bluuebunny/crossref_metadata_2025_split huggingface dataset:
Climate Change and Trade Facilitation: Estimating Greenhouse Gas Emission Savings from Implementation of Cross-Border Paperless Trade in Asia and the Pacific
Authors: Duval Yann , Hardy Simon 
Published: August 2021

The Framework Agreement on Facilitation of Cross-Border Paperless Trade in Asia and the Pacific entered into force in February 2021. While economic benefits associated with paperless trade facilitation are well known, little attention has been paid to measuring the potential environmental benefits. Accordingly, this article sets out to quantify the amount of greenhouse gas emissions that could be saved if all trade-related paper documents in the region are ultimately replaced by digital documents and data exchange, as foreseen in the regional framework agreement. This is carried out by combining detailed descriptions of trade transactions, data on trading volumes and relevant emission factors. Even with conservative assumptions, the emissions saved by fully digitalising a single end-to-end trade transaction are equivalent to planting 1.5 trees. For the Asia-Pacific, this implies savings of about 13 million tons of CO2e annually, equivalent to the carbon absorbed by 400 million trees. The results are driven by efficiency gains from handling data digitally rather than by the direct savings of paper and ink. JEL Codes: F18, H83, Q56
Lung Ultrasonography in Ruling Out COVID-19 Among Health Care Workers in Two Italian Emergency Departments: A Multicenter Study
Authors: Copetti Roberto , Amore Giulia , Giudice Caterina Anna , Orso Daniele , Cola Silvia , Pillinini Pierpaolo , Rocco Chiara , Cappello Dario , Dibenedetto Alessia Geneve , Meduri Stefano 
Published: August 2021

Objective: The low sensitivity of the real-time reverse transcription-polymerase chain reaction (rRT-PCR) test on the nasopharyngeal swab for SARS-CoV2 virus could cause infections among health care professionals and could be a source of viral spread. The aim of this study was to verify whether lung ultrasonography (LUS) had a negative predictive value (NPV) high enough to rule out coronavirus disease 2019 (COVID-19) in a cohort of health care employees, working in emergency departments (EDs). Materials and Methods: A multicenter prospective observational study was conducted in two EDs in Northeast Italy. An adjudication committee established the definitive diagnosis of COVID-19. Results: A cohort was enrolled of 155 possible patient cases (two true positives). Twenty-one health care employees presented with suggestive symptoms for COVID-19. The rRT-PCR test was positive in one of the two patients. LUS was suggestive for COVID-19 pneumonia in four patients. The diagnostic accuracy of LUS was 98.7% (95% confidence interval [CI] = 95.4%–99.8%). The NPV was 100% (95% CI = 100%–100%). Conclusion: LUS has a high enough NPV for excluding a COVID-19-related pneumonia in a cohort of health care employees who were exposed to the SARS-CoV2 virus.
Excess heme upregulates heme oxygenase 1 and promotes cardiac ferroptosis in mice with sickle cell disease
Authors: Menon Archita Venugopal , Liu Jing , Tsai Hanting Phoebe , Zeng Lingxue , Yang Seungjeong , Asnani Aarti , Kim Jonghan 
Published: August 2021

Abstract
Sickle cell disease (SCD) is characterized by increased hemolysis, which results in plasma heme overload and ultimately cardiovascular complications. Here, we hypothesized that increased heme in SCD causes upregulation of heme oxygenase 1 (Hmox1), which consequently drives cardiomyopathy through ferroptosis, an iron-dependent non-apoptotic form of cell death. First, we demonstrated that the Townes SCD mice had higher levels of hemopexin-free heme in the serum and increased cardiomyopathy, which was corrected by hemopexin supplementation. Cardiomyopathy in SCD mice was associated with upregulation of cardiac Hmox1, and inhibition or induction of Hmox1 improved or worsened cardiac damage, respectively. Because free iron, a product of heme degradation through Hmox1, has been implicated in toxicities including ferroptosis, we evaluated the downstream effects of elevated heme in SCD. Consistent with Hmox1 upregulation and iron overload, levels of lipid peroxidation and ferroptotic markers increased in SCD mice, which were corrected by hemopexin administration. Moreover, ferroptosis inhibitors decreased cardiomyopathy, whereas a ferroptosis inducer erastin exacerbated cardiac damage in SCD and induced cardiac ferroptosis in nonsickling mice. Finally, inhibition or induction of Hmox1 decreased or increased cardiac ferroptosis in SCD mice, respectively. Together, our results identify ferroptosis as a key mechanism of cardiomyopathy in SCD.
Whole-brain morphological alterations associated with trigeminal neuralgia
Authors: Mo Jiajie , Zhang Jianguo , Hu Wenhan , Luo Fang , Zhang Kai 
Published: August 2021

Abstract
Background
Novel neuroimaging strategies have the potential to offer new insights into the mechanistic basis for trigeminal neuralgia (TN). The present study aims to conduct whole-brain morphometry analyses of TN patients and to assess the value of group-level neocortical and subcortical structural patterns as tools for diagnostic biomarker exploration.

Methods
Cortical thickness, surface area, and myelin levels in the neocortex were measured via magnetic resonance imaging (MRI). The radial distance and the Jacobian determinant of the subcortex in 43 TN patients and 43 matched controls were compared. Pattern learning algorithms were employed to establish the utility of group-level MRI findings as tools for predicting TN. An additional 40 control patients with hemifacial spasms were then evaluated to assess algorithm sensitivity and specificity.

Results
TN patients exhibited reductions in cortical indices in the anterior cingulate cortex (ACC), the midcingulate cortex (MCC), and the posterior cingulate cortex (PCC) relative to controls. They further presented with widespread subcortical volume reduction that was most evident in the putamen, the thalamus, the accumbens, the pallidum, and the hippocampus. Whole brain-level morphological alterations successfully enable automated TN diagnosis with high specificity (TN: 95.35 %; disease controls: 46.51 %).

Conclusions
TN is associated with a distinctive whole-brain structural neuroimaging pattern, underscoring the value of machine learning as an approach to differentiating between morphological phenotypes, ultimately revealing the full spectrum of this disease and highlighting relevant diagnostic biomarkers.
OVarFlow: a resource optimized GATK 4 based Open source Variant calling workFlow
Authors: Bathke Jochen , Lühken Gesine 
Published: August 2021

Abstract
Background
The advent of next generation sequencing has opened new avenues for basic and applied research. One application is the discovery of sequence variants causative of a phenotypic trait or a disease pathology. The computational task of detecting and annotating sequence differences of a target dataset between a reference genome is known as "variant calling". Typically, this task is computationally involved, often combining a complex chain of linked software tools. A major player in this field is the Genome Analysis Toolkit (GATK). The "GATK Best Practices" is a commonly referred recipe for variant calling. However, current computational recommendations on variant calling predominantly focus on human sequencing data and ignore ever-changing demands of high-throughput sequencing developments. Furthermore, frequent updates to such recommendations are counterintuitive to the goal of offering a standard workflow and hamper reproducibility over time.

Results
A workflow for automated detection of single nucleotide polymorphisms and insertion-deletions offers a wide range of applications in sequence annotation of model and non-model organisms. The introduced workflow builds on the GATK Best Practices, while enabling reproducibility over time and offering an open, generalized computational architecture. The workflow achieves parallelized data evaluation and maximizes performance of individual computational tasks. Optimized Java garbage collection and heap size settings for the GATK applications SortSam, MarkDuplicates, HaplotypeCaller, and GatherVcfs effectively cut the overall analysis time in half.

Conclusions
The demand for variant calling, efficient computational processing, and standardized workflows is growing. The Open source Variant calling workFlow (OVarFlow) offers automation and reproducibility for a computationally optimized variant calling task. By reducing usage of computational resources, the workflow removes prior existing entry barriers to the variant calling field and enables standardized variant calling.
Integrated ionomic and transcriptomic dissection reveals the core transporter genes responsive to varying cadmium abundances in allotetraploid rapeseed
Authors: Zhou Ting , Yue Cai-peng , Zhang Tian-yu , Liu Ying , Huang Jin-yong , Hua Ying-peng 
Published: August 2021

AbstractBackgroundOilseed rape (B. napusL.) has great potential for phytoremediation of cadmium (Cd)-polluted soils due to its large plant biomass production and strong metal accumulation. Soil properties and the presence of other soluble compounds or ions, cause a heterogeneous distribution of Cd.ResultsThe aim of our study was to reveal the differential responses ofB. napusto different Cd abundances. Herein, we found that high Cd (50 μM) severely inhibited the growth ofB. napus, which was not repressed by low Cd (0.50 μM) under hydroponic culture system. ICP-MS assays showed that the Cd2+concentrations in both shoots and roots under 50 μM Cd were over 10 times higher than those under 0.50 μM Cd. Under low Cd, the concentrations of only shoot Ca2+/Mn2+and root Mn2+were obviously changed (both reduced); under high Cd, the concentrations of most cations assayed were significantly altered in both shoots and roots except root Ca2+and Mg2+. High-throughput transcriptomic profiling revealed a total of 18,021 and 1408 differentially expressed genes under high Cd and low Cd conditions, respectively. The biological categories related to the biosynthesis of plant cell wall components and response to external stimulus were over-accumulated under low Cd, whereas the terms involving photosynthesis, nitrogen transport and response, and cellular metal ion homeostasis were highly enriched under high Cd. Differential expression of the transporters responsible for Cd uptake (NRAMPs), transport (IRTsandZIPs), sequestration (HMAs,ABCs, andCAXs), and detoxification (MTPs,PCR,MTs, andPCSs), and some other essential nutrient transporters were investigated, and gene co-expression network analysis revealed the core members of these Cd transporters. Some Cd transporter genes, especiallyNRAMPsandIRTs, showed opposite responsive patterns between high Cd and low Cd conditions.ConclusionsOur findings would enrich our understanding of the interaction between essential nutrients and Cd, and might also provide suitable gene resources and important implications for the genetic improvement of plant Cd accumulation and resistance through molecular engineering of these core genes under varying Cd abundances in soils.
Loci and natural alleles for cadmium-mediated growth responses revealed by a genome wide association study and transcriptome analysis in rice
Authors: Yu Jianping , Liu Chaolei , Lin Hai , Zhang Bin , Li Xiaoxia , Yuan Qiaoling , Liu Tianjiao , He Huiying , Wei Zhaoran , Ding Shilin , Zhang Chao , Gao Hongsheng , Guo Longbiao , Wang Quan , Qian Qian , Shang Lianguang 
Published: August 2021

AbstractBackgroundCadmium (Cd) is a toxic heavy metal that is harmful to the environment and human health. Cd pollution threatens the cultivation of rice (Oryza sativaL.) in many countries. Improving rice performance under Cd stress could potentially improve rice productivity.ResultsIn this study, 9 growth traits of 188 different cultivated rice accessions under normal and Cd stress conditions were found to be highly variable during the seedling stage. Based on ~3.3 million single nucleotide polymorphisms (SNPs), 119 Cd-mediated growth response (CGR) quantitative trait loci (QTL) were identified by a genome-wide association study (GWAS), 55 of which have been validated by previously reported QTL and 64 were new CGR loci. Combined with the data from the GWAS, transcriptome analysis, gene annotations from the gene ontology (GO) Slim database, and annotations and functions of homologous genes, 148 CGR candidate genes were obtained. Additionally, several reported genes have been found to play certain roles in CGRs. Seven Cd-related cloned genes were found among the CGR genes. Natural elite haplotypes/alleles in these genes that increased Cd tolerance were identified by a haplotype analysis of a diverse mini core collection. More importantly, this study was the first to uncover the natural variations of 5 GST genes that play important roles in CGRs.ConclusionThe exploration of Cd-resistant rice germplasm resources and the identification of elite natural variations related to Cd-resistance will help improve the tolerance of current major rice varieties to Cd, as well as provide raw materials and new genes for breeding Cd-resistant varieties.
A timed activity protocol to address sleep-wake disorders in home dwelling persons living with dementia: the healthy patterns clinical trial
Authors: Hodgson Nancy A. , Gooneratne Nalaka , Perez Adriana , Talwar Sonia , Huang Liming 
Published: August 2021

AbstractBackgroundSleep-wake disorders occur in most persons living with dementia and include late afternoon or evening agitation, irregular sleep-wake rhythms such as daytime hypersomnia, frequent night awakenings, and poor sleep efficiency. Sleep-wake disorders pose a great burden to family caregivers, and are the principal causes of distress, poor quality of life, and institutionalization. Regulating the sleep-wake cycle through the use of light and activity has been shown to alter core clock processes and suggests that a combination of cognitive, physical, and sensory-based activities, delivered at strategic times, may be an effective mechanism through which to reduce sleep-wake disorders.MethodsA definitive Phase III efficacy trial of the Healthy Patterns intervention, a home-based activity intervention designed to improve sleep-wake disorders and quality of life, is being conducted using a randomized two-group parallel design of 200 people living with dementia and their caregivers (dyads). Specific components of this one-month, home-based intervention involve 4 in-home visits and includes: 1) assessing individuals’ functional status and interests; 2) educating caregivers on environmental cues to promote activity and sleep; and 3) training caregivers in using timed morning, afternoon, and evening activities based on circadian needs across the day. The patient focused outcomes of interest are quality of life, measures of sleep assessed by objective and subjective indicators including actigraphy, subjective sleep quality, and the presence of neuropsychiatric symptoms. Caregiver outcomes of interest are quality of life, burden, confidence using activities, and sleep disruption. Salivary measures of cortisol and melatonin are collected to assess potential intervention mechanisms.DiscussionThe results from the ongoing study will provide fundamental new knowledge regarding the effects of timing activity participation based on diurnal needs and the mechanisms underlying timed interventions which can lead to a structured, replicable treatment protocol for use with this growing population of persons living with dementia.Clinical trial registrationClinicaltrials.gov# NCT03682185 athttps://clinicaltrials.gov/; Date of clinical trial registration: 24 September 2018.
Erythema induratum of Bazin as an indicative manifestation of cavitary tuberculosis in an adolescent: a case report
Authors: Yang Kun , Li Tingying , Zhu Xiaomei , Zou Yun , Liu Dongxian 
Published: August 2021

Abstract
Background
Erythema induratum of Bazin (EIB) is a rare cutaneous manifestation of tuberculosis (TB) that frequently occurs in middle-aged women. The clinical manifestations of EIB can mimic various skin diseases, easily leading to misdiagnosis or underdiagnosis. We report a case of a 16-year-old Chinese girl who initially presented with EIB and was subsequently diagnosed with cavitary TB.

Case presentation
The patient is a 16-year-old Chinese girl who presented with clusters of erythematous subcutaneous nodules on the posterior part of her right lower leg matching the clinical manifestations of EIB but was otherwise asymptomatic. The patient was subsequently diagnosed with cavitary TB on the basis of a positive result from a T-SPOT.TB test and the observation of cavitary lung lesions in chest computed tomography scanning. A good clinical response was observed in the patient after the initial phase of a standard 6-month antibiotic regimen.

Conclusions
Adolescents infected with Mycobacterium tuberculosis frequently present atypical symptoms. Cutaneous manifestations of tuberculosis in adolescents can be considered good clinical indicators to predict the underlying disease. Strong clinical suspicion is required for a prompt diagnosis in adolescents with EIB.
Association between CD4+ T cell counts and gut microbiota and serum cytokines levels in HIV-infected immunological non-responders
Authors: Lu Danfeng , Zhang Jian-Bo , Wang Yue-Xin , Geng Shi-Tao , Zhang Zunyue , Xu Yu , Li Shao-You , Wang Kun-Hua , Kuang Yi-Qun 
Published: August 2021

Abstract
Background
CD4+ T cell counts in certain human immunodeficiency virus (HIV)-infected patients called immunological non-responders (INRs) could not return to a normal level even with sustained antiretroviral therapy (ART) because of persistent immune activation, which is associated with pro-inflammatory cytokines production and an altered intestinal microbiome profile. Changes in gut bacterial composition have been linked to low CD4+ T cell counts in HIV-infected individuals. However, the association between CD4+ T cell counts and gut microbiota community composition and cytokines levels in INRs (CD4+ T cell counts < 500 cells/μL) from Yunnan Province, China, has not been previously investigated.

Methods
To address this issue, we carried out a cross-sectional study of 34 HIV-infected INRs. The patients were divided into CD4 count > 200 cells/μL group and CD4 count < 200 cells/μL group. The gut microbiota composition of each subject was analyzed by 16S rRNA gene sequencing. We also compared CD8+ T cell counts, pro-inflammatory cytokines levels, and nutritional status between the two groups.

Results
Compared to INRs with CD4 count > 200 cells/μL, those with CD4 count < 200 cells/μL had a lower CD4/CD8 ratio, lower nutritional status and higher serum levels of tumor necrosis factor (TNF)-α, interferon-γ-inducible protein (IP)-10 and interleukin (IL)-1α. Ruminococcaceae was less abundant in the CD4 count < 200 cells/μL group than in the CD4 count > 200 cells/μL group, and difference in alpha diversity was observed between the two groups. Moreover, CD4+ T cell counts were negatively associated with TNF-α and IL-1α levels and positively associated with the relative abundance of Ruminococcaceae.

Conclusions
Our study demonstrated that lower CD4+ T cell counts in INRs are associated with a reduced abundance of Ruminococcaceae in the gut and elevated serum pro-inflammatory cytokines levels. Thus, interventions targeting gut microbiota to increase CD4+ T cell counts are a potential strategy for promoting immune reconstitution in HIV-infected INRs.
Peripheral neuropathy in HIV-infected children attending care and treatment clinic, at Muhimbili National Hospital, Dar es Salaam: a cross sectional study
Authors: Amiji Insiyah A , Naburi Helga E , Kija Edward , Mumburi Livin P 
Published: August 2021

Abstract
Background
Peripheral neuropathy (PN) is a neurological complication of untreated Human Immunodeficiency Virus (HIV) infection or exposure to certain antiretroviral drugs. In Tanzania where HIV is a major public health problem, the burden of HIV associated peripheral neuropathy has not yet been well defined in children.Thisstudy investigated the prevalence and associated factors for peripheral neuropathy among children living with HIV, attending Care and Treatment Clinic (CTC) at Muhimbili National Hospital (MNH).

Materials and methods
A cross-sectional study was conducted among 383 HIV positive children aged 5 to 18 years at MNH, CTC in Dar es Salaam between October to December 2019. All participants provided written assent/consent. Structured questionnaires designed for this study was used to collect data and screening for peripheral neuropathy was done on each participant using the Pediatric modified Total Neuropathy Score (Ped m TNS) that includes subjective and objective assessment. A score of 5 or greater on the Ped m TNS was used to define peripheral neuropathy. Data analysis was done using SPSS Version 23.

Results
The prevalence of peripheral neuropathy among HIV infected children was 14.1 % (95 % CI (10.8 − 18 %). Common neuropathic symptoms were numbness, tingling sensation, reduced ankle reflexes and reduced sensation to light touch and pain that was limited to the toes. Low CD4 cell count (OR = 12.21; 95 % CI3.75–39.66; p = 0.0001), high viral load (OR = 10.54; 95 % CI 3.19–34.77; p = 0.0001), ART regime containing NRTI plus PI (OR = 3.93; 95 % CI 1.43– 10.74; p = 0.01) and the last exposure to isoniazid more than 6 months ago (OR = 3.71; 95 % CI 1.57–8.77; p = 0.003) were independent predictors for peripheral neuropathy.

Conclusion
Peripheral neuropathy is common among HIV infected children attending CTC at MNH and its frequency increases with advanced disease. The choice of ART regimen and other drugs for treating comorbid conditions should carefully be evaluated.