bluuebunny/crossref_metadata_2025_split huggingface dataset:
The longitudinal evaluation of COVID-19 in pediatric patients and the impact of delta variant
Authors: Arslan Asli , Sahbudak Bal Zumrut , Yildirim Arslan Sema , Bilen Nimet Melis , Guner Ozenen Gizem , Yazıcı Özkaya Pınar , Yurtseven Ali , Çiçek Candan , Durusoy İsabel Raika , Ozkinay Ferda , Kurugol Zafer 
Published: January 2023

Abstract

Background
Pediatric patients infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) displayed milder symptoms than adults. However, they play an important role in case numbers and virus transmission. Therefore, we aimed to determine the epidemiological features of all pediatric patients infected with SARS-CoV-2 and put forth case numbers longitudinally throughout the delta variant dominant period.

Methods
A retrospective study was conducted at a university hospital and included patients between 0 and18 years old with a SARS-CoV-2 polymerase chain reaction (PCR) positive result, including inpatients and outpatients. Epidemiological and clinical features were recorded from electronic files, and telephone visits were performed between March 2020 and December 2021.

Results
During the study period, 3175 coronavirus disease 2019 (COVID-19) pediatric patients were admitted to our hospital with a mean age of 10.61 ± 4.6 years. Of the 1815 patients who could be interviewed, 85.7% reported at least one symptom. Before the delta variant period, 0–4 years aged children were more commonly infected, while school-aged children and adolescents were more common, and the rate of pediatric cases to all COVID-19 cases increased to 35.8% after the delta variant became dominant. Symptomatic cases were significantly higher before the delta variant (87.8% vs. 84.06%, p = 0.016). The hospitalization rate was higher before the delta variant (p &lt; 0.001), whereas PICU admission showed no statistical difference.

Conclusions
The frequency of school-aged children and adolescents raised with the impact of both school openings and the delta variant, and the rate of pediatric cases increased in total COVID-19 patient numbers.
Decomplexation proteomic analysis and purity assessment of a biologic for snakebite envenoming: Philippine Cobra Antivenom
Authors: Palasuberniam Praneetha , Tan Kae Yi , Chan Yi Wei , Blanco Francis Bonn , Tan Choo Hock 
Published: January 2023

Abstract

Background
Philippine Cobra Antivenom (PCAV) is the only snake antivenom manufactured in the Philippines. It is used clinically to treat envenoming caused by the Philippine Spitting Cobra (Naja philippinensis). While PCAV is effective pharmacologically, it is crucial to ensure the safety profile of this biologic that is derived from animal plasma.

Methods
This study examined the composition purity of PCAV through a decomplexation proteomic approach, applying size-exclusion chromatography (SEC), sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and tandem mass spectrometry liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Results
SDS-PAGE and SEC showed that the major protein in PCAV (constituting ∼80% of total proteins) is approximately 110 kDa, consistent with the F(ab’)2 molecule. This protein is reducible into two subunits suggestive of the light and heavy chains of immunoglobulin G. LC-MS/MS further identified the proteins as equine immunoglobulins, representing the key therapeutic ingredient of this biologic product. However, protein impurities, including fibrinogens, alpha-2-macroglobulins, albumin, transferrin, fibronectin and plasminogen, were detected at ∼20% of the total antivenom proteins, unveiling a concern for hypersensitivity reactions.

Conclusions
Together, the findings show that PCAV contains a favorable content of F(ab’)2 for neutralization, while the antibody purification process awaits improvement to minimize the presence of protein impurities.
A prospective study of snakebite in a tertiary care hospital in south-western Nepal
Authors: Pandey Deb Prasad , Shrestha Bhola Ram , Acharya Krishna Prasad , Shah Khagendra Jang , Thapa-Magar Chhabilal , Dhakal Ishwari Prasad , Mohamed Fahim , Isbister Geoffrey K 
Published: January 2023

Abstract

Background
Snakebite is a neglected public health issue in Nepal. We aimed to characterize patients with snake envenoming admitted to hospital in south-western Nepal.

Methods
This was a prospective cohort study of 476 snakebite patients admitted to Bheri Hospital from May to December 2017. Data were collected on patient demographics, bite circumstances, snake type, treatment-seeking behavior, clinical effects, complications and treatment.

Results
There were 139/476 (29%) patients with clinical features of envenomation and 10 deaths (8%), of which six were prehospital deaths; 325/476 (68%) patients used non-recommended prehospital first aid, including 278 (58%) who applied a tourniquet and 43 (9%) consulting traditional healers. Median time to hospital arrival was 1.5 (IQR: 0.8–4) h. Also, 127 envenomated patients (91%) developed neurotoxicity and 12 (9%) hemotoxicity, while 124 patients (89%) received antivenom, with a median dose of 10 (4–30) vials. Three patients developed anaphylaxis following antivenom administration; 111 of 139 (80%) cases were admitted to the ICU and 48 (35%) were intubated. Median length of hospital stay for all cases was 0.5 (IQR: 0.5–1.2) d, but it was 2.2 (IQR: 1.5–3.8) d for envenomated cases.

Conclusions
The majority of snakebite patients used non-recommended first aid or attended traditional healers. Almost one-third of patients developed systemic envenomation and required antivenom. The case fatality rate was high, but many died prior to arriving in hospital.
Outpatient parenteral antimicrobial therapy for leishmaniasis: 13 years’ experience at a large UK infectious diseases centre
Authors: Parkash Vivak , Laundy Nicholas , Durojaiye Oyewole Christopher 
Published: January 2023

Abstract

Background
Leishmaniasis is a neglected tropical disease that is imported by travellers returning to the UK. Given the prolonged therapy required, outpatient treatment has been proven to be cost-effective and safe.

Methods
We describe cases of leishmaniasis treated through outpatient parenteral antimicrobial therapy (OPAT) over a 13-y period (March 2006–September 2018) at a large teaching hospital.

Results
A total of 26 episodes of leishmaniasis were treated successfully, with a mean saving of 14.2 bed-days/episode. Sodium stibogluconate was the most used antileishmanial (92%).

Conclusions
Treatment of chronic infections via OPAT is now commonplace and this approach may be considered for other imported infectious diseases.
Conflict resolution between EU law and bilateral investment treaties of the EU Member States in the aftermath of Achmea
Authors: Georgaki Konstantina 
Published: January 2023

Abstract
This article examines how conflicts between European Union (EU) law and Bilateral Investment Treaties (BITs) between EU Member States (intra-EU BITs) are to be tacked following the judgment of the Court of Justice of the EU (CJEU) in Achmea (C-284/16). Starting from an analysis of the CJEU’s ruling and its aftermath (Sections II and III respectively), the article argues that conflicts in the interrelation of EU law with inter se agreements, such as intra-EU BITs, are to be approached as normative conflicts between different sub-systems within the broader system of public international law and resolved in favour of EU law. This argument is based on a two-fold premise, analysed in Section IV: first, that EU law does not constitute a ‘new legal order’, outside of and cut off from international law, but rather a ‘self-contained regime’, operating ‘within’ the broader system of international law. Since EU law is treaty law, conflicts in its relationship with (other) inter se agreements are, therefore, to be addressed using the conflict rules of international law. Against this background, the second premise of the article is that the EU Member States have agreed on a special conflict rule to regulate conflicts between EU law and inter se agreements. That rule is the principle of primacy of EU law. Having established the applicable conflict rule, Section V expands on the consequences of its application to the conflict between EU law and investor-state arbitration clauses in intra-EU BITs affirmed by the CJEU in Achmea.
Complete Genome Sequencing of Three Clade-1 Xanthomonads Reveals Genetic Determinants for a Lateral Flagellin and the Biosynthesis of Coronatine-Like Molecules in Xanthomonas
Authors: Peduzzi Chloé , Sagia Angeliki , Burokienė Daiva , Nagy Ildikó Katalin , Fischer-Le Saux Marion , Portier Perrine , Dereeper Alexis , Cunnac Sébastien , Roman-Reyna Veronica , Jacobs Jonathan M. , Bragard Claude , Koebnik Ralf 
Published: January 2023

Evolutionarily, early-branching xanthomonads, also referred to as clade-1 xanthomonads, include major plant pathogens, most of which colonize monocotyledonous plants. Seven species have been validly described, among them the two sugarcane pathogens Xanthomonas albilineans and Xanthomonas sacchari, as well as Xanthomonas translucens, which infects small-grain cereals and diverse grasses but also asparagus and pistachio trees. Single-gene sequencing and genomic approaches have indicated that this clade likely contains more, yet-undescribed species. In this study, we sequenced representative strains of three novel species using long-read sequencing technology. Xanthomonas campestris pv. phormiicola strain CFBP 8444 causes bacterial streak on New Zealand flax, another monocotyledonous plant. Xanthomonas sp. strain CFBP 8443 has been isolated from common bean, and Xanthomonas sp. strain CFBP 8445 originated from banana. Complete assemblies of the chromosomes confirmed their unique phylogenetic position within clade 1 of Xanthomonas. Genome mining revealed novel genetic features, hitherto undescribed in other members of the Xanthomonas genus. In strain CFBP 8444, we identified genes related to the synthesis of coronatine-like compounds, a phytotoxin produced by several pseudomonads, which raises interesting questions about the evolution and pathogenicity of this pathogen. Furthermore, strain CFBP 8444 was found to contain a second, atypical flagellar gene cluster in addition to the canonical flagellar gene cluster. Overall, this research represents an important step toward better understanding the evolutionary history and biology of early-branching xanthomonads.
Reconstructing the phylodynamic history and geographic spread of the CRF01_AE-predominant HIV-1 epidemic in the Philippines from PR/RT sequences sampled from 2008-2018
Authors: Polotan Francisco Gerardo M. , Salazar Carl Raymund P. , Morito Hannah Leah E. , Abulencia Miguel Francisco B. , Pantoni Roslind Anne R. , Mercado Edelwisa S. , Hué Stéphane , Ditangco Rossana A. 
Published: January 2023

AbstractThe Philippines has had a rapidly growing HIV epidemic with a shift in the prevalent subtype from B to CRF01_AE. However, the phylodynamic history of CRF01_AE in the Philippines has yet to be reconstructed. We conducted a descriptive retrospective study reconstructing the history of HIV-1 CRF01_AE transmissions in the Philippines through molecular epidemiology. Partial polymerase sequences (n= 1429) collected between 2008 and 2018 from 13 Philippine regions were collated from the RITM drug resistance genotyping database. Subsampling was performed on these Philippine and Los Alamos National Laboratory HIV international sequences followed by estimation of the time to the most recent common ancestor (tMRCA), effective reproductive number (Re), effective viral population size (Ne), relative migration rates and geographic spread of CRF01_AE with BEAST.ReandNewere compared between CRF01_AE and B. Most CRF01_AE sequences formed a single clade with a tMRCA of 1999 [95% HPD: 1996, 2001]. Exponential growth ofNewas observed from 1999 to 2013. TheRereached peaks of 3.71 [95% HPD: 1.71, 6.14] in 2009 and 2.87 [95% HPD: 1.78, 4.22] between 2012 and 2015. A transient decrease to 0.398 [95% HPD: 0.0105, 2.28] occurred between 2010 and 2012. The epidemic most likely started in Luzon in the National Capital Region, which then spread diffusely to the rest of the country. Both CRF01_AE and subtype B exhibited similar but unsynchronized patterns ofReover time. These results characterize the subtype-specific phylodynamic history of the CRF01_AE epidemic in the Philippines, which contextualizes and may inform past, present, and future public health measures toward controlling the HIV epidemic in the Philippines.
A Fresh View at Sports PSM-Systems
Authors: Savostyanov Vladimir , Kobelev Alexander 
Published: January 2023

AbstractBackground/ObjectivesThe purpose of the proposed study is disclosure of correlations between the dynamics of the Breathe Rate (BR) and Heart Rate (HR) when performing the intermittent physical operation at maximum power on a cycle ergometer.MethodsThe stage on the study of the General functional athlete readiness (GFAR) performed using the sports standard “Red Engine” and the cycle ergometer in 16 volunteers (10 men, 6 women) whose average age was 21±1.17 years. To determine the sports potential of the volunteers in this study, we used own Coefficient of Anaerobic Capacity (CANAC Q, beats). Continuous recording of the heart rate and respiratory rate of volunteers in the maximum power sports test was carried out by the “RheoCardioMonitor” device with an athlete functional readiness module based on the method of Transthoracic electrical impedance rheography (TEIRG).ResultsThe degree of correlation of functional indicators (M, HRM, GFAR) with CANAC Q for the group in full (n=80) occurred at a very high level, which confirmed the effectiveness of using the Coefficient of Anaerobic Capacity (CANAC Q) in assessing the general functional athlete readiness of the volunteers.ConclusionsCANAC Q measured in “beats” of the heart and recorded very accurately using the method of transthoracic electrical impedance rheography (TEIRG). For this reason as promising sports PSM-system, CANAC Q can replace the methods for determining the functional athlete readiness by blood lactate concentration and maximum oxygen consumption.
Sex difference in the associations of socioeconomic status, cognitive function and brain volume with dementia in old adults: Findings from the OASIS study
Authors: Liu Sophia Z , Tahmasebi Ghazaal , Sheng Ying , Dinov Ivo D , Tsilimingras Dennis , Liu Xuefeng 
Published: January 2023

AbstractBackgroundSex differences in the association of cognitive function and imaging measures with dementia have not been fully investigated while sex-based investigation of dementia has been discussed. Understanding sex differences in the dementia-related socioeconomic, cognitive, and imaging measurements is important for uncovering sex-related pathways to dementia and facilitating early diagnosis, family planning, and cost control.MethodsWe selected data from the Open Access Series of Imaging Studies with longitudinal measurements of brain volumes on 150 individuals aged 60 to 96 years. Dementia status was determined using the Clinical Dementia Rating (CDR) scale, and Alzheimer’s disease was diagnosed as a CDR of ≥ 0.5. Generalized estimating equation models were used to estimate the associations of socioeconomic, cognitive and imaging factors with dementia in men and women.ResultsLower education affected dementia more in women than in men. Age, education, Mini-Mental State Examination (MMSE), and normalized whole-brain volume (nWBV) were associated with dementia in women whereas only MMSE and nWBV were associated with dementia in men. Lower socioeconomic status was associated with a reduced estimated total intracranial volume in men, but not in women. Ageing and lower MMSE scores were associated with reduced nWBV in both men and women.ConclusionsThe association between education and prevalence of dementia differs in men and women. Women may have more risk factors for dementia than men.
The Use of Class Imbalanced Learning Methods on ULSAM Data to Predict the Case-Control Status in Genome-Wide Association Studies
Authors: Öztornaci R. Onur , Syed Hamzah , Morris Andrew P. , Taşdelen Bahar 
Published: January 2023

AbstractMachine learning (ML) methods for uncovering single nucleotide polymorphisms (SNPs) in genome-wide association study (GWAS) data that can be used to predict disease outcomes are becoming increasingly used in genetic research. Two issues with the use of ML models are finding the correct method for dealing with imbalanced data and data training. This article compares three ML models to identify SNPs that predict type 2 diabetes (T2D) status using the Support vector machine SMOTE (SVM SMOTE), The Adaptive Synthetic Sampling Approach (ADASYN), Random under sampling (RUS) on GWAS data from elderly male participants (165 cases and 951 controls) from the Uppsala Longitudinal Study of Adult Men (ULSAM). It was also applied to SNPs selected by the SMOTE, SVM SMOTE, ADASYN, and RUS clumping method. The analysis was performed using three different ML models: (i) support vector machine (SVM), (ii) multilayer perceptron (MLP) and (iii) random forests (RF). The accuracy of the case-control classification was compared between these three methods. The best classification algorithm was a combination of MLP and SMOTE (97% accuracy). Both RF and SVM achieved good accuracy results of over 90%. Overall, methods used against unbalanced data, all three ML algorithms were found to improve prediction accuracy.
Hetnet connectivity search provides rapid insights into how two biomedical entities are related
Authors: Himmelstein Daniel S. , Zietz Michael , Rubinetti Vincent , Kloster Kyle , Heil Benjamin J. , Alquaddoomi Faisal , Hu Dongbo , Nicholson David N. , Hao Yun , Sullivan Blair D. , Nagle Michael W. , Greene Casey S. 
Published: January 2023

AbstractHetnets, short for “heterogeneous networks”, contain multiple node and relationship types and offer a way to encode biomedical knowledge. One such example, Hetionet connects 11 types of nodes — including genes, diseases, drugs, pathways, and anatomical structures — with over 2 million edges of 24 types. Previous work has demonstrated that supervised machine learning methods applied to such networks can identify drug repurposing opportunities. However, a training set of known relationships does not exist for many types of node pairs, even when it would be useful to examine how nodes of those types are meaningfully connected. For example, users may be curious not only how metformin is related to breast cancer, but also how theGJA1gene might be involved in insomnia. We developed a new procedure, termed hetnet connectivity search, that proposes important paths between any two nodes without requiring a supervised gold standard. The algorithm behind connectivity search identifies types of paths that occur more frequently than would be expected by chance (based on node degree alone). We find that predictions are broadly similar to those from previously described supervised approaches for certain node type pairs. Scoring of individual paths is based on the most specific paths of a given type. Several optimizations were required to precompute significant instances of node connectivity at the scale of large knowledge graphs. We implemented the method on Hetionet and provide an online interface athttps://het.io/search. We provide an open source implementation of these methods in our new Python package namedhetmatpy.
A self-inactivating invertebrate opsin with resistance to retinal depletion optically drives biased signaling toward Gβγ-dependent ion channel modulation
Authors: Tsukamoto Hisao , Kubo Yoshihiro 
Published: January 2023

AbstractAnimal opsins, light-sensitive G protein-coupled receptors (GPCRs), have been utilized for optogenetic tools to control G protein-dependent signaling pathways. Upon G protein activation, the Ga and Gβγ subunits drive different intracellular signaling pathways, leading to complex cellular responses. For some purposes, Ga-, Gβγ-dependent signaling needs to be separately modulated, but these responses are simultaneously evoked due to the 1:1 stoichiometry of Ga and Gβγ. Nevertheless, we show temporal activation of G protein using a self-inactivating invertebrate opsin,Platynereisc-opsin1, drives biased signaling for Gβγ-dependent GIRK channel activation in a light-dependent manner by utilizing the kinetic difference between Gβγ-dependent and Ga-dependent responses. The opsin-induced transient Gi/o activation preferably causes activation of the kinetically-fast Gβγ-dependent GIRK channels rather than slower Gi/oα-dependent adenylyl cyclase inhibition. Although similar Gβγ-biased signaling properties were observed in a selfinactivating vertebrate visual pigment,Platynereisc-opsin1 needs fewer retinal molecules to evoke cellular responses. Furthermore, the Gβγ-biased signaling properties ofPlatynereisc-opsinl are enhanced by genetically fused with RGS8 protein which accelerates G protein inactivation. The self-inactivating invertebrate opsin and its RGS8-fusion protein can function as optical control tools biased for Gβγ-dependent ion channel modulation.
Therapeutic effects of human amnion-derived mesenchymal stem cells on hypercoagulability in a uremic calciphylaxis patient
Authors: Bian Anning , Ye Xiaoxue , Wang Jing , Zeng Ming , Liu Jiayin , Liu Kang , Ning Song , Cui Yugui , Tang Shaowen , Xu Xueqiang , Yuan Yanggang , Su Zhonglan , Lu Yan , Zhou Jing , Ma Xiang , Yang Guang , Huang Yaoyu , Lv Xiaolin , Wang Ling , Zhao Jing , Wang Xiuqin , Liang Ningxia , Xing Changying , Qin Lianju , Wang Ningning 
Published: January 2023

AbstractCalciphylaxis is a rare cutaneous vascular disease with clinical manifestations of intolerable pains, non-healing skin wounds, histologically characterized by calcification, fibrointimal hyperplasia, and thrombosis in microvessels. Currently, there are no approved guidelines for this disease. High prevalence of thrombophilias and hypercoagulable conditions in calciphylaxis patients have been recognized in recent years. Here, we report a case of uremic calciphylaxis patient whom was refractory to conventional treatments and then received a salvage strategyviahuman amnion-derived mesenchymal stem cell (hAMSC) intravenous combined with local application. In order to investigate the therapeutic mechanism of hMASCs from the novel perspective of hypercoagulability, coagulation-related indicators, wound status and quality of life were followed up. Improvement of hypercoagulable condition involving correction of platelet, D-dimer and plasminogen levels, skin regeneration and pain alleviation were revealed after hAMSC administration for one year. We propose that hypercoagulability is the therapeutic target of calciphylaxis patients which can be improved by hAMSC treatment.