bluuebunny/crossref_metadata_2025_split huggingface dataset:
The crosstalk between reactive oxygen species and noncoding RNAs: from cancer code to drug role
Authors: Zuo Jing , Zhang Zhe , Li Maomao , Yang Yun , Zheng Bohao , Wang Ping , Huang Canhua , Zhou Shengtao 
Published: January 2022

AbstractOxidative stress (OS), characterized by the excessive accumulation of reactive oxygen species (ROS), is an emerging hallmark of cancer. Tumorigenesis and development driven by ROS require an aberrant redox homeostasis, that activates onco-signaling and avoids ROS-induced programmed death by orchestrating antioxidant systems. These processes are revealed to closely associate with noncoding RNAs (ncRNAs). On the basis of the available evidence, ncRNAs have been widely identified as multifarious modulators with the involvement of several key redox sensing pathways, such as NF-κB and Nrf2 signaling, therefore potentially becoming effective targets for cancer therapy. Furthermore, the vast majority of ncRNAs with property of easy detected in fluid samples (e.g., blood and urine) facilitate clinicians to monitor redox homeostasis, indicating a novel method for cancer diagnosis. Herein, focusing on carcinoma initiation, metastasis and chemoradiotherapy resistance, we aimed to discuss the ncRNAs-ROS network involved in cancer progression, and the potential clinical application as biomarkers and therapeutic targets.
Analysis of plasma proteins using 2D gels and novel fluorescent probes: in search of blood based biomarkers for Alzheimer’s disease
Authors: Laffoon Scott B. , Doecke James D. , Roberts Anne M. , Vance Jennifer A. , Reeves Benjamin D. , Pertile Kelly K. , Rumble Rebecca L. , Fowler Chris J. , Trounson Brett , Ames David , Martins Ralph , Bush Ashley I. , Masters Colin L. , Grieco Paul A. , Dratz Edward A. , Roberts Blaine R. 
Published: January 2022

Abstract
Background
The Australian Imaging and Biomarker Lifestyle (AIBL) study of aging is designed to aid the discovery of biomarkers. The current study aimed to discover differentially expressed plasma proteins that could yield a blood-based screening tool for Alzheimer’s disease.

Methods
The concentration of proteins in plasma covers a vast range of 12 orders of magnitude. Therefore, to search for medium to low abundant biomarkers and elucidate mechanisms of AD, we immuno-depleted the most abundant plasma proteins and pre-fractionated the remaining proteins by HPLC, prior to two-dimensional gel electrophoresis. The relative levels of approximately 3400 protein species resolved on the 2D gels were compared using in-gel differential analysis with spectrally resolved fluorescent protein detection dyes (Zdyes™). Here we report on analysis of pooled plasma samples from an initial screen of a sex-matched cohort of 72 probable AD patients and 72 healthy controls from the baseline time point of AIBL.

Results
We report significant changes in variants of apolipoprotein E, haptoglobin, α1 anti-trypsin, inter-α trypsin inhibitor, histidine-rich glycoprotein, and a protein of unknown identity. α1 anti-trypsin and α1 anti-chymotrypsin demonstrated plasma concentrations that were dependent on APOE ε4 allele dose. Our analysis also identified an association with the level of Vitamin D binding protein fragments and complement factor I with sex. We then conducted a preliminary validation study, on unique individual samples compared to the discovery cohort, using a targeted LC-MS/MS assay on a subset of discovered biomarkers. We found that targets that displayed a high degree of isoform specific changes in the 2D gels were not changed in the targeted MS assay which reports on the total level of the biomarker.

Conclusions
This demonstrates that further development of mass spectrometry assays is needed to capture the isoform complexity that exists in theses biological samples. However, this study indicates that a peripheral protein signature has potential to aid in the characterization of AD.
Interplay between nitric oxide and gonadotrophin-releasing hormone in the neuromodulation of the corpus luteum during late pregnancy in the rat
Authors: Vallcaneras Sandra , Morales Laura , Delsouc María Belén , Ramirez Darío , Filippa Verónica , Fernández Marina , Telleria Carlos M. , Casais Marilina 
Published: January 2022

Abstract
Background
Nitric oxide and GnRH are biological factors that participate in the regulation of reproductive functions. To our knowledge, there are no studies that link NO and GnRH in the sympathetic ganglia. Thus, the aim of the present work was to investigate the influence of NO on GnRH release from the coeliac ganglion and its effect on luteal regression at the end of pregnancy in the rat.

Methods
The ex vivo system composed by the coeliac ganglion, the superior ovarian nerve, and the ovary of rats on day 21 of pregnancy was incubated for 180 min with the addition, into the ganglionic compartment, of L-NG-nitro arginine methyl ester (L-NAME), a non-selective NO synthase inhibitor. The control group consisted in untreated organ systems.

Results
The addition of L-NAME in the coeliac ganglion compartment decreased NO as well as GnRH release from the coeliac ganglion. In the ovarian compartment, and with respect to the control group, we observed a reduced release of GnRH, NO, and noradrenaline, but an increased production of progesterone, estradiol, and expression of their limiting biosynthetic enzymes, 3β-HSD and P450 aromatase, respectively. The inhibition of NO production by L-NAME in the coeliac ganglion compartment also reduced luteal apoptosis, lipid peroxidation, and nitrotyrosine, whereas it increased the total antioxidant capacity within the corpora lutea.

Conclusion
Collectively, the results indicate that NO production by the coeliac ganglion modulates the physiology of the ovary and luteal regression during late pregnancy in rats.
‘Finishing the race’ – a cohort study of weight and blood glucose change among the first 36,000 patients in a large-scale diabetes prevention programme
Authors: Marsden Antonia M. , Bower Peter , Howarth Elizabeth , Soiland-Reyes Claudia , Sutton Matt , Cotterill Sarah 
Published: January 2022

Abstract
Background
The NHS Diabetes Prevention Programme for England, “Healthier You”, encourages behaviour change regarding healthy eating and physical exercise among people identified to be at high risk of developing type 2 diabetes. The aim of this research was to examine change, and factors associated with change, in measures of HbA1c and weight in participants and completers of the programme between 2016 and 2019.

Methods
Participant-level data collected by programme service providers on referrals prior to March 2018 was analysed. Changes from baseline to both 6 months and completion in HbA1c and weight were examined using mixed effects linear regression, adjusting for patient characteristics, service provider and site.

Results
Completers had average improvements in HbA1c of 2.1 mmol/mol [95% CI: − 2.2, − 2.0] (0.19% [95% CI: − 0.20, − 0.18]) and reductions of 3.6 kg [95% CI: − 3.6, − 3.5] in weight, in absolute terms. Variation across the four providers was observed at both time points: two providers had significantly smaller average reductions in HbA1c and one provider had a significantly smaller average reduction in weight compared to the other providers. At both time points, ex- or current smokers had smaller reductions in HbA1c than non-smokers and those from minority ethnic groups lost less weight than White participants. For both outcomes, associations with other factors were small or null and variation across sites remained after adjustment for provider and case mix.

Conclusions
Participants who completed the programme, on average, experienced improvements in weight and HbA1c. There was substantial variation in HbA1c change and smaller variation in weight loss between providers and across different sites. Aside from an association between HbA1c change and smoking, and between weight loss and ethnicity, results were broadly similar regardless of patient characteristics.
Bone marrow stromal antigen 2 (BST-2) genetic variants influence expression levels and disease outcome in HIV-1 chronically infected patients
Authors: Mlimi Hlelolwenkosi , Naidoo Kewreshini K. , Mabuka Jenniffer , Ndung’u Thumbi , Madlala Paradise 
Published: January 2022

Abstract
Background
Bone marrow stromal antigen 2 (BST-2) also known as Tetherin (CD317/HM1.24), is a host restriction factor that blocks the release of HIV-1 virions from infected cells. Previous studies reported that BST-2 genetic variants or single nucleotide polymorphims (SNPs) have a preventative role during HIV-1 infection. However, the influence of BST-2 SNPs on expression levels remains unknown. In this study, we investigated the influence of BST-2 SNPs on expression levels and disease outcome in HIV-1 subtype C chronically infected antiretroviral therapy naïve individuals.

Results
We quantified BST-2 mRNA levels in peripheral blood mononuclear cells (PBMCs), determined BST-2 protein expression on the surface of CD4+ T cells using flow cytometry and genotyped two intronic single nucleotide polymorphisms (SNPs) rs919267 and rs919266 together with one SNP rs9576 located in the 3’ untranslated region (UTR) of bst-2 gene using TaqMan assays from HIV-1 uninfected and infected participants. Subsequently, we determined the ability of plasma antibody levels to mediate antibody-dependent cellular phagocytosis (ADCP) using gp120 consensus C and p24 subtype B/C protein. Fc receptor-mediated NK cell degranulation was evaluated as a surrogate for ADCC activity using plasma from HIV-1 positive participants. BST-2 mRNA expression levels in PBMCs and protein levels on CD4+ T cells were lower in HIV-1 infected compared to uninfected participants (p = 0.075 and p < 0.001, respectively). rs919267CT (p = 0.042) and rs919267TT (p = 0.045) were associated with lower BST-2 mRNA expression levels compared to rs919267CC in HIV-1 uninfected participants. In HIV-1 infected participants, rs919267CT associated with lower CD4 counts, (p = 0.003), gp120-IgG1 (p = 0.040), gp120-IgG3 (p = 0.016) levels but higher viral loads (p = 0.001) while rs919267TT was associated with lower BST-2 mRNA levels (p = 0.046), CD4 counts (p = 0.001), gp120-IgG1 levels (p = 0.033) but higher plasma viral loads (p = 0.007). Conversely, rs9576CA was associated with higher BST-2 mRNA expression levels (p = 0.027), CD4 counts (p = 0.079), gp120-IgG1 (p = 0.009), gp120-IgG3 (p = 0.039) levels but with lower viral loads (p = 0.037).

Conclusion
Our findings show that bst-2 SNPs mediate BST-2 expression and disease outcome, correlate with gp120-IgG1, gp120-IgG3 levels but not p24-IgG levels, ADCC and ADCP activity.

Graphical Abstract
Motorized 2–3 wheelers death rates over a decade: a global study
Authors: Yasin Yasin J. , Grivna Michal , Abu-Zidan Fikri M. 
Published: January 2022

Abstract
Background
Motorized 2–3-wheelers-related death is high due to the exposed body of the driver/passenger and the high speed. The United Nation (UN) Decade of Action for road safety aimed to reduce road traffic deaths by 50% by the year 2020. We aimed to study the factors affecting the death rates of motorized 2–3 wheelers injured victims and whether the reduction in the death rates has met the UN target.

Methods
Data were retrieved from the WHO Global Status Reports on Road Safety published over 2009 to 2018 which covered the years of 2007 to 2016. Studied variables included motorized 2–3 wheelers death rates, percentage of helmet-wearing rate, helmet law enforcement, speed law enforcement, gross national income per capita, vehicles/person ratio, and motorized 2–3 wheelers/person ratio. A mixed linear model was used to define factors affecting the change of motorized 2–3 wheelers death rates over time.

Results
The global mean motorized 2–3 wheelers death rates increased from 2.37/100,000 population to 3.23/100,000 population over the studied decade (a relative ratio of 1.36) which was not statistically significant. Factors that affected mortality included GNI (p = 0.025), motorized 2–3 wheelers per person ratio (p < 0.0001), percentage of helmet wearing rate (p = 0.046), and the interaction between vehicle/person ratio and motorized 2–3 wheelers/person ratio (p = 0.016). There was a significant increase in the death rates over time in the low-income countries (a relative ratio of 2.52, p = 0.019, Friedman test), and middle-income countries (a relative ratio of 1.46, p < 0.0001, Friedman test), compared with a significant decrease in the high-income countries (a relative ratio of 0.72, p < 0.0001, Friedman test).

Conclusions
Global mortality of motorized 2–3 wheelers has increased by a relative ratio of 1.36 over a recent decade. The UN target of reducing death was not met. The increase was related to the increase in motorized 2–3 wheelers per person ratio and economic inequity which has to be addressed globally. The economic global gap significantly impacts the mortality rates of motorized 2–3 wheelers.
A 6-year case series of resuscitative thoracotomies performed by a helicopter emergency medical service in a mixed urban and rural area with a comparison of blunt versus penetrating trauma
Authors: Almond Phillip , Morton Sarah , OMeara Matthew , Durge Neal 
Published: January 2022

Abstract
Background
Resuscitative thoracotomy (RT) is an intervention that can be performed in the prehospital setting for relieving cardiac tamponade and/or obtaining vascular control of suspected sub-diaphragmatic haemorrhage in patients in traumatic cardiac arrest. The aim of this retrospective case study is to compare the rates of return of spontaneous circulation (ROSC) in RTs performed for both penetrating and blunt trauma over 6 years in a mixed urban and rural environment.

Methods
The electronic records of a single helicopter emergency medical service were reviewed between 1st June 2015 and 31st May 2021 for RTs. Anonymised data including demographics were extracted for relevant cases. Data were analysed with independent t-tests and Χ2 tests. A p value < 0.05 was considered statistically significant.

Results
Forty-four RTs were preformed within the 6 years (26 for blunt trauma). Eleven ROSCs were achieved (nine blunt, two penetrating) but no patient survived to discharge. In contrast to RTs for penetrating trauma, twelve of the RTs for blunt trauma had a cardiac output present on arrival of the prehospital team (p = 0.01). Two patients had an RT performed in a helicopter (one ROSC) and two on a helipad (both achieving ROSC), likely due to the longer transfer times seen in a more rural setting. Four of the RTs for blunt trauma (15%) were found to have a cardiac tamponade versus seven (39%) of the penetrating trauma RTs.

Conclusion
Prehospital RT remains a procedure with low rates of survival but may facilitate a ROSC to allow patients to reach hospital and surgery, particularly when distances to hospitals are greater. A higher-than-expected rate of cardiac tamponade was seen in RTs for blunt trauma, although not caused by a right ventricular wound but instead due to underlying vessel damage.
Measured body size and serum estrogen metabolism in postmenopausal women: the Ghana Breast Health Study
Authors: Geczik Ashley M. , Falk Roni T. , Xu Xia , Ansong Daniel , Yarney Joel , Wiafe-Addai Beatrice , Edusei Lawrence , Dedey Florence , Vanderpuye Verna , Titiloye Nicholas , Adjei Ernest , Aitpillah Francis , Osei-Bonsu Ernest , Oppong Joseph , Biritwum Richard , Nyarko Kofi , Wiafe Seth , Awuah Baffour , Clegg-Lamptey Joe-Nat , Ahearn Thomas U. , Figueroa Jonine , Garcia-Closas Montserrat , Brinton Louise A. , Trabert Britton 
Published: January 2022

Abstract
Background
Several anthropometric measures have been associated with hormone-related cancers, and it has been shown that estrogen metabolism in postmenopausal women plays an important role in these relationships. However, little is known about circulating estrogen levels in African women, and the relevance to breast cancer or breast cancer risk factors. To shed further light on the relationship of anthropometric factors and estrogen levels in African women, we examined whether measured body mass index (BMI), waist-to-hip ratio (WHR), height, and self-reported body size were associated with serum estrogens/estrogen metabolites in a cross-sectional analysis among postmenopausal population-based controls of the Ghana Breast Health Study.

Methods
Fifteen estrogens/estrogen metabolites were quantified using liquid chromatography-tandem mass spectrometry in serum samples collected from postmenopausal female controls enrolled in the Ghana Breast Health Study, a population-based case–control study conducted in Accra and Kumasi. Geometric means (GMs) of estrogens/estrogen metabolites were estimated using linear regression, adjusting for potential confounders.

Results
Measured BMI (≥ 30 vs. 18.5–24.9 kg/m2) was positively associated with parent estrogens (multivariable adjusted GM for unconjugated estrone: 78.90 (66.57–93.53) vs. 50.89 (43.47–59.59), p-value < 0.0001; and unconjugated estradiol: 27.83 (21.47–36.07) vs. 13.26 (10.37–16.95), p-value < 0.0001). Independent of unconjugated estradiol, measured BMI was associated with lower levels of 2-pathway metabolites and higher levels of 16-ketoestradriol. Similar patterns of association were found with WHR; however, the associations were not entirely independent of BMI. Height was not associated with postmenopausal estrogens/estrogen metabolite levels in African women.

Conclusions
We observed strong associations between measured BMI and parent estrogens and estrogen metabolite patterns that largely mirrored relations that have previously been associated with higher breast cancer risk in postmenopausal White women. The consistency of the BMI-estrogen metabolism associations in our study with those previously noted among White women suggests that estrogens likely explain part of the BMI-postmenopausal breast cancer risk in both groups. These findings merit evaluation in Black women, including prospective studies.
CellPhy: accurate and fast probabilistic inference of single-cell phylogenies from scDNA-seq data
Authors: Kozlov Alexey , Alves Joao M. , Stamatakis Alexandros , Posada David 
Published: January 2022

AbstractWe introduce CellPhy, a maximum likelihood framework for inferring phylogenetic trees from somatic single-cell single-nucleotide variants. CellPhy leverages a finite-site Markov genotype model with 16 diploid states and considers amplification error and allelic dropout. We implement CellPhy into RAxML-NG, a widely used phylogenetic inference package that provides statistical confidence measurements and scales well on large datasets with hundreds or thousands of cells. Comprehensive simulations suggest that CellPhy is more robust to single-cell genomics errors and outperforms state-of-the-art methods under realistic scenarios, both in accuracy and speed. CellPhy is freely available athttps://github.com/amkozlov/cellphy.
Comparative assessment of genes driving cancer and somatic evolution in non-cancer tissues: an update of the Network of Cancer Genes (NCG) resource
Authors: Dressler Lisa , Bortolomeazzi Michele , Keddar Mohamed Reda , Misetic Hrvoje , Sartini Giulia , Acha-Sagredo Amelia , Montorsi Lucia , Wijewardhane Neshika , Repana Dimitra , Nulsen Joel , Goldman Jacki , Pollitt Marc , Davis Patrick , Strange Amy , Ambrose Karen , Ciccarelli Francesca D. 
Published: January 2022

Abstract
Background
Genetic alterations of somatic cells can drive non-malignant clone formation and promote cancer initiation. However, the link between these processes remains unclear and hampers our understanding of tissue homeostasis and cancer development.

Results
Here, we collect a literature-based repertoire of 3355 well-known or predicted drivers of cancer and non-cancer somatic evolution in 122 cancer types and 12 non-cancer tissues. Mapping the alterations of these genes in 7953 pan-cancer samples reveals that, despite the large size, the known compendium of drivers is still incomplete and biased towards frequently occurring coding mutations. High overlap exists between drivers of cancer and non-cancer somatic evolution, although significant differences emerge in their recurrence. We confirm and expand the unique properties of drivers and identify a core of evolutionarily conserved and essential genes whose germline variation is strongly counter-selected. Somatic alteration in even one of these genes is sufficient to drive clonal expansion but not malignant transformation.

Conclusions
Our study offers a comprehensive overview of our current understanding of the genetic events initiating clone expansion and cancer revealing significant gaps and biases that still need to be addressed. The compendium of cancer and non-cancer somatic drivers, their literature support, and properties are accessible in the Network of Cancer Genes and Healthy Drivers resource at http://www.network-cancer-genes.org/.
Vitamin D3 and calcium carbonate supplementation for adolescents with HIV to reduce musculoskeletal morbidity and immunopathology (VITALITY trial): study protocol for a randomised placebo-controlled trial
Authors: Dzavakwa Nyasha Veronica , Chisenga Molly , McHugh Grace , Filteau Suzanne , Gregson Celia Louise , Kasonka Lackson , Kranzer Katharina , Mabuda Hildah Banda , Mujuru Hilda , Redzo Nicol , Rowland-Jones Sarah , Schaible Ulrich E. , Simms Victoria , Ferrand Rashida Abbas ,   the VITALITY team
Published: January 2022

Abstract
Background
Of the 2 million children living with HIV globally, 90% live in sub-Saharan Africa. Despite antiretroviral therapy, longstanding HIV infection is associated with several chronic complications in children including growth failure, particularly stunting and delayed puberty. Vitamin D deficiency, which is highly prevalent among children living with HIV in sub-Saharan Africa, has a further adverse impact on bone health. This trial aims to establish whether supplementation with vitamin D3 and calcium carbonate improves musculoskeletal health among peripubertal children living with HIV.

Methods/design
We will conduct an individually randomised, double-blinded, placebo-controlled trial of weekly high-dose vitamin D3 (20,000 IU) plus daily calcium carbonate (500mg) supplementation for 48 weeks. Eight hundred and forty children living with HIV aged 11–19 years taking ART for ≥6 months will be enrolled and followed up for 96 weeks. The primary outcome is total body less-head bone mineral content for lean mass adjusted for height (TBLH-BMCLBM) Z-score at 48 weeks, measured by dual-energy X-ray absorptiometry (DEXA). Secondary outcomes are DEXA-measured lumbar spine bone mineral apparent density Z-score, number of respiratory infections, lean muscle mass and grip strength at 48 and 96 weeks and TBLH-BMCLBMZ-scores at 96 weeks. Sub-studies will investigate the effect of the intervention on vitamin D3 pathway metabolites and markers of bone turnover, intestinal microbiota, and innate and acquired immune function.

Discussion
This is the largest trial to date of vitamin D supplementation in children living with HIV. Intervening to address deficits in bone accrual in childhood is critical for optimising adolescent and early adult bone health and prevention of later adult osteoporotic fractures. Trial results will draw attention to the need to screen for and treat long-term comorbidities in children living with HIV in resource-limited settings.

Trial registration
Pan African Clinical Trials Registry PACTR20200989766029. Registered on 3 September 2020