bluuebunny/crossref_metadata_2025_split huggingface dataset:
Novel variants in CSF1R associated with adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP)
Authors: Schmitz Anne S. , Raju Janani , Köhler Wolfgang , Klebe Stephan , Cheheb Khaled , Reschke Franziska , Biskup Saskia , Haack Tobias B. , Roeben Benjamin , Kellner Melanie , Rahner Nils , Bloch Thomas , Lemke Johannes , Bender Benjamin , Schöls Ludger , Hengel Holger , Hayer Stefanie N. 
Published: July 2024

AbstractThe CSF1R gene, located on chromosome 5, encodes a 108 kDa protein and plays a critical role in regulating myeloid cell function. Mutations in CSF1R have been identified as a cause of a rare white matter disease called adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP, also known as CSF1R-related leukoencephalopathy), characterized by progressive neurological dysfunction. This study aimed to broaden the genetic basis of ALSP by identifying novel CSF1R variants in patients with characteristic clinical and imaging features of ALSP. Genetic analysis was performed through whole-exome sequencing or panel analysis for leukodystrophy genes. Variant annotation and classification were conducted using computational tools, and the identified variants were categorized following the recommendations of the American College of Medical Genetics and Genomics (ACMG). To assess the evolutionary conservation of the novel variants within the CSF1R protein, amino acid sequences were compared across different species. The study identified six previously unreported CSF1R variants (c.2384G>T, c.2133_2919del, c.1837G>A, c.2304C>A, c.2517G>T, c.2642C>T) in seven patients with ALSP, contributing to the expanding knowledge of the genetic diversity underlying this rare disease. The analysis revealed considerable genetic and clinical heterogeneity among these patients. The findings emphasize the need for a comprehensive understanding of the genetic basis of rare diseases like ALSP and underscored the importance of genetic testing, even in cases with no family history of the disease. The study’s contribution to the growing spectrum of ALSP genetics and phenotypes enhances our knowledge of this condition, which can be crucial for both diagnosis and potential future treatments.
Remeshing and eigenvalue stabilization in the finite cell method for structures undergoing large elastoplastic deformations
Authors: Sartorti Roman , Garhuom Wadhah , Düster Alexander 
Published: July 2024

AbstractLarge strain analysis is a challenging task, especially in fictitious or immersed boundary domain methods, since badly broken elements/cells can lead to an ill-conditioned global tangent stiffness matrix, resulting in convergence problems of the incremental/iterative solution approach. In this work, the finite cell method is employed as a fictitious domain approach, in conjunction with an eigenvalue stabilization technique, to ensure the stability of the solution procedure. Additionally, a remeshing strategy is applied to accommodate highly deformed configurations of the geometry. Radial basis functions and inverse distance weighting interpolation schemes are utilized to map the displacement gradient and internal variables between the old and new meshes during the remeshing process. For the first time, we demonstrate the effectiveness of the remeshing approach using various numerical examples in the context of finite strain elastoplasticity.
The role of pathologists in the diagnosis of occupational lung diseases: an expert opinion of the European Society of Pathology Pulmonary Pathology Working Group
Authors: Calabrese Fiorella , Montero-Fernandez M. Angeles , Kern Izidor , Pezzuto Federica , Lunardi Francesca , Hofman Paul , Berezowska Sabina , Attanoos Richard , Burke Louise , Mason Paola , Balestro Elisabetta , Molina Molina Maria , Giraudo Chiara , Prosch Helmut , Brcic Luka , Galateau-Salle Francoise 
Published: July 2024

AbstractOccupational lung/thoracic diseases are a major global public health issue. They comprise a diverse spectrum of health conditions with complex pathology, most of which arise following chronic heavy workplace exposures to various mineral dusts, metal fumes, or following inhaled organic particulate reactions. Many occupational lung diseases could become irreversible; thus accurate diagnosis is mandatory to minimize dust exposure and consequently reduce damage to the respiratory system. Lung biopsy is usually required when exposure history is inconsistent with imaging, in case of unusual or new exposures, in case of unexpected malignancy, and in cases in which there are claims for personal injury and legal compensation. In this paper, we provide an overview of the most frequent occupational lung diseases with a focus on pathological diagnosis. This is a paper that summarizes the expert opinion from a group of European pathologists, together with contributions from other specialists who are crucial for the diagnosis and management of these diseases. Indeed, tight collaboration of all specialists involved in the workup is mandatory as many occupational lung diseases are misdiagnosed or go unrecognized. This document provides a guide for pathologists in practice to facilitate the accurate diagnosis of occupational lung disease. The review article reports relevant topics discussed during an educational course held by expert pathologists, active members of the Pulmonary Pathology Working Group of the European Society of Pathology. The course was endorsed by the University of Padova as a “winter school” (selected project in the call for “Shaping a World-class University” 2022).
EWSR1::ATF1 fusions characterize a group of extra-abdominal epithelioid and round cell mesenchymal neoplasms, phenotypically overlapping with sclerosing epithelioid fibrosarcomas, and intra-abdominal FET::CREB fusion neoplasms
Authors: Rekhi Bharat , Dermawan Josephine K. , Fritchie Karen J. , Zimpfer Annette , Mohammad Tareq M. , Ali Fatima S. , Nandy Koushik , Zou Youran , Stoehr Robert , Agaimy Abbas 
Published: July 2024

AbstractWith the increasing use of next generation sequencing in soft tissue pathology, particularly in neoplasms not fitting any World Health Organization (WHO) category, the spectrum of EWSR1 fusion-associated soft tissue neoplasms has been expanding significantly. Although recurrent EWSR1::ATF1 fusions were initially limited to a triad of mesenchymal neoplasms including clear cell sarcoma of soft tissue, angiomatoid fibrous histiocytoma and malignant gastrointestinal neuroectodermal tumor (MGNET), this family has been expanding. We herein describe 4 unclassified extra-abdominal soft tissue (n = 3) and bone (n = 1) neoplasms displaying epithelioid and round cell morphology and carrying an EWSR1::ATF1 fusion. Affected were 3 males and 1 female aged 20–56 years. All primary tumors were extra-abdominal and deep-seated (chest wall, mediastinum, deltoid, and parapharyngeal soft tissue). Their size ranged 4.4–7.5 cm (median, 6.2). One patient presented with constitutional symptoms. Surgery with (2) or without (1) neo/adjuvant therapy was the treatment. At last follow-up (8–21 months), 2 patients developed progressive disease (1 recurrence; 1 distant metastasis). The immunophenotype of these tumors is potentially misleading with variable expression of EMA (2 of 3), pankeratin (2 of 4), synaptophysin (2 of 3), MUC4 (1 of 3), and ALK (1 of 3). All tumors were negative for S100 and SOX10. These observations point to the existence of heretofore under-recognized group of epithelioid and round cell neoplasms of soft tissue and bone, driven by EWSR1::ATF1 fusions, but distinct from established EWSR1::ATF1-associated soft tissue entities. Their overall morphology and immunophenotype recapitulate that of the emerging EWSR1/FUS::CREB fusion associated intra-abdominal epithelioid/round cell neoplasms. Our cases point to a potentially aggressive clinical behavior. Recognizing this tumor type is mandatory to delineate any inherent biological and/or therapeutic distinctness from other, better-known sarcomas in the differential diagnosis including sclerosing epithelioid fibrosarcoma.
Promising microRNAs in pre-diagnostic serum associated with lung cancer up to eight years before diagnosis: a HUNT study
Authors: Fotopoulos Ioannis , Nguyen Olav Toai Duc , Nøst Therese Haugdahl , Markaki Maria , Lagani Vincenzo , Mjelle Robin , Sandanger Torkjel Manning , Sætrom Pål , Tsamardinos Ioannis , Røe Oluf Dimitri 
Published: July 2024

Abstract
Introduction
Blood biomarkers for early detection of lung cancer (LC) are in demand. There are few studies of the full microRNome in serum of asymptomatic subjects that later develop LC. Here we searched for novel microRNA biomarkers in blood from non-cancer, ever-smokers populations up to eight years before diagnosis.

Methods
Serum samples from 98,737 subjects from two prospective population studies, HUNT2 and HUNT3, were considered initially. Inclusion criteria for cases were: ever-smokers; no known cancer at study entrance; 0–8 years from blood sampling to LC diagnosis. Each future LC case had one control matched to sex, age at study entrance, pack-years, smoking cessation time, and similar HUNT Lung Cancer Model risk score. A total of 240 and 72 serum samples were included in the discovery (HUNT2) and validation (HUNT3) datasets, respectively, and analysed by next-generation sequencing. The validated serum microRNAs were also tested in two pre-diagnostic plasma datasets from the prospective population studies NOWAC (n = 266) and NSHDS (n = 258). A new model adding clinical variables was also developed and validated.

Results
Fifteen unique microRNAs were discovered and validated in the pre-diagnostic serum datasets when all cases were contrasted against all controls, all with AUC > 0.60. In combination as a 15-microRNAs signature, the AUC reached 0.708 (discovery) and 0.703 (validation). A non-small cell lung cancer signature of six microRNAs showed AUC 0.777 (discovery) and 0.806 (validation). Combined with clinical variables of the HUNT Lung Cancer Model (age, gender, pack-years, daily cough parts of the year, hours of indoor smoke exposure, quit time in years, number of cigarettes daily, body mass index (BMI)) the AUC reached 0.790 (discovery) and 0.833 (validation). These results could not be validated in the plasma samples.

Conclusion
There were a few significantly differential expressed microRNAs in serum up to eight years before diagnosis. These promising microRNAs alone, in concert, or combined with clinical variables have the potential to serve as early diagnostic LC biomarkers. Plasma is not suitable for this analysis. Further validation in larger prospective serum datasets is needed.
Schadstoffbedingte Herausforderungen für PVC-Kreisläufe im Bausektor in Deutschland
Authors: Schmidt Sarah , Verni Xavier-François , Aguirre Molina Lucia , Biwer Arno , Gibon Thomas , Laner David 
Published: July 2024

ZusammenfassungEtwa drei Viertel des in Deutschland verarbeiteten Polyvinylchlorids (PVC) wird zu Bauprodukten verarbeitet. Aufgrund langer Produktlebensdauern sind die PVC-Abfallmengen aus diesem Sektor aktuell deutlich geringer als die Verarbeitungsmengen. Langfristig ist jedoch mit einem Anstieg der Abfallmengen zu rechnen. Die langen Produktlebensdauern haben auch zur Folge, dass PVC-Abfälle aus dem Bausektor Stoffe enthalten können, die vor mehreren Jahren oder Jahrzehnten in der PVC-Produktion eingesetzt wurden, inzwischen jedoch als problematisch eingestuft sind. Ziel der vorliegenden Studie ist es, schadstoffbedingte Herausforderungen für PVC-Kreisläufe im Bausektor in Deutschland zu identifizieren und anhand eines dynamischen Materialflussmodells zu quantifizieren. Das Materialflussmodell basiert auf einer Analyse regulatorischer Rahmenbedingungen, Literatur- und Datenrecherchen sowie Abfallcharakterisierungen. Anhand der Analyse regulatorischer Rahmenbedingungen wurden etwa 680 Stoffe identifiziert, die in PVC-Anwendungen im Bausektor eingesetzt wurden und werden. Der Einsatz von 188 dieser Stoffe wird durch die EU-POP-Verordnung, REACH oder CLP-Verordnung reguliert. Eine Abfallanalyse ergibt, dass PVC-Altprodukte aus dem Bausektor relevante Konzentrationen an Problemstoffen, wie Blei, Cadmium und DEHP aufweisen. Anhand des dynamischen Materialflussmodells wird für die Anwendungen Profile, Rohre und Bodenbeläge gezeigt, dass derzeit ein Nutzlager von etwa 19,0 Mio. Tonnen PVC besteht. Bis 2050 ist zu erwarten, dass die PVC-Abfälle aus diesen Anwendungen von 246.000 t im Jahr 2022 auf 449.000 t steigen werden. Außerdem zeigt das Materialflussmodell, dass PVC-Abfälle aus dem Bausektor mit hoher Wahrscheinlichkeit auch im Jahr 2050 noch relevante Konzentrationen an Problemstoffen enthalten werden. Um zukünftig eine stoffliche Verwertung dieser Abfälle sowie die Etablierung sauberer Materialkreisläufe zu ermöglichen, sind neue Abfallbehandlungsverfahren notwendig, die auf das Ausschleusen der Schadstoffe abzielen, sodass steigende Recyclingmengenpotenziale ausgeschöpft werden können.
Risk factors and incidence of short-term complications following open reduction and internal fixation of scapula fractures
Authors: Kiritsis Nicholas R. , Reiter Charles R. , Satalich James R. , Protzuk Omar , O’Neill Conor N. , Vanderbeck Jennifer L. 
Published: July 2024

Abstract
Purpose
To determine the short-term complication rates following open reduction and internal fixation of scapula fractures, factors affecting the development of adverse events, and complication rates based on the anatomic location of the fracture.

Methods
Thirty-day complication rates for patients who underwent open reduction and internal fixation of the scapula were compared between glenoid, body, coracoid, and acromion fracture locations, as identified by International Classification of Disease codes. Possible adverse events included postoperative surgical site infection, renal insufficiency, intubation, pneumonia, deep vein thrombosis, pulmonary embolism, urinary tract infection, wound dehiscence, stroke, and blood transfusion.

Results
A total of 251 scapula fractures were identified, with 161 having known fracture locations: 105 glenoid, 20 body, 9 coracoid, and 27 acromial fractures. The rate of any adverse event for all scapular fractures was 2.0%, with no significant difference between anatomic locations (p = 0.79). The overall rates of transfusion, surgical site infection, and return to OR were 0.4%, 0.8%, and 3.98%. Steroid use associated with a significantly increased risk of any adverse event (OR: 55.57, p = 0.038) and outpatient status demonstrated a protective effect on reoperation (OR: 0.11, p = 0.014). There were no significant differences in the rates between groups [transfusion (p = 0.91); surgical site infection (p = 0.17); reoperation (p = 0.85)].

Conclusion
Complication rates within thirty days of ORIF for scapula fracture were low. Reoperation was the most common complication, followed by surgical site infection, wound dehiscence, stroke, transfusion, and pneumonia. Steroid use was a risk factor for developing any adverse event, and outpatient status was protective against reoperation. The 30-day complication profile of glenoid, body, coracoid, and acromial fractures was not significantly different. The low complication rates support the relative short-term safety of operative intervention with internal fixation.

Level of Evidence
Level III.
The Key Ripper: a specialized fixed suture-cutting device to facilitate drain removal
Authors: Nagamatsu Shogo , Sasaki Ayano , Fujioka Yumiwo , Shibata Yoshiaki , Nomimura Ken , Aoki Yuki , Koshima Isao 
Published: July 2024

Abstract
The removal of post-surgical drains requires suture cutting. We developed a novel and specialized device that can safely remove the threads fixing the drains, making drain removal safer and easier than the current removal approach using scissors or a scalpel.
Clinical effects of omega-3 fatty acids supplementation in the periodontal treatment of smokers and non-smokers with periodontitis: a retrospective study
Authors: Savran Levent , Sağlam Mehmet 
Published: July 2024

Abstract
Objectives
Omega-3 supplementation as an adjunct to nonsurgical periodontal treatment has been reported to have a positive effect on healing in periodontitis patients. However, there is a lack of information on the effects of periodontal healing in smokers with periodontitis. The aim of this retrospective study was to investigate the effect of omega-3 supplementation given as an adjunct to nonsurgical periodontal treatment on clinical parameters in smoker and non-smoker periodontitis patients.

Methods
This study included a total of 80 periodontitis patients, 40 non-smokers and 40 smokers who were systemically healthy. In this study, patients were divided into 4 groups as follows: Group 1 (Subgingival instrumentation (SI) alone/nonsmoker), Group 2 (SI alone/smoker), Group 3 (SI + Omega-3/nonsmoker) and Group 4 (SI + Omega-3/smoker). Group 3 and 4 consumed 1320 mg Omega-3 capsule (640 mg EPA, 480 mg DHA) once a day for 3 months. Probing depth (PD), clinical attachment level (CAL), gingival index (GI), plaque index (PI) and bleeding on probing (BOP %) were recorded at baseline, 1 month and 3 months after treatment.

Results
Significant improvement of all clinical parameters at 1 and 3 months was observed in all groups. Whole mouth CAL, GI and BOP% were significantly reduced in group 4 compared to group 2 at 1 and 3 months postoperatively (p < 0.05). For moderately deep pockets (4–6 mm) and deep pockets (7 mm≤), PD and CAL reductions were significantly greater in groups taking omega − 3 (group 3 and group 4) compared to groups not taking omega-3 (group 1 and group 2) between baseline and 1 month and between baseline and 3 months (p ˂ 0.05).

Conclusion
Omega-3 supplementation given as an adjunct to nonsurgical periodontal treatment provided significant benefit in the improvement of clinical parameters (especially for CAL and PD) in the short term in smokers and non-smokers with periodontitis.

Clinical relevance
Nonsurgical periodontal treatment with omega-3 supplementation resulted in significant improvements in clinical parameters in smokers and non-smokers with periodontitis.
Maternal child maltreatment and trajectories of offspring behavioural and emotional difficulties from age 4 to 7 years – results from a prospective birth cohort study
Authors: Clemens Vera , Wernecke Deborah , Fegert Jörg M. , Genuneit Jon , Rothenbacher Dietrich , Braig Stefanie 
Published: July 2024

AbstractMaternal experience of child maltreatment (CM) has been associated with maternal and child mental health. However, evidence about the course of child mental health and maternal CM is scarce. Therefore, this study aims to compare trajectories of mental health in children according to maternal CM exposure and maternal mental health. We included 327 mothers and their singleton child from the Ulm SPATZ Health Study, a prospective birth cohort study. Child mental health was determined by the Strength and Difficulties Questionnaire (SDQ) at the age of 4, 5, 6, and 7 years and maternal CM by the Childhood Trauma Questionnaire (CTQ). Results display that maternal CM is associated with more behavioural and emotional difficulties in children, a trend that tends to increase with older child age. The sum of maternal mental health problems across this time course mediates this association. Male child sex is associated with more mental health problems in the child and the mother. These results provide an important first insight into the relevance of maternal CM on the trajectories of mental health in the offspring and highlight the importance of chronicity and severity of maternal mental health. Further prospective research in cohorts with longer follow-ups up into adolescence and adulthood is needed.
Functional genomics reveals an off-target dependency of drug synergy in gastric cancer therapy
Authors: Leylek Ozen , Honeywell Megan E. , Lee Michael J. , Hemann Michael T. , Ozcan Gulnihal 
Published: July 2024

Abstract
Background
Integrating molecular-targeted agents into combination chemotherapy is transformative for enhancing treatment outcomes in cancer. However, realizing the full potential of this approach requires a clear comprehension of the genetic dependencies underlying drug synergy. While the interactions between conventional chemotherapeutics are well-explored, the interplay of molecular-targeted agents with conventional chemotherapeutics remains a frontier in cancer treatment. Hence, we leveraged a powerful functional genomics approach to decode genomic dependencies that drive synergy in molecular-targeted agent/chemotherapeutic combinations in gastric adenocarcinoma, addressing a critical need in gastric cancer therapy.

Methods
We screened pharmacological interactions between fifteen molecular-targeted agent/conventional chemotherapeutic pairs in gastric adenocarcinoma cells, and examined the genome-scale genetic dependencies of synergy integrating genome-wide CRISPR screening with the shRNA-based signature assay. We validated the synergy in cell death using fluorescence-based and lysis-dependent inference of cell death kinetics assay, and validated the genetic dependencies by single-gene knockout experiments.

Results
Our combination screen identified SN-38/erlotinib as the drug pair with the strongest synergism. Functional genomics assays unveiled a genetic dependency signature of SN-38/erlotinib identical to SN-38. Remarkably, the enhanced cell death with improved kinetics induced by SN-38/erlotinib was attributed to erlotinib’s off-target effect, inhibiting ABCG2, rather than its on-target effect on EGFR.

Conclusion
In the era of precision medicine, where emphasis on primary drug targets prevails, our research challenges this paradigm by showcasing a robust synergy underpinned by an off-target dependency. Further dissection of the intricate genetic dependencies that underlie synergy can pave the way to developing more effective combination strategies in gastric cancer therapy.
Immunometabolic alteration of CD4+ T cells in the pathogenesis of primary Sjögren’s syndrome
Authors: Chen Yingying , Luo Xuan , Deng Chuiwen , Zhao Lidan , Gao Hui , Zhou Jiaxin , Peng Linyi , Yang Huaxia , Li Mengtao , Zhang Wen , Zhao Yan , Fei Yunyun 
Published: July 2024

AbstractPrimary Sjögren’s syndrome (pSS) is a prevalent autoimmune disorder wherein CD4+ T cells play a pivotal role in its pathogenesis. However, the underlying mechanisms driving the hyperactivity of CD4+ T cells in pSS remain poorly understood. This study aimed to investigate the potential role of immunometabolic alterations in driving the hyperactivity of CD4+ T cells in pSS. We employed Seahorse XF assay to evaluate the metabolic phenotype of CD4+ T cells, conducted flow cytometry to assess the effector function and differentiation of CD4+ T cells and measured the level of intracellular reactive oxygen species (ROS). Additionally, transcriptome sequencing, PCR, and Western blotting were utilized to examine the expression of glycolytic genes. Our investigation revealed that activated CD4+ T cells from pSS patients exhibited elevated aerobic glycolysis, rather than oxidative phosphorylation, resulting in excessive production of IFN-γ and IL-17A. Inhibition of glycolysis by 2-Deoxy-D-glucose reduced the expression of IFN-γ and IL-17A in activated CD4+ T cells and mitigated the differentiation of Th1 and Th17 cells. Furthermore, the expression of glycolytic genes, including CD3E, CD28, PIK3CA, AKT1, mTOR, MYC, LDHA, PFKL, PFKFB3, and PFKFB4, was upregulated in activated CD4+ T cells from pSS patients. Specifically, the expression and activity of LDHA were enhanced, contributing to an increased level of intracellular ROS. Targeting LDHA with FX-11 or inhibiting ROS with N-acetyl-cysteine had a similar effect on reversing the dysfunction of activated CD4+ T cells from pSS patients. Our study unveils heightened aerobic glycolysis in activated CD4+ T cells from pSS patients, and inhibition of glycolysis or its metabolite normalizes the dysfunction of activated CD4+ T cells. These findings suggest that aerobic glycolysis may be a promising therapeutic target for the treatment of pSS.