bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assigning Protein Function from Domain-Function Associations Using DomFun
Authors: Rojano Elena , Jabato Fernando Moreno , Perkins James Richard , Caballero José Córdoba , Sillitoe Ian , Orengo Christine , Ranea Juan Antonio García , Zonjic Pedro Seoane 
Published: October 2020

Abstract
Background: Protein function prediction remains a key challenge. Domain composition is key to understanding protein function, and domain-based prediction methods consistently perform well in challenges such as CAFA. Here we present DomFun, a Ruby gem that uses associations between protein domains and functions, calculated using multiple indices based on tripartite network analysis. These domain-function associations are combined at the protein level, to generate protein-function predictions. Results: We analysed 14 tripartite networks connecting homologous superfamily and FunFam domains from CATH-Gene3D with functional annotations from the Gene Ontology, KEGG, Reactome and the Human Phenotype Ontology. We validated the results using the CAFA 2 benchmark platform for GO and HPO annotation, finding Simpson's index combined with Stouffer's method led to the best performance in almost all scenarios. We also found that FunFams led to better performance than superfamilies, and better results were found for GO molecular function compared to GO biological process terms. Results were similar to other high-performing domain-based methods in CAFA 2. We also implemented our own benchmark procedure, Pathway Prediction Performance (PPP), which can be used to validate function prediction for additional annotations sources, such as KEGG and Reactome. Using PPP, we found similar results to those found with CAFA 2 for GO, moreover we found good performance for the other annotation sources. As with CAFA 2, Simpson's index with Stouffer's method led to the top performance in most scenarios. Conclusions: DomFun shows comparable performance to other methods evaluated in CAFA 2 when predicting human proteins function with GO. Through our own benchmark procedure, PPP we have shown it can also make accurate predictions for KEGG and Reactome. It performs best when using FunFams, combining Simpson's index derived domain-function associations combined using Stouffer's method. The tool has been implemented so that it could be easily adapted to incorporate other protein features, such as domain data from other sources. The DomFun Ruby gem is available from https://rubygems.org/gems/DomFun and its code is available at https://github.com/ElenaRojano/DomFun .
Circulating Tight-Junction Proteins Are Potential Biomarkers for Blood-Brain Barrier Function in a Model of Neonatal Hypoxic/Ischemic Brain Injury
Authors: Andersson Axel Erik , Mallard Carina , Ek Carl Joakim 
Published: October 2020

Abstract
BackgroundNeonatal hypoxia-ischemia often leads to lifelong disabilities with limited treatments currently available. The brain vasculature is an important factor in many neonatal brain pathologies but there is a lack of diagnostic tools to evaluate the brain vascular health of neonates in a clinical setting. Measurement of blood-brain barrier tight-junction proteins have shown promise as biomarkers for brain injury in the adult. Here we tested the biomarker potential of tight-junctions in the context of neonatal brain injury.MethodsThe levels of TJ-proteins (occluding, claudin-5, and zonula occludens-1) in both blood plasma and cerebrospinal fluid (CSF) as well as blood-brain barrier function were measured in a clinically relevant hypoxia/ischemia model in neonatal rats.ResultsTemporally acute elevated levels of occludin and claudin-5 could be measured in blood and CSF after hypoxia/ischemia with males generally having higher levels than females. The levels of claudin-5 in CSF correlated with the severity of the brain injury at 24h post- hypoxia/ischemia. Simultaneously, we detected early increase in blood-brain barrier-permeability at 6 and 24h after hypoxia/ischemia.ConclusionsLevels of circulating claudin-5 and occludin are increased after hypoxic/ischemic brain injuries and blood-brain barrier-impairment and have promise as early biomarkers for cerebral vascular health and as a tool for risk assessment of neonatal brain injuries.
The Epidemiology and Detectability of Asymptomatic Plasmodium Vivax and Plasmodium Falciparum Infections in Low, Moderate and High Transmission Settings in Ethiopia&nbsp;
Authors: Hailemeskel Elifaged , Tebeje Surafel K , Behaksra Sinknesh , Shumie Girma , Shitaye Getasew , Keffale Migbaru , Chali Wakweya , Gashaw Abrham , Ashine Temesgen , Drakeley Chris , Bousema Teun , Gadisa Endalamaw , Tadesse Fitsum G 
Published: October 2020

Abstract
Background: As countries move to malaria elimination, detecting and targeting asymptomatic malaria infections might be needed. Here, we investigated the epidemiology and detectability of asymptomatic Plasmodium falciparum and P. vivax infections in different transmission settings in Ethiopia.Method: A total of 1093 dried blood spot (DBS) samples were collected from afebrile and apparently healthy individuals across ten study sites in Ethiopia from 2016 to 2020. Of these, 862 were from community and 231 from school based cross-sectional surveys. Malaria infection status was determined by microscopy or rapid diagnostics tests (RDT) and 18S rRNA based nested PCR (nPCR). The annual parasite index (API) was used to classify endemicity as low (API>0 and<5), moderate (API ≥5 and <100) and high transmission (API≥100) and detectability of infections was assessed in these settings. Results: In community surveys, the overall prevalence of asymptomatic Plasmodium infections by microscopy/RDT, nPCR and all methods combined was 12.2% (105/860), 21.6% (183/846) and 24.1% (208/862), respectively. The proportion of nPCR positive infections that was detectable by microscopy/RDT was 48.7% (73/150) for P. falciparum and 4.6% (2/44) for P. vivax. Compared to low transmission settings, the likelihood of detecting infections by microscopy/RDT was increased in moderate (Adjusted odds ratio [AOR]: 3.4; 95% confidence interval [95%CI]:1.6-7.2, P=0.002) and high endemic settings (AOR=5.1; 95%CI=2.6-9.9, P<0.001). After adjustment for site and correlation between observations from the same survey, the likelihood of detecting asymptomatic infections by microscopy/RDT (AOR per year increase = 0.95, 95%CI=0.9-1.0, P=0.013) declined with age.Conclusion: Conventional diagnostics missed nearly half of the asymptomatic Plasmodium reservoir detected by nPCR. The detectability of infections was particularly low in older age groups and low transmission settings. These findings highlight the need for sensitive diagnostic tools to detect the entire parasite reservoir and potential infection transmitters.
Patient Participation and Associated Factors in the Discussions on Do-Not-Attempt-Resuscitation and End-of-Life Disclosure: A Retrospective Chart Review Study
Authors: Abe Akiko , Kobayashi Masato , Kohno Takashi , Takeuchi Mari , Hashiguchi Saori , Mimura Masaru , Fujisawa Daisuke 
Published: October 2020

Abstract
BackgroundPatient participation is a key foundation for advance care planning (ACP). However, a patient himself/herself may be left out from sensitive conversations such as end-of-life (EOL) care discussions. The objectives of this study were to investigate patients’ participation rate in the discussion of Cardiopulmonary Resuscitation (CPR) / Do-Not-Attempt-Resuscitation (DNAR) order, and in the discussion that the patient is at his/her EOL stage (EOL disclosure), and explore their associated factors.MethodsThis is a retrospective chart review study. The participants were all the patients who were hospitalized and died in a university-affiliated teaching hospital (tertiary medical facility) in central Tokyo, Japan during the period from April 2018 to March 2019. The following patients were excluded: (1) cardiopulmonary arrest on arrival (CPAOA); (2) stillbirth; (3) under 18 years old at the time of death; and (4) refusal by their bereaved family. Presence or absence of CPR/DNAR discussion and EOL disclosure, patients’ involvement in those discussions, and their related factors were investigated.ResultsCPR/DNAR discussion was observed in 336 out of the 359 patients (93.6%). The patient participation rate was 33.3% (n= 112). Male gender (odds ratio (OR) = 2.37 [95% confident interval (CI) 1.32-4.25]), living alone (OR = 2.51 [1.34 - 4.71]) and one year or more from diagnosis (OR = 1.78 [1.03 - 3.10]) were associated with patient’s participation in CPR/DNAR discussion. EOL disclosure was observed in 341 out of the 359 patients (95.0%). Half of the patients (n=171; 50.1%) participated in the discussion. Patients who died of cancer (OR = 2.41[1.45-4.03]) and patients without mental illness (OR=2.41 [1.11-5.25]) were more likely to participate in EOL disclosure.ConclusionsIn this clinical sample, only up to half of the patients participated in CPR/DNAR discussion and EoL disclosure. Further attempts to facilitate patients' participation, based on their preference, are warranted. A few sociodemographic, psychosocial, and medical factors that relate to patients’ participation in the discussion on CPR/DNAR and EOL disclosure were demonstrated.
Growth Patterns and Clinical Outcomes in Association with Breastfeeding in HIV Exposed and Unexposed Infants in KwaZulu Natal, South Africa
Authors: Pillay Larisha , Moodley Dhayendre , Emel Lynda Marie , Nkwanyana Ntombifikile Maureen , Naidoo Kimesh Loganathan 
Published: October 2020

Abstract
BackgroundExclusive breastfeeding for six months and breastfeeding with complementary feeds until 12 months for infants exposed to HIV (IEH) or 24 months for infants unexposed to HIV (IUH) is the current World Health Organisation (WHO) recommendation for LMICs to improve clinical outcomes and growth trajectories in infants. In a post hoc evaluation of IEH and IUH cohorts, we examine growth patterns and clinical outcomes in the first six months of infancy in association with breastfeeding duration. MethodsTwo non–contemporaneous cohorts of infants born to women living with HIV and women without HIV, from a low-socioeconomic township in South Africa, were evaluated from birth until nine months of age. Clinical, anthropometric and infant feeding data were analysed. Standard descriptive statistics and regression analysis were performed to determine the effect of HIV exposure and breastfeeding duration on growth and clinical outcomes. ResultsIncluded in this secondary analysis were 123 IEH and 157 IUH infants breastfed for a median of 26 weeks and 14 weeks respectively. Median WLZ score was consistently and significantly lower in IEH than IUH at 3, 6 and 9 months (-0.19 vs 2.09; -0.81 vs 0.28; 0.05 vs 0.97 respectively). In contrast, the median LAZ score was significantly lower among IUH at 3 and 6 (-1.63 vs 0.91; -0.37 vs 0.51). A significantly higher proportion of IUH was classified as stunted (LAZ<-2SD) at 3 and 6 months (3.9% vs 44.9%, 4.8% vs 20.9% respectively) and a higher proportion of IEH experienced one or more episodes of skin rash (44.5% vs 12.8%) and upper respiratory tract infection (30.1% vs 10.9%) (p<0.0001). In a multivariable analysis, the odds of occurrence of wasting, skin rash, URTI or any clinical adverse event in IEH were 2.86, 7.06, 3.01 and 8.89 times higher than IUH after adjusting for breastfeeding duration. ConclusionOur study has generated additional evidence that IEH is at substantial risk of infectious morbidity and decreased growth trajectories independent of breastfeeding duration. We further report shorter breastfeeding duration in infants not exposed to HIV and the higher prevalence of stunting in this cohort is also independent of breastfeeding duration.
Pretreatment neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio to guide the treatment decision (radical surgery versus definitive chemoradiotherapy) for locally advanced squamous cell carcinoma located in the middle and upper esophagus
Authors: Chen Wang , Tong Jia Qi , Tang Meng Qiu , Lu Yun Yun , Liang Gao Feng , Zhang Zhan Chun , Chen Tian 
Published: October 2020

Abstract
Background: Various inflammatory biomarkers, such as the neutrophil lymphocyte ratio (NLR) and platelet lymphocyte ratio (PLR), have been well authenticated to predict clinical outcomes in numerous types of cancer. The optimal treatment for patients with locally advanced esophageal squamous cell carcinoma (ESCC) located in middle or upper region is still inconclusive. The aim of the study was to examine pretreatment NLR and PLR to select from radical surgery or definitive chemoradiotherapy (dCRT) for these patients. The linkage between pretreatment NLR / PLR and prognosis was also analyzed.Methods: NLR and PLR were calculated in 113 locally advanced ESCC located in middle or upper esophagus of patients who underwent radical surgery or dCRT between January 2014 and December 2019. A receiver operating characteristic curve was plotted to select the best cut-off value of NLR and PLR for predicting survival. A survival curve was plotted using the Kaplan–Meier method. Univariate and multivariate Cox regression analyses were applied to assess predictors for survival. Results: NLR and PLR was both associated with the extent of lymph node metastasis (NLR: P = 0.045; PLR: P = 0.002). Additionally, high PLR and recurrence with distant organs metastasis were closely related (P = 0.014), and NLR was related to the tumor stage (P = 0.043). The results of multivariate analysis revealed that NLR (> 2.07) and PLR (> 183.06) were independently associated with poor prognosis. It is noteworthy that surgery was associated with a superior OS compared with dCRT in the low NLR population (P = 0.045). Conclusions: Low pretreatment NLR patients made a decision to undergo radical surgery with a substantial therapeutic benefit. Pretreatment NLR and PLR are independent predictors for patients with locally advanced ESCC located in the middle and upper esophagus who underwent radical surgery or dCRT.
Comparison of epidermal growth factor receptor tyrosine kinase inhibitors for patients with lung adenocarcinoma harboring different epidermal growth factor receptor mutation types
Authors: Park Sojung , Lee Sung Yong , Kim Dojin , Sim Yun Su , Ryu Jeong-Seon , Choi Juwhan , Lee Su Hwan , Ryu Yon Ju , Lee Jin Hwa , Chang Jung Hyun 
Published: October 2020

Abstract
Background: Epidermal growth factor receptor (EGFR) mutations in non–small-cell lung cancer predict sensitivity to EGFR tyrosine kinase inhibitors (TKIs). EGFR mutation types are associated with efficacy of EGFR TKIs. We investigated the clinical outcomes of afatinib, erlotinib, and gefitinib according to EGFR mutation type in patients with lung adenocarcinoma.Methods: Between May 2010 and December 2018, we investigated 363 patients with advanced lung adenocarcinoma harboring EGFR mutations who received EGFR TKIs. Efficacies of EGFR TKIs such as response rate, progression-free survival (PFS), and overall survival (OS) were retrospectively evaluated according to exon 19 deletion (E19del), L858R point mutation (L858R) and uncommon mutations. Results: The frequency of E19del was 48.2%, that of L858R was 42.4%, and that of uncommon mutations was 9.4%. E19del and L858R were associated with superior PFS and OS compared with uncommon mutations. Erlotinib showed significantly inferior OS than other TKIs (30.8 ± 3.3 in erlotinib vs. 39.1 ± 4.3 in afatinib vs. 48.4 ± 6.3 in gefitinib; p = 0.031) in patients with L858R. Gefitinib showed significantly inferior PFS (4.6 ± 1.1 in gefitinib vs. 11.6 ± 2.7 in afatinib vs. 10.6 ± 2.7 in erlotinib; p = 0.049) in patients with uncommon mutations. Conclusion: Afatinib was significantly associated with a longer PFS, presenting constant effectiveness in all EGFR mutation types. Caution may be needed on the use of erlotinib for L858R and the use of gefitinib for uncommon EGFR mutations.
Preoperative nutritional risk index and postoperative one-year skeletal muscle loss can predict the prognosis of patients with gastric cancer: a registry based study
Authors: Kim Kyung Won , Lee Koeun , Lee Jung-Bok , Park Taeyong , Khang Seungwoo , Jeong Heeryeol , Ko Chang-Seok , Yook Jeong-Hwan , Kim Byung-Sik , Lee Inseob 
Published: October 2020

Abstract
Background: Patients with gastric cancer have increased nutritional risk and experience a significant skeletal muscle loss after surgery. We aimed to determine whether muscle loss during the first postoperative year and nutritional status are indicators for predicting prognosis. Methods: From a gastric cancer registry, a total of 958 patients who received curative gastrectomy followed by chemotherapy for stage 2 and 3 gastric cancer and survived longer than 1 year were investigated. Clinical and laboratory data were collected. Skeletal muscle index (SMI) was assessed based on the muscle area at the L3 level on abdominal computed tomography. Results: Preoperative nutritional risk index (NRI) and postoperative decrement of SMI (dSMI) were significantly associated with overall survival (hazards ratio: 0.972 [95% CI: 0.958-0.986] and 1.058 [95% CI: 1.033-1.085], respectively) in a multivariate Cox regression analysis. Recurrence, tumor stage, comorbidity, and the preoperative muscle and subcutaneous fat area were also significant prognostic indicators. Kaplan-Meier analyses exhibited that patients with higher NRI had a significantly longer survival than those with lower NRI (3-year overall survival: 84.6% vs. 72.9%, P < 0.001). In addition, a significantly better prognosis was observed in a patient group with less decrease of SMI (3-year overall survival: 85.6% vs. 74.5%, P = 0.009). A logistic regression analysis demonstrated that the performance of preoperative NRI and dSMI in mortality prediction was quite significant (AUC: 0.63, P < 0.001) and the combination of clinical factors enhanced the predictive accuracy to the AUC of 0.90 (P < 0.001). This prognostic relevance of NRI and dSMI was maintained in patients experiencing tumor recurrence. Conclusions: Skeletal muscle loss during the first postoperative year and preoperative NRI are predictors of overall survival in stage 2 or 3 gastric cancer patients regardless of relapse. Our results support the potential importance of exercise and nutritional support along with standard treatment.
A haemagglutination test for rapid detection of antibodies to SARS-CoV-2
Authors: Joly Etienne , Townsend Alain , Rijal Pramila , Xiao Julie , Tan Tiong Kit , Schimanski Lisa , Rahikainen Rolle , Hoosdally Sarah , Street Teresa , Rudkin Justine , Stoesser Nicole , Karpe Fredrik , Neville Matthew , Ploeg Rutger , Oliveira Marta , Mentzer Alexander , Knight Julian , Kwok Andrew , Screaton Gavin , Mongkolsapaya Juthathip , Dejnirattisai Wanwisa , Supasa Piyasa , Klenerman Paul , Dold Christina , Allcock Alice , Bibi Sagida , Clutterbuck Elizabeth , Huang Kuan-Ying , Huo Jiandong , Gupta Nimesh , Crook Derrick , Roberts David , Lamikanra Abigail , Tsang Hoi , Bown Abbie , Vipond Richard , Baillie J , Moore Shona , Semple Malcolm , Turtle Lance , Openshaw Peter , Ainsworth Mark , Beer Sally , Espinosa Alexis , Mendoza Maria , Georgiou Dominique , Lockett Teresa , Martinez Jose , Perez Elena , Sanchez Veronica , Scozzafava Giuseppe , Sobrinodiaz Alberto , Thraves Hannah , Matthews Philippa 
Published: October 2020

Abstract
Serological detection of antibodies to SARS-CoV-2 is essential for establishing rates of seroconversion in populations, detection of seroconversion after vaccination, and for seeking evidence for a level of antibody that may be protective against COVID-19 disease. Several high-performance commercial tests have been described, but these require centralised laboratory facilities that are comparatively expensive, and therefore not available universally. Red cell agglutination tests have a long history in blood typing, and general serology through linkage of reporter molecules to the red cell surface. They do not require special equipment, are read by eye, have short development times, low cost and can be applied as a Point of Care Test (POCT). We describe a red cell agglutination test for the detection of antibodies to the SARS-CoV-2 receptor binding domain (RBD). We show that the Haemagglutination Test (HAT) has a sensitivity of 90% and specificity of 99% for detection of antibodies after a PCR diagnosed infection. The HAT can be titrated, detects rising titres in the first five days of hospital admission, correlates well with a commercial test that detects antibodies to the RBD, and can be applied as a point of care test. The developing reagent is composed of a previously described nanobody to a conserved glycophorin A epitope on red cells, linked to the RBD from SARS-CoV-2. It can be lyophilised for ease of shipping. We have scaled up production of this reagent to one gram, which is sufficient for ten million tests, at a cost of ~0.27 UK pence per test well. Aliquots of this reagent are ready to be supplied to qualified groups anywhere in the world that need to detect antibodies to SARS-CoV-2, but do not have the facilities for high throughput commercial tests.
Surge of Severe Acute Respiratory Syndrome Coronavirus 2 Infections Linked to Single Introduction of a Virus Strain in Myanmar, 2020
Authors: Nyunt Myat Htut , Soe Hnin Ohnmar , Aye Kay Thi , Aung Wah Wah , Kyaw Yi Yi , Kyaw Aung Kyaw , Myat Theingi Win , Latt Aung Zaw , Win Min Min , Win Aye Aye , Htun Yin Min , Zaw Khaing Mar , Ei Phyu Win , Hein Kyaw Thu , San Lai Lai , Oo Nan Aye Thida , Lin Htin , Mon Nan Cho Nwe , Yee Khin Than , Htun Khin Lapyae , Aye Lynn Pa Pa , Ko Yamin Ko , Htoo Thitsar Htet Htet , Aung Kham Mo , Azili Hnin , Han Soe Soe , Zaw Ni Ni , Win Su Mon , Thwe Wai Myat , Aye Thin Thin , Hlaing Myat Su , Minn Wai Yan , Thu Pyae Phyo , Thu Hlaing Myat , Htun Zaw Than 
Published: October 2020

Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is a major health concern globally. Genomic epidemiology is an important tool to assess the pandemic of the coronavirus disease 2019 (COVID-19). Several mutations have been reported by genome analysis of the SARS-CoV-2. In the present study, we investigate mutational and phylogenetic analysis of 30 whole genome sequences for genomic characteristics of the virus in the specimens collected early phase of pandemic, (March-June, 2020) and sudden surge of infection (August-September, 2020). Phylogenetic analysis revealed that 4 samples of L strain and 1 GR strain in early stage of local transmission, while 6 returnees by rescue flights showed GH (India) and GR strains (China and Philippines) with no evidence of local spread. However, all 19 whole genome sequences in sudden surge of local transmission showed genetically distinct clade GH (Lineage B.1.36). Surge of second wave on SARS-CoV-2 infection was linked to the single-introduction of the GH strain that may be a result of strict restriction of international travel and containment efforts. These genomic data provides the useful information to disease control and prevention strategy.
Changing Clusters of Indian States with respect to number of Cases of COVID-19 using incrementalKMN Method
Authors: Prasad Rabinder Kumar , Sarmah Rosy , Chakraborty Subrata 
Published: October 2020

Abstract
The novel Coronavirus (COVID-19) incidence in India is currently experiencing exponential rise with apparent spatial variation in growth rate and doubling time. We classify the states into five clusters with low to high-risk category and identify how the different states moved from one cluster to the other since the onset of the first case on $30^{th}$ January 2020 till the end of $15^{th}$ September 2020. We cluster the Indian states into $5$ groups using incrementalKMN clustering \cite{b1}. We observed and comment on the changing scenario of the formation of the clusters starting from before lockdown, through lockdown and the various unlock phases.