bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of statistical detection of change algorithm for triaging multiple sclerosis patients with new lesion activity on longitudinal brain MRI
Authors: Homssi Moayad , Sweeney Elizabeth M. , Demmon Emily , Mannheim William , Sakirsky Michael , Wang Yi , Gauthier Susan A. , Gupta Ajay , Nguyen Thanh D. 
Published: February 2023

ABSTRACTBackground and PurposeIdentification of new MS lesions on longitudinal MRI by human readers is time-consuming and prone to error. Our objective was to evaluate the improvement in a subject-level detection performance by readers when assisted by the automated statistical detection of change (SDC) algorithm.Materials and MethodsA total of 200 MS patients with mean inter-scan interval of 13.2 ± 2.4 months were included. SDC was applied to the baseline and follow-up FLAIR images to detect potential new lesions for confirmation by readers (Reader+SDC method). This method was compared with readers operating in the clinical workflow (Reader method) for a subject-level detection of new lesions.ResultsReader+SDC found 30 subjects (15.0%) with at least one new lesion, while Reader detected 16 subjects (8.0%). As a subject-level triage tool, SDC achieved a perfect sensitivity of 1.00 (95% CI: [0.88, 1.00]) and a moderate specificity of 0.67 (95% CI: [0.59, 0.74]). The agreement on a subject-level was 0.91 (95% CI: [0.87, 0.95]) between Reader+SDC and Reader, and 0.72 (95% CI: [0.66, 0.78]) between Reader+SDC and SDC.ConclusionSDC improves the detection accuracy of human readers and can serve as a time-saving patient triage tool for detecting new MS lesion activity on longitudinal FLAIR images.
Clinical Characteristics and Long-term Symptomology of Post-COVID-19 Olfactory and Gustatory Dysfunction
Authors: Boyd Amelia , Minichetti Dante , Lemire Evan , Haber Adam L , Roditi Rachel E , Laidlaw Tanya , Bankova Lora 
Published: February 2023

ABSTRACTOlfactory and gustatory dysfunction persists in 2-4% of patients who have recovered from COVID-19 beyond 6 months. Dysosmia (distorted smell) and dysgeusia (distorted taste) are frequently observed in the acute phase of many upper respiratory viral infections. However, persistent dysosmia in these patients is associated with persistent nasal inflammation. The purpose of this study was to determine the extent of patient self-assessed post-COVID-19 olfactory and gustatory dysfunction and to understand the quality and severity of the subjective symptoms over a year. A total of 426 registry participants were recruited to complete initial online questionnaires and follow up at three post-enrollment time points: 3 months, 6 months, 12 months. The Registry questionnaires assessed nasal inflammation (Sino-Nasal Outcome Test - SNOT-22), mental health (The Patient Health Questionnaire-2 -PHQ-2; Neuro-QoL Positive Affect and Well-Being - PAW-23), sleep quality (The Pittsburgh Sleep Quality Index – PSQI), In a cohort of 74 patients, clinical measurements of smell (Smell Identification Test (UPSIT) and taste (Waterless Taste Test (B-WETT)) were performed to validate self-reported measures of sensory impairment. Our data indicate that persistent COVID-19 olfactory and gustatory dysfunction is not associated with subjective measures of nasal inflammation. However, dryness of the nose/mouth, mood disturbance, and poor sleep quality are reported by the majority of participants. Participants struggle with detecting specific foul/dangerous odorants and tasting subtle flavors, which could have a negative effect on patient safety and well-being. Those infected during the earlier waves of the pandemic have more persistent and severe symptoms. Objective measure of both smell and taste are significantly reduced in the majority of participants with self-reported olfactory and gustatory dysfunction. Finally, standard anti-inflammatory topical and systemic therapy does not improve the subjective sense of smell while olfactory training is marginally more effective. This establishes persistent COVID19 olfactory and gustatory dysfunction as a chronic and difficult to treat syndrome resistant to standard anti-inflammatory therapy.
Characterisation of the neonatal brain using myelin-sensitive magnetisation transfer imaging
Authors: Blesa Cábeza Manuel , Vaher Kadi , York Elizabeth N. , Galdi Paola , Sullivan Gemma , Stoye David Q. , Hall Jill , Corrigan Amy E. , Quigley Alan J. , Waldman Adam D. , Bastin Mark E. , Thrippleton Michael J. , Boardman James P. 
Published: February 2023

AbstractA cardinal feature of the encephalopathy of prematurity is dysmaturation of developing white matter and subsequent hypomyelination. Magnetisation transfer imaging (MTI) offers surrogate markers for myelination including magnetisation transfer ratio (MTR) and magnetisation transfer saturation (MTsat). Using data from 105 neonates, we characterise MTR and MTsat in the developing brain and investigate how these markers are affected by gestational age at scan and preterm birth. We explore correlations of the two measures with fractional anisotropy (FA), radial diffusivity (RD) and T1w/T2w ratio which are commonly used markers of white matter integrity in early life. We used two complementary analysis methods: voxel-wise analysis across the white matter skeleton, and tract-of-interest analysis across 16 major white matter tracts. We found that MTR and MTsat positively correlate with gestational age at scan. Preterm infants at term-equivalent age had lower values of MTsat in the genu and splenium of the corpus callosum, while MTR was higher in central white matter regions, the corticospinal tract and the uncinate fasciculus. Correlations of MTI metrics with other MRI parameters revealed that there were moderate positive correlations between T1w/T2w and MTsat and MTR at voxel-level, but at tract-level FA had stronger positive correlations with these metrics. RD had the strongest correlations with MTI metrics, particularly with MTsat in major white matter tracts. The observed changes in MTI metrics are consistent with an increase in myelin density during early postnatal life, and lower myelination and cellular/axonal density in preterm infants at term-equivalent age compared to term controls. Furthermore, correlations between MTI-derived features and conventional measures from dMRI provide new understanding about the contribution of myelination to non-specific imaging metrics that are often used to characterise early brain development.
Gender and ethnicity intersect to reduce participation at a large European Hybrid HIV Conference
Authors: Howe A. , Wan YI. , Gilleece Y , Aebi-Popp K , Dhairyawan R , Bhagani S , Paparini S. , Orkin C. 
Published: February 2023

AbstractIntroductionThe negative effect of female gender identity on participation at face-to-face academic conferences for delegates, speakers, chairs and panellists has previously been reported. Little is known about how ethnicity may affect conference participation, or about how gender and ethnicity intersect. To our knowledge, this is the first study describing conference participation by both ethnicity and gender in panellists and delegates, and the first to describe this within a hybrid conference setting.MethodsWe collaborated with the European AIDS Clinical Society (EACS), the organisers of the 18th European AIDS Conference, a large, 3223 delegate, hybrid conference held online and in London, over four days in October 2021. During the conference, we observed the number and type of questions asked at 12 of 69 sessions and described characteristics of the panel composition by ethnicity, gender and seniority. A post-conference survey of conference attendees collated demographic information, number of questions asked during the conference and the reasons for not asking questions.ResultsMen asked the most questions and were more likely to ask multiple questions in the observed sessions (61.5%). People from White ethnic groups asked >95% of the questions in the observed sessions. The fewest questions were asked in the sessions with the least diverse panels in terms of both ethnicity and gender. Barriers to asking questions differed between genders and ethnicities.ConclusionsImprovement in access and participation at medical conferences is needed. Our study aims to raise awareness and provide evidence to help improve equality, diversity and inclusion in the professional medical conference setting and support equitable dissemination and sharing of knowledge. Intersections of gender and ethnicity shape inequality and need to be examined in combination. Further work is needed to evaluate the role of other social identities. We recommend future work takes such intersectionality into account and that conference organisers strive for diversity on panels to improve education and engagement of delegates.
Population mobility and the development of Botswana’s generalized HIV epidemic: a network analysis
Authors: Song Janet , Okano Justin T. , Ponce Joan , Busang Lesego , Seipone Khumo , Valdano Eugenio , Blower Sally 
Published: February 2023

ABSTRACTThe majority of people with HIV live in sub-Saharan Africa, where HIV epidemics are generalized. For these epidemics to develop, populations need to be mobile. However, population-level mobility has not yet been studied in the context of the development of generalized HIV epidemics. Here we do so by studying historical migration data from Botswana which has one of the most severe generalized HIV epidemics worldwide; in 2021, HIV prevalence was 21%. The country reported its first AIDS case in 1985 when it began to rapidly urbanize. We hypothesize that, during the development of Botswana’s epidemic, the population was highly mobile and there were substantial urban-to-rural and rural-to-urban migratory flows. We test this hypothesis by conducting a network analysis using a historical time series (1981 to 2011) of micro-census data from Botswana. We found 10% of the population moved their residency annually, complex migration networks connected urban with rural areas, and there were very high rates of rural-to-urban migration. Notably, we also found mining towns were both important in-flow and out-flow migration hubs; consequently, there was a very high turnover of residents in towns. Our results support our hypothesis, and together, provide one explanation for the development of Botswana’s generalized epidemic.
Influence of autozygosity on common disease risk across the phenotypic spectrum
Authors: Malawsky Daniel S. , van Walree Eva , Jacobs Benjamin M , Heng Teng Hiang , Huang Qin Qin , Sabir Ataf H. , Rahman Saadia , Sharif Saghira Malik , Khan Ahsan , Mirkov Maša Umićević ,   23andMe Research Team,   Genes & Health Research Team, Posthuma Danielle , Newman William G. , Griffiths Christopher J. , Mathur Rohini , van Heel David A. , Finer Sarah , O’Connell Jared , Martin Hilary C. 
Published: February 2023

AbstractAutozygosity is associated with rare Mendelian disorders and clinically-relevant quantitative traits. We investigated associations between FROH(fraction of the genome in runs of homozygosity) and common diseases in Genes & Health (N=23,978 British South Asians), UK Biobank (N=397,184), and 23andMe, Inc. We show that restricting analysis to offspring of first cousins is an effective way of removing confounding due to social/environmental correlates of FROH. Within this group in G&H+UK Biobank, we found experiment-wide significant associations between FROHand twelve common diseases. We replicated the associations with type 2 diabetes (T2D) and post-traumatic stress disorder via between-sibling analysis in 23andMe (median N=480,282). We estimated that autozygosity due to consanguinity accounts for 5-18% of T2D cases amongst British Pakistanis. Our work highlights the possibility of widespread non-additive effects on common diseases and has important implications for global populations with high rates of consanguinity.
Minimal mRNA uptake and inflammatory response to COVID-19 mRNA vaccine exposure in human placental explants
Authors: Gonzalez Veronica , Li Lin , Buarpung Sirirak , Prahl Mary , Robinson Joshua F. , Gaw Stephanie L. 
Published: February 2023

SummaryDespite universal recommendations for COVID-19 mRNA vaccination in pregnancy, uptake has been lower than desired. There have been limited studies of the direct impact of COVID-19 mRNA vaccine exposure in human placental tissue. Using a primary human villous explant model, we investigated the uptake of two common mRNA vaccines (BNT162b2 Pfizer-BioNTech or mRNA-1273 Moderna), and whether exposure altered villous cytokine responses. Explants derived from second or third trimester chorionic villi were incubated with vaccines at supraphysiologic concentrations and analyzed at two time points. We observed minimal uptake of mRNA vaccines in placental explants by in situ hybridization and quantitative RT-PCR. No specific or global cytokine response was elicited by either of the mRNA vaccines in multiplexed immunoassays. Our results suggest that the human placenta does not readily absorb the COVID-19 mRNA vaccines nor generate a significant inflammatory response after exposure.
FPsim: An agent-based model of family planning
Authors: O’Brien Michelle L. , Valente Annie , Kerr Cliff C. , Proctor Joshua L. , Noori Navideh , Root Elisabeth D. , Olsen Helen , Buxton Samuel , Chabot-Couture Guillaume , Klein Daniel J. , Zimmermann Marita 
Published: February 2023

AbstractThe biological and behavioral underpinnings of family planning (FP) unfold on an individual level, across a full reproductive life course, and within a complex system of social and structural constraints. Yet, much of the existing FP modeling landscape has focused solely on macro- or population-level dynamics of family planning. There is a need for an individual-based approach to provide a deeper understanding of how family planning is intertwined with individuals’ lives and health at the micro-level, which can contribute to more effective, person-centered design of both contraceptive technologies and programmatic interventions. This article introduces the Family Planning Simulator (FPsim), a data-driven, agent-based model of family planning, which explicitly models individual heterogeneity in biology and behavior over the life course. Agents in FPsim can experience a wide range of life-course events, such as increases in fecundability (and primary infertility), sexual debut, contraceptive choice, postpartum family planning, abortion, miscarriage, stillbirth, infant mortality, and maternal mortality. The core components of the model – fecundability and contraceptive choice, are represented individually and probabilistically, following age-specific patterns observed in demographic data and prospective cohort studies. Once calibrated to a setting leveraging multiple sources of data, FPsim can be used to build hypothetical scenarios and interrogate counterfactual research questions about the use, non-use, and/or efficacy of family planning programs and contraceptive methods. To our knowledge, FPsim is the first open-source, individual-level, woman-centered model of family planning.Author SummaryAlthough the causes and consequences of family planning unfold on an individual level, few models of family planning consider individual heterogeneity over the life course. To that end, we introduce the methodology, parameters, and use-case(s) of the family planning simulator (FPsim). FPsim is a data-driven agent-based model of family planning, which explicitly models individual heterogeneity in biology and behaviors over a woman’s full life course to better understand the micro-level dynamics leading to more or less successful family planning programs and policies. FPsim is a data-driven model that leverages multiple sources of data to simulate realistic populations in settings that reflect real-life contexts. It is designed to be flexible and user-friendly, allowing for custom calibrations and providing integrated functions for straightforward use. This manuscript describes the model design, including its parameters, potential data sources, and limitations. We illustrate the functionality of FPsim using hypothetical scenarios that improve upon existing injectable contraceptives and introduce new injectable contraceptives into a Senegal-like setting.
Lessons Learned from Health Coverage Expansion in Massachusetts: Primary Care for Individuals with Serious Psychiatric Illness: Pre- and Post- 2006 Coverage Mandates
Authors: Murphy Beth L. , Mellen Emily , Hodgkin Dominic , Doonan Michael T. , Cohen Bruce M. 
Published: February 2023

AbstractPurposeImproved access to care, particularly primary care, is a key goal of healthcare reform proposals. Individuals with severe psychiatric illness have high rates of emergency room use rather than primary/preventive care. Massachusetts implemented health care reform in 2006 intended to provide more individuals with health care insurance and, thereby, access to primary care. To our knowledge no study has assessed whether this legislation impacted barriers to primary care access among individuals with serious mental illness.MethodsThis study looked at effects of the 2006 Massachusetts legislation among individuals being hospitalized at a large psychiatric hospital drawing patients from throughout Eastern Massachusetts. A retrospective review of records noted whether a primary care physician was identified, along with demographic and clinical characteristics for each patient.ResultsPrimary care affiliation was significantly lower in 2008 than 2005. Affiliation increased 9 years after legislation, though not to the levels of the year prior to the legislation. Risk ratios for PCP non-affiliation were similar whether the model controlled for demographic characteristics only; primary and drug and alcohol related diagnoses in addition to demographic characteristics; or insurance type in addition to demographic characteristics and diagnoses.ConclusionsThe risk of being unaffiliated with a PCP 2 years after legislative reform was nearly 20% higher than 1 year before. Our findings are concerning in that patients at this large regional psychiatry hospital may have been receiving less primary/preventive care in 2008 than in 2005, despite legislation aimed at improving primary care access for the general population.
Single-molecule FRET probes allosteric effects on protein-translocating pore loops of a AAA+ machine
Authors: Iljina Marija , Mazal Hisham , Dayananda Ashan , Zhang Zhaocheng , Stan George , Riven Inbal , Haran Gilad 
Published: February 2023

AbstractAAA+ proteins (ATPases associated with various cellular activities) comprise a family of powerful ring-shaped ATP-dependent translocases that carry out numerous vital substrate-remodeling functions. ClpB is a AAA+ protein disaggregation machine that forms a two-tiered hexameric ring, with flexible pore loops protruding into its center and binding to substrate-proteins. It remains unknown whether these pore loops contribute only passively to substrate-protein threading or have a more active role. Recently, we have applied single-molecule FRET (smFRET) spectroscopy to directly measure the dynamics of substrate-binding pore loops in ClpB. We have reported that the three pore loops of ClpB (PL1-3) undergo large-scale fluctuations on the microsecond timescale that are likely to be mechanistically important for disaggregation. Here, using smFRET, we study the allosteric coupling between the pore loops and the two nucleotide binding domains of ClpB (NBD1-2). By mutating the conserved Walker B motifs within the NBDs to abolish ATP hydrolysis, we demonstrate how the nucleotide state of each NBD tunes pore loop dynamics. This effect is surprisingly long-ranged; in particular, PL2 and PL3 respond differentially to a Walker B mutation in either NBD1 or NBD2, as well as to mutations in both. We characterize the conformational dynamics of pore loops and the allosteric paths connecting NBDs to pore loops by molecular dynamics simulations and find that both principal motions and allosteric paths can be altered by changing the ATPase state of ClpB. Remarkably, PL3, which is highly conserved in AAA+ machines, is found to favor an upward conformation when only NBD1 undergoes ATP hydrolysis, but a downward conformation when NBD2 is active. These results explicitly demonstrate a significant long-range allosteric effect of ATP hydrolysis sites on pore-loop dynamics. Pore loops are therefore established as active participants that undergo ATP-dependent conformational changes to translocate substrate proteins through the central pores of AAA+ machines.Statement of SignificanceMolecular machines function by coupling the energy of ATP hydrolysis to mechanical motion. How this coupling occurs and what timescales are involved remains an open question. In this study, we use a powerful single-molecule FRET technique to measure the real-time dynamics of pore loops, which are essential protein-translocating elements of the ATP-dependent disaggregation machine ClpB. Using a series of mutations of the ATP-hydrolysis motifs of ClpB, we find that, although the motions of these pore loops take place on the microsecond time scale, they are markedly affected by the much slower changes in the nucleotide state of the machine. Generally, this study shows that protein machines, such as ClpB, are wired to harness ATP binding and hydrolysis to allosterically affect distal events, such as the function-related mechanics of pore-loops.
Lifelong tissue memory relies on spatially organised dedicated progenitors located distally from the injury
Authors: Levron Chiara Levra , Watanabe Mika , Proserpio Valentina , Piacenti Gabriele , Lauria Andrea , Kaltenbach Stefan , Nohara Takuma , Anselmi Francesca , Duval Carlotta , Donna Daniela , Baev Denis , Natsuga Ken , Hagai Tzachi , Oliviero Salvatore , Donati Giacomo 
Published: February 2023

AbstractIt is believed epithelial cells that have participated in a wound repair elicit a more efficient but locally restricted response to future injuries. However here we show that the cell adaptation resulting from a localised tissue damage has a wide spatial impact at a scale not previously noticed. We demonstrate that away from injured site, after a first injury a specific epithelial stem cell population gives rise to long term wound-memory progenitors residing in their own niche of origin. Notably these progenitors have not taken part in the first wound healing but become pre-activated throughpriming. This adaptation differs from classical features oftrained immunitypreviously shown to be adopted by other epithelial stem cells. Our newly identified wound-distal memory cells display a cell-autonomous transcriptional pre-activated state leading to an enhanced wound repair ability that can be partially recapitulated through epigenetic perturbation even in absence of an injury. Importantly, the harmful consequences of wound repair, such as exacerbated tumorigenesis, occur within these primed cells and follow their spatial distribution. Overall, we show that sub-organ scale adaptation of an injury relies on spatially organised and memory-dedicated progenitors, characterised by an epigenetic actionable cell state, that predisposes to tumour onset.