functional assay with increasing PF4/heparin immunoglobulin-G (IgG) level (odds ratio [OR], 16.53; 95% confidence interval [CI], 13.83-19.74; P = 1.51 × 10−209) and female sex (OR, 1.15; 95% CI, 1.01-1.32; P = .034). The rs8176719 C insertion variant in ABO was significantly associated with positive functional assay status in the discovery cohort (frequency = 0.41; OR, 0.751; 95% CI, 0.682-0.828; P = 7.80 × 10−9) and in the replication cohort (OR, 0.467; 95% CI, 0.228-0.954; P = .0367). The rs8176719 C insertion, which encodes all non-O blood group alleles, had a protective effect, indicating that the rs8176719 C deletion and the O blood group were risk factors for HIT (O blood group OR, 1.42; 95% CI, 1.26-1.61; P = 3.09 × 10−8). Meta-analyses indicated that the ABO association was independent of PF4/heparin IgG levels and was stronger when functional assay-positive cases were compared with antibody-positive (functional assay-negative) controls than with antibody-negative controls. Sequencing and fine-mapping of ABO demonstrated that rs8176719 was the causal single nucleotide polymorphism (SNP). Our results clarify the biology underlying HIT pathogenesis with ramifications for prediction and may have important implications for related conditions, such as vaccine-induced thrombotic thrombocytopenia.
Investigation of improving the pre-training and fine-tuning of BERT model for biomedical relation extraction
Authors: Su Peng , Vijay-Shanker K. 
Published: April 2022

AbstractBackgroundRecently, automatically extracting biomedical relations has been a significant subject in biomedical research due to the rapid growth of biomedical literature. Since the adaptation to the biomedical domain, the transformer-based BERT models have produced leading results on many biomedical natural language processing tasks. In this work, we will explore the approaches to improve the BERT model for relation extraction tasks in both the pre-training and fine-tuning stages of its applications. In the pre-training stage, we add another level of BERT adaptation on sub-domain data to bridge the gap between domain knowledge and task-specific knowledge. Also, we propose methods to incorporate the ignored knowledge in the last layer of BERT to improve its fine-tuning.ResultsThe experiment results demonstrate that our approaches for pre-training and fine-tuning can improve the BERT model performance. After combining the two proposed techniques, our approach outperforms the original BERT models with averaged F1 score improvement of 2.1% on relation extraction tasks. Moreover, our approach achieves state-of-the-art performance on three relation extraction benchmark datasets.ConclusionsThe extra pre-training step on sub-domain data can help the BERT model generalization on specific tasks, and our proposed fine-tuning mechanism could utilize the knowledge in the last layer of BERT to boost the model performance. Furthermore, the combination of these two approaches further improves the performance of BERT model on the relation extraction tasks.
Novel drug-target interactions via link prediction and network embedding
Authors: Amiri Souri E. , Laddach R. , Karagiannis S. N. , Papageorgiou L. G. , Tsoka S. 
Published: April 2022

AbstractBackgroundAs many interactions between the chemical and genomic space remain undiscovered, computational methods able to identify potential drug-target interactions (DTIs) are employed to accelerate drug discovery and reduce the required cost. Predicting new DTIs can leverage drug repurposing by identifying new targets for approved drugs. However, developing an accurate computational framework that can efficiently incorporate chemical and genomic spaces remains extremely demanding. A key issue is that most DTI predictions suffer from the lack of experimentally validated negative interactions or limited availability of target 3D structures.ResultsWe report DT2Vec, a pipeline for DTI prediction based on graph embedding and gradient boosted tree classification. It maps drug-drug and protein–protein similarity networks to low-dimensional features and the DTI prediction is formulated as binary classification based on a strategy of concatenating the drug and target embedding vectors as input features. DT2Vec was compared with three top-performing graph similarity-based algorithms on a standard benchmark dataset and achieved competitive results. In order to explore credible novel DTIs, the model was applied to data from the ChEMBL repository that contain experimentally validated positive and negative interactions which yield a strong predictive model. Then, the developed model was applied to all possible unknown DTIs to predict new interactions. The applicability of DT2Vec as an effective method for drug repurposing is discussed through case studies and evaluation of some novel DTI predictions is undertaken using molecular docking.ConclusionsThe proposed method was able to integrate and map chemical and genomic space into low-dimensional dense vectors and showed promising results in predicting novel DTIs.
Transcriptome analysis of blastoderms exposed to prolonged egg storage and short periods of incubation during egg storage
Authors: Brady K. , Talbot C. C. , Long J. A. , Welch G. , French N. , Nicholson D. , Bakst M. R. 
Published: April 2022

Abstract
Background
Cool temperature egg storage prior to incubation is a common practice in the broiler industry; however, prolonged egg storage causes increased embryonic mortality and decreased hatchability and growth in surviving chicks. Exposing eggs to short periods of incubation during egg storage (SPIDES) reduces the adverse consequences of prolonged storage. SPIDES increases blastodermal cell viability by reducing apoptosis, though the counteracting mechanisms are unclear. To define the impact of prolonged storage and SPIDES, transcriptome analysis compared gene expression from blastoderms isolated from eggs exposed to the following treatments: control (CR, stored at 17 °C for 4 days), prolonged storage (NSR, stored at 17 °C for 21 days), SPIDES (SR, stored at 17 °C for 21 days with SPIDES), and incubated control (C2, stored at 17 °C for 4 days followed by incubation to HH (Hamburger–Hamilton) stage 2, used as the ideal standard development) (n = 3/group). Data analysis was performed using the CLC Genomics Workbench platform. Functional annotation was performed using DAVID and QIAGEN Ingenuity Pathway Analysis.

Results
In total, 4726 DEGs (differentially expressed genes) were identified across all experimental group comparisons (q < 0.05, FPKM> 20, |fold change| > 1.5). DEGs common across experimental comparisons were involved in cellular homeostasis and cytoskeletal protein binding. The NSR group exhibited activation of ubiquitination, apoptotic, and cell senescence processes. The SR group showed activation of cell viability, division, and metabolic processes. Through comparison analysis, cellular respiration, tRNA charging, cell cycle control, and HMBG1 signaling pathways were significantly impacted by treatment and potential regulatory roles for ribosomal protein L23a (RPL23A) and MYC proto-oncogene, BHLH transcription factor (MYC) were identified.

Conclusions
Prolonged egg storage (NSR) resulted in enriched cell stress and death pathways; while SPIDES (SR) resulted in enriched basic cell and anti-apoptotic pathways. New insights into DNA repair mechanisms, RNA processing, shifts in metabolism, and chromatin dynamics in relation to egg storage treatment were obtained through this study. Although egg storage protocols have been examined through targeted gene expression approaches, this study provided a global view of the extensive molecular networks affected by prolonged storage and SPIDES and helped to identify potential upstream regulators for future experiments to optimize egg storage parameters.
Abundant small RNAs in the reproductive tissues and eggs of the honey bee, Apis mellifera
Authors: Watson Owen T. , Buchmann Gabriele , Young Paul , Lo Kitty , Remnant Emily J. , Yagound Boris , Shambrook Mitch , Hill Andrew F. , Oldroyd Benjamin P. , Ashe Alyson 
Published: April 2022

Abstract
Background
Polyandrous social insects such as the honey bee are prime candidates for parental manipulation of gene expression in offspring. Although there is good evidence for parent-of-origin effects in honey bees the epigenetic mechanisms that underlie these effects remain a mystery. Small RNA molecules such as miRNAs, piRNAs and siRNAs play important roles in transgenerational epigenetic inheritance and in the regulation of gene expression during development.

Results
Here we present the first characterisation of small RNAs present in honey bee reproductive tissues: ovaries, spermatheca, semen, fertilised and unfertilised eggs, and testes. We show that semen contains fewer piRNAs relative to eggs and ovaries, and that piRNAs and miRNAs which map antisense to genes involved in DNA regulation and developmental processes are differentially expressed between tissues. tRNA fragments are highly abundant in semen and have a similar profile to those seen in the semen of other animals. Intriguingly we also find abundant piRNAs that target the sex determination locus, suggesting that piRNAs may play a role in honey bee sex determination.

Conclusions
We conclude that small RNAs may play a fundamental role in honey bee gametogenesis and reproduction and provide a plausible mechanism for parent-of-origin effects on gene expression and reproductive physiology.
Identification and functional validation of HLA-C as a potential gene involved in colorectal cancer in the Korean population
Authors: Lim Eun Bi , Oh Ho-Suk , Kim Kang Chang , Kim Moon-Ho , Kim Young Jin , Kim Bong Jo , Nho Chu Won , Cho Yoon Shin 
Published: April 2022

Abstract
Background
Colorectal cancer (CRC) is the third most common cancer worldwide and is influenced by environmental and genetic factors. Although numerous genetic loci for CRC have been identified, the overall understanding of the genetic factors is yet to be elucidated. We sought to discover new genes involved in CRC applying genetic association analysis and functional study.

Results
We conducted exome array analysis on 194 CRC and 600 control subjects for discovering new candidate CRC genes. Fisher’s exact test detected one exome-wide significant functional locus for CRC on SMCO1 (P < 10–6) and two suggestive functional loci on HLA-C and NUTM1 (10–6 ≤ P < 10–4). To evaluate the biological role of three candidate CRC genes, the differential expression of these genes between CRC and non-cancer colorectal cells was analyzed using qRT-PCR and publicly available gene expression data. Of three genes, HLA-C consistently revealed the significant down-regulation in CRC cells. In addition, we detected a reduction in cell viability in the HLA-C overexpression CRC cell line, implying the functional relevance of HLA-C in CRC. To understand the underlying mechanism exerted by HLA-C in CRC development, we conducted RNA sequencing analyses of HLA-C overexpression CRC cells and non-cancer colorectal cells. Pathway analysis detected that significantly down-regulated genes in HLA-C overexpression CRC cells were highly enriched in cancer-related signaling pathways such as JAK/STAT, ErbB, and Hedgehog signaling pathways.

Conclusions
Exome array CRC case–control analysis followed by functional validation demonstrated that HLA-C likely exerts its influence on CRC development via cancer-related signaling pathways.
The effects of moderate neuromuscular blockade combined with transverse abdominal plane block on surgical space conditions during laparoscopic colorectal surgery: a randomized clinical study
Authors: Ke Fang , Shen Zijin , Wu Cheng , Zhang Lin , Dong Rong 
Published: April 2022

Abstract
Background
Deep neuromuscular blockade may be beneficial on surgical space conditions during laparoscopic surgery. The effects of moderate neuromuscular blockade combined with transverse abdominal plane block (TAPB) on surgical space conditions during laparoscopic surgery have not been described. This work investigated whether the above combination is associated with similar surgical space conditions to those of deep neuromuscular blockade.

Methods
Eighty patients undergoing elective laparoscopic surgery for colorectal cancer were randomly divided into two groups. The intervention group was treated with moderate neuromuscular blockade (train-of-four (TOF) count between 1 and 3) combined with TAPB (M group), while the control group was treated with deep neuromuscular blockade (D group), with a TOF count of 0 and a post-tetanic count (PTC) ≥1. Both groups received the same anesthesia management. The distance between the sacral promontory and the umbilical skin during the operation was compared between the two groups. The surgeon scored the surgical space conditions according to a five-point ordinal scale. Patients’ pain scores were evaluated 8 h after the operation.

Results
The distance from the sacral promontory to the umbilical skin after pneumoperitoneum was similar between the D group and M group (16.03 ± 2.17 cm versus 16.37 ± 2.78 cm; P = 0.544). The 95% confidence intervals of the difference in the distance from the sacral promontory to the umbilical skin between the two groups were − 1.45–0.77 cm. According to the preset non-inferior standard of 1.5 cm, (− 1.45, ∞) completely fell within (− 1.50, ∞), and the non-inferior effect test was qualified. No significant difference was found in the surgical rating score between the two groups. The dosage of rocuronium in the group D was significantly higher than that in the group M (P < 0.01). The M group had significantly lower pain scores than the D group 8 h after the operation (P < 0.05).

Conclusions
Moderate neuromuscular blockade combined with TAPB applied to laparoscopic colorectal cancer surgery can provide surgical space conditions similar to those of deep neuromuscular blockade. In addition, it reduces the use of muscle relaxants, relieves postoperative pain within 4 h after operation, and shorten the extubation time and stay in PACU when neostigmine was used as muscle relaxant antagonist.

Trial registration
chictr.org.cn (ChiCTR2000034621), registered on July 12, 2020.
Cognitive impairment and edentulism among older adults: an observational study using claims data
Authors: Choi Sung Eun , Mo Emily , Palmer Nathan , Fox Kathe , Da Silva John D. , Nagai Shigemi , Barrow Jane R. 
Published: April 2022

Abstract
Background
The scientific link between mastication strength and cognitive function has not yet been strongly corroborated in population studies. Utilizing large-scale claims, we aim to investigate the association between edentulism and cognitive impairment in older American adults.

Methods
Using de-identified claims from a commercial insurer from 2015–2019, we conducted a retrospective cohort study using multilevel regression models to evaluate the association between denture status and clinically diagnosed cognitive impairment. Secondary analysis included symptomatic cognitive impairment in the outcome.

Results
Adjusting for individual-level risk factors, denture status was significantly associated with clinical cognitive impairment with odds ratios of 1.13 (95%CI: 1.02–1.25) and 1.26, (95%CI: 1.09–1.45) for complete dentures on one or both jaws, respectively. Including symptomatic cognitive impairment in the analysis did not substantially change our fundamental findings.

Conclusion
Prevention and treatment of oral diseases should be considered a key component in preserving the overall wellness of older adults.
Analysis of national surveillance of respiratory pathogens for community-acquired pneumonia in children and adolescents
Authors: Roh Eui Jeong , Lee Mi-Hee , Lee Ji Young , Kim Hyo-Bin , Ahn Young Min , Kim Ja Kyoung , Kim Hyoung Young , Jung Sung-Su , Kim Minji , Kang Eun Kyeong , Yang Eun-Ae , Lee Soo Jin , Park Yang , Seo Ju-Hee , Lee Eun , Yang Eun Seok , Park Kang Seo , Shin Meeyong , Chung Hai Lee , Jang Yoon Young , Choi Bong Seok , Jung Jin-A. , Yu Seung Taek , Sung Myongsoon , Kim Jin Tack , Kim Bong-Seong , Hwang Yoon Ha , Sol In-Suk , Yang Hyeon-Jong , Han Man Yong , Yew Hae Young , Cho Hyoung Min , Kim Hye-young , Ahn Yeon-Hwa , Lee Eun Sil , Kim Dong Hyeok , Hwang Kyujam , Jung Sang Oun , Shim Jung Yeon , Chung Eun Hee 
Published: April 2022

Abstract
Background
Respiratory infections among children, particularly community-acquired pneumonia (CAP), is a major disease with a high frequency among outpatient and inpatient visits. The causes of CAP vary depending on individual susceptibility, the epidemiological characteristics of the community, and the season. We performed this study to establish a nationwide surveillance network system and identify the causative agents for CAP and antibiotic resistance in Korean children with CAP.

Methods
The monitoring network was composed of 28 secondary and tertiary medical institutions. Upper and lower respiratory samples were assayed using a culture or polymerase chain reaction (PCR) from August 2018 to May 2020.

Results
A total of 1023 cases were registered in patients with CAP, and PCR of atypical pneumonia pathogens revealed 422 cases of M. pneumoniae (41.3%). Respiratory viruses showed a positivity rate of 65.7% by multiplex PCR test, and human rhinovirus was the most common virus, with 312 cases (30.5%). Two hundred sixty four cases (25.8%) were isolated by culture, including 131 cases of S. aureus (12.8%), 92 cases of S. pneumoniae (9%), and 20 cases of H. influenzae (2%). The cultured, isolated bacteria may be colonized pathogen. The proportion of co-detection was 49.2%. The rate of antibiotic resistance showed similar results as previous reports.

Conclusions
This study will identify the pathogens that cause respiratory infections and analyze the current status of antibiotic resistance to provide scientific evidence for management policies of domestic respiratory infections. Additionally, in preparation for new epidemics, including COVID-19, monitoring respiratory infections in children and adolescents has become more important, and research on this topic should be continuously conducted in the future.
Correlation between intestinal flora disruption and protein–energy wasting in patients with end-stage renal disease
Authors: Hu Jianguang , Zhong Xiaoshi , Liu Yan , Yan Jing , Zhou Daoyuan , Qin Danping , Xiao Xiao , Zheng Yuanyuan , Wen Luona , Tan Rongshao , Liang Pan , Liu Yun 
Published: April 2022

AbstractBackgroundDifferent dialysis treatments may affect the composition and structure of the intestinal flora of dialysis-treated chronic kidney disease (CKD) patients. This study aimed to analyze the correlations between the different flora and the nutritional indexes and further explore the potential metabolic pathways in patients with CKD in end-stage renal disease (ESRD).MethodsAltogether, 102 patients with ESRD were recruited and categorized into the hemodialysis (HD) group (N = 49) and the peritoneal dialysis (PD) group (N = 53). Their biochemical indexes, anthropometric indicators, and inflammatory markers were determined. The total genomic DNA was extracted for 16S ribosomal DNA sequencing. Furthermore, bioinformatics analysis was employed for functional analysis.ResultsAnthropometric indicators, including handgrip strength, mid-upper arm circumference, mid-upper arm muscle circumference, and body mass index, in the HD and PD groups showed a positive correlation with butyric acid-producing bacteria (RosellaandPhascolarctobacterium) and a negative correlation with conditional pathogens (Escherichiaspp.). Meanwhile, the inflammatory markers, including high-sensitivity C-reactive protein and interleukin-6, were significantly higher in the PD-protein–energy wasting (PEW) group than in the PD-non-protein–energy wasting (NPEW) group; although they showed an increasing trend in the HD-PEW group, no significant difference was noted.Rosellawas considerably scarce in the HD-PEW group than in the HD-NPEW group, whereasEscherichiawas substantially more abundant in the PD-PEW group than in the PD-NPEW group. Compared with the HD group, the essential amino acid synthesis pathway, amino acid metabolism-related enzyme pathways, and aminoacyl-transfer RNA biosynthesis pathways were weakened in the PD group. Most carbohydrate metabolic pathways were weakened, although the tricarboxylic acid cycle was slightly enhanced. Concurrently, the fatty acid metabolism was enhanced, whereas fatty acid synthesis was weakened; the metabolic pathways of B vitamins were also weakened. These potential metabolic pathways of the various compounds released by intestinal flora showed a significant correlation with blood biochemical indexes, anthropometric indicators, and inflammatory markers.ConclusionIn patients with ESRD, different dialysis treatments affected the abundance of butyric acid-producing bacteria (RosellaandPhascolarctobacterium) and conditional pathogens (Escherichiaspp.). Butyric acid-producing bacteria showed a positive correlation with PEW and showed a negative correlation withEscherichia. Improving the intestinal diversity and increasing the amount of butyric acid-producing bacteria, such asBlautella, Faecococcus, andPhascolarctobacterium, are potential therapeutic approaches to enhance protein–energy consumption in patients with ESRD.