bluuebunny/crossref_metadata_2025_split huggingface dataset:
An externally validated fully automated deep learning algorithm to classify COVID-19 and other pneumonias on chest computed tomography
Authors: Vaidyanathan Akshayaa , Guiot Julien , Zerka Fadila , Belmans Flore , Van Peufflik Ingrid , Deprez Louis , Danthine Denis , Canivet Gregory , Lambin Philippe , Walsh Sean , Occhipinti Mariaelena , Meunier Paul , Vos Wim , Lovinfosse Pierre , Leijenaar Ralph T.H. 
Published: March 2022

PurposeIn this study, we propose an artificial intelligence (AI) framework based on three-dimensional convolutional neural networks to classify computed tomography (CT) scans of patients with coronavirus disease 2019 (COVID-19), influenza/community-acquired pneumonia (CAP), and no infection, after automatic segmentation of the lungs and lung abnormalities.MethodsThe AI classification model is based on inflated three-dimensional Inception architecture and was trained and validated on retrospective data of CT images of 667 adult patients (no infection n=188, COVID-19 n=230, influenza/CAP n=249) and 210 adult patients (no infection n=70, COVID-19 n=70, influenza/CAP n=70), respectively. The model's performance was independently evaluated on an internal test set of 273 adult patients (no infection n=55, COVID-19 n= 94, influenza/CAP n=124) and an external validation set from a different centre (305 adult patients: COVID-19 n=169, no infection n=76, influenza/CAP n=60).ResultsThe model showed excellent performance in the external validation set with area under the curve of 0.90, 0.92 and 0.92 for COVID-19, influenza/CAP and no infection, respectively. The selection of the input slices based on automatic segmentation of the abnormalities in the lung reduces analysis time (56 s per scan) and computational burden of the model. The Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis (TRIPOD) score of the proposed model is 47% (15 out of 32 TRIPOD items).ConclusionThis AI solution provides rapid and accurate diagnosis in patients suspected of COVID-19 infection and influenza.
Genome-wide analysis identified novel susceptible genes of restless legs syndrome in migraineurs
Authors: Jiang Yun-Jin , Fann Cathy Shen-Jang , Fuh Jong-Ling , Chung Ming-Yi , Huang Hui-Ying , Chu Kuo-Chang , Wang Yen-Feng , Hsu Chia-Lin , Kao Lung-Sen , Chen Shih-Pin , Wang Shuu-Jiun 
Published: March 2022

Abstract
Background
Restless legs syndrome is a highly prevalent comorbidity of migraine; however, its genetic contributions remain unclear.

Objectives
To identify the genetic variants of restless legs syndrome in migraineurs and to investigate their potential pathogenic roles.

Methods
We conducted a two-stage genome-wide association study (GWAS) to identify susceptible genes for restless legs syndrome in 1,647 patients with migraine, including 264 with and 1,383 without restless legs syndrome, and also validated the association of lead variants in normal controls unaffected with restless legs syndrome (n = 1,053). We used morpholino translational knockdown (morphants), CRISPR/dCas9 transcriptional knockdown, transient CRISPR/Cas9 knockout (crispants) and gene rescue in one-cell stage embryos of zebrafish to study the function of the identified genes.

Results
We identified two novel susceptibility loci rs6021854 (in VSTM2L) and rs79823654 (in CCDC141) to be associated with restless legs syndrome in migraineurs, which remained significant when compared to normal controls. Two different morpholinos targeting vstm2l and ccdc141 in zebrafish demonstrated behavioural and cytochemical phenotypes relevant to restless legs syndrome, including hyperkinetic movements of pectoral fins and decreased number in dopaminergic amacrine cells. These phenotypes could be partially reversed with gene rescue, suggesting the specificity of translational knockdown. Transcriptional CRISPR/dCas9 knockdown and transient CRISPR/Cas9 knockout of vstm2l and ccdc141 replicated the findings observed in translationally knocked-down morphants.

Conclusions
Our GWAS and functional analysis suggest VSTM2L and CCDC141 are highly relevant to the pathogenesis of restless legs syndrome in migraineurs.
SETD8 cooperates with MZF1 to participate in hyperglycemia-induced endothelial inflammation via elevation of WNT5A levels in diabetic nephropathy
Authors: Wang Fei , Hou Wenting , Li Xue , Lu Lihong , Huang Ting , Zhu Minmin , Miao Changhong 
Published: March 2022

Abstract
Objective
Diabetic nephropathy (DN) is regarded as the main vascular complication of diabetes mellitus, directly affecting the outcome of diabetic patients. Inflammatory factors were reported to participate in the progress of DN. Wingless-type family member 5 (WNT5A), myeloid zinc finger 1 (MZF1), and lysine methyltransferase 8 (SETD8) have also been reported to elevate inflammatory factor levels and activate the nuclear factor kappa B (NF-κB) pathway to induce endothelial dysfunction. In the current study, it was assumed that MZF1 associates with SETD8 to regulate WNT5A transcription, thus resulting in hyperglycemia-induced glomerular endothelial inflammation in DN.

Methods
The present study recruited 25 diagnosed DN patients (type 2 diabetes) and 25 control participants (nondiabetic renal cancer patients with normal renal function, stage I–II) consecutively. Moreover, a DN rat and cellular model was constructed in the present study. Immunohistochemistry, Western blot, and quantitative polymerase chain reaction (qPCR) were implemented to determine protein and messenger RNA (mRNA) levels. Coimmunoprecipitation (CoIP) and immunofluorescence were implemented in human glomerular endothelial cells (HGECs). Chromatin immunoprecipitation assays and dual luciferase assays were implemented to determine transcriptional activity.

Results
The results of this study indicated that levels of WNT5A expression, p65 phosphorylation (p-p65), and inflammatory factors were all elevated in DN patients and rats. In vitro, levels of p-p65 and inflammatory factors increased along with the increase of WNT5A expression in hyperglycemic HGECs. Moreover, high glucose increased MZF1 expression and decreased SETD8 expression. MZF1 and SETD8 inhibit each other under the stimulus of high glucose, but cooperate to regulate WNT5A expression, thus influencing p-p65 and endothelial inflammatory factors levels. Overexpression of MZF1 and silencing of SETD8 induced endothelial p-p65 and inflammatory factors levels, which can be reversed by si-WNT5A. Mechanistic research indicated that MZF1, SETD8, and its downstream target histone H4 lysine 20 methylation (H4K20me1) all occupied the WNT5A promoter region. sh-SETD8 expanded the enrichment of MZF1 on WNT5A promoter. Our in vivo study proved that SETD8 overexpression inhibited levels of WNT5A, p-p65 expression, and inflammatory factors in DN rats.

Conclusions
MZF1 links with SETD8 to regulate WNT5A expression in HGECs, thus elevating levels of hyperglycemia-mediated inflammatory factors in glomerular endothelium of DN patients and rats.
Trial registration ChiCTR, ChiCTR2000029425. 2020/1/31, http://www.chictr.org.cn/showproj.aspx?proj=48548
Genome-wide identification and characterization of PdbHLH transcription factors related to anthocyanin biosynthesis in colored-leaf poplar (Populus deltoids)
Authors: Wang Xiao-jing , Peng Xu-qian , Shu Xiao-chun , Li Yu-hang , Wang Zhong , Zhuang Wei-bing 
Published: March 2022

AbstractBasic helix-loop-helix (bHLH) proteins are transcription factors (TFs) that have been shown to regulate anthocyanin biosynthesis in many plant species. However, the bHLH gene family in Populus deltoids has not yet been reported. In this study, 185 PdbHLH genes were identified in the Populus deltoids genome and were classified into 15 groups based on their sequence similarity and phylogenetic relationships. Analysis of the gene structure, chromosome location and conserved motif of the PdbHLH genes were performed by bioinformatic methods. Gene duplication analyses revealed that 114 PdbHLH were expanded and retained after WGD/segmental and proximal duplication. Investigation of cis-regulatory elements of PdbHLH genes indicated that many PdbHLH genes are involved in the regulation of anthocyanin biosynthesis. The expression patterns of PdbHLHs were obtained from previous data in two colored-leaf poplar (QHP and JHP) and green leaf poplar (L2025). Further analysis revealed that 12 candidate genes, including 3 genes (PdbHLH57, PdbHLH143, and PdbHLH173) from the subgroup III(f) and 9 gene from other groups, were positively associated with anthocyanin biosynthesis. In addition, 4 genes (PdbHLH4, PdbHLH1, PdbHLH18, and PdbHLH164) may be involved in negatively regulating the anthocyanin biosynthesis. These results provide a basis for the functional characterization of bHLH genes and investigations on the molecular mechanisms of anthocyanin biosynthesis in colored-leaf poplar.
Clonal spread of carbapenemase-producing Enterobacteriaceae in a region, China
Authors: Yin Changfu , Yang Weiwei , Lv Yuanpeng , Zhao Peng , Wang Jiansheng 
Published: March 2022

Abstract
Background
The increasing number of carbapenemase-producing Enterobacterales (CPE) has become a serious problem globally. This study aimed to elucidate their geographically epidemiological characteristics.

Methods
Resistance genes were identified by polymerase chain reaction (PCR) and sequencing. Bacterial genotyping was studied using multilocus sequence typing (MLST) and wzi typing. The transferability of carbapenemase genes was determined by a broth mating method. The relationships between the rates of antimicrobial consumption and the prevalence of CRE were performed by Pearson's or Spearman's correlation analyses.

Results
A total of 930 phenotypically confirmed carbapenem-resistant Enterobacterales (CRE) isolates collected from 19 hospitals were genotypically characterized. K. pneumoniae (KP) and E. coli isolates were 785 (85.14%) and 96 (10.41%) among 922 CPE isolates. Two major carbapenemase genes blaKPC-2 and blaNDM in CPE isolates accounted for 84.6% (n = 780) and 13.77% (n = 127). ST11 comprised 86.83% (633/729) of KPC-2 KP isolates. Different combinations of extended spectrum-β-lactamase (ESBL) genes of blaSHV, blaCTX, and blaTEM were found in KPC-2 producing KP isolates, and blaCTM-M-14/15, blaSHV-11/12 and blaTEM-1 were common ESBL genotypes. The wzi typing method could further subdivide ST11 KP group into at least five subgroups, among which wzi209 (69.83%, 442/633) was the most frequently isolated, followed by wzi141 (25.28%, 160/633). Conjugation assays showed that high conjugation rates were observed in CPE (15.24%, 32/210) for NDM plasmids, but relatively low (8.1%, 17/210) for KPC-2 plasmids. Different STs, different wzis and temperature could influence plasmid conjugation efficiency. No associations between the rates of antibiotics consumption and CPE prevalence were observed. The number of intra-hospital and inter-hospital transfers of CPE patients increased gradually from 18 (17.82%, 101) and 12 (11.88%, 101) in 2015 to 63 (30.73%, 205) and 51 (24.88%, 205) in 2018 (p = 0.016 and p = 0.008), respectively. Evidence-based measures could effectively reduce the prevalence of ST11-wzi209 clone but failed to control the dissemination of ST11-wzi141 KP clone.

Conclusions
Clonal spread of CPE, especially KPC-2 ST11 KP was the key factor contributing to the CPE increase in the region. Continued vigilance for the importations should be maintained. Coordinated regional interventions are urgently needed to reduce CPE threat.
An integrated omics analysis reveals the gene expression profiles of maize, castor bean, and rapeseed for seed oil biosynthesis
Authors: Liu Nian , Liu Jing , Fan Shihang , Liu Hongfang , Zhou Xue-Rong , Hua Wei , Zheng Ming 
Published: March 2022

AbstractBackgroundSeed storage lipids are valuable for human diet and for the sustainable development of mankind. In recent decades, many lipid metabolism genes and pathways have been identified, but the molecular mechanisms that underlie differences in seed oil biosynthesis in species with developed embryo and endosperm are not fully understood.ResultsWe performed comparative genome and transcriptome analyses of castor bean and rapeseed, which have high seed oil contents, and maize, which has a low seed oil content. These results revealed the molecular underpinnings of the low seed oil content in maize. First of all, transcriptome analyses showed that more than 61% of the lipid- and carbohydrate-related genes were regulated in castor bean and rapeseed, but only 20.1% of the lipid-related genes and 22.5% of the carbohydrate-related genes were regulated in maize. Then, compared to castor bean and rapeseed, fewer lipid biosynthesis genes but more lipid metabolism genes were regulated in the maize embryo. More importantly, most maize genes encoding lipid-related transcription factors, triacylglycerol (TAG) biosynthetic enzymes, pentose phosphate pathway (PPP) and Calvin Cycle proteins were not regulated during seed oil synthesis, despite the presence of many homologs in the maize genome. Additionally, we observed differential regulation of vital oil biosynthetic enzymes and extremely high expression levels of oil biosynthetic genes in castor bean, which were consistent with the rapid accumulation of oil in castor bean developing seeds.ConclusionsCompared to high-oil seeds (castor bean and rapeseed), less oil biosynthetic genes were regulated during the seed development in low-oil seed (maize). These results shed light on molecular mechanisms of lipid biosynthesis in maize, castor bean, and rapeseed. They can provide information on key target genes that may be useful for future experimental manipulation of oil production in oil plants.
Postpolypectomy fever in patients with serious infection: a report of two cases
Authors: Jing Wang , Qinghua Li , Zhiwen Yang 
Published: March 2022

Abstract
Background
Postpolypectomy fever (PPF) is a rare complication in patients after colonoscopy. Because of the absence of evidence of microperforation and abdominal tenderness, patients with PPF usually present mild clinical symptoms with a good prognosis.

Case presentation
In this study, all patients who underwent colonoscopic examination in our hospital between January 2019 and December 2019 were enrolled. Of these, two patients developed PPF after polypectomy, exhibiting serious infection without definitive fever foci. One patient experienced rapidly aggravated type 1 respiratory failure and abnormal hepatic function, which were attributed to colonoscopy-associated infection. After active antibiotic therapy, both patients were discharged without any complications.

Conclusions
In summary, our study provides novel insights into patients with PPF who develop serious infections with life-threatening complications.
Clinical characteristics and treatment outcomes of primary malignant melanoma of esophagus: a single center experience
Authors: Kim Tae-Se , Min Byung-Hoon , Min Yang Won , Lee Hyuk , Rhee Poong-Lyul , Kim Jae J. , Lee Jun Haeng 
Published: March 2022

Abstract
Background
Primary malignant melanoma of esophagus (PMME) is an extremely rare disease with poor prognosis. We aimed to determine the clinical characteristics and treatment outcomes of patients with PMME.

Methods
We retrospectively reviewed 17 patients diagnosed with PMME in Samsung Medical Center between 2000 and 2020 with median 34 months of follow-up. Survival outcomes were analyzed with Kaplan–Meier method.

Results
15 patients (88.2%) were male and the most common presenting symptom was dysphagia (9/17, 52.9%). On endoscopy, tumors were mass-forming in 15 patients (88.2%) and diffusely infiltrative in two patients (11.8%). Lesions were melanotic in 13 patients (76.5%) and amelanotic in four patients (23.5%). The most common tumor location was lower esophagus (11/17, 64.7%). The disease was metastatic at the time of diagnosis in four patients (23.5%). As for treatment, 10 patients (58.8%) underwent surgery. In all 17 patients, the median overall survival was 10 months. In surgically treated patients, all patients experienced recurrence and the median disease-free survival was 4 months. There was no statistical difference in overall survival between patients with or without surgery. Patients with diffusely infiltrative tumor morphology had better overall survival compared to those with mass-forming tumor morphology (P = 0.048). Two patients who received immunotherapy as the first-line treatment without surgery showed overall survival of 34 and 18 months, respectively.

Conclusions
As radical resection for patients with PMME does not guarantee favorable treatment outcomes, novel treatment strategy is required. Further large-scale studies are warranted to determine the efficacy of immunotherapy for patients with PMME.
Primary care provider notions on instituting community-based geriatric support in Uganda
Authors: Ssensamba Jude Thaddeus , Nakafeero Mary , Musana Hellen , Amollo Mathew , Ssennyonjo Aloysius , Kiwanuka Suzanne N. 
Published: March 2022

Abstract
Background
Understanding of the most economical and sustainable models of providing geriatric care to Africa’s rising ageing population is critical. In Uganda, the number of old adults (60 years and above) continues to rise against absence of policies and guidelines, and models for providing care to this critical population. Our study explored public primary health care provider views on how best community-based geriatric support (CBGS) could be instituted as an adaptable model for delivering geriatric care in Uganda’s resource-limited primary public health care settings.

Methods
We interviewed 20 key informants from four districts of Bukomansimbi, Kalungu, Rakai, and Lwengo in Southern Central Uganda. Respondents were leads (in-charges) of public primary health units that had spent at least 6 months at the fore said facilities. All interviews were audio-recorded, transcribed verbatim, and analysed based on Hsieh and Shannon’s approach to conventional manifest content analysis.

Results
During analysis, four themes emerged: 1) Structures to leverage for CBGS, 2) How to promote CBGS, 3) Who should be involved in CBGS, and 4) What activities need to be leveraged to advance CBGS? The majority of the respondents viewed using the existing village health team and local leadership structures as key to the successful institutionalization of CBGS; leveraging community education and sensitization using radio, television, and engaging health workers, family relatives, and neighbors. Health outreach activities were mentioned as one of the avenues that could be leveraged to provide CBGS.

Conclusion
Provider notions pointed to CBGS as a viable model for instituting geriatric care in Uganda’s public primary healthcare system. However, this requires policymakers to leverage existing village health team and local governance structures, conduct community education and sensitization about CBGS, and bring onboard health workers, family relatives, and neighbors.
Dynapenic abdominal obesity is associated with mild cognitive impairment in patients with cardiometabolic disease: a cross-sectional study
Authors: Oba Kazuhito , Tamura Yoshiaki , Ishikawa Joji , Suzuki Hiroyuki , Fujiwara Yoshinori , Tachibana Aya , Kodera Remi , Toyoshima Kenji , Chiba Yuko , Araki Atsushi 
Published: March 2022

Abstract
Background
Dementia is an important health issue for older people and requires early intervention in the mild cognitive impairment (MCI) stage to manage risk factors. Both dynapenia (DP) and abdominal obesity (AO) are associated with inflammation and oxidative stress, which may be involved in the pathogenesis of cognitive impairment. Therefore, in this cross-sectional study, we aimed to evaluate the association between MCI and dynapenic abdominal obesity (DAO), a combination of DP and AO.

Methods
A total of 417 older outpatients with cardiometabolic diseases without severe cognitive impairment were studied to compare cognitive function in four groups: control, DP, AO, and DAO groups. DAO was defined as the combination of DP (handgrip strength of < 28 kg and < 18 kg in men and women, respectively) and AO (waist circumference of ≥ 85 cm and ≥ 90 cm in men and women, respectively). MCI was defined as a score of ≤ 25 in the Japanese version of the Montreal Cognitive Assessment. Multiple regression analyses were performed to examine if MCI was independently associated with DAO, low handgrip strength, or high waist circumference.

Results
The DAO group obtained the lowest cognitive test scores and had the highest prevalence of MCI. Furthermore, after adjusting for covariates, the logistic regression analysis showed that patients in the DAO group were at an increased risk of MCI (odds ratio [OR] = 3.98, 95% confidence interval [CI]: 1.15–13.77). Further logistic regression analyses revealed that both low handgrip strength (OR = 2.19, 95% CI: 1.11–4.29) and high waist circumference (OR = 2.03, 95% CI: 1.03–3.99) were associated with MCI.

Conclusions
DAO, which can be easily diagnosed by a combination of handgrip strength and waist circumference, was associated with MCI in patents with cardiometabolic metabolic disease. This study suggests that screening for MCI in DAO patients could be important for early intervention of dementia prevention.
Bacteremia detection from complete blood count and differential leukocyte count with machine learning: complementary and competitive with C-reactive protein and procalcitonin tests
Authors: Lien Frank , Lin Huang-Shen , Wu You-Ting , Chiueh Tzong-Shi 
Published: March 2022

Abstract
Background
Biomarkers, such as leukocyte count, C-reactive protein (CRP), and procalcitonin (PCT), have been commonly used to predict the occurrence of life-threatening bacteremia and provide prognostic information, given the need for prompt intervention. However, such diagnosis methods require much time and money. Therefore, we propose a method with a high prediction capability using machine learning (ML) models based on complete blood count (CBC) and differential leukocyte count (DC) and compare its performance with traditional CRP or PCT biomarker methods and those of models incorporating CRP or PCT biomarkers.

Methods
We collected 366,586 daily blood culture (BC) results, of which 350,775 (93.2%), 308,803 (82.1%), and 23,912 (6.4%) cases were issued CBC/DC (CBC/DC group), CRP with CBC/DC (CRP&CBC/DC group), and PCT with CBC/DC (PCT&CBC/DC group), respectively. For the ML methods, conventional logistic regression and random forest models were selected, trained, applied, and validated for each group. Fivefold validation and prediction capability were also evaluated and reported.

Results
Overall, the ML methods, such as the random forest model, demonstrated promising performances. When trained with CBC/DC data, it achieved an area under the ROC curve (AUC) of 0.802, which is superior to the prediction conventionally made with CRP/PCT levels (0.699/0.731). Upon evaluating the performance enhanced by incorporating CRP or PCT biomarkers, it reported no substantial AUC increase with the addition of either CRP or PCT to CBC/DC data, which suggests the predicting power and applicability of using only CBC/DC data. Moreover, it showed competitive prognostic capability compared to the PCT test with similar all-cause in-hospital mortality (45.10% vs. 47.40%) and overall median survival time (27 vs. 25 days).

Conclusions
The ML models using only CBC/DC data yielded more accurate bacteremia predictions compared to those by methods using CRP and PCT data and reached similar prognostic performance as by PCT data. Thus, such models are potentially complementary and competitive with traditional CRP and PCT biomarkers for conducting and guiding antibiotic usage.