bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical Characteristics and Classification Criteria Performance in a Single-Center Cohort of 114 Patients With Immunoglobulin G4–Related Disease
Authors: Spandorfer Robert , Ahmad Madiha , Khosroshahi Arezou 
Published: July 2022

Introduction/Objectives
Immunoglobulin G4–related disease (IgG4-RD) is a heterogeneous fibroinflammatory condition. The 2019 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) Classification Criteria for IgG4-RD were published to provide unified classification criteria in clinical research. The purpose of this study was to characterize demographics, disease manifestations, and treatments of patients with IgG4-RD and assess performance of the Classification Criteria in a heterogeneous cohort with a large population of Black patients.

Methods
This was a medical records review of all patients referred to a specialized IgG4-RD clinic. Demographics, serology, histopathology, disease manifestations, and treatment information were collected and analyzed. An ACR/EULAR Classification Criteria score for IgG4-RD was calculated to compare performance in definite diagnosis, probable diagnosis, and mimicker groups.

Results
A total of 198 patients were evaluated. Eighty-five (43%) were mimickers. Of the remaining 114, 58 (51%) were classified as definite, and 56 (49%) as probable cases by treating clinicians. Pancreatitis was the most common presentation (37%) among 28 different organ manifestations of IgG4-RD. In patients with definite clinical diagnosis of IgG4-RD, 84% met the IgG4-RD Classification Criteria (i.e., score ≥20) with mean score of 29. Only 9% of the probable cases met this threshold with an average score of 8. None of the mimickers met the Classification Criteria.

Conclusions
This study highlights the broad spectrum of IgG4-RD and validates the use of the ACR/EULAR Classification Criteria for IgG4-RD, including a large proportion of Black patients. As shown in this study, IgG4-RD is a heterogeneous disease and continues to represent a diagnostic challenge to clinicians.
The roles of unrecognized monkeypox cases, contact isolation and vaccination in determining epidemic size in Belgium. A modelling study
Authors: Van Dijck Christophe , Hens Niel , Kenyon Chris , Tsoumanis Achilleas 
Published: July 2022

AbstractWe used a network model to simulate a monkeypox epidemic among men who have sex with men. Our findings suggest that unrecognized infections have an important impact on the epidemic, and that vaccination of individuals at highest risk of infection reduces epidemic size more than post-exposure vaccination of sexual partners.
Seroprevalence of anti-SARS-CoV-2 IgG antibodies in Tyrol, Austria: Updated analysis involving 22,607 blood donors covering the period October 2021 to April 2022
Authors: Seekircher Lisa , Siller Anita , Astl Manfred , Tschiderer Lena , Wachter Gregor A. , Pfeifer Bernhard , Huber Andreas , Gaber Manfred , Schennach Harald , Willeit Peter 
Published: July 2022

AbstractBackgroundBecause a large proportion of the Austrian population has been infected with SARS-CoV-2 during high incidence periods in winter 2021/2022, up-to-date estimates of seroprevalence of anti-SARS-CoV-2 antibodies are required to inform upcoming public health policies.MethodsWe quantified anti-Spike IgG antibody levels in 22,607 individuals that donated blood between October 2021 and April 2022 across Tyrol, Austria (participation rate: 96.0%).ResultsMedian age of participants was 45.3 years (IQR: 30.9-55.1); 41.9% were female. From October 2021 to April 2022, seropositivity increased from 84.9% (95% CI: 83.8–86.0%) to 95.8% (94.9–96.4%) and the geometric mean anti-Spike IgG levels among seropositive participants increased from 283 (95% CI: 271–296) to 1437 (1360–1518) BAU/mL. The percentages of participants in categories with undetectable levels, and detectable levels at <500, 500–<1000, 1000–<2000, 2000–<3000, and ≥3,000 BAU/mL were 15%, 54%, 15%, 10%, 3%, and 3% in October 2021 vs. 4%, 18%, 17%, 18%, 11%, and 32% in April 2022. Of 2711 participants that had repeat measurements taken a median 4.2 months apart, 61.8% moved to a higher, 13.9% to a lower, and 24.4% remained in the same category. Among seropositive participants, antibody levels were 16.8-fold in vaccinated individuals compared to unvaccinated individuals (95% CI: 14.2–19.9; p-value < 0.001).ConclusionAnti-SARS-CoV-2 seroprevalence in terms of seropositivity and average antibody levels has increased markedly during the winter 2021/2022 SARS-CoV-2 waves in Tyrol, Austria.
Cognitive training and remediation interventions for substance use disorders: A Delphi consensus study
Authors: Verdejo-Garcia Antonio , Rezapour Tara , Giddens Emily , Zonoozi Arash Khojasteh , Rafei Parnian , Berry Jamie , Caracuel Alfonso , Copersino Marc L. , Field Matt , Garland Eric L. , Lorenzetti Valentina , Malloy-Diniz Leandro , Manning Victoria , Marceau Ely M. , Pennington David L. , Strickland Justin , Wiers Reinout , Fairhead Rahia , Anderson Alexandra , Bell Morris , Boendermaker Wouter J. , Brooks Samantha , Bruno Raimondo , Campanella Salvatore , Cousijn Janna , Cox Miles , Dean Andrew C. , Ersche Karen D , Franken Ingmar , Froeliger Brett , Gamito Pedro , Gladwin Thomas E. , Goncalves Priscila D. , Houben Katrijn , Jacobus Joanna , Jones Andrew , Kaag Anne M. , Lindenmeyer Johannes , McGrath Elly , Nardo Talia , Oliveira Jorge , Pennington Charlotte R. , Perrykkad Kelsey , Piercy Hugh , Rupp Claudia I , Schulte Mieke H. J. , Squeglia Lindsay M. , Staiger Petra , Stein Dan J , Stein Jeff , Stein Maria , Stoops William W. , Sweeney Mary , Vo Hoa , Witkiewitz Katie , Woods Steven P , Yi Richard , Zhao Min , Ekhtiari Hamed 
Published: July 2022

AbstractBackground and AimsSubstance use disorders (SUD) are associated with cognitive deficits that are not always addressed in current treatments, and this hampers recovery. Cognitive training and remediation interventions are well suited to fill the gap for managing cognitive deficits in SUD. We aimed to reach consensus on recommendations for developing and applying these interventions.DesignDelphi approach with two sequential phases: survey development and iterative surveying of experts.SettingOnline study.ParticipantsDuring survey development, we engaged a group of 15 experts from a working group of the International Society of Addiction Medicine (Steering Committee). During the surveying process, we engaged a larger pool of experts (n=53) identified via recommendations from the Steering Committee and a systematic review.MeasurementsSurvey with 67 items covering four key areas of intervention development, i.e., targets, intervention approaches, active ingredients, and modes of delivery.FindingsAcross two iterative rounds (98% retention rate), the experts reached a consensus on 50 items including: (i) implicit biases, positive affect, arousal, executive functions, and social processing as key targets of interventions; (ii) cognitive bias modification, contingency management, emotion regulation training, and cognitive remediation as preferred approaches; (iii) practice, feedback, difficulty-titration, bias-modification, goal setting, strategy learning, and meta-awareness as active ingredients; and (iv) both addiction treatment workforce and specialized neuropsychologists facilitating delivery, together with novel digital-based delivery modalities.ConclusionsExpert recommendations on cognitive training and remediation for SUD highlight the relevance of targeting implicit biases, reward, emotion regulation, and higher-order cognitive skills via well-validated intervention approaches qualified with mechanistic techniques and flexible delivery options.
Indoor air pollutants and respiratory outcomes among residents of an informal urban setting in Uganda: a cross-sectional study
Authors: Wafula Solomon T. , Nalugya Aisha , Mendoza Hilbert , Kansiime Winnie K , Ssekamatte Tonny , Walekhwa Abel Wilson , Mugambe Richard K. , Walter Florian , Ssempebwa John C , Musoke David 
Published: July 2022

AbstractBackgroundIndoor air pollutants (IAP) such as particulate matter (PM) and carbon monoxide (CO) are a leading cause of acute respiratory symptoms, and long-term health impacts such as respiratory diseases, heart diseases and cancers. In Uganda, literature on the effects of IAP on respiratory outcomes in informal settlements is limited. This study investigated the association of selected IAPs and cooking fuels with respiratory symptoms among children and adults.MethodsThis study was conducted among 284 households in an informal settlement in Uganda from April to May 2022. Information on indoor air conditions, fuel type and adults reported the respiratory symptoms of their children as well as their respiratory symptoms within the previous 30 days. Same-day concentrations of PM less than 2.5 μm (PM2.5) and less than 10 μm(PM10) in diameter were monitored from 9 am to 2 pm using Temptop M2000c 2nd edition particle sensor while CO was measured using a carbon monoxide meter. Robust Poisson regression was used to model the associations between indoor air conditions, fuel type and respiratory health outcomes.ResultsApproximately 94.7% of the households were using biomass fuels. Cough (66.2%), shortness of breath (33.5%) and phlegm (17.6%) were common respiratory symptoms in adults while in children, morning cough (80.0%), day or night cough (34.4%) and shortness of breath (26.5%) were reported. The median PM2.5, PM10 and CO levels were 49.5(IQR= 31.1, 86.2) µg/m3, 73.6(IQR= 47.3,130.5) µg/m3 and 7.7(IQR= 4.1,12.5) ppm respectively. Increase in humidity was associated with higher levels of PM2.5 (ß = 2.74, p =0.004) and PM10 (ß= 4.14, p =0.002) however temperature increases were associated with lower levels of PM2.5 (ß = -11.72, p =0.009) and PM10 (ß= -16.36, p =0.008) but higher CO levels (ß=2.24, p = 0.032). Use of less polluting fuels such as electricity and gas were associated with low levels of PM2.5 (ß= -31.36, 95%CI =-60.7 – -2.02) while home dampness (ß = 3.39, 95%CI =0.07 – 6.72) was associated with higher indoor CO levels. Dampness was associated with acute phlegm in adults (PR= 2.78, 95%CI =1.57 – 4.90) and outdoor cooking was found to be associated with lower shortness of breath risk (PR = 0.60,95%CI =0.40 – 0.91).ConclusionThe prevalence of respiratory problems among adults and children was high. Poor indoor air conditions were associated with respiratory symptoms in adults and children. Efforts should be made to protect adults and children from the adverse effects of indoor air pollution.
Accurate prognosis for localized prostate cancer through coherent voting networks with multi-omic and clinical data
Authors: Pellegrini Marco 
Published: July 2022

ABSTRACTBackgroundProstate cancer is a very heterogeneous disease, from both a clinical and a biological/biochemical point of view, which makes the task of producing a stratification of patients into risk classes remarkably challenging. In particular, it is important an early detection and discrimination of the more indolent forms of the disease, from the more aggressive ones, requiring closer surveillance and timely treatment decisions.MethodsWe extend a recently developed supervised machine learning (ML) technique, called coherent voting networks (CVN) by incorporating novel model-selection technique to counter model overfitting. The CVN method is then applied to the problem of predicting an accurate prognosis (with a time granularity of 1 year) for patients affected by prostate cancer. The CVN is developed on a discovery cohort of 495 patients from the TCGA-PRAD collection, and validated on several other independent cohorts, comprising a gross total of 744 patients.FindingsWe uncover seven multi-gene fingerprints, each comprising six to seven genes, and a mixed clinical and genomic 5-marker fingerprint, that correspond to different input data types (clinical, mRNA expression, proteomic assays, methylation) and different time points, for the event of post-surgery progression-free survival (PFS) in patients diagnosed with prostate adenocarcinoma, who had not received prior treatment for their disease.With a mixed 5-marker genomic and clinical fingerprint comprising Gleason primary score, tumor stage, psa, and molecular protein expression levels for CDKN1B and NF2 we attain on three independent cohorts statistically significant AUC values of 0.85, 0.88, and 0.87 respectively for PFS prediction at 3 years.For purely genomic fingerprints, in seven independent cohorts for 21 combinations of cohort vs fingerprint, we report Odds Ratios ranging from a minimum of 9.0 and a maximum of 40.0, with average 17.5, geometric mean p-value 0.003; Cohen’s kappa values ranging from a minimum of 0.18 to a maximum of 0.65, with average 0.4; and AUC ranging from a minimum of 0.61 to a maximum of 0.88, with average 0.76, geometric mean p-value 0.001, for PFS prediction at 2, 3, and 4 years.Many of the genes in our fingerprint have recorded prognostic power in some form of cancer, and have been studied for their functional roles in cancer on animal models or cell lines.InterpretationThe development of novel ML techniques tailored to the problem of uncovering effective multi-gene prognostic biomarkers is a promising new line of attack for sharpening our capability to diversify and personalize cancer patient treatments. For the challenging problem of discriminating a fine time-scale for aggressive types of localized prostate cancer, we show that it is possible to attain more accurate prognostic predictions, with a granularity within a year, for the post-surgery early years.
Nardilysin-Regulated Scission Mechanism Activates Polo-like Kinase 3 to Suppress the Development of Pancreatic Cancer
Authors: Fu Jie , Ling Jianhua , Li Ching-Fei , Tsai Chi-Lin , Yin Wenjuan , Hou Junwei , Chen Ping , Cao Yu , Kang Ya’an , Sun Yichen , Xia Xianghou , Furukawa Kenei , Lu Yu , Wu Min , Huang Qian , Yao Jun , Hawke David H. , Pan Bih-Fang , Zhao Jun , Huang Jiaxing , Wang Huamin , Bahassi EI Mustapha , Stambrook Peter J. , Huang Peng , Fleming Jason B. , Maitra Anirban , Tainer John , Hung Mien-Chie , Chiao Paul J. 
Published: July 2022

ABSTRACTPancreatic ductal adenocarcinoma (PDAC) develops through step-wise genetic and molecular alterations including Kras mutation and inactivation of apoptotic pathways. Here, we find that development of anoikis resistance and metastasis of KrasG12D-driven PDAC in mice is accelerated by deleting Plk3, explaining the often reduced Plk3 expression in human PDAC. Importantly, a 41 kDa Plk3 (p41Plk3) that contained the entire kinase domain at the N-terminus (1-353 aa) is activated by scission of the precursor p72Plk3 at Arg354 by metalloendopeptidase Nardilysin (NRDC), and the resulting p32Plk3 C-terminal Polo-box domain (PBD) was quickly removed by proteasome degradation preventing the p41Plk3 inhibition by PBD. We found that p41Plk3 is the activated form of Plk3 that regulates a feedforward mechanism to promote anoikis and suppress PDAC and metastasis. p41Plk3 phosphorylates c-Fos on Thr164, which in turn, induces expression of Plk3 and pro-apoptotic genes. These findings uncovered an NRDC-regulated post-translational mechanism (PTM) that activates Plk3, establishing a prototypic regulation by scission mechanism.
LincRNA-Cox2 regulates smoke-induced inflammation in murine macrophages
Authors: Salih Mays Mohammed , Robinson Elektra Kantzari , Malekos Eric , Perez Elizabeth , Capili Allyson , Kim Kihwan , Zhang William Z. , Cloonan Suzanne M. , Carpenter Susan 
Published: July 2022

AbstractCigarette smoke (CS) exposure is a risk factor for many chronic diseases including chronic obstructive pulmonary disease (COPD), however the mechanism by which smoke exposure can alter homeostasis and bring about chronic inflammation is poorly understood. Here, we showcase a novel role for smoke in regulating long noncoding RNAs (lncRNAs), showing that it activates lincRNA-Cox2, which we previously characterized as functional in inflammatory regulation. Exposing lincRNA-Cox2 murine models to smoke in vivo confirmed lincRNA-Cox2 as a regulator of inflammatory gene expression in response to smoke both systemically and within the lung. We also report that lincRNA-Cox2 negatively regulates genes in smoked bone marrow derived macrophages exposed to LPS stimulation. In addition to the effects on lncRNAs, we also report dysregulated transcription and splicing of inflammatory protein-coding genes in the bone marrow niche following CS exposure in vivo. Collectively, this work provides insights into how innate immune signaling from gene expression to splicing is altered following in vivo exposure to CS and highlights an important new role for lincRNA-Cox2 in regulating immune genes following smoke exposure.
ArpC5 isoforms regulate Arp2/3 complex-dependent protrusion through differential Ena/VASP positioning
Authors: Fäßler Florian , Javoor Manjunath G , Datler Julia , Döring Hermann , Hofer Florian W , Dimchev Georgi , Hodirnau Victor-Valentin , Rottner Klemens , Schur Florian KM 
Published: July 2022

AbstractTight regulation of Arp2/3 complex is required to allow productive nucleation of force-generating, branched actin networks. An emerging aspect of regulation is the incorporation of subunit isoforms into Arp2/3 complex. Specifically, both isoforms of the ArpC5 subunit, ArpC5 and ArpC5L, have been reported to fine-tune nucleation activity and branch junction stability. Elevated levels of ArpC5 have also been linked to increased cancer progression and metastasis. Here, we have combined genetic engineering of cells and cellular structural biology to describe how ArpC5 and ArpC5L differentially regulate cell migration. They do so by defining the structural stability of ArpC1 in branch junctions and, in turn, by determining protrusion characteristics, protein dynamics, and actin network ultrastructure. ArpC5 isoforms also have an impact on the positioning of actin assembly factors from the Ena/VASP family, which act downstream of Arp2/3 complex-mediated nucleation. This suggests that ArpC5 and Ena/VASP proteins, both predictors for poor outcome in cancer, are part of a signaling pathway enhancing cell migration and, by inference, metastasis.
Bone marrow AdipoQ-lineage progenitors are a major cellular source of M-CSF that dominates bone marrow macrophage development, osteoclastogenesis and bone mass
Authors: Inoue Kazuki , Xia Yuhan , Qin Yongli , Jiang Jean X. , Greenblatt Matthew B. , Zhao Baohong 
Published: July 2022

AbstractM-CSF is a critical growth factor for myeloid lineage cells, including monocytes, macrophages and osteoclasts. Tissue resident macrophages in most organs rely on local M-CSF. However, it is unclear what specific cells in bone marrow produce M-CSF to maintain myeloid homeostasis. Here, we identify bone marrow AdipoQ-lineage progenitors, but not bone marrow mature adipocytes or peripheral adipose tissue, as a major cellular source of M-CSF, with these AdipoQ-lineage progenitors producing M-CSF at levels much higher than those produced by osteoblast lineage cells. Deficiency of M-CSF in bone marrow AdipoQ-lineage progenitors drastically reduces the generation of bone marrow macrophages and osteoclasts, leading to severe osteopetrosis in mice. Furthermore, the postmenopausal osteoporosis in a mouse model can be significantly alleviated by the lack of M-CSF in bone marrow AdipoQ-lineage progenitors. Our findings identify bone marrow AdipoQ-lineage progenitors as a major cellular source of M-CSF in bone marrow and reveal their crucial contribution to bone marrow macrophage development, osteoclastogenesis, bone homeostasis and pathological bone loss.
Unbiased identification of unknown cellular and environmental factors that mediate eQTLs using principal interaction component analysis
Authors: Vochteloo Martijn , Deelen Patrick , Vink Britt ,   BIOS Consortium, Tsai Ellen A. , Runz Heiko , Andreu-Sánchez Sergio , Fu Jingyuan , Zhernakova Alexandra , Westra Harm-Jan , Franke Lude 
Published: July 2022

AbstractExpression quantitative trait loci (eQTL) can reveal the regulatory mechanisms of trait associated variants. eQTLs are highly cell-type and context-specific, but often these contexts are unknown or not measured. Here, we introduce PICALO (Principal Interaction Component Analysis through Likelihood Optimization), an unbiased method to identify known and hidden contexts that influence eQTLs. PICALO uses expectation maximization to identify latent components, referred to as Principal Interaction Components (PIC), that interact with genotypes to maximize explained eQTL effect-sizes.We applied PICALO to bulk RNA-seq eQTL datasets in blood (n=2,932) and brain (n=2,440). We identify 31 PICs in blood, interacting with 4,169 (32%) unique cis-eQTLs (BH-FDR≤0.05). In brain, we identified 21 PICs, interacting with 4,058 (39%) unique cis-eQTLs (BH-FDR≤0.05). These PICs are associated with RNA quality, cell type composition or environmental influences. Furthermore, PICs clearly disentangle distinct eQTL contexts, for example technical from non-technical factors. Combined, 3,065 unique genes showed a cis-eQTL effect that is dependent on a cell type or other non-technical context, emphasizing the value of methods like PICALO. PICALO is robust, works well with heterogeneous datasets, yields reproducible interaction components, and identifies eQTL interactions and contexts that would have been missed when using cell counts or expression based principal components.Since PICALO allows for the identification of many context-dependent eQTLs without any prior knowledge of such contexts, this method can help to reveal and quantify the influence of previously unknown environmental factors that play a role in common diseases.
Cryo-electron tomography suggests tubulin chaperones form a subset of microtubule lumenal particles with a role in maintaining neuronal microtubules
Authors: Chakraborty Saikat , Martinez-Sanchez Antonio , Beck Florian , Toro-Nahuelpan Mauricio , Hwang In-Young , Noh Kyung-Min , Baumeister Wolfgang , Mahamid Julia 
Published: July 2022

AbstractThe functional architecture of the long-lived neuronal microtubule (MT) cytoskeleton is maintained by various MT-associated proteins (MAPs), most of which are known to bind to the MT outer surface. However, electron microscopy (EM) has long ago revealed the presence of particles inside the lumens of neuronal MTs, of yet unknown identity and function. Here, we use cryogenic electron tomography (cryo-ET) to analyze the three-dimensional (3D) structures and organizations of MT lumenal particles in primary hippocampal neurons, human induced pluripotent stem cell-derived neurons and pluripotent P19 cells. We obtain in-cell 3D maps of several lumenal particles from the respective cells and detect structural features that are common to all cell-types, underscoring their potential overarching functions. Mass spectrometry-based proteomics combined with structural modeling suggests a subset of lumenal particles could be tubulin-binding cofactors (TBCs) bound to tubulin monomers. A different subset of smaller particles, which remains unidentified, exhibits densities that bridge across the MT protofilaments. We show that increased lumenal particle concentration within MTs is concomitant with neuronal differentiation and correlates with higher MT curvatures. Enrichment of lumenal particles around MT lattice defects and at freshly polymerized MT open-ends suggest a MT protective role. Together with the identified structural resemblance of a subset of particles to TBCs, these results hint at a role in local tubulin proteostasis for the maintenance of long-lived neuronal MTs.