bluuebunny/crossref_metadata_2025_split huggingface dataset:
Beta-cell Metabolic Activity Rather than Gap Junction Structure Dictates Subpopulations in the Islet Functional Network
Authors: Briggs Jennifer K. , Kravets Vira , Dwulet JaeAnn M. , Albers David J. , Benninger Richard K. P. 
Published: February 2022

AbstractDiabetes is caused by dysfunction of electrically coupled heterogeneous β-cells within the pancreatic islet. Functional networks have been used to represent cellular synchronization and study β-cells subpopulations, which play an important role in driving dynamics. The mechanism by which highly synchronized β-cell subpopulations drive islet function is not clear. We used experimental and computational techniques to investigate the relationship between functional networks, structural (gap-junction) networks, and underlying β-cell dynamics. Highly synchronized subpopulations in the functional network were differentiated by metabolic dynamics rather than structural coupling. Consistent with this, metabolic similarities were more predictive of edges in the islet functional network. Finally, removal of gap junctions, as occurs in diabetes, caused decreases in the efficiency and clustering of the functional network. These results indicate that metabolism rather than structure drives connections in the function network, deepening our interpretation of functional networks and the formation of functional sub-populations in dynamic tissues such as the islet.
Individual and community-level determinants of intention to use contraceptive among married women in Ethiopia: A multi-level analysis of National Survey
Authors: Shitu Kegnie , Alem Adugnaw Zeleke , Alemneh Tesfa Sewunet , Terefe Bewuketu 
Published: February 2022

AbstractBackgroundContraceptives are the most effective strategies to prevent unwanted pregnancies and their consequences. Realizing intention to use contraceptives is a crucial stage to draft and implement a successful family planning program.ObjectiveThis study aimed to identify individual and community level of factors affecting women’s intention to use contraceptives in Ethiopia.MethodThis study was based on a large national survey, Ethiopian Demographic and Health Survey. A total weighted sample of 6,555 married/in union reproductive-age women were included. Because of the hierarchical nature of the DHS data, a multilevel logistic regression model was used to study individual and community-level factors that may influence intention to contraceptive use. A 95% confidence interval and a p value of less than 0.05 were used to declare statistical significance.ResultThe overall intention to use contraceptives was 48.63% (95% CI 47.42, 49.84). Participants’ age range of 25-34 years (AOR = 0.42, 95 CI% (0.22, 0.79)) and 35-49 years (AOR = 0.12, 95% CI: (0.05, 0.28)), husband with primary education (AOR = 1.60, 95% CI: (1.02, 2.50)), heard of contraceptives from their community (AOR = 1.91. 95% CI: (1.29, 2.83)), ever used contraceptives (AOR = 4.48, 95% CI: (2.91, 6.88)) and having six or more children (AOR = 0.46, 95% CI: (0.23, 0.9)) were individual factors significantly associated with interceptive intention. From community level factors, high community family planning utilization rate (AOR = 2.29, 95% CI: (1.36,3.86)) was associated with intention to use contraceptive.ConclusionMore than half of married women were not intended to use contraceptives. Intention to use contraceptive was affected by individual and community level attributes. Thus, public health interventions particularly that could increase information dissemination regarding contraceptives among the communities and enhance community level contraceptive utilization rate are required at the national level to improve contraceptive utilization.
Anti-spike antibody trajectories in individuals previously immunised with BNT162b2 or ChAdOx1 following a BNT162b2 booster dose
Authors: Yavlinsky Alexei , Beale Sarah , Nguyen Vincent , Shrotri Madhumita , Byrne Thomas , Geismar Cyril , Fragaszy Ellen , Hoskins Susan , Fong Wing Lam Erica , Navaratnam Annalan M D , Braithwaite Isobel , Patel Parth , Kovar Jana , Hayward Andrew , Aldridge Robert W 
Published: February 2022

AbstractThe two most commonly-used SARS-CoV-2 vaccines in the UK, BNT162b2 (Pfizer-BioNTech) and ChAdOx1 nCoV-19 (Oxford-AstraZeneca), employ different immunogenic mechanisms. Compared to BNT162b2, two-dose immunisation with ChAdOx1 induces substantially lower peak anti-spike antibody (anti-S) levels and is associated with a higher risk of breakthrough infections. To provide preliminary indication of how a third booster BNT162b2 dose impacts anti-S levels, we performed a cross-sectional analysis using capillary blood samples from vaccinated adults (aged ≥18 years) participating in Virus Watch, a prospective community cohort study in England and Wales. Blood samples were analysed using Roche Elecsys Anti-SARS-CoV-2 S immunoassay. We analysed anti-S levels by week since the third dose for vaccines administered on or after September 1, 2021 and stratified the results by second dose vaccine type (ChAdOx1 or BNT162b2), age, sex and clinical vulnerability. Anti-S levels peaked at two weeks post-booster for BNT162b2 (22,185 U/mL; 95%CI: 21,406-22,990) and ChAdOx1 second dose recipients (19,203 U/mL; 95%CI: 18,094-20,377). These were higher than the corresponding peak antibody levels post-second dose for BNT162b2 (12,386 U/mL; 95%CI: 9,801-15,653, week 2) and ChAdOx1 (1,192 U/mL; 95%CI: 818-1735, week 3). No differences emerged by second dose vaccine type, age, sex or clinical vulnerability. Anti-S levels declined post-booster for BNT162b2 (half-life=44 days) and ChAdOx1 second dose recipients (half-life=40 days). These rates of decline were steeper than those post-second dose for BNT162b2 (half-life=54 days) and ChAdOx1 (half-life=80 days). Our findings suggest that peak anti-S levels are higher post-booster than post-second dose, but that levels are projected to be similar after six months for BNT162b2 recipients. Higher peak anti-S levels post-booster may partially explain the increased effectiveness of booster vaccination compared to two-dose vaccination against symptomatic infection with the Omicron variant. Faster waning trajectories post third-dose may have implications for the timing of future booster campaigns or four-dose vaccination regimens for the clinically vulnerable.
Impaired reaching adaptation links to vestibular symptoms
Authors: Santos-Pata Diogo , Bellmunt Anna , María San Segundo Mozo Rosa , Sáez Sandra , Domènech-Vadillo Esther , Carballo Leticia , Verschure Paul F.M.J. , Rubio Ballester Belén 
Published: February 2022

AbstractAbout 30% of adults suffer from some mild to severe vestibular dysfunction. Vestibular disorders can be expressed as acute vestibular syndrome (AVS), episodic vestibular syndrome. Only half of the sufferers can compensate for their dysfunction after three months after the onset, while the other half of them become chronic, the mechanisms behind this compensation remain unclear. Several behavioural studies have explored the role of the vestibulo-ocular reflex and saccades in the process, linking to the interaction between the superior colliculus and the cerebellum. Yet, despite cerebellar involvement in vestibular function and oculomotor adaptation, thus far, no studies have focused on the specific role of the cerebellum in the compensation process in vestibular dysfunction.In this study, we test the hypothesis that undiagnosed cerebellar dysfunction might hinder chronic vestibulopathy sufferers from compensating and recovering. We recruited 19 patients who had suffered from an acute peripheral vestibular syndrome (10 clinically recovered and 9 with chronic symptoms) and ten individuals with no history of vestibular alterations (controls). We assessed their implicit motor learning capacity with a visuomotor rotation task and measured by the angular aiming error, which showed an impaired implicit motor adaptation in chronic patients (7.04 ± 1.6º) compared to recovered (11.06 ± 1.94º, p = 0.007) and control groups (10.89 ± 7.96º, p = 0.03). These findings indicate the involvement of the cerebellum in vestibular compensation and suggest that implicit motor adaptation of reaching movements could be potentially used as an early prognostic tool in unilateral peripheral vestibular dysfunction (UPVD) patients.
Chronic Disease and Workforce Participation Among Medicaid Enrollees Over 50: The Potential Impact of Medicaid Work Requirements Post-COVID-19
Authors: Sneed Rodlescia S. , Stubblefield Alexander , Gardner Graham , Jordan Tamara , Mezuk Briana 
Published: February 2022

ABSTRACTAs the COVID-19 pandemic wanes, states may reintroduce Medicaid work requirements to reduce enrollment. Using the Health and Retirement Study, we evaluated chronic disease burden among beneficiaries aged >50 (n=1460) who might be impacted by work requirements (i.e. working <20 hours per week). Seven of eight chronic conditions evaluated were associated with reduced workforce participation, including history of stroke (OR: 7.35; 95% CI: 2.98-18.14) and lung disease (OR: 4.39; 95% CI: 2.97-7.47). Those with more severe disease were also more likely to work fewer hours. Medicaid work requirements would likely have great impact on older beneficiaries with significant disease burden.Key PointsChronic disease linked to reduced work among older Medicaid beneficiaries.Work requirements would greatly impact those aged >50 with chronic conditions.Coverage loss would have negative implications for long-term disease management.
Quantifying the risks versus benefits of the Pfizer COVID-19 vaccine in Australia: a Bayesian network analysis
Authors: Sinclair Jane E , Mayfield Helen J , Short Kirsty R , Brown Samuel J , Puranik Rajesh , Mengersen Kerrie , Litt John CB , Lau Colleen L 
Published: February 2022

ABSTRACTThe Pfizer COVID-19 vaccine is associated with increased myocarditis incidence. Constantly evolving evidence regarding incidence and case fatality of COVID-19 and myocarditis related to infection or vaccination, creates challenge for risk-benefit analysis of vaccination programs. Challenges are complicated further by emerging evidence of waning vaccine effectiveness, and variable effectiveness against variants. Here, we build on previous work on the COVID-19 Risk Calculator (CoRiCal) by integrating Australian and international data to inform a Bayesian network that calculates probabilities of outcomes for the Delta variant under different scenarios of Pfizer COVID-19 vaccine coverage, age groups (≤12 years), sex, community transmission intensity and vaccine effectiveness. The model estimates that in a population where 5% were unvaccinated, 5% had one dose, 60% had two doses and 30% had three doses, the probabilities of developing and dying from COVID-19-related myocarditis were 239-5847 and 1430-384,684 times higher (depending on age and sex), respectively, than developing vaccine-associated myocarditis. For one million people with this vaccine coverage, where transmission intensity was equivalent to 10% chance of infection over two months, 68,813 symptomatic COVID-19 cases and 981 deaths would be prevented, with 42 and 16 expected cases of vaccine-associated myocarditis in males and females, respectively. The model may be updated to include emerging best evidence, data pertinent to different countries or vaccines, and other outcomes such as long COVID.
A Match Made in Cyberspace: Applicant Perspectives on a Virtual Residency Application Process
Authors: Chen Shirley , Schroeder Melanie , Pak Thomas Kun , Topolski Natasha , Zaworski Emelyn , Anishchenko Kseniya , Parsa Shyon , Zhu Christina , Bae Esther , Stuard Whitney , Patel Jay , Quach Shanon , Panjwani Sahar 
Published: February 2022

AbstractBackgroundThe COVID-19 pandemic precipitated an entirely virtual 2020-2021 residency application cycle. With many specialties continuing virtual interviews, it remains essential to evaluate all stakeholders perspectives.ObjectiveThis study aimed to evaluate applicants’ perspectives on the completely virtual 2020-2021 Match.MethodsAn online survey utilizing Likert scale and free response questions was distributed to residency applicants in 2021 post-Match to query their perspectives on the virtual application cycle.ResultsParticipants (n=158/2811, 5% estimated response rate) represented 24 states and applied to 31 specialties. Most were satisfied with their Match experience (73.1%) and thought virtual interviews should continue (68.6%). However, applicants felt that the virtual setting permitted interview hoarding (73.9%) and that their medical school did not provide adequate electronic equipment (66.1%). Applicants found Twitter (78.4%) and Instagram (69.1%) to be helpful social media platforms for evaluating fit. While many applicants (56.9%) did not support application limits, most supported interview limits (62.7%) and preference signaling mechanisms (59.7%). Free responses data elucidated applicants’ views on how the virtual Match impacted financial access, evaluation of program culture, and the future of residency interviews.ConclusionsOur study highlights that, across geography and specialty, many applicants support virtual interviews continuing. It also offers insight into how medical schools and residency programs can support applicants in the virtual environment. Additionally, the virtual setting provides an opportunity to evaluate mechanisms for addressing congestion within the Match, with most applicants supporting interview caps and preference signaling.
White matter abnormalities characterise the acute stage of sports-related mild Traumatic Brain Injury
Authors: Mito Remika , Parker Donna M. , Abbott David F. , Makdissi Michael , Pedersen Mangor , Jackson Graeme D. 
Published: February 2022

AbstractSports-related concussion, a form of mild traumatic brain injury (mTBI), is characterised by transient disturbances of brain function. There is increasing evidence that subtle abnormalities drive functional brain changes in white matter microstructure, and diffusion MRI has been instrumental in demonstrating these white matter abnormalities in vivo. However, the reported location and direction of the observed white matter changes in mTBI are variable, likely attributable to the inherent limitations of the white matter models used. This cross-sectional study applies an advanced and robust technique known as fixel-based analysis to investigate fibre tract-specific abnormalities in professional Australian Football League players with a recent mTBI. We used the fixel-based analysis framework to identify common abnormalities found in specific fibre tracts in participants with an acute mTBI (≤ 12 days after injury; n = 14). We then assessed whether similar changes exist in subacute mTBI (> 12 days and < 3 months after injury; n = 15). The control group was 29 neurologically healthy control participants. We assessed microstructural differences in fibre density and fibre bundle morphology and performed whole-brain fixel-based analysis to compare groups. Subsequent tract-of-interest analyses were performed within five selected white matter tracts to investigate the relationship between the observed tract-specific abnormalities and days since injury and the relationship between these tract-specific changes with cognitive abnormalities. Our whole-brain analyses revealed significant increases in fibre density and bundle cross-section in acute mTBI when compared to controls. Acute mTBI showed even more extensive differences when compared to subacute mTBI than to controls. The fibre structures affected in acute mTBI included the corpus callosum, left prefrontal and left parahippocampal white matter. The fibre density and cross-sectional increases were independent of time since injury in acute mTBI, and were not associated with cognitive deficits. Overall, this study demonstrates that acute mTBI is characterised by specific white matter abnormalities, which are compatible with tract-specific cytotoxic oedema. These potential oedematous changes were absent in our subacute mTBI participants, suggesting that they may normalise within 12 days after injury, although subtle abnormalities may persist in the subacute stage. Future longitudinal studies are needed to elucidate individualised recovery after brain injury.
Identification of Unusual Oxysterols Biosynthesised in Human Pregnancy by Charge-Tagging and Liquid Chromatography - Mass Spectrometry
Authors: Dickson Alison L. , Yutuc Eylan , Thornton Catherine A. , Wang Yuqin , Griffiths William J. 
Published: February 2022

AbstractThe aim of this study was to identify sterols, oxysterols and any down-stream metabolites in placenta, umbilical cord blood plasma, maternal plasma and amniotic fluid to enhance our knowledge of the involvement of these molecules in pregnancy. We confirm the identification of 20S- hydroxycholesterol in human placenta, previously reported in a single publication, and propose a pathway from 22R-hydroxycholesterol to a C27 bile acid of probable structure 3β,20R,22R- trihydroxycholest-5-en-(25R)26-oic acid. The pathway is evident not only in placenta, but pathway intermediates are also found in umbilical cord plasma, maternal plasma and amniotic fluid but not non-pregnant women.
A highly attenuated SARS-CoV-2 related pangolin coronavirus variant has a 104nt deletion at the 3′-terminus untranslated region
Authors: Lu Shanshan , Luo Shengdong , Liu Chang , Li Muli , An Xiaoping , Li Mengzhe , Hou Jun , Fan Huahao , Mao Panyong , Tong Yigang , Song Lihua 
Published: February 2022

AbstractSARS-CoV-2 related coronaviruses (SARS-CoV-2r) from Guangdong and Guangxi pangolins have been implicated in the emergence of SARS-CoV-2 and future pandemics. We previously reported the culture of a SARS-CoV-2r GX_P2V from Guangxi pangolins. Here we report the GX_P2V isolate rapidly adapted to Vero cells by acquiring two genomic mutations: an alanine to valine substitution in the nucleoprotein and a 104-nucleotide deletion in the hypervariable region (HVR) of the 3’-terminus untranslated region (3’-UTR). We further report the characterization of the GX_P2V variant in in vitro and in vivo infection models. In cultured Vero and BGM cells, the GX_P2V variant produced minimal cell damage and small plaques. The GX_P2V variant infected golden hamsters and BALB/c mice but was highly attenuated. Golden hamsters infected intranasally had a short duration of productive infection. These productive infections induced neutralizing antibodies against pseudoviruses of GX_P2V and SARS-CoV-2. Collectively, our data show that the GX_P2V variant is highly attenuated in in vitro and in vivo infection models. Attenuation of the variant is likely due to the 104-nt deletion in the HVR in the 3’-UTR. This study furthers our understanding of pangolin coronaviruses pathogenesis and provides novel insights for the design of live attenuated vaccines against SARS-CoV-2.
High-performance GPCR optogenetics based on molecular properties of animal opsins, MosOpn3 and LamPP
Authors: Koyanagi Mitsumasa , Shen Baoguo , Nagata Takashi , Sun Lanfang , Wada Seiji , Kamimura Satomi , Kage-Nakadai Eriko , Terakita Akihisa 
Published: February 2022

AbstractOptogenetics for GPCR signaling is highly valuable but still requires effective and versatile tools with performance evaluation from molecular properties. Here we investigated performance of two animal opsins, mosquito Opn3 (MosOpn3) and lamprey parapinopsin (LamPP) in optical manipulationin vivoby usingC. elegans. MosOpn3 introduced in a nociceptor neurons induced avoidance responses light-dependently with a retinal isomer ubiquitously present in every tissue, like ChR2 and unlike canonical vertebrate opsins. Remarkably, the sensitivity is ~7000 times higher than the case of ChR2 in the light-induced behavior. LamPP introduced in motor neurons induced violet light-dependent stop and green light-dependent go, demonstrating color-dependent manipulation of behaviors using LamPP. Furthermore, our molecular engineering extended the usability of MosOpn3 and LamPP to different signaling cascades and kinetics. Current findings demonstrated that the availability of two animal opsins is equivalent to that of ChR2 in terms of retinal requirement, providing solid strategies for GPCR optogenetics.
Transcriptional profiles predict treatment outcome in patients with tuberculosis and diabetes at diagnosis and at two weeks after initiation of anti-tuberculosis treatment
Authors: van Doorn Cassandra L.R. , Eckold Clare , Ronacher Katharina , Ruslami Rovina , van Veen Suzanne , Lee Ji-Sook , Kumar Vinod , Kerry-Barnard Sarah , Malherbe Stephanus T. , Kleynhans Léanie , Stanley Kim , Hill Philip C. , Joosten Simone A. , van Crevel Reinout , Wijmenga Cisca , Critchley Julia A. , Walzl Gerhard , Alisjahbana Bachti , Haks Mariëlle C. , Dockrell Hazel M. , Ottenhoff Tom H. M. , Vianello Eleonora , Cliff Jacqueline M. 
Published: February 2022

AbstractBackgroundGlobally, the anti-tuberculosis (TB) treatment success rate is approximately 85%, with treatment failure, relapse and death occurring in a significant proportion of pulmonary TB patients. Treatment success is lower among people with diabetes mellitus (DM). Predicting treatment failure early after diagnosis would allow early treatment adaptation and may improve global TB control.MethodsSamples were collected in a longitudinal cohort study of adult TB patients with or without concomitant DM from South Africa and Indonesia to characterize whole blood transcriptional profiles before and during anti-TB treatment, using unbiased RNA-Seq and targeted gene dcRT-MLPA.FindingsWe report differences in whole blood transcriptome profiles, which were observed before initiation of treatment and throughout treatment, between patients with a good versus poor anti- TB treatment outcome. An eight-gene and a 22-gene blood transcriptional signature distinguished patients with a good treatment outcome from patients with a poor treatment outcome at diagnosis (AUC=0·815) or two weeks (AUC=0·834) after initiation of anti-TB treatment, respectively. High accuracy was obtained by cross-validating this signature in an external cohort (AUC=0·749).InterpretationThese findings suggest that transcriptional profiles can be used as a prognostic biomarker for treatment failure and success, even in patients with concomitant DM.FundingThe research leading to these results, as part of the TANDEM Consortium, received funding from the European Community’s Seventh Framework Programme (FP7/2007-2013 Grant Agreement No. 305279) and the Netherlands Organization for Scientific Research (NWO-TOP Grant Agreement No. 91214038).