bluuebunny/crossref_metadata_2025_split huggingface dataset:
Which inflamed tissues explain a positive metatarsophalangeal squeeze test? A large imaging study to clarify a common diagnostic procedure
Authors: van Dijk Bastiaan T , Dakkak Yousra J , Krijbolder Doortje I , (Jendé) van Zeben D , Tchetverikov Ilja , Reijnierse Monique , van der Helm-van Mil Annette H M 
Published: January 2022

Abstract

Objectives
The squeeze test of MTP joints is frequently used because it is easy and cheap. It is traditionally perceived as a test for synovitis. Besides classic intra-articular synovitis, also tenosynovitis and intermetatarsal bursitis (IMB) represent synovial inflammation, albeit juxta-articularly located. Both are frequently present in RA and occasionally in other arthritides. Therefore we hypothesized that tenosynovitis and IMB contribute to a positive MTP squeeze test.

Methods
A cross-sectional study design was used. A total of 192 early arthritis patients and 693 clinically suspect arthralgia patients underwent the MTP squeeze test and forefoot MRI at first presentation. MRI measurements in age-matched healthy controls were used to define positivity for synovitis, tenosynovitis and IMB. Logistic regression was used.

Results
In early arthritis patients, synovitis [odds ratio (OR) 4.8 (95% CI 2.5, 9.5)], tenosynovitis [2.4 (1.2, 4.7)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity. Synovitis [OR 3.2 (95% CI 1.4, 7.2)] and IMB [3.9 (1.7, 8.8)] remained associated in multivariable analyses. Of patients with a positive MTP squeeze test, 79% had synovitis or IMB: 12% synovitis, 15% IMB and 52% both synovitis and IMB. In clinically suspect arthralgia patients, subclinical synovitis [OR 3.0 (95% CI 2.0, 4.7)], tenosynovitis [2.7 (1.6, 4.6)] and IMB [1.7 (1.2, 2.6)] associated with MTP squeeze test positivity, with the strongest association for synovitis in multivariable analysis. Of positive MTP squeeze tests, 39% had synovitis or IMB (10% synovitis, 15% IMB and 13% both synovitis and IMB).

Conclusion
Besides synovitis, IMB contributes to pain upon compression in early arthritis, presumably due to its location between MTP joints. This is the first evidence showing that MTP squeeze test positivity is not only explained by intra- but also juxta-articular inflammation.
Causes of Injury and Litigation in Cutaneous Laser Surgery: An Update From 2012 to 2020
Authors: Khalifian Saami , Vazirnia Aria , Mohan Girish C. , Thompson Kaitlyn V. , Jalian Hrak Ray , Avram Mathew M. 
Published: January 2022

OBJECTIVE
To identify common causes of injury and liability claims related to cutaneous laser surgery from 2012 to 2020.

MATERIALS AND METHODS
Search of online national legal database of public legal documents regarding cutaneous laser surgery litigation.

RESULTS
From 2012 to 2020, 69 cases of liability claims due to a cutaneous laser surgery device were identified. Of these, 49 (71%) involved a nonphysician operator (NPO); 12 incidents (17%) involved non–core physician operators performing the procedure; 6 cases (9%) involved a plastic surgeon operator; and 2 cases (3%) involved a dermatologist operator. Laser hair removal was most litigated (44 cases, 64%), followed by laser skin rejuvenation (20 cases, 30%). Thirty-six of 69 cases had a discernible outcome, 53% (n = 19) rendered judgements in favor of the plaintiff, with a mean indemnity payment of $320,975 (range, $1,665–$1.5 million).

CONCLUSION
Previous work evaluating trends in laser surgery litigation from 1985 to 2012 identified increasing injury and legal action when performed by NPOs. Data from this study are consistent with these previous findings. Both studies demonstrate that NPOs account for most cases of legal action with an increasing proportion of cases being performed by NPOs. In this study, unsupervised NPOs comprise nearly three-quarters of laser surgery lawsuits, but the data may underestimate the frequency of injury and litigation caused by unsupervised NPOs.
Impaired antibody response to COVID-19 vaccination in advanced HIV infection
Authors: Hassold Nolan , Brichler Ségolène , Ouedraogo Elise , Leclerc Delphine , Carroue Sophie , Gater Yamina , Alloui Chakib , Carbonnelle Etienne , Bouchaud Olivier , Mechai Frederic , Cordel Hugues , Delagreverie Heloise 
Published: January 2022

Objectives:
Coronavirus disease 2019 (COVID-19) vaccination is reportedly efficient in people with HIV (PWH) but vaccine trials included participants with normal CD4+ T-cell counts. We analyzed seroconversion rates and antibody titers following two-dose vaccination in PWH with impaired CD4+ T-cell counts.

Methods:
We collected retrospective postvaccination SARS-COV-2 serology results available in a university hospital for PWH vaccinated between March and September, 2021 who were tested for antispike antibodies from 8 to 150 days following dose 2. Antibody titers were compared in PWH with CD4+ T-cell count less than 200 cells/μl, 200 < CD4+ T-cell counts < 500 cells/μl and CD4+ T-cell count greater than 500 cells/μl at vaccination.

Results:
One hundred and five PWH were included: n = 54 in the CD4+ T-cell count less than 500 cells/μl group (n = 18 with CD4+ <200 cells/μl, n = 36 with 200 < CD4+ < 500 cells/μl) and 51 in the CD4+ T-cell count greater than 500 cells/μl group. They received two doses of BNT162b2 (75%), mRNA-1273 (8.5%), or ChAdOx1 nCoV-19 (16.5%). The median time from vaccine dose 2 to serology was consistent across all groups (73 days, interquartile range [29–97], P = 0.14). Seroconversion rates were 100% in the CD4+ T-cell count greater than 500 cells/μl group but 89% in participants with CD4+ T-cell counts less than 500 cells/μl (22 and 5.5% seronegative in the CD4+ T-cell counts <200 cells/μl and 200 < CD4+ < 500 cells/μl groups, respectively). Median antibody titers were 623.8 BAU/ml [262.2–2288] in the CD4+ greater than 500 cells/μl group versus 334.3 BAU/ml [69.9–933.9] in the CD4+ less than 500 cells/μl group (P = 0.003). They were lowest in the CD4+ less than 200 cells/μl group: 247.9 BAU/ml [5.88–434.9] (P = 0.0017) with only 44% achieving antibody titers above the putative protection threshold of 260 BAU/ml.

Conclusion:
PWH with CD4+ T-cell counts less than 500 cells/μl and notably less than 200 cells/μl had significantly lower seroconversion rates and antispike antibody titers compared with PWH with CD4+ T-cell counts greater than 500 cells/μl, warranting the consideration of targeted vaccine strategies in this fragile population.
Prevalence of nonalcoholic fatty liver disease using noninvasive techniques among children, adolescents, and youths living with HIV
Authors: Carrasco Itzíar , Olveira Antonio , Lancharro Ángel , Escosa Luis , Mellado María José , Busca Carmen , Montes María Luisa , Díez Cristina , Alcolea-Ruiz Sonia , Navarro María Luisa , Sainz Talía 
Published: January 2022

Objective:
The prevalence of subclinical liver abnormalities is high among people with HIV, but data regarding perinatally HIV-infected children and adolescents (PHIV) are scarce. Noninvasive image techniques offer an opportunity to address nonalcoholic fatty liver disease (NAFLD) in a population in which the scores validated for adults have not been tested.

Design:
Prospective cross-sectional study including PHIV and uninfected controls.

Methods:
Noninvasive imaging techniques for the diagnosis of NAFLD and/or fibrosis were performed, and four scores to predict NAFLD were evaluated.

Results:
Seventy-six participants (59.2% women) with a median of 19 years old (interquartile range: 15.5–25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; P = 0.02) by noninvasive imaging techniques. The performance of scores based on clinical and analytical parameters was very poor. Although nonsignificant, overweight was more common among participants with NAFLD, who had a significantly higher BMI. Differences in HIV-related parameters between the groups were nonsignificant, except for the CD4+/CD8+ T-cells ratio, decreased among PHIV diagnosed with NAFLD (P = 0.04).

Conclusions:
The prevalence of NAFLD was high (28.9%) among PHIV, and only partially explained by overweight and metabolic syndrome defining factors. The scores based on clinical and analytical parameters did not accurately identify participants at risk. Therefore, liver ultrasound assessment should be considered for the screening of NAFLD among PHIV in routine clinical practice.
Effects of Aging on Metabolic Characteristics of Human B Cells
Authors: Frasca Daniela , Pallikkuth Suresh , Pahwa Savita 
Published: January 2022

Abstract:
Metabolic changes represent the most common sign of aging and lead to increased risk of developing diseases typical of old age. Age-associated metabolic changes, such as decreased insulin sensitivity, decreased mitochondrial function, and dysregulated nutrient uptake, fuel the low-grade chronic systemic inflammation, known as inflammaging, a leading cause of morbidity and mortality, linked to the development of several diseases of old age. How aging affects the metabolic phenotype of immune cells, and B cells in particular, is not well known and is under intensive investigation by several groups. In this study, we summarized the few published results linking intrinsic B-cell metabolism and B-cell function in different groups of young and elderly individuals: healthy, with type-2 diabetes mellitus, or with HIV infection. Although preliminary, these results suggest the intriguing possibility that metabolic pathways can represent potential novel therapeutic targets to reduce inflammaging and improve humoral immunity.
Diabetic foot ulcer risk assessment and prevention in patients with diabetes: a best practice implementation project
Authors: Yang Lixiao , Wu Yanni , Zhou Chunlan , Xie Cuihua , Jiang Ya , Wang Run , Ye Xiaoling 
Published: January 2022

ABSTRACT

Introduction and aim:
Diabetic foot ulcer (DFU) is one of the most serious complications in patients with diabetes. Early identification of risk factors can prevent its occurrence and delay its progression. The aim of this project is to conduct an audit of DFU risk assessment protocols at a large tertiary hospital and evaluate the impact of any changes in compliance with the developed evidence-based best practice criteria.

Methods:
Preimplementation and postimplementation audits based on JBI's Practical Application of Clinical Evidence System were conducted at the Department of Endocrinology and Metabolism of a tertiary hospital in China. The Getting Research into Practice audit tool was used to analyze the barriers and inadequacies encountered in practice. A total of 12 nurses and 30 patients with diabetes were included in the baseline and follow-up audits.

Results:
There were 15 baseline audits that indicated deficits in DFU risk assessment by nurses, with 0% compliance for three criteria and 50% compliance or less for seven others. Strategies developed by the project team to address the identified barriers to compliance were adopted, leading to significant improvement in compliance with most criteria at the follow-up audit compared with baseline with 11 criteria achieving at least 90% compliance.

Conclusion:
The project showed that regular audits of foot ulcer risk assessment can help to identify barriers to their implementation. Advising patients of their risk status can support appropriate self-care practices. Further audits are needed to implement evidence-based practices in all aspects of diabetes patient care.
Germline predisposition to pediatric Ewing sarcoma is uniquely characterized by inherited pathogenic variants in DNA damage repair genes
Authors: Gillani Riaz , Camp Sabrina Y. , Han Seunghun , Jones Jill K. , O’Brien Schuyler , Young Erin L. , Hayes Lucy , Mitchell Gareth , Fowler Trent , Gusev Alexander , Kamihara Junne , Janeway Katherine A. , Schiffman Joshua D. , Crompton Brian D. , AlDubayan Saud H. , Van Allen Eliezer M. 
Published: January 2022

AbstractMore knowledge is needed around the role and importance of specific genes in germline predisposition to Ewing sarcoma to inform biological investigation and clinical practice. In this study, we evaluated the enrichment of pathogenic germline variants in Ewing sarcoma relative to other pediatric sarcoma subtypes, as well as patterns of inheritance of these variants. We carried out an ancestry-matched case-control analysis to screen for enrichment of pathogenic germline variants in 141 established cancer predisposition genes in 1138 individuals with pediatric sarcoma diagnoses (222 Ewing sarcoma cases) relative to identically processed cancer-free controls. Findings in Ewing sarcoma were validated with an additional cohort of 425 individuals, and 301 Ewing sarcoma parent-proband trios were analyzed for inheritance patterns of identified pathogenic variants. A distinct pattern of pathogenic germline variants was seen in Ewing sarcoma relative to other sarcoma subtypes.FANCCwas the only gene with an enrichment signal for heterozygous pathogenic variants in the discovery Ewing sarcoma cohort (OR 14.4, 95% CI 3.5 – 51.2, p = 0.002, FDR = 0.28). This enrichment inFANCCheterozygous pathogenic variants was seen again in the Ewing sarcoma validation cohort (OR 5.1, 95% CI 1.2 – 18.5, p = 0.03, single hypothesis), representing a broader importance of genes involved in DNA damage repair, which were also nominally enriched in Ewing sarcoma cases. Pathogenic variants in DNA damage repair genes were acquired through autosomal inheritance. Our study provides new insight into germline risk factors contributing to Ewing sarcoma pathogenesis.
Oncogenic role of a developmentally regulatedNTRK2splice variant
Authors: Pattwell Siobhan S. , Arora Sonali , Nuechterlein Nicholas , Zager Michael , Loeb Keith R. , Cimino Patrick J. , Holland Nikolas C. , Reche-Ley Noemi , Bolouri Hamid , Almiron Bonnin Damian A. , Szulzewsky Frank , Phadnis Vaishnavi V. , Ozawa Tatsuya , Wagner Michael J. , Haffner Michael C. , Cao Junyue , Shendure Jay , Holland Eric C. 
Published: January 2022

AbstractTemporally-regulated alternative splicing choices are vital for proper development yet the wrong splice choice may be detrimental. Here we highlight a novel role for the neurotrophin receptor splice variant TrkB.T1 in neurodevelopment, embryogenesis, transformation, and oncogenesis across multiple tumor types in both humans and mice. TrkB.T1 is the predominantNTRK2isoform across embryonic organogenesis and forced over-expression of this embryonic pattern causes multiple solid and nonsolid tumors in mice in the context of tumor suppressor loss. TrkB.T1 also emerges the predominantNTRKisoform expressed in a wide range of adult and pediatric tumors, including those harboring TRK fusions. Affinity purification-mass spectrometry (AP-MS) proteomic analysis reveals TrkB.T1 has distinct interactors with known developmental and oncogenic signaling pathways such as Wnt, TGF-ß, Hedgehog, and Ras. From alterations in splicing factors to changes in gene expression, the discovery of isoform specific oncogenes with embryonic ancestry has the potential to shape the way we think about developmental systems and oncology.
The transcriptomic signature of physiological trade-offs caused by larval overcrowding in Drosophila melanogaster
Authors: Morimoto Juliano , Derous Davina , Wenzel Marius , Henry Youn , Colinet Hervé 
Published: January 2022

AbstractIntraspecific competition at the larval stage is an important ecological factor affecting life-history, adaptation and evolutionary trajectory in holometabolous insects. However, the molecular pathways and physiological trade-offs underpinning these ecological processes are poorly characterised. We reared Drosophila melanogaster at three egg densities (5, 60 and 300 eggs/ml) and sequenced the transcriptomes of pooled third-instar larvae. We also examined emergence time, egg-to-adult viability, adult mass and adult sex-ratio at each density. Medium crowding had minor detrimental effects on adult phenotypes compared to low density and yielded 24 differentially expressed genes (DEGs) including several chitinase enzymes. In contrast, high crowding had substantial detrimental effects on adult phenotypes and yielded 2107 DEGs. Among these, upregulated gene sets were enriched in sugar, steroid and amino acid metabolism as well as DNA replication pathways, whereas downregulated gene sets were enriched in ABC transporters, Taurine, Toll/Imd signalling and P450 xenobiotics metabolism pathways. Overall, our findings show that larval overcrowding has a large consistent effect on several molecular pathways (i.e., core responses) with few pathways displaying density-specific regulation (i.e., idiosyncratic responses). This provides important insights into how holometabolous insects respond to intraspecific competition during development.
Evaluation of an optimized protocol and Illumina ARTIC V4 primer pool for sequencing of SARS-CoV-2 using COVIDSeq™ and DRAGEN™ COVID Lineage App workflow
Authors: Clark Cyndi R. , Hardison Matthew T. , Houdeshell Holly N. , Vest Alec C. , Whitlock Darcy A. , Skola Dylan D. , Koble Jeffrey S. , Oberholzer Michael , Schroth Gary P. 
Published: January 2022

AbstractNext-Generation Sequencing based genomic surveillance has been widely implemented for identification and tracking of emerging SARS-CoV-2 variants to guide the Public Health response to the COVID-19 pandemic. Amplicon-based assays, such as the Illumina® COVIDSeq™ Test (RUO) and COVIDSeq Assay (RUO), enable scalable sequencing of SARS-CoV-2, leveraging V3 and V4 primer designs from the ARTIC community and DRAGEN™ COVID Lineage App analysis available on Illumina BaseSpace™. We report here a comparison of COVIDSeq performance for SARS-CoV-2 genome reporting using the ARTIC V3 based primer pool (including primers for human control genes) that is provided with the COVIDSeq kit versus the ARTIC V4 based Illumina COVIDSeq V4 primer pool, using an optimized protocol and DRAGEN COVID Lineage App analysis. The data indicates that both primer pools enable robust reporting of SARS-CoV-2 variants. The Illumina COVIDSeq V4 primer pool has superior performance for SARS-CoV-2 genome reporting, particularly in samples with low virus load, and is therefore the recommended primer pool for genomic surveillance of SARS-CoV-2 for research use using COVIDSeq.
A graph-embedded topic model enables characterization of diverse pain phenotypes among UK Biobank individuals
Authors: Wang Yuening , Benavides Rodrigo , Diatchenko Luda , Grant Audrey V. , Li Yue 
Published: January 2022

SUMMARYLarge biobank repositories of clinical conditions and medications data open opportunities to investigate the phenotypic disease network. To enable systematic investigation of entire structured phenomes, we present graph embedded topic model (GETM). Our contributions are two folds in terms of method and applications. On the methodology side, we offer two main contributions in GETM. First, to aid topic inference, we integrate existing biomedical knowledge graph information in the form of pre-trained graph embedding into the embedded topic model. Second, leveraging deep learning techniques, we developed a variational autoencoder framework to infer patient phenotypic mixture by modeling multi-modal discrete patient medical records. In particular, for interpretability, we use a linear decoder to simultaneously infer the bi-modal distributions of the disease conditions and medications. On the application side, we applied GETM to UK Biobank (UKB) self-reported clinical phenotype data, which contains 443 self-reported medical conditions and 802 self-reported medications for 457,461 individuals. Compared to existing methods, GETM demonstrates overall superior performance in imputing missing conditions and medications. Here, we focused on characterizing pain phenotypes recorded in the questionnaire of the UKB individuals. GETM accurately predicts the status of chronic musculoskeletal (CMK) pain, chronic pain by body-site, and non-specific chronic pain using past conditions and medications. Our analyses revealed not only the known pain-related topics but also the surprising predominance of medications and conditions in the cardiovascular category among the most predictive topics across chronic pain phenotypes.
Quantifying biological carbon pump pathways with a data-constrained mechanistic model ensemble approach
Authors: Stukel Michael R. , Décima Moira , Landry Michael R. 
Published: January 2022

AbstractThe ability to constrain the mechanisms that transport organic carbon into the deep ocean is complicated by the multiple physical, chemical, and ecological processes that intersect to create, transform, and transport particles in the ocean. In this manuscript we develop and parameterize a data-assimilative model of the multiple pathways of the biological carbon pump (NEMUROBCP). The mechanistic model is designed to represent sinking particle flux, active transport by vertically migrating zooplankton, and passive transport by subduction and vertical mixing, while also explicitly representing multiple biological and chemical properties measured directly in the field (including nutrients, phytoplankton and zooplankton taxa, carbon dioxide and oxygen, nitrogen isotopes, and 234Thorium). Using 30 different data types (including standing stock and rate measurements related to nutrients, phytoplankton, zooplankton, and non-living organic matter) from Lagrangian experiments conducted on 11 cruises from four ocean regions, we conduct an objective statistical parameterization of the model and generate one million different potential parameter sets that are used for ensemble model simulations. The model simulates in situ parameters that were assimilated (net primary production and gravitational particle flux) and parameters that were withheld (234Thorium and nitrogen isotopes) with reasonable accuracy. Model results show that gravitational flux of sinking particles and vertical mixing of organic matter from the surface ocean are more important biological pump pathways than active transport by vertically-migrating zooplankton. However, these processes are regionally variable, with sinking particles most important in oligotrophic areas of the Gulf of Mexico and California, sinking particles and vertical mixing roughly equivalent in productive regions of the CCE and the subtropical front in the Southern Ocean, and active transport an important contributor in the Eastern Tropical Pacific. We further find that mortality at depth is an important component of active transport when mesozooplankton biomasses are high, but that it is negligible in regions with low mesozooplankton biomass. Our results also highlight the high degree of uncertainty, particularly amongst mesozooplankton functional groups, that is derived from uncertainty in model parameters, with important implications from results that rely on non-ensemble model outputs. We also discuss the implications of our results for other data assimilation approaches.