bluuebunny/crossref_metadata_2025_split huggingface dataset:
Disseminated intravascular coagulation and its immune mechanisms
Authors: Popescu Narcis I. , Lupu Cristina , Lupu Florea 
Published: August 2021

Abstract
Disseminated intravascular coagulation (DIC) is a syndrome triggered by infectious and noninfectious pathologies characterized by excessive generation of thrombin within the vasculature and widespread proteolytic conversion of fibrinogen. Despite diverse clinical manifestations ranging from thrombo-occlusive damage to bleeding diathesis, DIC etiology commonly involves excessive activation of blood coagulation and overlapping dysregulation of anticoagulants and fibrinolysis. Initiation of blood coagulation follows intravascular expression of tissue factor or activation of the contact pathway in response to pathogen-associated or host-derived, damage-associated molecular patterns. The process is further amplified through inflammatory and immunothrombotic mechanisms. Consumption of anticoagulants and disruption of endothelial homeostasis lower the regulatory control and disseminate microvascular thrombosis. Clinical DIC development in patients is associated with worsening morbidities and increased mortality, regardless of the underlying pathology; therefore, timely recognition of DIC is critical for reducing the pathologic burden. Due to the diversity of triggers and pathogenic mechanisms leading to DIC, diagnosis is based on algorithms that quantify hemostatic imbalance, thrombocytopenia, and fibrinogen conversion. Because current diagnosis primarily assesses overt consumptive coagulopathies, there is a critical need for better recognition of nonovert DIC and/or pre-DIC states. Therapeutic strategies for patients with DIC involve resolution of the eliciting triggers and supportive care for the hemostatic imbalance. Despite medical care, mortality in patients with DIC remains high, and new strategies, tailored to the underlying pathologic mechanisms, are needed.
Clinicopathological features and survival in EBV-positive diffuse large B-cell lymphoma not otherwise specified
Authors: Bourbon Estelle , Maucort-Boulch Delphine , Fontaine Juliette , Mauduit Claire , Sesques Pierre , Safar Violaine , Ferrant Emmanuelle , Golfier Camille , Ghergus Dana , Karlin Lionel , Lazareth Anne , Bouafia Fadhela , Pica Gian Matteo , Orsini-Piocelle Frédérique , Rocher Clément , Gros François-Xavier , Parrens Marie , Dony Arthur , Rossi Cédric , Ghesquières Hervé , Bachy Emmanuel , Traverse-Glehen Alexandra , Sarkozy Clémentine 
Published: August 2021

Abstract
In this retrospective study, we report 70 cases of Epstein-Barr virus (EBV)+ diffuse large B-cell lymphoma not otherwise specified (DLBCL-NOS) among 1696 DLBCL-NOS cases diagnosed between 2006 and 2019 (prevalence of 4.1%). At diagnosis, median age was 68.5 years; 79% of the cases presented with an advanced-stage disease (III-IV), 48% with extranodal lesions, and 14% with an hemophagocytic lymphohistiocytosis (HLH) (8 at diagnosis and 1 on therapy). A total of 46 cases presented a polymorphic pattern, and 21 were monomorphic. All had a non-germinal center B phenotype, with the majority of tumor cells expressing CD30 and programmed death ligand 1 (98% and 95%, respectively). Type II and III EBV latency was seen in 88% and 12% of the cases, respectively. Patients were treated with immunochemotherapy (59%) or chemotherapy (22%), and 19% received palliative care due to advanced age and altered performance status. After a median follow-up of 48 months, progression-free survival (PFS) and overall survival (OS) at 5 years were 52.7% and 54.8%, respectively. Older age (&gt;50 years) and HLH were associated with shorter PFS and OS in multivariate analysis (PFS: hazard ratio [HR], 14.01; 95% confidence interval [CI], 2.34-83.97; and HR, 5.78; 95% CI, 2.35-14.23; OS: HR, 12.41; 95% CI, 1.65-93.53; and HR, 6.09; 95% CI, 2.42-15.30, respectively). Finally, using a control cohort of 425 EBV− DLBCL-NOS, EBV positivity was associated with a shorter OS outcome within patients &gt;50 years (5-year OS, 53% [95% CI, 38.2-74] vs 60.8% [95% CI, 55.4-69.3], P = .038), but not in younger patients.
Benign and malignant hematologic manifestations in patients with VEXAS syndrome due to somatic mutations in UBA1
Authors: Obiorah Ifeyinwa Emmanuela , Patel Bhavisha A. , Groarke Emma M. , Wang Weixin , Trick Megan , Ombrello Amanda K. , Ferrada Marcela A. , Wu Zhijie , Gutierrez-Rodrigues Fernanda , Lotter Jennifer , Wilson Lorena , Hoffmann Patrycja , Cardona Daniela Ospina , Patel Nisha , Dulau-Florea Alina , Kastner Daniel L. , Grayson Peter C. , Beck David B. , Young Neal S. , Calvo Katherine R. 
Published: August 2021

Abstract
Somatic mutations in UBA1 involving hematopoietic stem and myeloid cells have been reported in patients with the newly defined VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Here, we report clinical hematologic manifestations and unique bone marrow (BM) features in 16 patients with VEXAS. All patients were male and had a history of severe autoinflammatory and rheumatologic manifestations and a somatic UBA1 mutation (p.Met41). Ten patients had hematologic disorders: myelodysplastic syndrome (MDS; 6 of 16), multiple myeloma (2 of 16), monoclonal gammopathy of undetermined significance (2 of 16), and monoclonal B-cell lymphocytosis (2 of 16), and a few of those patients had 2 co-existing clonal processes. Although macrocytic anemia (100%) and lymphopenia (80%) were prevalent in all patients with VEXAS, thrombocytopenia and neutropenia were more common in patients with progression to MDS. All BMs in VEXAS patients had prominent cytoplasmic vacuoles in myeloid and erythroid precursors. In addition, most BMs were hypercellular with myeloid hyperplasia, erythroid hypoplasia, and varying degrees of dysplasia. All patients diagnosed with MDS were lower risk (low blast count, very good to intermediate cytogenetics) according to standard prognostic scoring with no known progression to leukemia. In addition, 10 of 16 patients had thrombotic events, including venous thromboembolism and arterial stroke. Although VEXAS presents symptomatically as a rheumatologic disease, morbidity and mortality are associated with progression to hematologic disease. Given the increased risk of developing MDS and multiple myeloma, surveillance for disease progression is important.
Co-creating opportunities to incorporate cessation for electronic nicotine delivery systems in family medicine – a qualitative program evaluation
Authors: Kovach Kevin A. , Peterson Reshana , Bharati Rajani , Istas Kathryn , Monroe Michael 
Published: August 2021

AbstractBackgroundThe number of Americans who use tobacco has decreased in the twenty-first century, but electronic nicotine delivery systems (ENDS) have increased the complexity of treating tobacco dependence. The experiences of 18 family medicine practices were explored and opportunities to improve ENDS cessation were co-created in this study.MethodsEighteen family medicine practices were enrolled into an implementation project to incorporate ENDS cessation into their practice. The participants’ experiences were explored throughout the project using an iterative qualitative approach. The research team provided technical assistance. Semi-structured group interviews and focus groups were held with participants at the beginning, middle, and end of the project to explore participants’ experiences. The collective knowledge and experiences of participants, expert consultants and the research team were fused together to co-create opportunities to improve ENDS cessation.ResultsNine opportunities to improve ENDS cessation were identified in three larger categories. The first category was leading change. This included: creating a vision for change to establish buy-in from key stakeholders and educate health care professionals to improve their confidence to address ENDS. The second category was creating processes. This included: establishing criteria for screening and quality improvement for ENDS cessation; being specific when asking about ENDS; creating electronic health record systems to support incorporating ENDS cessation; using chart audits if electronic health records cannot support incorporating ENDS into tobacco cessation; and assigning roles and responsibilities to members of the clinical care team. The third category was assisting patients who use ENDS. This included: educating patients and their parents/caregivers about ENDS and their potential harms, avoiding dual use, and developing a plan to quit.ConclusionsThis study highlights challenges and opportunities for incorporating ENDS cessation into family medicine. The opportunities outlined here provide a practical approach which is rooted in the experiences of family physicians and their clinical care teams working to improve how they address ENDS and based on peer reviewed literature and expert input. Improving how ENDS are addressed in family medicine will require more than clinical expertise. It will also require leadership skills and the ability to create process improvements.Trial registrationNot applicable
Translation and validation of the German version of the Young Spine Questionnaire
Authors: Nyirö Luana , Potthoff Tobias , Siegenthaler Mette Hobaek , Riner Fabienne , Schweinhardt Petra , Wirth Brigitte 
Published: August 2021

Abstract
Background
Back pain in childhood and adolescence increases the risk for back pain in adulthood, but validated assessment tools are scarce. The aim of this study was to validate the Young Spine Questionnaire (YSQ) in a German version (G-YSQ) in children and adolescents.

Methods
Children and adolescents between 10 and 16 years (N = 240, 166 females, mean age = 13.05 ± 1.70 years), recruited in chiropractic practices and schools, completed the G-YSQ (translated according to scientific guidelines) and the KIDSCREEN-10 (assessing health-related quality of life) at three time points. Test-retest reliability was determined calculating intraclass correlation coefficients [ICC(3,1)] using start and two week-data. Construct validity was investigated testing a priori hypotheses. To assess responsiveness, the patients additionally filled in the Patient Global Impression of Change (PGIC) after three months and the area under the curve (AUC) of receiver operating curves was calculated.

Results
The ICC(3,1) was 0.88 for pain intensity and pain frequency, indicating good reliability, 0.68 for week prevalence and 0.60 for point prevalence, indicating moderate reliability. Pain intensity, frequency and prevalence differed between patients and controls (p < 0.001) and, except point prevalence, between older (> 12 years) and younger control participants (p < 0.01). Health-related quality of life of participants with severe pain (in one or several spinal regions) was lower (KIDSCREEN-10, total score: F(4,230) = 7.26, p < 0.001; KIDSCREEN-10, self-rated general health: H(4) = 51.94, p < 0.001) than that of participants without pain or with moderate pain in one spinal region. Thus, altogether these findings indicate construct validity of the G-YSQ. The AUC was 0.69 (95 % CI = 0.57–0.82) and 0.67 (95 % CI = 0.54–0.80) for week and point prevalence, respectively, indicating insufficient responsiveness of the G-YSQ.

Conclusions
Apart from the question on point prevalence, construct validity and sufficient test-retest reliability was shown for the G-YSQ. However, its responsiveness needs to be improved, possibly by asking for pain frequency during the last week instead of (dichotomous) week prevalence.

Trial registration
ClinicalTrials.gov, NCT02955342, registered 07/09/2016, https://clinicaltrials.gov/ct2/results?cond=&term=NCT02955342&cntry=CH&state=&city=Zurich&dist=.
Problem-solving training as an active ingredient of treatment for youth depression: a scoping review and exploratory meta-analysis
Authors: Krause Karolin R. , Courtney Darren B. , Chan Benjamin W. C. , Bonato Sarah , Aitken Madison , Relihan Jacqueline , Prebeg Matthew , Darnay Karleigh , Hawke Lisa D. , Watson Priya , Szatmari Peter 
Published: August 2021

Abstract
Background
Problem-solving training is a common ingredient of evidence-based therapies for youth depression and has shown effectiveness as a versatile stand-alone intervention in adults. This scoping review provided a first overview of the evidence supporting problem solving as a mechanism for treating depression in youth aged 14 to 24 years.

Methods
Five bibliographic databases (APA PsycINFO, CINAHL, Embase, MEDLINE, Web of Science) and the grey literature were systematically searched for controlled trials of stand-alone problem-solving therapy; secondary analyses of trial data exploring problem-solving-related concepts as predictors, moderators, or mediators of treatment response within broader therapies; and clinical practice guidelines for youth depression. Following the scoping review, an exploratory meta-analysis examined the overall effectiveness of stand-alone problem-solving therapy.

Results
Inclusion criteria were met by four randomized trials of problem-solving therapy (524 participants); four secondary analyses of problem-solving-related concepts as predictors, moderators, or mediators; and 23 practice guidelines. The only clinical trial rated as having a low risk of bias found problem-solving training helped youth solve personal problems but was not significantly more effective than the control at reducing emotional symptoms. An exploratory meta-analysis showed a small and non-significant effect on self-reported depression or emotional symptoms (Hedges’ g = − 0.34; 95% CI: − 0.92 to 0.23) with high heterogeneity. Removing one study at high risk of bias led to a decrease in effect size and heterogeneity (g = − 0.08; 95% CI: − 0.26 to 0.10). A GRADE appraisal suggested a low overall quality of the evidence. Tentative evidence from secondary analyses suggested problem-solving training might enhance outcomes in cognitive-behavioural therapy and family therapy, but dedicated dismantling studies are needed to corroborate these findings. Clinical practice guidelines did not recommend problem-solving training as a stand-alone treatment for youth depression, but five mentioned it as a treatment ingredient.

Conclusions
On its own, problem-solving training may be beneficial for helping youth solve personal challenges, but it may not measurably reduce depressive symptoms. Youth experiencing elevated depressive symptoms may require more comprehensive psychotherapeutic support alongside problem-solving training. High-quality studies are needed to examine the effectiveness of problem-solving training as a stand-alone approach and as a treatment ingredient.
Giant cell tumors of the mobile spine with invasion of adjacent vertebrae: an unusual imaging finding
Authors: Jiang Gang , Sun Ling-Ling , Ye Yong-Jun , Yang Zhi-Tao , Ji Qing-lian , Pang Jing , Gao Chuan-Ping 
Published: August 2021

AbstractBackgroundGiant cell tumors of the mobile spine invasion of the adjacent vertebrae are an ignored imaging finding.MethodsNine patients with giant cell tumors of the mobile spine with invasion of the adjacent vertebrae confirmed by pathology were enrolled. Eight patients had pure giant cell tumors (GCTs), while one patient also had an aneurysmal bone cyst. All patients underwent conventional computed tomography, three-dimensional reconstruction, and conventional magnetic resonance imaging, while seven patients also underwent post-contrast magnetic resonance imaging.ResultsAll patients showed GCTs of the mobile spine that arose from the vertebral body and extended to the vertebral arch. The tumors showed soft-tissue attenuation with no evidence of a mineralized matrix. Pathological fracture was seen in five patients. The margin of the original tumor showed partial sclerosis in four patients and involved an adjacent vertebral body with a sclerotic rim in two patients. The tumors showed a homogeneous and similar signal intensity to the normal spinal cord on T1WI (T1-weighted image) in five patients. The cystic area of the tumors was hyperintense on T2WI in the remaining four patients, while one patient showed hemorrhage that was hyperintense on T1WI. The solid components of the GCTs show marked enhancement in all cases, while the cystic area of the tumors was observed without enhancement on contrast-enhanced images in four patients. Bone destruction of the adjacent vertebral body showed a homogeneous signal on T1WI and T2WI and marked enhancement on contrast-enhanced images.ConclusionsGiant cell tumors of the mobile spine with invasion into adjacent vertebrae are an unusual imaging finding. Radiologists should be familiar with this imaging characteristic.
Smoking induces sex-specific changes in the small airway proteome
Authors: Kokelj Spela , Östling Jörgen , Georgi Benjamin , Fromell Karin , Ekdahl Kristina Nilsson , Olsson Henric K. , Olin Anna-Carin 
Published: August 2021

AbstractIntroductionCigarette smoke triggers many cellular and signaling responses in the lung and the resulting inflammation plays a central role in smoke-related lung diseases, such as COPD. We explored the effects of smoking on the small airway proteome in samples obtained by collection of exhaled particles with the aim to identify specific proteins dysregulated by smoking.MethodsExhaled particles were obtained from 38 current smokers, 47 former smokers and 22 healthy controls with the PExA method. 120 ng of sample was collected from individual subjects and analyzed with the SOMAscan proteomics platform. General linear model-based statistics were performed.ResultsTwo hundred and three proteins were detected in at least half of 107 total samples. Active smoking exerted a significant impact on the protein composition of respiratory tract lining fluid (RTLF), with 81 proteins altered in current smokers compared to never smokers (p < 0.05, q < 0.124). Among the proteins most clearly discriminating between current and never smokers were sRAGE, FSTL3, SPOCK2 and protein S, all of them being less abundant in current smokers. Analysis stratified for sex unveiled sex differences with more pronounced proteomic alterations due to active smoking in females than males. Proteins whose abundance was altered by active smoking in women were to a larger extent related to the complement system. The small airway protein profile of former smokers appeared to be more similar to that observed in never smokers.ConclusionsThe study shows that smoking has a strong impact on protein expression in the small airways, and that smoking affects men and women differently, suggesting PExA sampling combined with high sensitivity protein analysis offers a promising platform for early detection of COPD and identification of novel COPD drug targets.
Nanobody-armed T cells endow CAR-T cells with cytotoxicity against lymphoma cells
Authors: Wang Hongxia , Wang Liyan , Li Yanning , Li Guangqi , Zhang Xiaochun , Jiang Dan , Zhang Yanting , Liu Liyuan , Chu Yuankui , Xu Guangxian 
Published: August 2021

AbstractBackgroundTaking advantage of nanobodies (Nbs) in immunotherapy, we investigated the cytotoxicity of Nb-based chimeric antigen receptor T cells (Nb CAR-T) against lymphoma cells.MethodsCD19 Nb CAR-T, CD20 Nb CAR-T, and Bispecific Nb CAR-T cells were generated by panning anti-human CD19- and CD20-specific nanobody sequences from a natural Nb-expressing phage display library, integrating Nb genes with a lentiviral cassette that included other CAR elements, and finally transducing T cells that were expanded under an optimization system with the above generated CAR lentivirus. Prepared Nb CAR-T cells were cocultured with tumour cell lines or primary tumour cells for 24 h or 5 days to evaluate their biological function.ResultsThe nanobodies that we selected from the natural Nb-expressing phage display library had a high affinity and specificity for CD19 and CD20. CD19 Nb CAR-T, CD20 Nb CAR-T and Bispecific Nb CAR-T cells were successfully constructed, and these Nb CAR-T cells could strongly recognize Burkitt lymphoma cell lines (Raji and Daudi), thereby leading to activation, enhanced proliferation, and specific killing of target cells. Furthermore, similar results were obtained when using patient samples as target cells, with a cytotoxicity of approximately 60%.ConclusionsNanobody-based CAR-T cells can kill both tumour cell lines and patient-derived tumour cells in vitro, and Nb-based CAR-T cells may be a promising therapeutic strategy in future immunotherapy.
miR-499a inhibits the proliferation and apoptosis of prostate cancer via targeting UBE2V2
Authors: Chen Yougan , Sun Fanghao , Zhang Liansheng , Zhou Jian , Hou Jianquan 
Published: August 2021

Abstract
Background
Prostate cancer is one of the malignant tumors of the urinary system and ranks second among the fatal cancers in men. And with age, the incidence of prostate cancer will increase linearly.

Methods
In this study, we measured the expression of Ubiquitin Conjugating Enzyme E2 V2 (UBE2V2) in prostate cancer tissues and cell lines by WB and explored the effect of UBE2V2 on the proliferation characteristics of prostate cancer by MTT and colony formation test.

Results
In our research, we found that the UBE2V2 protein level in prostate cancer cell lines was significantly higher than the UBE2V2 protein level in normal prostate cells, and the mRNA expression level did not change significantly compared with normal prostate tissue cells. At the same time, we found that miR-499a combined with UBE2V2 inhibited the expression of UBE2V2 in prostate cancer cells.

Conclusions
In conclusion, our results indicate that miR-499a inhibits the proliferation of human prostate cancer cells by targeting UBE2V2, which will provide a potential target for the treatment of prostate cancer.
Novel variants in helicase for meiosis 1 lead to male infertility due to non-obstructive azoospermia
Authors: Tang Dongdong , Lv Mingrong , Gao Yang , Cheng Huiru , Li Kuokuo , Xu Chuan , Geng Hao , Li Guanjian , Shen Qunshan , Wang Chao , He Xiaojin , Cao Yunxia 
Published: August 2021

Abstract
Background
Non-obstructive azoospermia (NOA) is the most severe form of male infertility; more than half of the NOA patients are idiopathic. Although many NOA risk genes have been detected, the genetic factors for NOA in majority of the patients are unknown. In addition, it is difficult to retrieve sperm from these patients despite using the microsurgical testicular sperm extraction (microTESE) method. Therefore, we conducted this genetic study to identify the potential genetic factors responsible for NOA and investigate the sperm retrieval rate of microTESE for genetically deficient NOA patients.

Methods
Semen analyses, sex hormone testing, and testicular biopsy were performed to categorize the patients with NOA. The chromosome karyotypes and Y chromosome microdeletion analyses were used to exclude general genetic factors. Whole exome sequencing and Sanger sequencing were performed to identify potential genetic variants in 51 patients with NOA. Hematoxylin and eosin staining (H&E) and anti-phosphorylated H2AX were used to assess the histopathology of spermatogenesis. Quantitative real time-polymerase chain reaction, western blotting, and immunofluorescence were performed to verify the effects of gene variation on expression.

Results
We performed whole exome sequencing in 51 NOA patients and identified homozygous helicase for meiosis 1(HFM1) variants (NM_001017975: c.3490C > T: p.Q1164X; c.3470G > A: p.C1157Y) in two patients (3.9%, 2/51). Histopathology of the testis showed that spermatogenesis was completely blocked at metaphase in these two patients carrying the HFM1 homozygous variants. In comparison with unaffected controls, we found a significant reduction in the levels of HFM1 mRNA and protein expression in the testicular tissues from these two patients. The patients were also subjected to microTESE treatment, but the sperms could not be retrieved.

Conclusions
This study identified novel homozygous variants of HFM1 that are responsible for spermatogenic failure and NOA, and microTESE did not aid in retrieving sperms from these patients.