bluuebunny/crossref_metadata_2025_split huggingface dataset:
THE EFFECT OF ELECTIVE CATARACT EXTRACTION BY PHACOEMULSIFICATION IN EYES WITH VITREOMACULAR TRACTION SYNDROME
Authors: Mantopoulos Dimosthenis , Prenner Jonathan L. , Patel Vishal K. , Roth Daniel B. , Shah Sumit P. , Tsavaris Onoufrios , Fine Howard F. , Wheatley H. Matthew 
Published: February 2020

Purpose:
To evaluate the effect of cataract extraction (CE) by phacoemulsification on the vitreomacular interface (VMI) of eyes with preexisting vitreomacular traction (VMT).

Methods:
Retrospective, observational case series. Patients with VMT who elected to proceed with CE, before any vitreoretinal intervention, were studied. Eyes with at least a 12-month follow-up period were included. The status of the vitreomacular adhesion at different time points was assessed using spectral-domain optical coherence tomography. The best-corrected visual acuity was recorded at different time points. Other macular and systemic comorbidities were documented.

Results:
Fifteen eyes from 15 phakic patients with symptomatic VMT were included. Six of them were male subjects. Seven patients had diabetes mellitus and two of them also had nonproliferative diabetic retinopathy. The preoperative macular comorbidities included macular hole in six eyes (Stage 1 in 3 eyes and Stage 2 or 3 in another 3 eyes), epiretinal membrane in five eyes, and cystoid macular edema in four eyes. After uncomplicated CE, the VMT was released in 5 eyes, whereas in 10 eyes, CE did not significantly change the status of the vitreomacular adhesion. Three of 3 eyes with preexisting full-thickness macular hole (Stage 2 or 3 macular hole) were found to have Stage 4 macular hole shortly after CE. In seven of seven patients with diabetes mellitus, the status of the vitreomacular interface did not change after CE. Eventually, 7 of 15 patients underwent additional pars plana vitrectomy. Compared with the baseline vision, and vision before other interventions, the visual acuity after CE improved in 5 patients, remained unchanged in 7 patients, and decreased in the 3 patients with Stage 2 or 3 macular hole. The mean preoperative and early postoperative visual acuity was 20/59 and 20/68, respectively (P > 0.05).

Conclusion:
The effect of CE in phakic eyes with known VMT varies significantly. In the current case series, every eye with VMT and Stage 2 or 3 macular hole ended up with Stage 4 macular hole, although the VMT did not change significantly in the eyes of diabetic patients. Studies with larger sample size are needed to further elucidate the impact of elective CE on VMT.
Interactive Learning Modules With Visual Feedback Improve Resident Learning in Colposcopy
Authors: Nelson Erin L. , Knudtson Jennifer F. 
Published: February 2020

Objective
The Accreditation Council for Graduate Medical Education and the Council on Resident Education in Obstetrics and Gynecology have milestones and/or competencies relating to colposcopy; however, the optimal way to reach these objectives is not proscribed and left to individual programs. Here, we aim to assess resident skill, confidence levels, perceived level of knowledge, and satisfaction with colposcopic training before and after implementation of a new interactive learning module with visual feedback.

Materials and Methods
A new online educational intervention was developed by the author (E.L.N.) based on adult learning theory and introduced into our obstetrics and gynecology resident colposcopy curriculum in July 2014. We assessed performance on an objective competency examination administered at baseline and repeated after 6 months of our 24 residents.
In addition, we assessed resident confidence levels, perceived level of knowledge, and satisfaction with training before and 6 months after intervention.

Results
Scores on a national online examination improved after the intervention (p = .014). Significant improvements on the examination were seen in the sections of medical knowledge (p = .031) and management (p = .011). Residents' perceived knowledge increased significantly after the intervention (p = .030).

Conclusions
Learning outcomes improved after introduction of a novel teaching intervention.
Fingolimod for Relapsing-Remitting Multiple Sclerosis: The Experience From Saudi Arabia
Authors: Algahtani Hussein , Shirah Bader , Al Malik Yaser , Meftah Ibraheem 
Published: February 2020

Background
Fingolimod (Gilenya, Novartis pharmaceuticals) is the first oral disease-modifying therapy for reducing the frequency of clinical relapses and delaying disability progression in patients with relapsing-remitting multiple sclerosis (RRMS). In this study, we aimed to evaluate the outcome of Saudi patients with active RRMS treated with fingolimod.

Methods
We conducted a retrospective multicenter observational study at the King Abdulaziz Medical City in Jeddah and Riyadh, Saudi Arabia. The inclusion criteria consisted of patients 18 years and older who were diagnosed with RRMS according to the revised McDonald criteria who are currently receiving or received fingolimod treatment in the past for a minimum of 6 months.

Results
A total of 100 patients were treated with fingolimod. The mean ± SD duration of the disease was 9.23 ± 6.63 years. The mean ± SD duration of using fingolimod was 32.00 ± 24.83 months. The mean ± SD baseline expanded disability status scale (EDSS) score was 2.95 ± 2.58. The mean ± SD EDSS score at last follow-up was 2.95 ± 2.65. The mean ± SD annualized relapse rate was significantly reduced from 1.24 ± 1.39 at baseline to 0.43 ± 1.15 at the last follow-up (P = 0.001). In addition, radiological activity was significantly improved at follow-up magnetic resonance imaging studies when compared with the baseline.

Conclusions
Our multicenter study provides further evidence for the efficacy of fingolimod in reducing clinical and radiological disease activity in patients with RRMS. The reduction in relapse rate, stabilization of the EDSS score, and improvement in magnetic resonance imaging images were similar to other observational studies conducted in different countries worldwide. Fingolimod seems to be well tolerated for our multiple sclerosis population.
Parallel cortical-brainstem pathways to attentional analgesia
Authors: Oliva Valeria , Gregory Rob , Davies Wendy-Elizabeth , Harrison Lee , Moran Rosalyn , Pickering Anthony E. , Brooks Jonathan C.W. 
Published: February 2020

AbstractPain perception is diminished when attention is diverted. Our previous human fMRI study, using a 2×2 factorial design with thermal stimuli and concurrent visual attention task, linked the brainstem triad of locus coeruleus (LC), rostroventromedial medulla (RVM) and periaqueductal grey (PAG) to attentional analgesia. This study was repeated with a larger cohort, replicating our earlier findings. Pain intensity was encoded by the RVM, whilst activity in the contralateral LC correlated with the magnitude of attentional analgesia. Psycho-Physiological Interaction analysis informed subsequent Dynamic Causal Modelling and identified two parallel paths between forebrain and the brainstem regions involved in analgesia. These cortico-brainstem connections were modulated by attentional demand: a bidirectional anterior cingulate cortex (ACC) – right-LC loop, and a top-down influence of task on ACC-PAG-RVM. Under conditions of competing attentional demands the ACC recruits discrete brainstem circuits to modulate nociceptive input.
Independent and sensitive gait parameters for objective evaluation in knee and hip osteoarthritis using wearable sensors
Authors: Boekesteijn R.J. , Smolders J.M.H. , Busch V.J.J.F. , Geurts A.C.H. , Smulders K. 
Published: February 2020

AbstractObjectiveTo identify non-redundant gait parameters sensitive to end-stage knee and hip osteoarthritis (OA), with a specific focus on turning, dual task performance, and upper body motion in addition to straight-ahead gait.DesignGait was compared between individuals with unilateral, end-stage knee (n=25) or hip OA (n=26) scheduled for joint replacement, and healthy controls (n=27). For 2 minutes, subjects walked back-and-forth along a 6 meter trajectory making 180° turns, with and without a secondary cognitive task. Gait parameters were collected using 4 inertial measurement units on the feet and trunk. The dataset was reduced using factor analysis. One gait parameter from each factor was selected based on factor loading and effect size of the comparison between OA groups and healthy controls.ResultsFour independent domains of gait were obtained: speed-spatial, speed-temporal, dual task cost, and upper body motion. Turning parameters did not constitute a separate domain. From these domains, stride length (speed-spatial) and cadence (speed-temporal) had the strongest factor loadings and effect sizes for both knee and hip OA, and lumbar sagittal range of motion (upper body motion) for hip OA only.ConclusionsStride length, cadence, and lumbar sagittal range of motion were non-redundant and sensitive parameters, representing gait adaptations in individuals with knee or hip OA. Turning or dual task parameters had no additional value for evaluating gait in knee and hip OA. These findings hold promise for the objective evaluation of gait in the clinic. Future steps should include testing of responsiveness to interventions aiming to improve mobility.
Whole-brain estimates of directed connectivity for human connectomics
Authors: Frässle Stefan , Manjaly Zina M. , Do Cao T. , Kasper Lars , Pruessmann Klaas P. , Stephan Klaas E. 
Published: February 2020

ABSTRACTConnectomics is essential for understanding large-scale brain networks but requires that individual connection estimates are neurobiologically interpretable. In particular, a principle of brain organization is that reciprocal connections between cortical areas are functionally asymmetric. This is a challenge for fMRI-based connectomics in humans where only undirected functional connectivity estimates are routinely available. By contrast, whole-brain estimates of effective (directed) connectivity are computationally challenging, and emerging methods require empirical validation.Here, using a motor task at 7T, we demonstrate that a novel generative model can infer known connectivity features in a whole-brain network (>200 regions, >40,000 connections) highly efficiently. Furthermore, graph-theoretical analyses of directed connectivity estimates identify functional roles of motor areas more accurately than undirected functional connectivity estimates. These results, which can be achieved in an entirely unsupervised manner, demonstrate the feasibility of inferring directed connections in whole-brain networks and open new avenues for human connectomics.
Light-inducible generation of membrane curvature in live cells with engineered BAR domain proteins
Authors: Jones Taylor , Liu Aofei , Cui Bianxiao 
Published: February 2020

AbstractNanoscale membrane curvature is now understood to play an active role in essential cellular processes such as endocytosis, exocytosis and actin dynamics. Previous studies have shown that membrane curvatures directly affect protein functions and intracellular signaling. However, few methods are able to precisely manipulate membrane curvature in live cells. Here, we report the development of a new method of generating nanoscale membrane curvature in live cells that is controllable, reversible, and capable of precise spatial and temporal manipulation. For this purpose, we make use of BAR domain proteins, a family of well-studied membrane-remodeling and membrane-sculpting proteins. Specifically, we engineered two optogenetic systems, opto-FBAR and opto-IBAR, that allow light-inducible formation of positive and negative membrane curvature respectively. Using opto-FBAR, blue light activation results in the formation of tubular membrane invaginations (positive curvature), controllable down to the subcellular level. Using opto-IBAR, blue light illumination results in the formation of membrane protrusions or filopodia (negative curvature). These systems present a novel approach for light-inducible manipulation of nanoscale membrane curvature in live cells.HighlightsOpto-FBAR enables light-inducible positive membrane curvature formation.Opto-IBAR enables light-inducible negative membrane curvature formation.Light-inducible activation enables precise spatial and temporal control.Opto-BAR systems present a new approach for studying membranes in live cells.
Matrix metalloproteinase-2 mediates ribosomal RNA transcription by cleaving nucleolar histones
Authors: Ali Mohammad A.M. , Garcia-Vilas Javier A. , Cromwell Christopher R. , Hubbard Basil P. , Hendzel Michael J. , Schulz Richard 
Published: February 2020

AbstractCell proliferation and survival require continuous ribosome biogenesis and protein synthesis. Genes encoding ribosomal RNA (rRNA) are physically located in a specialized substructure within the nucleus known as the nucleolus, which has a central role in the biogenesis of ribosomes. Matrix metalloproteinase-2 (MMP-2) was previously detected in the nucleus. However, its role there is elusive. Herein we report that MMP-2 resides within the nucleolus to regulate rRNA transcription. MMP-2 is enriched at the promoter region of rRNA gene repeats and its inhibition downregulates pre-rRNA transcription. The N-terminal tail of histone H3 is clipped by MMP-2 in the nucleolus and is associated with increased rRNA transcription. Knocking down/out MMP-2 or inhibiting its activity prevents histone H3 cleavage and reduces both rRNA transcription and cell proliferation. In addition to the known extracellular roles of MMP-2 in tumor growth, our data reveal an epigenetic mechanism whereby intranucleolar MMP-2 regulates cell proliferation through histone proteolysis and facilitation of rRNA transcription.
Biased localization of actin binding proteins by actin filament conformation
Authors: Harris Andrew R , Jreij Pamela , Belardi Brian , Bausch Andreas , Fletcher Daniel A 
Published: February 2020

ABSTRACTThe assembly of actin filaments into distinct cytoskeletal structures plays a critical role in cell physiology, but how proteins localize differentially to these structures within a shared cytoplasm remains unclear. Here, we show that the actin-binding domains of accessory proteins can be sensitive to filament conformational changes. Using a combination of live cell imaging and in vitro single molecule binding measurements, we show that tandem calponin homology domains (CH1-CH2) can be mutated to preferentially bind actin networks at the front or rear of motile cells, and we demonstrate that the affinity of CH1-CH2 domain mutants varies as actin filament conformation is altered by perturbations that include stabilizing drugs, physical constraints, and other binding proteins. These findings suggest that conformational heterogeneity of actin filaments in cells could help to direct accessory binding proteins to different actin cytoskeletal structures through a biophysical feedback loop.
Allosteric regulation of lysosomal enzyme recognition by the cation-independent mannose 6-phosphate receptor
Authors: Olson Linda J. , Misra Sandeep K. , Ishihara Mayumi , Battaile Kevin P. , Grant Oliver C. , Sood Amika , Woods Robert J. , Kim Jung-Ja P. , Tiemeyer Michael , Ren Gang , Sharp Joshua S. , Dahms Nancy M. 
Published: February 2020

AbstractThe cation-independent mannose 6-phosphate receptor (CI-MPR), also known as the IGF2 receptor or CD222, is a multifunctional type I transmembrane glycoprotein ubiquitously expressed in most eukaryotic cell types. Through the receptor’s ability to bind a variety of unrelated extracellular and intracellular ligands, it is involved in a wide array of functions including protein trafficking, lysosomal biogenesis, internalization, regulation of cell growth, cell migration and apoptosis. CI-MPR has a large extracellular region comprised of 15 contiguous domains, four of which interact with phosphorylated glycans on lysosomal enzymes. Here we present a series of biophysical studies, along with crystal structures, providing information on how the N-terminal 5 domains of this receptor work in concert to bind and release carbohydrates. High-resolution electron microscopy as well as hydroxyl radical protein footprinting (HRPF) of this multifunctional multidomain construct demonstrates dynamic conformational changes occur as a consequence of ligand binding and different pH conditions, These data, coupled with surface plasmon resonance studies and molecular modeling, allow us to propose a bi-dentate oligosaccharide binding model, which could explain how high affinity carbohydrate binding is achieved through allosteric domain cooperativity.
Decreased Colonic Activin Receptor-Like Kinase 1 Disrupts Epithelial Barrier integrity and is associated with a poor clinical outcome in Crohn’s disease
Authors: Toyonaga Takahiko , Keith Benjamin P. , Barrow Jasmine B. , Schaner Matthew S. , Wolber Elisabeth A. , Beasley Caroline , Huling Jennifer , Wang Yuli , Allbritton Nancy L. , Chaumont Nicole , Sadiq Timothy S. , Koruda Mark J. , Rahbar Reza , Furey Terrence S. , Sethupathy Praveen , Sheikh Shehzad Z. 
Published: February 2020

AbstractObjectiveIntestinal epithelial cell (IEC) barrier dysfunction is critical to the development of Crohn’s disease (CD). However, the mechanism is understudied. We recently reported increased microRNA-31-5p (miR-31-5p) expression in colonic IECs of CD patients, but downstream targets are unknown.DesignMiR-31-5p target genes were identified by integrative analysis of RNA- and small RNA-sequencing data from colonic mucosa and confirmed by qPCR in colonic IECs. Functional characterization of Activin Receptor-Like Kinase 1 (ACVRL1 or ALK1) in IECs was performedex vivousing 2 dimensional-cultured human primary colonic IECs. The impact of altered colonic ALK1 signaling in CD for the risk of surgery and endoscopic relapse was evaluated by a multivariate regression analysis and a Kaplan-Meier estimator.ResultsALK1was identified as a target of miR-31-5p in colonic IECs of CD patients and confirmed using a 3’-UTR reporter assay. Activation of ALK1 restricted the proliferation of colonic IECs in an EdU proliferation assay and down-regulated the expression of stemness-related genes. Activated ALK1 signaling directed the fate of colonic IEC differentiation toward colonocytes. Down-regulated ALK1 signaling was associated with increased stemness and decreased colonocyte-specific marker expression in colonic IECs of CD patients compared to healthy controls. Activation of ALK1 enhanced epithelial barrier integrity in a trans-epithelial electrical resistance permeability assay. Lower colonicALK1expression was identified as an independent risk factor for surgery and associated with a higher risk of endoscopic relapse in CD patients.ConclusionDecreased colonic ALK1 disrupted colonic IEC barrier integrity and associated with deteriorated clinical outcomes in CD patients.
Proteasome-Bound UCH37 Debranches Ubiquitin Chains to Promote Degradation
Authors: Deol Kirandeep K. , Crowe Sean O. , Du Jiale , Bisbee Heather , Guenette Robert G. , Strieter Eric R. 
Published: February 2020

SUMMARYThe linkage, length, and architecture of ubiquitin (Ub) chains are all important variables in providing tight control over many biological paradigms. There are clear roles for branched architectures in regulating proteasome-mediated degradation, however the proteins that selectively recognize and process these atypical chains are unknown. Here, using synthetic and enzyme-derived ubiquitin chains along with intact mass spectrometry, we report that UCH37/UCHL5, a proteasome-associated deubiquitinase, exclusively cleaves K48 branched chains. The activity and selectivity toward branched chains is markedly enhanced by the proteasomal Ub receptor RPN13/ADRM1. Using proteasome complexes reconstituted with either active or inactive UCH37 together with protein substrates modified with branched chains, we find that chain debranching promotes degradation under multi-turnover conditions. These results are further supported by proteome-wide pulse-chase experiments, which show that the loss of UCH37 activity impairs global protein turnover. Our work therefore defines UCH37 as a debranching deubiquitinase important for promoting proteasomal degradation.
Accumulative deamidation of human lens protein γS-crystallin leads to partially unfolded intermediates with enhanced aggregation propensity
Authors: Vetter Calvin J. , Thorn David C. , Wheeler Samuel G. , Mundorff Charlie , Halverson Kate , Carver John A. , David Larry L. , Lampi Kirsten J. 
Published: February 2020

AbstractAge-related cataract is a major cause of blindness worldwide. Yet, the molecular mechanisms whereby large, light scattering aggregates form is poorly understood, because of the complexity of the aggregates isolated from human lenses. The predominant proteins in the lens are structural proteins called crystallins. The γS-crystallin is heavily modified in cataractous lenses by deamidation, which introduces a negative charge at labile asparagine residues. The effects of deamidation at asparagines, N14, N76, and N143, were mimicked by replacing the asparagine with aspartate using site-directed mutagenesis. The effects of these surface deamidations on the stability, unfolding, and aggregation properties of γS were determined using dynamic light scattering, chemical and thermal-denaturation, and hydrogen-deuterium exchange with mass spectrometry. We found that a small population of all the deamidation mimics aggregated directly into large light scattering bodies with a radius greater than 10 nm that contributed 14-60% of the total scattering intensity compared to 7% for WT under the same conditions. A possible mechanism was identified under partially denaturing conditions, where deamidation led to significantly more rapid unfolding and aggregation particularly for N76D compared to WT. The triple mutant was further destabilized, reflecting the enhanced aggregation properties of N14D and N143D. Thus, the effects of deamidation were both site-specific and cumulative. αA-crystallin was ineffective at acting as a chaperone to prevent the aggregation of destabilized, deamidated γS. It is concluded that surface deamidations, while causing minimal structural disruption individually, progressively destabilize crystallin proteins, leading to their unfolding and precipitation in aged and cataractous lenses.
Visualizing ultrastructural details of placental tissue with super-resolution structured illumination microscopy
Authors: Villegas-Hernández Luis E. , Nystad Mona , Ströhl Florian , Basnet Purusotam , Acharya Ganesh , Ahluwalia Balpreet S. 
Published: February 2020

AbstractSuper-resolution fluorescence microscopy is a widely employed technique in cell biology research, yet remains relatively unexplored in the field of histo-pathology. Here, we describe the sample preparation steps and acquisition parameters necessary to obtain fluorescent multicolor super-resolution structured illumination microscopy (SIM) images of both formalin-fixed paraffin-embedded and cryo-preserved placental tissue sections. We compare super-resolved images of chorionic villi against diffraction-limited deconvolution microscopy and demonstrate the significant contrast and resolution enhancement attainable with SIM. We show that SIM resolves ultrastructural details such as the syncytiotrophoblast’s microvilli brush border, which up until now has been only resolvable by electron microscopy.
WeChat, a Chinese social media, may early detect the SARS-CoV-2 outbreak in 2019
Authors: Wang Wenjun , Wang Yikai , Zhang Xin , Li Yaping , Jia Xiaoli , Dang Shuangsuo 
Published: February 2020

AbstractWe plotted daily data on the frequencies of keywords related to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from WeChat, a Chinese social media. Using “Feidian”, Chinese abbreviation for SARS, may detect the SARS-CoV-2 outbreak in 2019 two weeks earlier. WeChat offered a new approach to early detect disease outbreaks.