bluuebunny/crossref_metadata_2025_split huggingface dataset:
Specific gait changes in prodromal hereditary spastic paraplegia type 4 - preSPG4 study
Authors: Laßmann Christian , Ilg Winfried , Schneider Marc , Völker Maximilian , Haeufle Daniel F. B. , Schüle Rebecca , Giese Martin , Schöls Ludger , Rattay Tim W. 
Published: May 2022

AbstractBackgroundIn hereditary spastic paraplegia type 4 (SPG4), subclinical gait changes might occur years before patients realize gait disturbances. The prodromal phase of neurodegenerative disease is of particular interest to halt disease progression by future interventions before impairment has manifested.ObjectivesIdentification of specific movement abnormalities before manifestation of gait impairment and quantification of disease progression in the prodromal phase.Methods70 subjects participated in gait assessment, including 30 prodromal SPAST mutation carriers, 17 patients with mild-to-moderate manifest SPG4, and 23 healthy controls. Gait was assessed by an infrared-camera-based motion capture system to analyze features like range of motion and continuous angle trajectories. Those features were correlated with disease severity as assessed by the Spastic Paraplegia Rating Scale (SPRS) and neurofilament light chain (NfL) as a fluid biomarker indicating neurodegeneration.ResultsCompared to healthy controls, we found an altered gait pattern in prodromal mutation carriers during the swing phase in segmental angles of the lower leg (p<0.05) and foot (p<0.01), and in heel ground clearance (p<0.01). Furthermore, ranges of motion of segmental angles were reduced for foot (p<0.001) and lower leg (p<0.01). These changes occurred in prodromal mutation carriers without quantified leg spasticity in clinical examination. Gait features correlated with NfL levels and SPRS score.ConclusionGait analysis can quantify changes in prodromal and mild-to-moderate manifest SPG4 patients. Thus, gait features constitute promising motor biomarkers characterizing the subclinical progression of spastic gait and might help to evaluate interventions in early disease stages.
Systematic review of food insecurity and violence against women and girls: mixed methods findings from low- and middle-income settings
Authors: Hatcher Abigail M , Page Sabrina , Aletta van Eck Lele , Pearson Isabelle , Fielding-Miller Rebecca , Mazars Celine , Stöckl Heidi 
Published: May 2022

ABSTRACTIntroductionViolence against women and girls (VAWG) is a global human rights and public health concern. Food insecurity is a sign of severe poverty, and likely to heighten women’s vulnerability to VAWG and men’s perpetration of it. However, the extent of the association and the multiple pathways between food insecurity and VAWG are not well understood.MethodsWe systematically assessed peer reviewed quantitative and qualitative literature to explore this in low- and middle-income countries (LMIC). Fixed effects meta-analysis was used to synthesize quantitative evidence. Qualitative data was analyzed using thematic analysis.ResultsWe identified 23 quantitative and 19 qualitative or mixed-methods peer-reviewed manuscripts. In a meta-analysis of 21 cross-sectional studies with 20,378 participants, food insecurity was associated with doubled odds of reported VAWG (odds ratio [OR]=2.38, 95% confidence interval [CI]=1.82-3.10). This finding was consistent for both women’s experience or male perpetration of VAWG. Qualitative and mixed-methods papers offered insight that underlying conditions of inequitable gender norms, economic deprivation, and social isolation frame both food insecurity and VAWG. Food insecurity may trigger survival behaviors due to household stress and lack of meeting expected gender roles, which leads to VAWG. VAWG exposure may lead to food insecurity if women are more impoverished after leaving a violent household. Potential protective factors include financial stability, the involvement of men in VAWG programming, transformation of gender norms, and supporting women to develop new networks and social ties.ConclusionStrong evidence exists for a relationship between food security and IPV. Future funding should target causal directions and preventive options through longitudinal and interventional research. Strategies to ensure households have access to sufficient food and safe relationships are urgently needed to prevent VAWG.
Topographical differences in white matter hyperintensity burden and cognition in aging, MCI, and AD
Authors: Kamal Farooq , Morrison Cassandra , Maranzano Josefina , Zeighami Yashar , Dadar Mahsa ,   Alzheimer’s Disease Neuroimaging Initiative
Published: May 2022

AbstractBackgroundWhite matter hyperintensities (WMHs) are pathological changes that develop with increased age and are associated with cognitive decline. Most research on WMHs has neglected to examine regional differences and instead focuses on using a whole-brain approach. This study examined regional WMH differences between normal controls (NCs), people with mild cognitive impairment (MCI), and Alzheimer’s disease (AD). Another goal was to examine whether WMH burden was associated with declines in different cognitive domains in each of the groups.MethodsParticipants were selected from the Alzheimer’s Disease Neuroimaging Initiative and included if they had at least one WMH measurement and cognitive scores examining global cognition, executive functioning, and memory. MCI and AD participants were included only if they were amyloid positive. A total of 1573 participants with 7381 follow-ups met inclusion criteria. Linear mixed-effects models were completed to examine group differences in WMH burden and the association between WMH burden and cognition in aging, MCI, and AD.ResultsPeople with MCI and AD had increased total and regional WMH burden compared to cognitively healthy older adults. An association between WMH and cognition was observed for global cognition, executive functioning, and memory in NCs in all regions of interest. A steeper decline (stronger association between WMH and cognition) was observed in MCI compared to NCs for all cognitive domains in all regions. A steeper decline was observed in AD compared to NCs for global cognition in only the temporal region.ConclusionThese results suggest WMH burden increases from aging to AD. A strong association is observed between all cognitive domains of interest and WMH burden in healthy aging and MCI, while those with AD only had a few associations between WMH and memory and WMH and global cognition. These findings suggest that WMH burden is associated with changes in cognition in healthy aging and early cognitive decline, but other biological changes may have a stronger impact on cognition with AD.
A pipeline for tabular dataset formation from unstructured data provided by ACR Appropriateness Criteria guidelines
Authors: Eduardo Anderson A. , Loureiro Rafael M. , Tachibana Adriano , Netto Pedro V. , de Almeida Tatiana F. , Monteiro Luiz Henrique Alves , Santos André P. dos 
Published: May 2022

AbstractCurrently, data performns a critical concept for disparate human activities, from law to technology. Among data-centric technologies, clinical decision support systems (CDSS) figures out as one of the most promising for healthcare. Despite the technological advances facilitating its implementation, the maintainance of knowledge base for CDSS remains open to improvements. Here, we argue that the Appropriateness Criteria provided by ACR guidelines can be used as a open data-source that, combined with appropriate algorithms, can push forward basic research and technological developments regarding knowledge base for CDSS. Therefore, we developed a pipeline capable of forming tabular datasets from ACR guidelines, stored in a web site as textual PDF files. We also experimentally demonstrate that the proposed pipeline successfully recorvers the interested contents, and the best composition, in terms of its component algorithms, is discussed. Future research focused on algorithms flexibility in the face of PDF template updates could improve our work.
Minimal algorithms for knowledge representation in clinical decision support systems research: a theoretical and empirical analysis
Authors: Eduardo Anderson A. , Loureiro Rafael M. , Tachibana Adriano , Netto Pedro V. , Almeida Tatiana F. de , Monteiro Luiz Henrique Alves , Santos André P. dos 
Published: May 2022

AbstractClinical decision support systems (CDSS) figures out as one of the most promising technologies for data-centered and AI-prompted healthcare. Its current developments are mainly guided by two disparate mindsets, namely a machine learning-centered framework and a classical rule-based framework. These respective approaches presents contrastive pros and cons. In the present study we provide an analysis showing that these two mindsets are actually related to each other, and straightforward algorithms are feasible by combining current standards for machine learning and classic decision tables algorithms. A theoretical analysis are provided, as well a computational implementation (in python). A real case scenario on radiological immaging exam prescription is used to ilustrate the successfully application of our results. Future work on benchmarking the proposed algorithms embodied in a fully operational clinical decision support system could extend our findings towards daily used systems.
Assessing Depression and Suicidality Among Recently Unemployed Persons with Obstructive Sleep Apnea and Socioeconomic Inequality
Authors: Singh Vijay , Haynes Patricia L. , Quan Stuart F. 
Published: May 2022

AbstractBackgroundObstructive Sleep Apnea (OSA) is a common sleep-related breathing disorder that often is associated with several psychiatric conditions. Job loss is a stressful life event that can also affect mental health and socioeconomic status (SES). We investigated whether there was an association between the prevalence of OSA and several psychiatric conditions within a cohort of persons who recently became unemployed and whether SES was a contributing factor.MethodsData from 292 participants who completed the screening evaluation of the Assessing Daily Activity Patterns through occupational Transitions (ADAPT) Study were used to assess the association between the prevalence of OSA, and current and past depression, and past suicidality. A type III sleep home sleep monitor was used to identify the presence of OSA and assess its severity. Depression and suicidality were ascertained using the Mini-international neuropsychiatric interview. Years of education was used as a proxy for SES.ResultsThere were no significant associations between severity of OSA, SES and current depression, past depression, and suicidality. Past suicidality was noted to be more common among those who were single/widowed (17.4%) or those who were divorced or separated (11.1%) (p=0.027). Current depression was more common among Hispanics in comparison to non-Hispanics. Furthermore, prevalence rates of both depression and past suicidality were higher than previous reports in general populations.ConclusionsWithin a cohort of individuals who experienced recent job loss, there was no association between OSA and depression or past suicidality. Prevalence rates of both depression and past suicidality were higher than previous reports in the general population.
Mitochondrial effects on fertility and longevity in Tigriopus californicus contradict predictions of the mother’s curse hypothesis
Authors: Watson Eric T. , Flanagan Ben A. , Pascar Jane A. , Edmands Suzanne 
Published: May 2022

ABSTRACTStrict maternal inheritance of mitochondria favors the evolutionary accumulation of sex-biased fitness effects, as mitochondrial evolution occurs exclusively in female lineages. The “mother’s curse” hypothesis proposes that male-harming mutations should accumulate in mitochondrial genomes when they have neutral or beneficial effects on female fitness. Rigorous empirical tests have largely focused on Drosophila, where support for the predictions of mother’s curse has been mixed. We investigated the impact of mother’s curse mutations in Tigriopus californicus, a minute crustacean. Using nonrecombinant backcrosses, we introgressed four divergent mitochondrial haplotypes into two nuclear backgrounds and recorded measures of fertility and longevity. We found that the phenotypic effects of mitochondrial mutations were context-dependent, being influenced by the nuclear-background in which they were expressed, as well as the sex of the individual and rearing temperature. Mitochondrial haplotype effects were greater for fertility than longevity, and temperature effects were greater for longevity. However, in opposition to mother’s curse expectations, females had higher mitochondrial genetic variance than males for fertility and longevity, little evidence of sexual antagonism favoring females was found, and the impacts of mitonuclear mismatch harmed females but not males. Together, this indicates that selection on mitochondrial variation has not resulted in the accumulation of male mutation load in Tigriopus californicus.
A benchmark of Hi-C scaffolders using reference genomes and de novo assemblies
Authors: Sur Aakash , Noble William Stafford , Myler Peter J. 
Published: May 2022

AbstractBackgroundStudying a new species using high-throughput sequencing requires a high-quality reference genome. However, assembling chromosome length sequences remains challenging. Recent advances in chromatin conformation capture (Hi-C) have provided a new approach to scaffolding genome assemblies, and the last ten years have seen a proliferation of such methods. However, to our knowledge no comprehensive benchmarking of Hi-C scaffolders has been conducted to date.ResultsThrough a literature review we identified the most popular Hi-C scaffolders – Lachesis, HiRise, 3d-dna, SALSA, and AllHiC. We tested their ability to scaffold four well studied genomes – S. cerevisiae, L. tarentolae, A. thaliana, and H. sapiens. Scaffolders were tasked with both scaffolding fragmented versions of the reference genome as well as de novo assemblies derived from long read datasets. We found that all scaffolders can exceed 80% accuracy under ideal circumstances but that their performance quickly deteriorates under more challenging conditions. Surprisingly, many scaffolders also showed poor performance on the best assemblies, where contigs are near chromosome length. Overall, we found that HiRise and Lachesis offer the best performance on average across all conditions.ConclusionsWe compare the performance of five Hi-C scaffolders using multiple reference species under both ideal and real-life conditions, thereby illuminating their strengths and weaknesses.
The association of ubiquitin-associated protein 2-like and Ras-GTP-activating protein SH3 domain binding protein 1 mediated by small nucleolar RNA is essential for stress granule formation
Authors: Asano-Inami Eri , Yokoi Akira , Sugiyama Mai , Hyodo Toshinori , Hamaguchi Tomonari , Kajiyama Hiroaki 
Published: May 2022

AbstractStress granules (SGs) are dynamic, non-membranous structures composed of non-translating mRNAs and various proteins and play critical roles in cell survival under stressed conditions. Extensive proteomics analyses have been performed to identify proteins in SGs; however, the molecular functions of these components in SG formation remain unclear. In this report, we show that ubiquitin-associated protein 2-like (UBAP2L) is a novel component of SGs. UBAP2L localized to SGs in response to various stresses, and its depletion significantly suppressed SG organization. Proteomics and RNA sequencing analyses found that UBAP2L formed a protein-RNA complex with Ras-GTP-activating protein SH3 domain binding protein 1 (G3BP1) and small nucleolar RNAs (snoRNAs). In vitro binding analysis demonstrated that snoRNAs were required for UBAP2L association with G3BP1. In addition, decreased expression of snoRNAs reduced the interaction between UBAP2L and G3BP1 and suppressed SG formation. Our results reveal a critical role of a novel SG component, the UBAP2L/snoRNA/G3BP1 protein-RNA complex, and provide new insights into the regulation of SG assembly.
Linking cells across single-cell modalities by synergistic matching of neighborhood structure
Authors: Hristov Borislav H. , Bilmes Jeffrey A. , Noble William S. 
Published: May 2022

AbstractA wide variety of experimental methods are available to characterize different properties of single cells in a complex biosample. However, because these measurement techniques are typically destructive, researchers are often presented with complementary measurements from disjoint subsets of cells, providing a fragmented view of the cell’s biological processes. This creates a need for computational tools capable of integrating disjoint multi-omics data. Because different measurements typically do not share any features, the problem requires the integration to be done in unsupervised fashion. Recently, several methods have been proposed that project the cell measurements into a common latent space and attempt to align the corresponding low-dimensional manifolds. In this study we present an approach, Synmatch, which produces a direct matching of the cells between modalities by exploiting information about neighborhood structure in each modality. Synmatch relies on the intuition that cells which are close in one measurement space should be close in the other as well. This allows us to formulate the matching problem as a constrained supermodular optimization problem over neighborhood structures that can be solved efficiently. We show that our approach successfully matches cells in small real multi-omics datasets and performs favorably when compared to recently published state-of-the-art methods. Further, we demonstrate that Synmatch is capable of scaling to large datasets of thousands of cells. The Synmatch code and data used in this manuscript are available at https://github.com/orgs/Noble-Lab/synmatch
An Open-Source Computational Tool for Measuring Bacterial Biofilm Morphology and Growth Kinetics upon One-Sided Exposure to an Anti-Microbial Source
Authors: Gingichashvili Sarah , Steinberg Doron , Sionov Ronit V. , Feuerstein Osnat , Cohen Noa E. 
Published: May 2022

ABSTRACTBacillus subtilis biofilms are well known for their complex and highly adaptive morphology. Indeed, their phenotypical diversity and intra-biofilm heterogeneity make this gram-positive bacterium the subject of many scientific papers on the structure of biofilms. The ‘robustness’ of biofilms is a term often used to describe their level of susceptibility to anti-microbial agents and various mechanical and molecular inhibition/eradication methods. In this paper, we use computational analytics to quantify Bacillus subtilis morphological response to proximity to an anti-microbial source, in the form of the antiseptic chlorhexidine. Chlorhexidine droplets, placed in proximity to Bacillus subtilis macrocolonies at different distances result in morphological changes, quantified using Python-based code, which we have made publicly available. Our results quantify peripheral and inner core deformation as well as differences in cellular viability of the two regions. The results reveal that the inner core, which is often characterized by the presence of wrinkled formations in the macrocolony, is more preserved than the periphery. Furthermore, the paper describes a crescent shaped colony morphology which occurs when the distance from the chlorhexidine source is 0.5 cm, as well as changes observed in the growth substrate of macrocolonies exposed to chlorhexidine.
Profound geroprotection from brief rapamycin treatment in early adulthood by persistently increased intestinal autophagy
Authors: Juricic Paula , Lu Yu-Xuan , Leech Thomas , Drews Lisa F. , Paulitz Jonathan , Lu Jiongming , Nespital Tobias , Azami Sina , Regan Jennifer C. , Funk Emilie , Fröhlich Jenny , Grönke Sebastian , Partridge Linda 
Published: May 2022

AbstractThe licensed drug rapamycin has potential to be repurposed for geroprotection. A key challenge is to avoid adverse side-effects from continuous dosing regimes. Here we show a profound memory effect of brief, early rapamycin treatment of adults, which extended lifespan in Drosophila to the same degree as lifelong dosing. Lasting memory of earlier rapamycin treatment was mediated by elevated autophagy in enterocytes of the gut, accompanied by increased levels of intestinal lysosomal alpha-mannosidase V (LManV), proteins involved in branched-chain amino acid metabolism and lysozyme levels, and by maintained structure and function of the ageing intestine. Brief elevation of autophagy in early adulthood itself induced a long-term increase in autophagy. In mice, a short-term, 3-month treatment in early adulthood also induced a memory effect, with maintenance similar to that seen with chronic treatment, of lysozyme distribution, Man2B1 level in intestinal crypts, Paneth cell architecture and gut barrier function, even 6 months after rapamycin was withdrawn. The geroprotective effects of chronic rapamycin treatment can thus be obtained with a brief pulse of the drug in early adulthood.
Evaluation of sex differences in laser-induced choroidal neovascularization severity, phenotype and disease progression
Authors: Pearsall Elizabeth A. 
Published: May 2022

ABSTRACTAge-related macular degeneration (AMD) progresses through two phases: a non-exudative “dry” stage that compromises vision but does not involve angiogenesis, and an angiogenic “wet” phase characterized by choroidal neovascularization (CNV), in which neovessels from the choroid break through the Bruch’s membrane to form neovascular lesions in the macula. If left untreated, CNV leads to permanent central blindness, which the current standard of care (anti-VEGF therapy) arrests but does not reverse. In laser-induced CNV, a laser is used to rupture the Bruch’s membrane, prompting the outgrowth of choroidal blood vessels in a wound healing response. This model was used to develop currently available CNV therapeutics, such as intravitreal injection of anti-VEGF and corticosteroid therapies and is considered a gold standard model for CNV. Laser-induced CNV thus remains a highly clinically relevant model of CNV secondary to AMD and other pathologies, such as myopia. A rapidly growing body of research suggests that the pathogenesis of myriad diseases is highly dependent on biological sex, yet most studies use only male animals. This highlights the importance of determining whether the severity and pathogenesis of commonly used models of disease, for example laser-induced CNV, differ between sexes. In the present study, we tracked longitudinal progression and pathogenesis of laser-induced CNV in male and female animals, and found that CNV severity did not differ between sexes. This lack of difference recapitulates findings in human patients with CNV, which have also identified that both sexes are at equal risk of CNV development in the contexts of both age-related macular degeneration induced CNV and myopic CNV.
Mesostats — A multiplexed, low-cost, do-it-yourself continuous culturing system for experimental evolution of mesocosms
Authors: Hansson Erika M , Childs Dylan Z , Beckerman Andrew P 
Published: May 2022

ABSTRACTMicrobial experimental evolution allows studying evolutionary dynamics in action and testing theory predictions in the lab. Experimental evolution in chemostats (i.e. continuous flow through cultures) has recently gained increased interest as it allows tighter control of selective pressures compared to static batch cultures, with a growing number of efforts to develop systems that are easier and cheaper to construct. This protocol describes the design and construction of a multiplexed chemostat array (dubbed “mesostats”) designed for cultivation of algae in 16 concurrent populations, specifically intended for studying adaptation to herbicides. We also present control data from several experiments run on the system to show replicability, data illustrating the effects of common issues like leaks, contamination and clumps, and outline possible modifications and adaptations of the system for future research.