bluuebunny/crossref_metadata_2025_split huggingface dataset:
CT Imaging Changes of Corona Virus Disease 2019 (COVID-19): A multi-center study in Southwest China
Authors: Li Xiaoming , Zeng Wenbing , Li Xiang , Chen Haonan , Shi Linping , Li Xinghui , Xiang Hongnian , Cao Yang , Chen Hui , Liu Chen , Wang Jian 
Published: March 2020

Abstract
Background: Since the first case of a coronavirus disease 2019 (COVID-19) infection pneumonia was detected in Wuhan, China, a series of confirmed cases of the COVID-19 were found in Southwest China. The aim of this study was to describe the imaging manifestations of hospitalized patients with confirmed COVID-19 infection in southwest China. Methods: In this retrospective study, data were collected from 131 patients with confirmed coronavirus disease 2019 (COVID-19) from 3 Chinese hospitals. Their common clinical manifestations, as well as characteristics and evolvement features of chest CT images, were analyzed. Results: A total of 100 (76%) patients had a history of close contact with people living in Wuhan , Hubei. The clinical manifestations of COVID-19 included cough, fever. Most of the lesions identified in chest CT images were multiple lesions of bilateral lungs, lesions were more localized in the peripheral lung, 109 (83%) patients had more than two lobes involved, 20 (15%) patients presented with patchy ground glass opacities, patchy ground glass opacities and consolidation of lesions co-existing in 61 (47%) cases. Complications such as pleural thickening, hydrothorax, pericardial effusion, and enlarged mediastinal lymph nodes were detected but only in rare cases. For the follow-up chest CT examinations (91 cases), We found 66 (73%) cases changed very quickly, with an average of 3.5 days, 25 cases (27%) presented absorbed lesions, progression was observed in 41 cases (46%), 25 (27%) cases showed no significant changes. Conclusion: Chest CT plays an important role in diagnosing COVID-19. The imaging pattern of multifocal peripheral ground glass or mixed consolidation is highly suspicious of COVID-19, that can quickly change over a short period of time.
BIRC7 and STC2 expression are associated with tumorigenesis and poor outcome in extrahepatic cholangiocarcinoma
Authors: Li Jiequn , Yang Zhulin , Huang Shengfu , Li Daiqiang 
Published: March 2020

Abstract
Background: Extrahepatic cholangiocarcinoma (EHCC) is a highly aggressive epithelial malignancy and has a poor prognosis for the insensitivity to therapies and difficulty in detection. Novel targets and biomarkers are urgently needed to develop for functional, diagnostic and prognostic application on EHCC.Methods: Immunohistochemical staining technique using the EnVision antibody complex was performed on the samples obtained from 100 EHCC，30 peritumoral extrahepatic biliary tract (EHBT), 10 EHBT adenomas and 15 normal EHBT tissues.Results: The positive rates of BIRC7 and STC2 expression in tissues obtained from peritumoral EHBT, EHBT adenomas and normal EHBT were significantly lower than those in EHCC tissues. BIRC7 and STC2 proteins were expressed at significantly higher levels in patients with lymph node metastasis, invasion of adjacent tissues, and higher TNM stage (III and/or IV) and unable to undergo resection (biopsy only). Kaplan-Meier survival curves indicated that significantly decreased overall survival rate in patients with positive-BIRC7 or positive-STC2 expression compared with patients of negative-BIRC7 or negative-STC2 expression, respectively. Cox-proportional regression analysis demonstrated that positive-BIRC7 and positive-STC2 expression, along with poor differentiation of EHCC, tumor size >3cm, lymph node metastasis, invasion of adjacent tissues and unable to undergo resection are independent prognostic factors of EHCC patients.Conclusions：The levels of BIRC7 and STC2 expression were correlated with clinicopathological characteristics of EHCC, and positive expression of BIRC7 and STC2 are associated with progression and poor clinical outcomes of EHCC. BIRC7 and STC2 might be a potential biomarker for EHCC diagnosis and prognosis.
Non-Active Site Mutants of HIV-1 Protease Influence Resistance and Sensitization Towards Protease Inhibitors
Authors: Bastys Tomas , Gapsys Vytautas , Walter Hauke , Heger Eva , Doncheva Nadezhda T , Kaiser Rolf , de Groot Bert L , Kalinina Olga V 
Published: March 2020

Abstract
BackgroundHIV-1 can develop resistance to antiretroviral drugs, mainly through mutations within the target regions of the drugs. In HIV-1 protease, a majority of resistance-associated mutations that develop in response to the therapy with protease inhibitors are found in the protease’s active site that serves also as a binding pocket for the protease inhibitors, thus directly impacting the protease-inhibitor interactions. Some resistance-associated mutations, however, are found in more distant regions, and the exact mechanisms how these mutations aﬀect protease-inhibitor interactions are unclear. Furthermore, some of these mutations, e.g. N88S and L76V, do not only induce resistance to the currently administered drugs, but contrarily induce sensitivity towards other drugs. In this study, mutations N88S and L76V, along with two other resistance-associated mutations, M46I and I84V, are analysed by means of molecular dynamics simulations to investigate their role in complexes of the protease with diﬀerent inhibitors and in diﬀerent background sequence contexts.ResultsUsing these simulations for alchemical calculations to estimate the eﬀects of mutations M46I, I84V, N88S, and L76V on binding free energies shows they are in general in line with the mutations’ eﬀect on IC50 values. For the primary mutation L76V, however, the presence of a background mutation M46I in our analysis inﬂuences whether the unfavourable eﬀect of L76V on inhibitor binding is suﬃcient to outweigh the accompanying reduction in catalytic activity of the protease. Finally, we show that L76V and N88S changes the hydrogen bond stability of these residues with residues D30/K45 and D30/T31/T74, respectively.ConclusionsWe demonstrate that estimating the eﬀect of both binding pocket and distant mutations on inhibitor binding free energy using alchemical calculations can reproduce their eﬀect on the experimentally measured IC50 values. We show that distant site mutations L76V and N88S aﬀect the hydrogen bond network in the protease’s active site, which oﬀers an explanation for the indirect eﬀect of these mutations on inhibitor binding. This work thus provides valuable insights on interplay between primary and background mutations and mechanisms how they aﬀect inhibitor binding.
Single-cell RNA expression profiling shows that ACE2, the putative receptor of COVID-2019, has significant expression in nasal and mouth tissue, and is co-expressed with TMPRSS2 and not co-expressed with SLC6A19 in the tissues
Authors: Wu Chao , Zheng Min 
Published: March 2020

Abstract
A novel coronavirus (COVID-2019) was first identified in Wuhan, Hubei Province, and then spreads to the other Provinces of China. COVID-2019 was reported to share the same receptor, Angiotensin-converting enzyme 2 (ACE2), with SARS-CoV. But the infection rate of COVID-2019 is much higher than SARS-CoV. The biophysical and structural evidence showed that the COVID-2019 binds ACE2 with 10~20 times affinity than SARS-CoV. TMPRSS2 cleaves ACE2 and facilitates the entry of the virus into host cells. The presence of SLC6A19 may block the access of TMPRSS2 to the cutting site on ACE2 and weaken the entry of COVID-2019 into host cells. Here based on the public single-cell RNA-Seq datasets, we analyzed the ACE2 expression in the nasal, mouth, lung, and colon tissues. We find that the number of ACE2-expressing cells in the nasal and mouth tissues is comparable to the number of ACE2-expressing cells in the lung and colon tissues. We also find that ACE2 tends to be co-expressed with TMPRSS2 and not co-expressed with SLC6A19 in the nasal and mouth tissues. With the results, we infer that nasal and mouth tissues may be the first host cells of COVID-2019 infection. In our previous report in medRxiv and a recurrent report in New England Journal of Medicine, the COVID-2019 load tends to be higher in the nasal-swabs than in throat-swabs. We believe the roles of nasal and mouth tissues in COVID-2019 infection should be investigated, and we need to pay more attention to protect nose and mouth from COVID-2019 infection.
Anti-inflammatory Mechanism of Rhein in Treating Asthma Based on Network Pharmacology
Authors: Feng Junfang , Chen Ou , Wang Yibiao 
Published: March 2020

Abstract
Background: Network pharmacological methods were used to predict the anti-inflammatory targets and related pathways of rhein in the treatment of asthma and to elucidate its mechanism of action. In addition, we validated the anti-inflammatory effects of rhein in vitro.Methods: The corresponding targets of rhein were obtained from the TCMSP database, and molecular docking was performed. A network of predicted rhein targets was established and analysed with Cytoscape 3.7.1. The anti-inflammatory targets in the TTD database were searched to build a PPI network, which was merged with the ingredient-target network to screen anti-inflammatory targets associated with rhein. A network of anti-inflammatory rhein targets during the in vivo treatment of asthma was constructed to screen the anti-inflammatory targets related to asthma. KEGG enrichment analysis was performed with the Enrichr database and Cytoscape 3.7.1. The expression levels of proteins in the MAPK/NF-κB signalling pathway were assessed by Western blot analysis.Results: Altogether, 17 targets were obtained. Epidermal active growth factor receptor (EGFR), E-selectin (SELE), macrophage migration inhibitory factor (MIF), and mitogen-activated protein kinase 14 (MAPK14) might be important anti-inflammatory targets of rhein during asthma treatment. We selected the MAPK signalling pathway to determine the anti-inflammatory effects of rhein.Conclusion: The anti-inflammatory mechanism of the treatment of asthma with rhein may be related to MAPK14, EGFR, SELE, and MIF, as well as their signalling pathways. To prevent the exacerbation of asthma, instead of targeting a single pathway or a single target, all these targets and their signalling pathways should be controlled holistically. Rhein may reduce inflammation by inhibiting the MAPK/NF-κB pathway.
Modified NUTRIC score: a predictor for mortality in patients with septic shock-a single center retrospective study
Authors: Hou Jiatong , Liu Wentao , Wu Yina , Wu Xiaoqing , Duan Jun 
Published: March 2020

Abstract
Objective

to evaluate the modified NUTRIC score in identifying nutritional risk patients and predicting mortality in septic shock patients.

Methods

A retrospective study was performed with septic shock patients admitted to the intensive care unit (ICU) from January 2018 to December 2019. A receiver operating characteristic (ROC) curve was used to identify the performance of the instruments to predict mortality.

Results

Among the patients, 46 patients were non-survivors and 78 were survivors. The median mNUTRIC score was 5.41±1.69 vs 4.29±1.58(P<0.0001). 28-day mortality increased with higher modified NUTRIC score. In the ROC curve of mNUTRIC score, the best cut-off point was at 4. It was identified for our sample, showing the best parameters of both sensitivity and specificity for the prediction of mortality 28 days after ICU admission. The area under the curves (AUCs) of the mNUTRIC score for predicting 28-day mortality was 0.664(95%CI:0.574, 0.746).

Conclusions

The modified NUTRIC score was a good nutritional risk assessment tool for septic shock patients. mNUTRIC score showed a good performance for the prediction of 28-day mortality. A new cutoff value was identified for septic shock patients.
The relationship between a microfinance-based healthcare delivery platform, health insurance coverage, health screenings, and disease management in rural Western Kenya
Authors: Rosenberg Molly , Amisi James Akiruga , Szkwarko Daria , Tran Dan N. , Genberg Becky , Luetke Maya , Kianersi Sina , Namae Jane , Laktabai Jeremiah , Pastakia Sonak 
Published: March 2020

Abstract
Introduction Structural barriers often prevent rural Kenyans from receiving healthcare and diagnostic testing. The Bridging Income Generation through grouP Integrated Care (BIGPIC) Family intervention facilitates microfinance groups, provides health screenings and treatment, and delivers education about health insurance coverage to address some of these barriers. This study evaluated the association between participation in BIGPIC microfinance groups and health screening/disease management outcomes.Methods From November 2018 to March 2019, we interviewed a sample of 300 members of two rural communities in Western Kenya, 100 of whom were BIGPIC microfinance members. We queried participants about their experiences with health screening and disease management for HIV, diabetes, hypertension, tuberculosis, and cervical cancer. We used log-binomial regression models to estimate the association between microfinance membership and each health outcome, adjusting for key covariates. We also examined the individual and joint effects of microfinance and health insurance coverage on each health outcome.Results Microfinance members were more likely to be screened for the health conditions we queried, including those provided by BIGPIC [e.g. diabetes: aPR (95% CI): 3.46 (2.60, 4.60)] and those not provided [e.g. cervical cancer: aPR (95% CI): 2.43 (1.21, 4.86)]. Only 11% had active health insurance, yet we found some trends of better disease management among microfinance group members and those with health insurance.Conclusions In rural Kenya, a microfinance program integrated with healthcare delivery may be effective at increasing health screening. Interventions designed to thoughtfully and sustainably address structural barriers to healthcare will be critical to improving the health of those living in low-resource settings.
A genome-wide association study in Indian wild rice accessions for resistance to the root-knot nematode Meloidogyne graminicola
Authors: Hada Alkesh , Dutta Tushar K. , Singh Nisha , Rai Vandna , Singh Nagendra K. , Rao Uma 
Published: March 2020

Abstract
Background: Rice root-knot nematode (RRKN), Meloidogyne graminicola is one of the major biotic constraints in rice-growing countries of Southeast Asia. Host plant resistance is an environmentally-friendly and cost-effective mean to mitigate RRKN damage to rice. Considering the limited availability of genetic resources in the Asian rice (Oryza sativa) cultivars, exploration of novel sources and genetic basis of RRKN resistance is necessary. Results: We screened 272 diverse wild rice accessions (O. nivara, O. rufipogon, O. sativa f. spontanea) to identify genotypes resistant to RRKN. We dissected the genetic basis of RRKN resistance using a genome-wide association study with SNPs (single nucleotide polymorphism) genotyped by 50K “OsSNPnks” genic Affymetrix chip. Population structure analysis revealed that these accessions were stratified into three major sub-populations. Overall, 40 resistant accessions (nematode gall number and multiplication factor/MF < 2) were identified, with 17 novel SNPs being significantly associated with phenotypic traits such as number of galls, egg masses, eggs/egg mass and MF per plant. SNPs were localized to the quantitative trait loci (QTL) on chromosome 1, 2, 3, 4, 6, 10 and 11 harboring the candidate genes including NBS-LRR, Cf2/Cf5 resistance protein, MYB, bZIP, ARF, SCARECROW and WRKY transcription factors. Expression of these identified genes was significantly (P < 0.01) upregulated in RRKN-infected plants compared to mock-inoculated plants at 7 days after inoculation. Conclusion: The identified SNPs enrich the repository of candidate genes for future marker-assisted breeding program to alleviate the damage of RRKN in rice.
Partial trisomy 4q and monosomy 5p inherited from a maternal translocationt(4;5)(q33;p15) in three adverse pregnancies
Authors: Zhang Jingbo , Zhang Bei , Liu Tong , Xie Huihui , Zhai Jingfang 
Published: March 2020

Abstract
Background Carriers of balanced reciprocal chromosomal translocations are at known reproductive risk for offspring with unbalanced genotypes and resultantly abnormal phenotypes. After fertilization of a balanced translocation carrier with a normal gamete, the partial monomer or partial trisomy embryo will undergo abortion, fetal arrest or fetal malformatio. We reported a woman with balanced translocation who had two adverse pregnancies. Prenatal diagnosis was made for her third pregnancy to provide genetic counseling and guide her fertility. Case presentation Routine G banding was used to analyze the chromosome karyotypes of amniotic fluid, pregnant women and her son in peripheral blood, and then the chromosomal abnormalities were precisely located by CNV-seq detection. The karyotype of the women was 46,XX,t(4;5)(q33;p15). The karyotypethe of the boy was 46,XY,add(5)(p14). CNV-seq was used for further analysis of the structural chromosomal rearrangement in the boy.The results were shown a deletion of short arm of chromosome 5 capturing regions 5p15.33p15.2, a copy gain of the distal region of chromosome 4 at segment 4q32.3q35.2, a duplication of chromosome 1 at segment 1q41q42.11 and a duplication of chromosome 17 at segment 17p12. Amniocentesis was performed at 17 weeks of gestation. Chromosome karyotype hinted 46,XY,add(5)(p14). Further detection of chromosomal aberrations by CNV-seq showed a deletion of short arm (p) of chromosome 5 at the segment 5p15.33p15.2 and a duplication of the distal region of chromosome 4 at segment 4q32.3q35.2. Conclusions Chromosomal abnormalities in three pregnancies were inherited from the mother. Preimplantation genetic diagnosis is recommended to prevent the birth of children with chromosomal abnormalities.
Autoantibodies directed against α1-adrenergic receptor and endothelin receptor A in patients with prostate cancer
Authors: Wallukat Gerd , Jandrig Burkhand , Becker Niels-Peter , Wendler Johann J. , Göttel Peter , Müller Johannes , Schostak Martin , Schimke Ingolf 
Published: March 2020

Abstract
Background: For prostate cancer, signaling pathways induced by over-boarding stimulation of G-protein coupled receptors (GPCR) such as the endothelin, α1- and β-adrenergic, muscarinic and angiotensin 1 receptors were accused to support the carcinogenesis. However, excessive receptor stimulation by physiological receptor ligands is minimized by a control system that induces receptor sensitization and down-regulation. This system is missing when so-called "functional autoantibodies" bind to the GPCR (GPCR-AAB). If GPCR-AAB were found in patients with prostate cancer, uncontrolled GPCR stimulation could make these autoantibodies an additional supporter in prostate cancer. Methods: Using the bioassay of spontaneously beating cultured rat neonatal cardiomyocytes, GPCR-AAB were identified, quantified and characterized in the serum of 25 patients (aged 56-78 years, median 70 years) with prostate cancer compared to 10 male patients (aged 48-82 years, median 64) with urinary stone disorders (controls). Results: Of the cancer patients, 24 (96%) and 17 (68%), respectively, carried autoantibodies directed against the α1-adrenergic receptor (α1-AAB) and endothelin receptor A (ETA-AAB). No patient was negative for both GPCR-AAB. In contrast, ETA-AAB and α1-AAB were absent in all (100%) and 9 (90%) of the 10 control patients, respectively. While α1-AAB targeted a specific epitope of the first extracellular loop of the α1-adrenergic receptor subtype A, an epitope of the second extracellular loop of the ETA receptor was identified as a target of ETA-AAB. As demonstrated in vitro, the functional activity of both autoantibodies found in prostate cancer can be neutralized by the aptamer BC007. Conclusions: We hypothesized that α1-AAB and ETA-AAB, which are highly present in prostate cancer patients, could by their functional activity support carcinogenesis by excessive receptor stimulation. The in vitro demonstrated neutralization of α1- and ETA-AAB by the aptamer BC007 could open the door to complement the treatments already available for prostate cancer.
A multifunctional platform with single-NIR-laser-triggered photothermal and NO release for synergistic therapy against multidrug-resistant Gram-negative bacteria and their biofilms
Authors: Zhao Baohua , Wang He , Dong Wenjing , Cheng Shaowen , Li Haisheng , Tan Jianglin , Zhou Junyi , He Weifeng , Li Lanlan , Zhang Jianxiang , Luo Gaoxing , Qian Wei 
Published: March 2020

Abstract
Background Infectious diseases caused by multidrug-resistant (MDR) bacteria, especially MDR Gram-negative strains, have become a global public health challenge. Multifunctional nanomaterials for controlling MDR bacterial infections via eradication of planktonic bacteria and their biofilms are of great interest. Results In this study, we developed a multifunctional platform (TG-NO-B) with single NIR laser-triggered PTT and NO release for synergistic therapy against MDR Gram-negative bacteria and their biofilms. When located at the infected sites, TG-NO-B was able to selectively bind to the surfaces of Gram-negative bacterial cells and their biofilm matrix through covalent coupling between the BA groups of TG-NO-B and the bacterial LPS units, which could greatly improve the antibacterial efficiency, and reduce side damages to ambient normal tissues. Upon single NIR laser irradiation, TG-NO-B could generate hyperthermia and simultaneously release NO, which would synergistically disrupt bacterial cell membrane, further cause leakage and damage of intracellular components, and finally induce bacteria death. On one hand, the combination of NO and PTT could largely improve the antibacterial efficiency. On the other hand, the bacterial cell membrane damage could improve the permeability and sensitivity to heat, decrease the photothermal temperature and avoid damages caused by high temperature. Moreover, TG-NO-B could be effectively utilized for synergistic therapy against the in vivo infections of MDR Gram-negative bacteria and their biofilms and accelerate wound healing as well as exhibit excellent biocompatibility both in vitro and in vivo. Conclusions Our study demonstrates that TG-NO-B can be considered as a promising alternative for treating infections caused by MDR Gram-negative bacteria and their biofilms.