bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying the molecular drivers of ALS-implicated missense mutations
Authors: Portelli Stephanie , Albanaz Amanda , Pires Douglas Eduardo Valente , Ascher David Benjamin 
Published: September 2022

BackgroundAmyotrophic lateral sclerosis (ALS) is a progressively fatal, neurodegenerative disease associated with both motor and non-motor symptoms, including frontotemporal dementia. Approximately 10% of cases are genetically inherited (familial ALS), while the majority are sporadic. Mutations across a wide range of genes have been associated; however, the underlying molecular effects of these mutations and their relation to phenotypes remain poorly explored.MethodsWe initially curated an extensive list (n=1343) of missense mutations identified in the clinical literature, which spanned across 111 unique genes. Of these, mutations in genesSOD1,FUSandTDP43were analysed using in silico biophysical tools, which characterised changes in protein stability, interactions, localisation and function. The effects of pathogenic and non-pathogenic mutations within these genes were statistically compared to highlight underlying molecular drivers.ResultsCompared with previous ALS-dedicated databases, we have curated the most extensive missense mutation database to date and observed a twofold increase in unique implicated genes, and almost a threefold increase in the number of mutations. Our gene-specific analysis identified distinct molecular drivers across the different proteins, where SOD1 mutations primarily reduced protein stability and dimer formation, and those in FUS and TDP-43 were present within disordered regions, suggesting different mechanisms of aggregate formation.ConclusionUsing our three genes as case studies, we identified distinct insights which can drive further research to better understand ALS. The information curated in our database can serve as a resource for similar gene-specific analyses, further improving the current understanding of disease, crucial for the development of treatment strategies.
Artificial intelligence aneurysm measurement tool finds growth in all aneurysms that ruptured during conservative management
Authors: Sahlein Daniel H , Gibson Daniel , Scott John A , DeNardo Andrew , Amuluru Krishna , Payner Troy , Rosenbaum-Halevi David , Kulwin Charles 
Published: September 2022

BackgroundCerebral aneurysm rupture is associated with high rates of morbidity and mortality. Detecting aneurysms at high risk of rupture is critical in management decision making. Rupture risk has traditionally been associated with size—measured as a maximum dimension. However, aneurysms are morphologically dynamic, a characteristic ignored by large prospective aneurysm risk studies. Manual measurement is challenging and fraught with error. We used an artificial intelligence (AI) measurement tool to study aneurysms that ruptured during conservative management to detect changes in size not appreciated by manual linear measurement.MethodsA single practice database with >5000 aneurysms was queried. Patients followed conservatively for an unruptured aneurysm were identified using appropriate diagnosis codes. This cohort was screened for subsequent rupture using procedure codes. Only patients with two vascular imaging studies before rupture were included.ResultsFive patients met the criteria. All patients had aneurysm enlargement, two of which were not detected from manual linear measurements, including adjudication and analysis, during a multidisciplinary neurovascular conference in a high volume practice. Maximum dimension increased at a minimum of 1.8% (range 1.8–63.3%) from the first scan to the last, and aneurysm volume increased at a minimum of 5.9% (5.9–385.5%), highlighting the importance of volumetric measurement.ConclusionsAI-enabled volumetric measurements are more sensitive to changes in size and detected enlargement in all aneurysms that ruptured during conservative management. This finding has major implications for clinical practice and methods used for interval aneurysm measurement in patients being conservatively followed.
Early predictors of disability in paediatric multiple sclerosis: evidence from a multi-national registry
Authors: Sharmin Sifat , Malpas Charles B , Roos Izanne , Diouf Ibrahima , Alroughani Raed , Ozakbas Serkan , Izquierdo Guillermo , Eichau Sara , Horakova Dana , Havrdova Eva K , Patti Francesco , Terzi Murat , Boz Cavit , Yamout Bassem , Khoury Samia J , Onofrj Marco , Lugaresi Alessandra , Altintas Ayse , Prat Alexandre , Girard Marc , Duquette Pierre , Sá Maria José , La Spitaleri Daniele , Sidhom Youssef , Gouider Riadh , Mrabet Saloua , Soysal Aysun , Turkoglu Recai , Amato Maria Pia , Fragoso Yara D , Kalincik Tomas 
Published: September 2022

BackgroundEarly recognition of markers of faster disability worsening in paediatric-onset multiple sclerosis (MS) is a key requisite of personalised therapy for children with MS at the earliest possible time.ObjectiveTo identify early predictors of rapid disability accrual in patients with paediatric-onset MS.MethodsUsing the global MSBase registry, we identified patients who were <18 years old at the onset of MS symptoms. The clinico-demographic characteristics examined as predictors of future MS Severity Score (MSSS) included sex, age at symptom onset, absence of disability at the initial assessment, maximum Expanded Disability Status Scale (EDSS) score, relapse frequency and presence of brainstem, pyramidal, visual or cerebellar symptoms in the first year. A Bayesian log-normal generalised linear mixed model adjusted for cumulative proportion of time on higher-efficacy disease-modifying therapies (DMTs) was used to analyse the data.Results672 patients (70% female) contributing 9357 visits were included. The median age at symptom onset was 16 (quartiles 15–17) years. Older age at symptom onset (exp(β)=1.10 (95% CI 1.04 to 1.17)), higher EDSS score (1.22 (1.12 to 1.34)) and pyramidal (1.31 (1.11 to 1.55)), visual (1.25 (1.10 to 1.44)) or cerebellar (1.18 (1.01 to 1.38)) symptoms in the first year were associated with higher MSSS. MSSS was reduced by 4% for every 24% increase in the proportion of time on higher-efficacy DMTs (0.96 (0.93 to 0.99)).ConclusionsA relatively later onset of MS in childhood, higher disability and pyramidal, visual or cerebellar symptoms during the first year predicted significant worsening in disability in patients with paediatric-onset MS. Persistent treatment with higher-efficacy DMTs was associated with a reduced rate of disability worsening.
CD4+T-cell cooperation promoted pathogenic function of activated naïve B cells of patients with SLE
Authors: Wangriatisak Kittikorn , Kochayoo Piyawan , Thawornpan Pongsakorn , Leepiyasakulchai Chaniya , Suangtamai Thanitta , Ngamjanyaporn Pintip , Khowawisetsut Ladawan , Khaenam Prasong , Pisitkun Prapaporn , Chootong Patchanee 
Published: September 2022

ObjectiveTo explore cooperation between activated naïve (aNAV) B cells and CD4+T cells in the pathogenesis of SLE through autoantibody production, T-cell differentiation and inflammatory cytokine secretion.MethodsPeripheral blood mononuclear cell samples were obtained from 31 patients with SLE and used to characterise phenotype of aNAV B cells (n=14) and measured the phosphorylation of B-cell receptor (BCR) signalling molecules (n=5). Upregulation of T-cell costimulatory molecules after BCR and toll-like receptor (TLR)-7/TLR-8 stimulation was detected in cells from four subjects. To explore the role of these cells in SLE pathogenesis via T cell-dependent mechanisms, four subjects were analysed to detect the promotion of CD4+T-cell activation and antibody-secreting cell (ASC) differentiation after CD4+T-cell–B-cell cocultures. The aNAV B cells from four patients were used to assess cytokine secretion.ResultsThe aNAV B cells of patients with SLE had increased expression of surface CD40, HLA-DR and interleukin-21 receptor (IL-21R) and FCRL5 molecules. With BCR stimulation, these cells greatly increased PLCγ2 phosphorylation. Integrated BCR and TLR-7/TLR-8 signals induced overexpression of CD40, CD86, IL-21R and HLA-DR on lupus aNAV B cells. In T-cell–B-cell cocultures, lupus aNAV B cells (with upregulated costimulatory molecules) promoted CD4+T-cell proliferation and polarisation toward effector Th2and Th17cells. Importantly, in this coculture system, CD4+T-cell signals enhanced aNAV B-cell differentiation into auto-ASCs and produced anti-DNA antibodies. The interaction between CD4+T cell and aNAV B cell increased production of inflammatory cytokines (IL-6, IL-8 and IL-23).ConclusionCooperation between aNAV B cells and CD4+T cells contributed to SLE pathogenesis by promoting both differentiation of pathogenic T cells (Th2and Th17) and autoantibody secretion.
Prevalence of sarcopenia in patients with rheumatoid arthritis using the revised EWGSOP2 and the FNIH definition
Authors: Dietzel Roswitha , Wiegmann Sabine , Borucki Diana , Detzer Christian , Zeiner Kim Nikola , Schaumburg Désirée , Buehring Bjoern , Buttgereit Frank , Armbrecht Gabriele 
Published: September 2022

ObjectiveIn rheumatoid arthritis (RA), chronic inflammation can enhance the development of sarcopenia with a depletion of muscle mass, strength and performance. Currently, a consensus definition for sarcopenia and solid results for the prevalence of sarcopenia in patients with RA are lacking.MethodsIn this cross-sectional study, 289 patients ≥18 years with RA were recruited. Dual X-ray absorptiometry was performed to measure appendicular lean mass. Assessment of muscle function included grip strength, gait speed and chair rise time. Prevalence of sarcopenia was defined using the updated European Working Group on Sarcopenia in Older People (EWGSOP2) and the Foundation for the National Institutes of Health (FNIH) definition. In addition, the RA study population was compared with existing data of healthy controls (n=280).Results4.5% of patients (59.4±11.3 years) and 0.4% of controls (62.9±11.9 years) were affected by sarcopenia according to the EWGSOP2 definition. Body weight (OR 0.92, 95% CI 0.86 to 0.97), body mass index (BMI) (OR 0.70, 95% CI 0.57 to 0.87), C reactive protein (CRP) (OR 1.05, 95% CI 1.01 to 1.10), disease duration (OR 1.08, 95% CI 1.02 to 1.36), current medication with glucocorticoids (OR 5.25, 95% CI 2.14 to 24.18), cumulative dose of prednisone equivalent (OR 1.04, 95% CI 1.02 to 1.05) and Health Assessment Questionnaire (HAQ) (OR 2.50, 95% CI 1.27 to 4.86) were associated with sarcopenia in patients with RA. In contrast, the prevalence was 2.8% in patients compared with 0.7% in controls when applying the FNIH definition, and body height (OR 0.75, 95% CI 0.64 to 0.88), BMI (OR 1.20, 95% CI 1.02 to 1.41), CRP (OR 1.06, 95% CI 1.01 to 1.11) and HAQ (OR 2.77, 95% CI 1.17 to 6.59) were associated with sarcopenia.ConclusionSarcopenia is significantly more common in patients with RA compared with controls using the EWGSOP2 criteria. The FNIH definition revealed sarcopenia in individuals with high BMI and fat mass, regardless of the presence of RA.Trial registration numberIt was registered at the German Clinical Trials Registry (DRKS) as well as WHO Clinical Trials Registry (ICTRP) (DRKS00011873, registered on 16 March 2017).
Differentiation of malignant from benign pleural effusions based on artificial intelligence
Authors: Wang Sufei , Tan Xueyun , Li Piqiang , Fan Qianqian , Xia Hui , Tian Shan , Pan Feng , Zhan Na , Yu Rong , Zhang Liang , Duan Yanran , Xu Juanjuan , Ma Yanling , Chen Wenjuan , Li Yan , Zhao Zilin , Liu Chaoyang , Bao Qingjia , Yang Lian , Jin Yang 
Published: September 2022

IntroductionThis study aimed to construct artificial intelligence models based on thoracic CT images to perform segmentation and classification of benign pleural effusion (BPE) and malignant pleural effusion (MPE).MethodsA total of 918 patients with pleural effusion were initially included, with 607 randomly selected cases used as the training cohort and the other 311 as the internal testing cohort; another independent external testing cohort with 362 cases was used. We developed a pleural effusion segmentation model (M1) by combining 3D spatially weighted U-Net with 2D classical U-Net. Then, a classification model (M2) was built to identify BPE and MPE using a CT volume and its 3D pleural effusion mask as inputs.ResultsThe average Dice similarity coefficient, Jaccard coefficient, precision, sensitivity, Hausdorff distance 95% (HD95) and average surface distance indicators in M1 were 87.6±5.0%, 82.2±6.2%, 99.0±1.0%, 83.0±6.6%, 6.9±3.8 and 1.6±1.1, respectively, which were better than those of the 3D U-Net and 3D spatially weighted U-Net. Regarding M2, the area under the receiver operating characteristic curve, sensitivity and specificity obtained with volume concat masks as input were 0.842 (95% CI 0.801 to 0.878), 89.4% (95% CI 84.4% to 93.2%) and 65.1% (95% CI 57.3% to 72.3%) in the external testing cohort. These performance metrics were significantly improved compared with those for the other input patterns.ConclusionsWe applied a deep learning model to the segmentation of pleural effusions, and the model showed encouraging performance in the differential diagnosis of BPE and MPE.
Cyclic Testing of a Modified Pull-Out Suture Repair Technique for Flexor Digitorum Profundus Avulsion in a Turkey Foot Model
Authors: SINCLAIR Sonia , CLOUT Andrew , PELTZ Tim S. , PELLETIER Matthew , SCOUGALL Peter , WALSH William R. 
Published: September 2022

Background: Numerous repair techniques have been described for closed flexor digitorum profundus (FDP) avulsion. One option is a pull-out suture tied over the nail plate (Bunnell repair). We modified the Bunnell repair by incorporating a portion of the distal interphalangeal (DIP) joint volar plate into the repair to improve strength and reduce gapping. The aim of this study is to compare gap formation and load to failure between the Bunnell repair and our modification in a turkey foot model. Methods: Twenty-four fresh-frozen cadaveric turkey feet were divided into two repair groups namely the conventional Bunnell pull-out suture technique and the modified Bunnell pull-out suture technique, incorporating the middle-third of the DIP joint volar plate into the repair. Both repairs were carried out with 3-0 prolene suture and underwent ex-vivo cyclic loading at 2-12 n in a sinusoidal wave for 100 cycles to simulate a passive range of motion (ROM) protocol. Subsequently, specimens were loaded to failure at 12 mm/minute. Gap formation and load to failure were measured. Results: No repair ruptures occurred during cyclical testing. Mean gap formation was 9.2 mm (±1.49) in the Bunnell repair, and 3.5 mm (±1.19) in the modified Bunnell repair (p < 0.0001). The mean load to failure for the Bunnell repair was 35.4 n compared to 45 n for the modified repair (p = 0.0017). Conclusions: Gap formation was reduced and load to failure increased by augmenting the Bunnell pull-out suture repair with the central portion of the DIP joint volar plate.
Biomechanical Study of Asymmetric Flexor Tendon Repair Using a 6-Strand 4-0 Supramid Suture Versus a 4-Strand 2-0 Tenoflex Suture
Authors: CHUANG Xue Ling , LIM Qian Ru REBECCA , WONG Yoke Rung 
Published: September 2022

Background: Multi-strand repair of flexor tendons are important for increased strength but this may cause ischemia during the intrinsic healing process. In this study, we aim to compare the strength of the 4-strand modified Asymmetric repair using 2-0 Tenoflex® suture with the original description of the Asymmetric repair using a 6-strand 4-0 Supramid® suture under cyclic loading in a porcine tendon model. We hypothesise that the number of core sutures through the repair site can be reduced with advanced suture material. Methods: Two groups consisting of 10 porcine tendons each were repaired using the Asymmetric repair technique. One group underwent the original description using a 6-strand 4-0 Supramid® suture and the other group underwent a modified 4-strand technique using 2-0 Tenoflex® suture. The repaired tendons were subjected to a two-stage cyclic loading test. Survival rate and gap formation at the repaired site were analysed. The failure mechanism of each repair was also analysed. Additionally, the cross-sectional area of each strand of core suture used was also calculated. Results: The 1st and 2nd stage survival rates were 90% and 30% for the 6-strand repair and 100% and 60% for the 4-strand repair respectively. The mean gap formation at the end of stage 2 was 1.79 mm (SD 1.57) for the 4-strand repair, which is comparable to that of the 6-strand repair (1.82 mm; [SD 1.20]). The total mean cross-sectional area of 2-0 Tenoflex® and 4-0 Supramid® suture strands were 0.078 and 0.086 mm2, respectively. Conclusions: These results demonstrate that despite having fewer core sutures, the 4-strand modified Asymmetric repair using 2-0 Tenoflex® may be a better option as compared to the original 6-strand Asymmetric repair using 4-0 Supramid®.
Migration of Broken Kirschner Wire to the Brachial Plexus after Fixation of Fracture Dislocation of the Acromioclavicular Joint
Authors: GALLEGO PALMERO Claudia , DE LA RED GALLEGO Maria De los Angeles , VELEZ GARCIA Olga Maria , GUTIÉRREZ OLIVERA Natalia 
Published: September 2022

A complication of Kirschner (K) wire fixation is the migration of the wire. We report a patient who had undergone fixation of a right clavicle fracture associated with acromioclavicular joint (ACJ) dislocation 15 years ago. He presented with features of pain and dysaesthesia in the right ulnar nerve dermatome on the movement of the neck and shoulder. Radiographic investigations showed a broken K-wire that had migrated to the lower brachial plexus. He underwent surgical removal of the K-wire and recovered uneventfully. We summarise the literature on K-wire migration reported following clavicle and ACJ injuries. Level of Evidence: Level V (Therapeutic)
Canadian Arctic Prograded Margin Tectono-Sedimentary Element, SE Canada Basin
Authors: Embry Ashton , Ricketts Brian , Stephenson Randell 
Published: September 2022

Abstract
The Canadian Arctic Prograded Margin Tectono-Stratigraphic Element (TSE) is located on the continental shelf and slope, which lie to the NW of the Canadian Arctic Archipelago. The TSE comprises a post-rift succession deposited on the eastern margin of the Amerasia Basin, and the strata range in age from Late Cretaceous to Pleistocene. Over much of the TSE, a major unconformity marks the base of the succession, and the underlying strata vary from Jurassic to Lower Cretaceous strata of the Canadian Arctic Rift Margin TSE to older Upper Paleozoic–Triassic strata of the Sverdrup Basin Composite Tectono-Sedimentary Element. Sparse reflection and refraction seismic data indicate that the succession can be more than 10 km thick. The TSE is divided into three structural domains with deformation increasing to the NE. The Southern Domain is extensional and is characterized by listric growth faults with rollover anticlines and tilted fault blocks. The pre-Oligocene portion of the Central Domain is deformed by broad folds with extensional faults in the younger strata. The pre-Oligocene succession in the Northern Domain is likely to be strongly folded and cut by thrust faults of the Eurekan Orogeny with extrusive and intrusive igneous rocks occurring in the Upper Cretaceous strata. Petroleum source rocks, as well as abundant reservoir and seal strata, occur throughout the TSE, indicating good potential for the presence of petroleum resources. The remote and environmentally sensitive location of the TSE, however, makes it likely that it will never be a target for petroleum exploration.
PAV-SOD: A New Task towards Panoramic Audiovisual Saliency Detection
Authors: Zhang Yi , Chao Fang-Yi , Hamidouche Wassim , Deforges Olivier 
Published: September 2022

Object-level audiovisual saliency detection in 360° panoramic real-life dynamic scenes is important for exploring and modeling human perception in immersive environments, also for aiding the development of virtual, augmented, and mixed reality applications in fields such as education, social network, entertainment, and training. To this end, we propose a new task,
p
anoramic
a
udio
v
isual
s
alient
o
bject
d
etection, (

PAV-SOD

1

), which aims to segment the objects grasping most of the human attention in 360° panoramic videos reflecting real-life daily scenes. To support the task, we collect

PAVS10K

, the first
p
anoramic video dataset for
a
udio
v
isual
s
alient object detection, which consists of 67 4K-resolution equirectangular videos with per-video labels including hierarchical scene categories and associated attributes depicting specific challenges for conducting
PAV-SOD
, and 10,465 uniformly sampled video frames with manually annotated object-level and instance-level pixel-wise masks. The coarse-to-fine annotations enable multi-perspective analysis regarding
PAV-SOD
modeling. We further systematically benchmark 13 state-of-the-art salient object detection (SOD)/video object segmentation (VOS) methods based on our
PAVS10K
. Besides, we propose a new baseline network, which takes advantage of both visual and audio cues of 360° video frames by using a new conditional variational auto-encoder (CVAE). Our
C
VAE-based
a
udio
v
isual
net
work, namely,

CAV-Net

, consists of a spatial-temporal visual segmentation network, a convolutional audio-encoding network, and audiovisual distribution estimation modules. As a result, our
CAV-Net
outperforms all competing models and is able to estimate the aleatoric uncertainties within
PAVS10K
. With extensive experimental results, we gain several findings about
PAV-SOD
challenges and insights towards
PAV-SOD
model interpretability. We hope that our work could serve as a starting point for advancing SOD towards immersive media.