bluuebunny/crossref_metadata_2025_split huggingface dataset:
Establishing a baseline for human cortical folding morphological variables: a multicenter study
Authors: Hansen Pacheco de Moraes Fernanda , Mello Victor B. B. , Tovar-Moll Fernanda , Mota Bruno 
Published: March 2022

AbstractDifferences in the way human cerebral cortices fold have been correlated to health, disease, development, and aging. But to obtain a deeper understating of the mechanisms that generate such differences it is useful to derive one’s morphometric variables from first principles. This work explores one such set of variables that arise naturally from a model for universal self-similar cortical folding that was validated on comparative neuroanatomical data. We aim to establish a baseline for these variables across the human lifespan using a heterogeneous compilation of cross-sectional datasets, as the first step to extend the model to incorporate the time evolution of brain morphology. We extracted the morphological features from structural MRI of 3650 subjects: 3095 healthy controls (CTL) and 555 Alzheimer’s Disease (AD) patients from 9 datasets, which were harmonized with a straightforward procedure to reduce the uncertainty due to heterogeneous acquisition and processing. The unprecedented possibility of analyzing such a large number of subjects in this framework allowed us to compare CTL and AD subjects’ lifespan trajectories, testing if AD is a form of accelerated aging at the brain structural level. After validating this baseline from development to aging, we estimate the variables’ uncertainties and show that Alzheimer’s Disease is similar to premature aging when measuring global and local degeneration. This new methodology may allow future studies to explore the structural transition between healthy and pathological aging and may be essential to generate data for the cortical folding process simulations.Significance StatementUnderstating Cortical folding is of increasing interest in neurosciences as it has been used to discriminate disease in humans while integrating pieces of knowledge from compared neuroanatomy and neuroproliferations programs. Here we propose estimating the baseline of cortical folding variables from multi-site MRI human images, evaluating the changing rate of its independent variables through the human lifespan, and proposing a simple harmonization procedure to combine multicentric datasets. Finally, we present a practical application of these techniques comparing Alzheimer’s Disease and Cognitive Unimpaired Controls based on the estimated changing rates.HighlightsBaseline of independent cortical folding variables from 3650 multi-site human MRIPropose a simple harmonization procedure to combine multicentric datasetsEvaluate the changing rate of independent variables through the human lifespanPractical application comparing Alzheimer’s Disease and Controls rates
HIV testing uptake according to opt-in, opt-out or risk-based testing approaches: a systematic review and meta-analysis
Authors: Soh Qi Rui , Oh Leon Y.J. , Chow Eric P.F. , Johnson Cheryl C. , Jamil Muhammad S. , Ong Jason J. 
Published: March 2022

ABSTRACTPurpose of reviewImproving HIV testing uptake is essential to ending the HIV pandemic. HIV testing approaches can be opt-in, opt-out or risk-based. This systematic review examines and compares the uptake of HIV testing in opt-in, opt-out and risk-based testing approaches.Recent findingsThere remains missed opportunities for HIV testing in a variety of settings using different approaches: opt-in (a person actively accepts to be tested for HIV), opt-out (a person is informed that HIV testing is routine/standard of care, and they actively decline if they do not wish to be tested for HIV) or risk-based (using risk-based screening tools to focus testing on certain individuals or sub-populations at greater risk of HIV). It is not clear how the approach could impact HIV test uptake when adjusted for other factors (e.g. rapid testing, country-income level, test setting and population tested).SummaryWe searched four databases for studies reporting on HIV test uptake. In total, 18,238 records were screened, and 150 studies were included in the review. Most studies described an opt-in approach (87 estimates), followed by opt-out (76) and risk-based (19). Opt-out testing was associated with 64.3% test uptake (I2=99.9%), opt-in testing with 59.8% (I2=99.9%), and risk-based testing with 54.4% (I2=99.9%). When adjusted for settings that offered rapid testing, country income level, setting and population tested, opt-out testing had a significantly higher uptake (+12% (95% confidence intervals: 3-21), p=0.007) than opt-in testing. We also found that emergency department patients and hospital outpatients had significantly lower HIV test uptake than other populations.
Nocturnal Respiratory Rate Dynamics Enable Early Recognition of Impending Hospitalizations
Authors: Harrington Nicholas , Barba David Torres , Bui Quan M. , Wassell Andrew , Khurana Sukhdeep , Rubarth Rodrigo B. , Sung Kevin , Owens Robert L. , Agnihotri Parag , King Kevin R. 
Published: March 2022

ABSTRACTThe days and weeks preceding hospitalization are poorly understood because they transpire before patients are seen in conventional clinical care settings. Home health sensors offer opportunities to learn signatures of impending hospitalizations and facilitate early interventions, however the relevant biomarkers are unknown. Nocturnal respiratory rate (NRR) is an activity-independent biomarker that can be measured by adherence-independent sensors in the home bed. Here, we report automated longitudinal monitoring of NRR dynamics in a cohort of high-risk recently hospitalized patients using non-contact mechanical sensors under patients’ home beds. Since the distribution of nocturnal respiratory rates in populations is not well defined, we first quantified it in 2,000 overnight sleep studies from the NHLBI Sleep Heart Health Study. This revealed that interpatient variability was significantly greater than intrapatient variability (NRR variances of 11.7 brpm2and 5.2 brpm2respectively, n=1,844,110 epochs), which motivated the use of patient-specific references when monitoring longitudinally. We then performed adherence-independent longitudinal monitoring in the home beds of 34 high-risk patients and collected raw waveforms (sampled at 80 Hz) and derived quantitative NRR statistics and dynamics across 3,403 patient-nights (n= 4,326,167 epochs). We observed 23 hospitalizations for diverse causes (a 30-day hospitalization rate of 20%). Hospitalized patients had significantly greater NRR deviations from baseline compared to those who were not hospitalized (NRR variances of 3.78 brpm2and 0.84 brpm2respectively, n= 2,920 nights). These deviations were concentrated prior to the clinical event, suggesting that NRR can identify impending hospitalizations. We analyzed alarm threshold tradeoffs and demonstrated that nominal values would detect 11 of the 23 clinical events while only alarming 2 times in non-hospitalized patients. Taken together, our data demonstrate that NRR dynamics change days to weeks in advance of hospitalizations, with longer prodromes associating with volume overload and heart failure, and shorter prodromes associating with acute infections (pneumonia, septic shock, and covid-19), inflammation (diverticulitis), and GI bleeding. In summary, adherence-independent longitudinal NRR monitoring has potential to facilitate early recognition and management of pre-symptomatic disease.
JAK signaling was involved in the pathogenesis of Polymyalgia Rheumatica
Authors: Yang Fan , Ma Xinlei , Xu Bei , Sun Yiduo , Jiang Mengdi , Ren Chunyun , Sun Chuanying , Liang Junyu , Cao Heng , Xu Danyi , Yue Lihuan , Xu Liqin , Lin Jin , Chen Weiqian 
Published: March 2022

AbstractObjectivesPolymyalgia Rheumatica (PMR) is a common inflammatory disease in elderly persons whose pathogenesis is unclear. We aimed to explore the pathogenetic features of PMR and find a new therapeutic strategy.MethodsWe included 11 patients with PMR and 20 age-matched and sex-matched healthy controls (HC) in this study. The disease features were described. The gene expression profiles were analyzed in peripheral blood mononuclear cells (PBMCs) by RNA sequencing and were confirmed by RT-PCR. We also tested gene expression profiles in five patients with PMR after tofacitinib therapy.ResultsPatients with PMR experienced pain with high disease activity scores. The gene expression of PBMCs in patients with PMR differed from that in HC by RNA sequencing. GO and KEGG analysis demonstrated that inflammatory response and cytokine-cytokine receptor interaction were the most remarkable pathways. There were markedly expanded IL6R, IL1B, IL1R1, JAK2, TLR2, TLR4, TLR8, CCR1, CR1, S100A8, S100A12, and IL17RA expressions. Those genes may trigger the JAK signaling. Furthermore, tofacitinib, a pan JAK inhibitor, effectively treated five patients with PMR, leading to clinical remission and a significant decrease in inflammatory genes.ConclusionsMany inflammatory genes associated with JAK signaling were increased in patients with PMR, suggesting an important role of JAK signaling in PMR disease development. JAK inhibitors may effectively treat PMR.Key messagesPatients with PMR had significant inflammatory genes expression. JAK signaling may be highly activated.Tofacitinib may treat PMR with clinical remission and a significant decrease in inflammatory genes.
Anatomical, ontogenetic, and genomic homologies guide reconstructions of the teeth-to-baleen transition in mysticete whales
Authors: Gatesy John , Ekdale Eric G. , Deméré Thomas A. , Lanzetti Agnese , Randall Jason , Berta Annalisa , El Adli Joseph J. , Springer Mark S. , McGowen Michael R. 
Published: March 2022

AbstractThe transition in Mysticeti (Cetacea) from capture of individual prey using teeth to bulk filtering batches of small prey using baleen ranks among the most dramatic evolutionary transformations in mammalian history. We review phylogenetic work on the homology of mysticete feeding structures from anatomical, ontogenetic, and genomic perspectives. Six characters with key functional significance for filter-feeding behavior are mapped to cladograms based on 11 morphological datasets to reconstruct evolutionary change across the teeth-to-baleen transition. This comparative summary within a common parsimony framework reveals extensive conflicts among independent systematic efforts but also broad support for the newly named clade Kinetomenta (Aetiocetidae + Chaeomysticeti). Complementary anatomical studies using CTscans and ontogenetic series hint at commonalities between the developmental programs for teeth and baleen, lending further support for a ‘transitional chimaeric feeder’ scenario that best explains current knowledge on the transition to filter feeding. For some extant mysticetes, the ontogenetic sequence in fetal specimens recapitulates the inferred evolutionary transformation: from teeth, to teeth and baleen, to just baleen. Phylogenetic mapping of inactivating mutations reveals mutational decay of ‘dental genes’ related to enamel formation before the emergence of crown Mysticeti, while ‘baleen genes’ that were repurposed or newly derived during the evolutionary elaboration of baleen currently are poorly characterized. Review and meta-analysis of available data suggest that the teeth-to-baleen transition in Mysticeti ranks among the best characterized macroevolutionary shifts due to the diversity of data from the genome, the fossil record, comparative anatomy, and ontogeny that directly bears on this remarkable evolutionary transformation.
Taxonomic investigation of the zooplanktivorous Lake Malawi cichlids Copadichromis mloto (Iles) and C. virginalis (Iles)
Authors: Turner G.F. , Crampton D.A. , van Huysduynen A. Hooft , Svardal H. 
Published: March 2022

AbstractThe taxonomic status of the zooplanktivorous cichlids Copadichromis mloto and C. virginalis has been confused since their original descriptions by lles in 1960. While two forms of C. virginalis, Kaduna and Kajose, were distinguished in the type material, C. mloto has not been positively identified since its original description. Here we re-examined the types as well as 54 recently collected specimens from multiple sampling locations. Genome sequencing of 51 recent specimens revealed two closely related but reciprocally monophyletic clades. Geometric morphological analysis indicated that one clade morphologically encompasses the type specimens of C. virginalis identified by Iles as the ‘Kaduna’ form, including the holotype, while the other clade encompasses not only the paratypes identified as the ‘Kajose’ form, but also the type series of C. mloto. Given that all three forms have the same type locality, that there are no meristic or character states to differentiate them and that there are no records of adult male C. mloto in breeding colours, we conclude that the ‘Kajose’ form previously identified as C. virginalis represents relatively deeper bodied sexually active or maturing individuals of C. mloto.
Systemic circulating microRNA landscape in Lynch syndrome
Authors: Sievänen Tero , Korhonen Tia-Marje , Jokela Tiina , Ahtiainen Maarit , Lahtinen Laura , Kuopio Teijo , Lepistö Anna , Sillanpää Elina , Mecklin Jukka-Pekka , Seppälä Toni T. , Laakkonen Eija K. 
Published: March 2022

AbstractMicroRNAs (miRs) are non-coding RNA-molecules that regulate gene expression. Global circulating miR (c-miR) expression patterns (c-miRnome) change with carcinogenesis in various sporadic cancers. Therefore, aberrantly expressed c-miRs could have diagnostic, predictive and prognostic potential in molecular profiling of cancers. c-miR functions in carriers of inherited pathogenic mismatch-repair gene variants (path_MMR), also known as Lynch syndrome (LS), have remained understudied. LS cohort provides an ideal population for biomarker mining due to increased lifelong cancer risk and excessive cancer occurrence. Using high-throughput sequencing and bioinformatic approaches, we conducted an exploratory analysis to characterize systemic c-miRnomes ofpath_MMRcarriers. Our discovery cohort included 81 healthypath_MMRcarriers and 37 non-LS controls. Our analysis also included cancer cohort comprised of 13path_MMRcarriers with varying cancers and 24 sporadic rectal cancer patients. We showed for the first time that c-miRnome can discern healthypath_MMRcarriers from non-LS controls but does not distinguish healthypath_MMRcarriers from cancer patients with or withoutpath_MMR. Our c-miR expression analysis combined within silicotools suggest ongoing alterations of biological pathways shared in LS and sporadic carcinogenesis. We observed that these alterations can produce a c-miR signature which can be used to track oncogenic stress in cancer-freepath_MMRcarriers. Thus, c-miRs hold potential in monitoring which cancer patients would require more intensive surveillance or clinical management.SignificanceC-miRnome can discern between healthy persons with or withoutpath_MMRbut does not distinguish healthypath_MMRcarriers from cancer patients with or withoutpath_MMR, indicating an ongoing alteration of biological pathways that can be used to track oncogenic stress at cancer-free state.
Familial ALS-associated SFPQ variants promote the formation of SFPQ cytoplasmic aggregates that reduce surface AMPA receptor expression in primary neurons
Authors: Widagdo Jocelyn , Udagedara Saumya , Bhembre Nishita , Tan Jing Zhi Anson , Neureiter Lara , Huang Jie , Anggono Victor , Lee Mihwa 
Published: March 2022

ABSTRACTSFPQ is a nuclear RNA-binding protein that is involved in a wide range of physiological processes including neuronal development and homeostasis. However, the mislocalization and cytoplasmic aggregation of SFPQ are associated with the pathophysiology of amyotrophic lateral sclerosis (ALS). We have previously reported that zinc mediates SFPQ polymerization and promotes the formation of cytoplasmic aggregates in neurons. Here we characterize two familial ALS (fALS)-associated SFPQ variants, which cause amino acid substitutions in the proximity of the SFPQ zinc-coordinating center (N533H and L534I). Both mutants display increased zinc-binding affinities, which can be explained by the presence of a secondary zinc-binding site revealed by the 1.83Å crystal structure of the human SFPQ L534I mutant. Overexpression of these fALS-associated mutants significantly increases the number of SFPQ cytoplasmic aggregates in primary neurons. Although they do not affect the density of dendritic spines, the presence of SFPQ cytoplasmic aggregates causes a marked reduction in the levels of the GluA1, but not the GluA2 subunit of AMPA-type glutamate receptors on the neuronal surface. Taken together, our data demonstrate that fALS-associated mutations enhance the propensity of SFPQ to bind zinc and form aggregates, leading to the dysregulation of AMPA receptor subunit composition, which may contribute to neuronal dysfunction in ALS.
Identifying transcription factor-DNA interactions using machine learning
Authors: Bang Sohyun , Galli Mary , Crisp Peter A. , Gallavotti Andrea , Schmitz Robert J. 
Published: March 2022

ABSTRACTMachine learning approaches have been applied to identify transcription factor (TF)-DNA interaction important for gene regulation and expression. However, due to the enormous search space of the genome, it is challenging to build models capable of surveying entire reference genomes, especially in species where models were not trained. In this study, we surveyed a variety of methods for classification of epigenomics data in an attempt to improve the detection for 12 members of the Auxin Response Factor (ARF) binding DNAs from maize and soybean as assessed by DNA Affinity Purification and sequencing (DAP-seq). We used the classification for prediction by minimizing the genome search space by only surveying unmethylated regions (UMRs). For identification of DAP-seq binding events within the UMRs, we achieved 93.54% accuracy, 6.2% false positive, and a 43.29% false negative rate across 12 members of ARFs of maize on average by encoding DNA with count vectorization for k-mer with a logistic regression classifier with up-sampling and feature selection. Importantly, feature selection helps to uncover known and potentially novel ARF binding motifs. This demonstrates an independent method for identification of transcription factor binding sites. Finally, we tested the model built with maize DAP-seq data and applied it directly to the soybean genome and found unacceptably high false positive rates, which accounted for more than 40% across the ARF TFs tested. The findings in this study suggest the potential use of various methods to predict TF-DNA interactions within and between species with varying degrees of success.
Continuous extraction and concentration of secreted metabolites from engineered microbes using membrane technology
Authors: Overmans Sebastian , Ignacz Gergo , Beke Aron K. , Xu Jiajie , Saikaly Pascal , Szekely Gyorgy , Lauersen Kyle J. 
Published: March 2022

AbstractMicroalgal cultivation in photobioreactors and membrane separations are both considered sustainable processes. Here we explore their synergistic combination to extract and concentrate a heterologous sesquiterpenoid produced by engineered green algal cells. A hydrophobic hollow-fiber membrane contactor was used to allow interaction of culture broth and cells with a dodecane solvent phase to accumulate algal produced patchoulol. Subsequent continuous membrane extraction of patchoulol from dodecane enabled product concentration in a methanol stream as well as dodecane recovery for its reuse. A structure-based prediction using machine learning was used to model a process whereby 100% patchoulol recovery from dodecane could be achieved with solvent-resistant nanofiltration membranes. Solvent consumption, E-factor, and economic sustainability were assessed and compared with existing patchoulol production processes. Our extraction and product purification process offers six- and two-orders of magnitude lower solvent consumption compared to synthetic production and thermal-based separation, respectively. Our proposed methodology is transferable to other microbial systems for the isolation of high-value isoprenoid and hydrocarbon products.
ATR-I774Yfs*5 promotes genomic instability through micronuclei formation
Authors: Holcomb Nathaniel , Dhar Bithika , Pu Hong , Bautista Robert-Marlo , Overmann Anna Heink , Corum Lauren , Shelton Brent , D’Orazio John 
Published: March 2022

AbstractAlthough mismatch repair (MMR) defects are associated with high risk of malignancy, the specific oncogenic drivers pertinent to MMR-affected cancers are poorly characterized. The heterozygous ATR-I774Yfs*5 mutation, the result of strand slippage in a poly-A tract of the Ataxia Telangiectasia and Rad3 related (ATR) gene, is overexpressed in MMR-defective malignancies including colorectal carcinoma (CRC) and is the most common ATR mutation in cancer. Here, we explore the contribution of ATR-I774Yfs*5 to genomic integrity. Using heterozygous ATR-I774Yfs*5 HCT-116 cells to mimic the native mutation, we found this mutation reduced ATR activity as measured by damage-induced Chk1 phosphorylation at S317 and ATR autophosphorylation ATR at T1989. ATR-I774Yfs*5 expression impaired genomic stability as visualized by the appearance of micronuclei in two stable expression models as well as in cell lines transfected with ATR-I774Yfs*5. Micronucleus development was dependent on replication and independent of ATR copy number. ATR-I774Yfs*5 expression did not alter cellular viability, cell cycle progression, or replicative rate, suggesting this mutation is well-tolerated despite its destabilizing effect on the genome. Taken together, these data suggest that the ATR-I774Yfs*5, whose development is favored in the context of MMR deficiency, may represent an important driver of a mutator phenotype by promoting genomic instability.
Single-cell microfluidic analysis unravels individual cellular fates during Double-Strand Break Repair
Authors: Vertti-Quintero Nadia , Levien Ethan , Poggi Lucie , Amir Ariel , Richard Guy-Franck , Baroud Charles N. 
Published: March 2022

AbstractTrinucleotide repeat expansions are responsible for two dozen human disorders. Contracting expanded repeats by Double-Strand Break Repair (DSBR) might be a therapeutic approach. Given the complexity of manipulating human cells, recent assays were made to quantify DSBR efficacy in yeast, using a fluorescent reporter. In this study DSBR is characterized with an interdisciplinary approach, linking large population dynamics and individual cells. Time-resolved molecular measurements of changes in the population are first confronted to a coupled differential equation model to obtain repair processes rates. Comparisons with measurements in microfluidic devices, where the progeny of 80-150 individual cells are followed, show good agreement between individual trajectories and mathematical and molecular results. Further analysis of individual progenies shows the heterogeneity of individual cell contributions to global repair efficacy. Three different categories of repair are identified: high-efficacy error-free, low-efficacy error-free and low-efficacy error-prone. These categories depend on the type of endonuclease used and on the target sequence.