bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hip Pain in Patients With Spinal Muscular Atrophy: Prevalence, Intensity, Interference, and Factors Associated With Moderate to Severe Pain
Authors: Xu Amy L. , Crawford Thomas O. , Sponseller Paul D. 
Published: February 2022

Background:
A subset of patients with spinal muscular atrophy (SMA) develop hip pain. We analyzed (1) the characteristics of hip pain in patients with SMA (prevalence, intensity, interference with activities, and responsiveness to treatment) and (2) factors (patient, clinical, and radiographic) associated with moderate to severe pain.

Methods:
We performed a retrospective record review and telephone survey of 104 patients with SMA (77% response rate; 44% female; mean age, 22±13 y) who presented for treatment between 2010 and 2020. Patient, clinical, and radiographic characteristics (when available) were recorded. Patients with current or past hip pain were asked about pain characteristics. Pain intensity and interference were assessed with the Brief Pain Inventory, modified for SMA (scale, 0 to 10 with 0 indicating no pain/interference). We used univariate analysis and ordered logistic regression to determine associations between patient factors and hip pain (α=0.05).

Results:
Hip pain occurred in 60/104 patients (58%), with 15 (14%) indicating moderate to severe pain. Compared with patients with normal body mass index values, patients who were obese had 5.4 times the odds [95% confidence interval (CI), 1.3-23] of moderate to severe pain. Hip contractures [adjusted odds ratio (aOR), 3.2; 95% CI, 1.2-8.8] and dislocations (aOR, 2.9; 95% CI, 1.1-7.9) were associated with greater odds of pain compared with hips without these presentations. Surgical correction for scoliosis (aOR, 2.6; 95% CI, 1.1-6.5) was also associated with greater odds of moderate to severe pain. Femoral head migration percentage was the only radiographic parameter associated with pain. Mean modified Brief Pain Inventory pain intensity was 2.1±2.3. Prolonged sitting, sleep, and transfers (eg, bed to wheelchair) were the activities most affected by pain.

Conclusions:
Hip pain was moderate to severe in 14% of patients with SMA. Obesity, hip contractures, surgical correction of scoliosis, and hip dislocations were independently associated with pain. Although mean pain intensity was low, hip pain interfered with daily activities, including prolonged sitting, sleep, and transfers.

Level of Evidence:
Level III.
Three-Dimensional Biomechanics of the Trunk and Upper Extremity During Overhead Throwing in Wheelchair Lacrosse Athletes With Spinal Cord Injury
Authors: Hanks Matthew M. , Schnorenberg Alyssa J. , Lee Kenneth K. , Slavens Brooke A. 
Published: February 2022

Objective
Quantify differences in overhead throwing kinematics between wheelchair lacrosse athletes with spinal cord injury and able-bodied lacrosse athletes.

Design
This is a cross-sectional, prospective study. Motion analysis captured overhead throwing motions of five wheelchair lacrosse athletes with spinal cord injury and six able-bodied lacrosse athletes seated in a wheelchair and standing. Three-dimensional thorax and dominant arm sternoclavicular, acromioclavicular, glenohumeral, elbow, and wrist joint angles, ranges of motion, as well as angular velocities were computed using an inverse kinematics model. Nonparametric tests assessed group differences (P < 0.05).

Results
Participants with spinal cord injury exhibited less peak thorax axial rotation, ranges of motion, and angular velocity, as well as greater wrist flexion than able-bodied participants seated. Participants with spinal cord injury exhibited less peak thorax axial rotation and lateral bending, ranges of motion, and three-dimensional angular velocities; less peak two-dimensional sternoclavicular joint motion, ranges of motion, and peak angular velocities; less peak acromioclavicular joint protraction angular velocity; less glenohumeral joint adduction-abduction and internal-external rotation motion, ranges of motion, and angular velocities; and greater wrist flexion than able-bodied participants standing.

Conclusions
Kinematic differences were observed between groups, with athletes with spinal cord injury exhibiting less thorax and upper extremity joint motion and slower joint angular velocities than able-bodied athletes. This knowledge may provide insights for movement patterns and potential injury risk in wheelchair lacrosse.
Psychopharmacology of agitation in acute psychotic and manic episodes
Authors: Stetson Sean R. , Osser David N. 
Published: February 2022

Purpose of review
To provide updated guidance for the medication treatment of acute agitation in the setting of psychosis or mania on inpatient psychiatric units.

Recent findings
This topic presented challenges: studies are sparse, tend to be under-powered, and are difficult to compare. Though there have been few recent studies, there have been several recent meta-analyses, Cochrane reviews, and published guidelines that sift through the primarily older evidence as well as more recent trials. The reviewers often do not agree on what seems to have the best evidence for efficacy and safety.

Summary
We conclude that the best approach is to summarize in some detail the evidence for each possible treatment and the interpretations published recently on each of those treatments, and then present recommendations for medication management in tiered rankings, based on the authors’ qualitative review of the data and opinions. For oral treatment, the first-tier options are (alphabetically) haloperidol with lorazepam, lorazepam alone, and olanzapine. The second tier includes haloperidol with promethazine, loxapine inhaler, and risperidone alone. Tier 3 includes asenapine and quetiapine. For intramuscular treatment, the first-tier includes haloperidol plus promethazine, and olanzapine alone, and the second-tier includes haloperidol with lorazepam, and lorazepam alone.
Interpretable Deep Learning Model Reveals Subsequences of Various Functions for Long Non-coding RNA Identification
Authors: Lin Rattaphon , Wichadakul Duangdao 
Published: February 2022

AbstractLong non-coding RNAs (lncRNAs) play crucial roles in many biological processes and are implicated in several diseases. With the next-generation sequencing technologies, substantial un-annotated transcripts have been discovered. Classifying unannotated transcripts using biological experiments is more time-consuming and expensive than computational approaches. Several tools for identifying long non-coding RNAs are available. These tools, however, did not explain which features in their tools contributed to the prediction results. Here, we present Xlnc1DCNN, a tool for distinguishing long non-coding RNAs (lncRNAs) from protein-coding transcripts (PCTs) using a one-dimensional convolutional neural network with prediction explanations. The evaluation results of the human test set showed that Xlnc1DCNN outperformed other state-of-the-art tools in terms of accuracy and F1-score. The explanation results revealed that lncRNA transcripts were mainly identified as sequences with no conserved regions or with a region of transmembrane helix while protein-coding transcripts were mostly classified by conserved protein domains or families. The explanation results also conveyed the probably inconsistent annotations among the public databases, lncRNA transcripts which contain protein domains or families, as well as protein-coding transcripts which are nonsense-mediated decay or processed transcripts. Xlnc1DCNN is freely available at https://github.com/cucpbioinfo/Xlnc1DCNN.
Multidimensional single-cell analysis identifies a role of CD2-CD58 interactions for clinical antitumor T cell responses
Authors: Romain Gabrielle , Strati Paolo , Rezvan Ali , Fathi Mohsen , Bandey Irfan N , Adolacion Jay R T , Heeke Darren , Liadi Ivan , Marques-Piubelli Mario L , Solis Luisa M. , Mahendra Ankit , Vega Francisco , Cooper Laurence J.N. , Singh Harjeet , Mattie Mike , Bot Adrian , Neelapu Sattva , Varadarajan Navin 
Published: February 2022

ABSTRACTThe in vivo persistence of adoptively transferred T cells is predictive of anti-tumor response. Identifying functional properties of infused T cells that lead to in vivo persistence and tumor eradication has remained elusive. We profiled CD19-specific CAR T cells that comprise the infusion products used to treat large B cell lymphomas using high-throughput single-cell technologies based on Timelapse Imaging Microscopy In Nanowell Grids (TIMING) that integrates killing, cytokine secretion, and transcriptional profiling. Our results show that the directional migration of CD19-specific CAR T cells is correlated with polyfunctionality. We identified that CD2 on T cells is associated with directional migration and that the interaction between CD2 on T cells and CD58 on lymphoma cells accelerates killing and serial killing. Consistent with this, we observed elevated CD58 expression on pre-treatment tumor samples in patients with relapsed or refractory large B cell lymphomas treated with CD19-specific CAR T cell therapy was associated with complete clinical response and survival. These results highlight the importance of studying dynamic T-cell tumor cell interactions in identifying optimal antitumor responses.KEY POINTS- Profiling patient infusion products revealed that polyfunctional CAR T cells show directional migration, which is associated with higher CD2 expression- The ligand for CD2, CD58 is expressed at higher levels in the tumors of lymphoma patients who respond better to CAR T cell treatment
Expansion and differentiation ofex vivocultured erythroblasts in scalable stirred bioreactors
Authors: Gallego-Murillo Joan Sebastián , Iacono Giulia , van der Wielen Luuk A.M. , van den Akker Emile , von Lindern Marieke , Wahl Sebastian Aljoscha 
Published: February 2022

AbstractTransfusion of donor-derived red blood cells (RBCs) is the most common form of cell therapy. Production of transfusion-ready cultured RBCs (cRBCs) is a promising replacement for the current fully donor-dependent therapy. However, very large number of cells are required for transfusion. Here we scale-up cRBC production from static cultures to 0.5 L stirred tank bioreactors, and identify the effect of operating conditions on the efficiency of the process. Oxygen requirement of proliferating erythroblasts (0.55-2.01 pg/cell/h) required sparging of air to maintain the dissolved oxygen concentration at the tested setpoint (2.88 mg O2/L). Erythroblasts could be cultured at dissolved oxygen concentrations as low as 0.7 O2mg/mL without negative impact on proliferation, viability or differentiation dynamics. Stirring speeds of up to 600 rpm supported erythroblast proliferation, while 1800 rpm led to a transient halt in growth and accelerated differentiation followed by a recovery after 5 days of culture. Erythroblasts could also be differentiated in bioreactors, with final enucleation levels and hemoglobin content similar to parallel cultures under static conditions. After defining optimal mixing and aeration strategies, erythroblast proliferation cultures were successfully scaled up to 3 L bioreactors.
Examining clustered somatic mutations with SigProfilerClusters
Authors: Bergstrom Erik N. , Kundu Mousumy , Tbeileh Noura , Alexandrov Ludmil B. 
Published: February 2022

ABSTRACTSummaryClustered mutations are found in the human germline as well as in the genomes of cancer and normal somatic cells. Clustered events can be imprinted by a multitude of mutational processes, and they have been implicated in both cancer evolution and development disorders. Existing tools for identifying clustered mutations have been optimized for a particular subtype of clustered event and, in most cases, relied on a predefined inter-mutational distance (IMD) cutoff combined with a piecewise linear regression analysis. Here we present SigProfilerClusters, an automated tool for detecting all types of clustered mutations by calculating a sample-dependent IMD threshold using a simulated background model that takes into account extended sequence context, transcriptional strand asymmetries, and regional mutation densities. SigProfilerClusters disentangles all types of clustered events from non-clustered mutations and annotates each clustered event into an established subclass, including the widely used classes of doublet-base substitutions, multi-base substitutions, omikli, and kataegis. SigProfilerClusters outputs non-clustered mutations and clustered events using standard data formats as well as provides multiple visualizations for exploring the distributions and patterns of clustered mutations across the genome.AvailabilitySigProfilerClusters is freely available at https://github.com/AlexandrovLab/SigProfilerClusters with support across most operating systems and extensive documentation at https://osf.io/qpmzw/wiki/home/.Contactebergstr@eng.ucsd.edu or L2alexandrov@health.ucsd.edu
Residual force enhancement within the human quadriceps is greatest during submaximal stretch-hold contractions at a very long muscle length
Authors: Bakenecker Patrick , Weingarten Tobias , Hahn Daniel , Raiteri Brent 
Published: February 2022

AbstractLittle is known about how muscle length affects residual force enhancement (rFE) in humans. We therefore investigated rFE at short, long, and very long muscle lengths within the human quadriceps and patellar tendon (PT) using conventional dynamometry with motion capture (rFETQ) and a new, non-invasive shear-wave tensiometry technique (rFEWS). Eleven healthy male participants performed submaximal (50% max.) EMG-matched fixed-end reference and stretch-hold contractions across these muscle lengths while muscle fascicle length changes of the vastus lateralis (VL) were captured using B-mode ultrasound. We found significant rFETQ at long (7±5%) and very long (12±8%) but not short (2±5%) muscle lengths, whereas rFEWS was only significant at the very long (38±27%), but not short (8±12%) or long (6±10%) muscle lengths. We also found significant relationships between VL fascicle length and rFETQ (r=0.63, p=.001) and rFEWS (r=0.52, p=.017), but relationships were not significant between VL fascicle stretch amplitude and rFETQ (r=0.33, p=.126) or rFEWS (r=0.29, p=.201). PT shear-wave speed-angle relationships did not agree with estimated quadriceps muscle force-angle relationships, which indicates that estimating PT loads from shear-wave tensiometry might be inaccurate. We conclude that increasing muscle length rather than stretch amplitude contributes more to rFE during submaximal voluntary contractions of the human quadriceps.
Environmental contributions to the evolution of trait differences inGeum triflorum: implications for restoration
Authors: Volk Kate , Braasch Joseph , Ahlering Marissa , Hamilton Jill A. 
Published: February 2022

ABSTRACTPremise of the StudyUnderstanding how environment influences the distribution of trait variation across a species’ range has important implications for seed transfer during restoration. Heritable genetic differences associated with environment could impact fitness when transferred into new environments. Here, we test the degree to which the environment shapes the evolution and distribution of genetic effects for traits important to adaptation.MethodsIn a common garden experiment, we quantified trait differentiation for populations ofGeum triflorumsourced from three distinct ecoregions and evaluated the ability of climate to predict trait variation. Populations were sourced from alvar ecoregions which experience predictable extremes in seasonal water availability and the prairie ecoregion which exhibits unpredictable changes in water availability.Key ResultsPlants sourced from alvar ecoregions exhibited smaller but more numerous stomata and greater intrinsic water use efficiency relative to prairie plant populations supporting the evolution of ecotypic differences. Estimates of standing genetic variance and heritable genetic variation for quantitative traits suggest alvar populations have greater adaptive potential. However, reduced evolvability suggest all populations ofG. triflorummay have limited capacity to evolve in response to environmental change.ConclusionsThese results point towards the importance of understanding the role of environment in shaping the distribution and evolution of genetic differences across seed populations and how these data may inform recommendations for seed transfer across novel environments and our expectations of populations’ adaptive potential.
Joint structural annotation of small molecules using liquid chromatography retention order and tandem mass spectrometry data
Authors: Bach Eric , Schymanski Emma L. , Rousu Juho 
Published: February 2022

AbstractWe present LC-MS2Struct, a machine learning framework for structural annotation of small molecule data arising from liquid chromatography-tandem mass spectrometry (LC-MS2) measurements. LC-MS2Struct jointly predicts the annotations for a set of mass spectrometry features in a sample, using a novel structured prediction model trained to optimally combine the output of state-of-the-art MS2scorers and observed retention orders. We evaluate our method on a dataset covering all publicly available reversed phase LC-MS2data in the MassBank reference database, including 4327 molecules measured using 18 different LC conditions from 16 contributors, greatly expanding the chemical analytical space covered in previous multi-MS2scorer evaluations. LC-MS2Struct obtains significantly higher annotation accuracy than earlier methods and improves the annotation accuracy of state-of-the-art MS2scorers by up to 106%. The use of stereochemistry-aware molecular fingerprints improves prediction performance, which highlights limitations in existing approaches and has strong implications for future computational LC-MS2developments.
Stress-induced phase separation of ERES components into Sec bodies precedes ER exit inhibition in mammalian cells
Authors: van Leeuwen Wessel , Nguyen Dan T.M. , Grond Rianne , Veenendaal Tineke , Farías Ginny G. , Rabouille Catherine 
Published: February 2022

AbstractPhase separation of ER-exit-sites (ERES) components into membraneless compartments, the Sec bodies, occurs in Drosophila cells upon specific cellular stressors, i.e., salt stress and amino acid starvation, and their formation is linked to the inhibition of the early secretory pathway. Here, we show Sec bodies also form in secretory mammalian INS-1 cells upon the same stress. These reversible and membraneless structures are positive for ERES components, including both isoforms of Sec16 (A and B) and COPII subunits. We find that Sec16A, but not Sec16B, is a driver for Sec body formation. We show that the coalescence of ERES components into Sec bodies occurs by fusion, in line with their liquid-droplet properties. Lastly, we demonstrate that stress-induced ER-exit inhibition is a consequence of the significant coalescence of Sec16A into Sec bodies, leading to its depletion from ERES that become non-functional. Stress relief causes an immediate dissolution of Sec bodies and the concomitant restoration of protein exit from the ER. We propose a model in which dynamic conversion between ERES and Sec body assembly, driven by Sec16A, regulates protein exit from the ER during stress and upon stress relief in mammalian cells, thus providing a conserved pro-survival mechanism in response to stress.
The global exposure of species ranges and protected areas to forest management
Authors: Jung Martin , Lewis Matt , Lesiv Myroslava , Arnell Andy , Fritz Steffen , Visconti Piero 
Published: February 2022

AbstractThe majority of vertebrate species globally are dependent on forests, most of which require active protection to safeguard global biodiversity. Forests, however, are increasingly either being disturbed, planted or managed in the form of timber or food plantations. Because of a lack of spatial data, forest management has commonly been ignored in previous conservation assessments. Here we show – using a new global map of forest management - that disturbed and human managed forests cover the distributional ranges of most forest-associated species. Even more worrying, protected areas are increasingly being established in areas dominated by disturbed forests. Our results imply that species extinction risk and habitat assessments might have been overly optimistic with forest management practices being ignored. With forest restoration being in the centre of climate and conservation policies in this decade, we caution that policy makers should explicitly consider forest management.
Neurodevelopmental Patterns of Early Postnatal White Matter Maturation Represent Distinct Underlying Microstructure and Histology
Authors: Nazeri Arash , Krsnik Željka , Kostović Ivica , Ha Sung Min , Kopić Janja , Alexopoulos Dimitrios , Kaplan Sydney , Meyer Dominique , Luby Joan L. , Warner Barbara B. , Rogers Cynthia E. , Barch Deanna M. , Shimony Joshua S. , McKinstry Robert C. , Neil Jeffrey J. , Smyser Christopher D. , Sotiras Aristeidis 
Published: February 2022

AbstractDuring the early postnatal period, cerebral white matter undergoes rapid maturation through a complex series of interrelated cellular and histogenetic processes. Accurately quantifying these processes is important for improving understanding of early brain development, developmental abnormalities related to prematurity, and neurodevelopmental diseases. Past efforts have used magnetic resonance imaging (MRI) to track these developmental processes in vivo. However, most previous studies have relied on single imaging modality data and have often been limited by small samples and analytics that do not evaluate complex multivariate imaging patterns. Here, we applied an advanced unsupervised multivariate pattern analysis technique, non-negative matrix factorization (NMF), to T2w/T1w signal ratio maps from a large cohort of newborns (Developing Human Connectome Project [dHCP], n=342), revealing patterns of synchronous white matter maturation. These patterns showed divergent age-related maturational trajectories and differential susceptibility to premature birth, which were replicated in an independent large sample of newborns (Early Life Adversity, Biological Embedding, and Risk for Developmental Precursors of Mental Disorders [eLABE], n=239). Furthermore, we showed that T2w/T1w signal variations in white matter maturational patterns are explained by differential contributions of white matter microstructure indices (i.e., free water content and neurite density index) derived from neurite orientation dispersion and density imaging (NODDI) modeling of diffusion-weighted MRI. Finally, we demonstrated how white matter maturation patterns relate to distinct histological features by comparing our findings with postmortem late fetal/early postnatal brain tissue staining. Together, these results delineate a novel MRI representation of white matter microstructural and histological reorganization during the early postnatal development.