bluuebunny/crossref_metadata_2025_split huggingface dataset:
High antibody levels against human herpesvirus-6A interact with lifestyle factors in multiple sclerosis development
Authors: Wu Jing , Engdahl Elin , Gustafsson Rasmus , Fogdell-Hahn Anna , Waterboer Tim , Hillert Jan , Olsson Tomas , Alfredsson Lars , Hedström Anna Karin 
Published: June 2021

Background: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied. Methods: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 controls. Using logistic regression models, subjects with different HHV-6A antibody levels, environmental exposures, and lifestyle habits were compared regarding MS risk, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). Potential interactions between high HHV-6A antibody levels and common environmental exposures and lifestyle factors were evaluated on the additive scale. Results: High HHV-6A antibody levels were associated with increased risk of developing MS (OR = 1.5, 95% CI = 1.4–1.6). Regarding MS risk, significant interactions were observed between high HHV-6A antibody levels and both smoking (attributable proportion (AP) = 0.2, 95% CI = 0.1–0.3), low ultraviolet radiation (UVR) exposure (AP = 0.3, 95% CI = 0.1–0.4), and low vitamin D levels (AP = 0.3, 95% CI = 0.0–0.6). Conclusion: High HHV-6A antibody levels are associated with increased MS risk and act synergistically with common environmental/lifestyle risk factors for MS. Further research is needed to investigate potential mechanisms underlying the interactions presented in this study.
Anaemia: A risk factor for death and adverse outcomes following surgery for acute lower limb ischaemia
Authors: Perren Daniel , Shelmerdine Lauren , Boylan Luke , Nesbitt Craig , Prentis James , Nandhra Sandip 
Published: June 2021

Introduction Acute limb ischaemia (ALI) forms a significant part of the vascular surgery workload and carries with it high rates of morbidity and mortality. Anaemia is also common amongst vascular surgical patients and has been linked with poor outcomes in some subgroups. We aimed to assess the frequency of anaemia in patients with ALI and its impact on survival and complications following revascularisation to help direct future efforts to optimise outcomes in this patient group. Methods A retrospective analysis of prospectively collected departmental data on patients undergoing surgical intervention for ALI between 2014 and 2018 was performed. Anaemia was defined as a pre-operative haemoglobin (Hb) of <120 g/L for women and <130 g/L for men. The primary outcome was overall survival, assessed with the Kaplan–Meier estimator, with application of Cox proportional hazard modelling to adjust for confounding covariates. Results There were 158 patients who underwent treatment for ALI: 89 (56.3%) of these were non-anaemic with a mean Hb of 146 (SD = 18.4), and 69 (43.7%) were anaemic with a mean Hb of 106 (SD = 13.4). Anaemic patients had a significantly higher risk of death than their non-anaemic counterparts on univariate analysis (HR = 2.11, 95% CIs, 1.28–3.5, p = 0.0036). There was ongoing divergence in survival up to around 6 months between anaemic and non-anaemic groups. Under the Cox model, anaemia was similarly significant as a predictor of death (HR = 2.15, 95% CIs, 1.17–3.95, p = 0.013), accounting for recorded comorbidities, medication use and blood transfusion. Conclusions Anaemia is a significant and independent risk factor for death following revascularisation for ALI and can be potentially be modified. Vascular surgical centres should ensure they have robust pathways in place to identify and consider treating anaemia. There is scope for further work to assess how to best optimise a patient’s levels of circulating haemoglobin.
Products for Monitoring Glucose Levels in the Human Body With Noninvasive Optical, Noninvasive Fluid Sampling, or Minimally Invasive Technologies
Authors: Shang Trisha , Zhang Jennifer Y. , Thomas Andreas , Arnold Mark A. , Vetter Beatrice N. , Heinemann Lutz , Klonoff David C. 
Published: June 2021

Background: Conventional home blood glucose measurements require a sample of blood that is obtained by puncturing the skin at the fingertip. To avoid the pain associated with this procedure, there is high demand for medical products that allow glucose monitoring without blood sampling. In this review article, all such products are presented. Methods: In order to identify such products, four different sources were used: (1) PubMed, (2) Google Patents, (3) Diabetes Technology Meeting Startup Showcase participants, and (4) experts in the field of glucose monitoring. The information obtained were filtered by using two inclusion criteria: (1) regulatory clearance, and/or (2) significant coverage in Google News starting in the year 2016, unless the article indicated that the product had been discontinued. The identified bloodless monitoring products were classified into three categories: (1) noninvasive optical, (2) noninvasive fluid sampling, and (3) minimally invasive devices. Results: In total, 28 noninvasive optical, 6 noninvasive fluid sampling, and 31 minimally invasive glucose monitoring products were identified. Subsequently, these products were characterized according to their regulatory, technological, and consumer features. Products with regulatory clearance are described in greater detail according to their advantages and disadvantages, and with design images. Conclusions: Based on favorable technological features, consumer features, and other advantages, several bloodless products are commercially available and promise to enhance diabetes management. Paths for future products are discussed with an emphasis on understanding existing barriers related to both technical and non-technical issues.
Successful treatment of pulmonary hypertension following hematopoietic stem cell transplant with a single oral tadalafil: a case report
Authors: Tanaka Toshikazu D. , Ishizawar David C. , Saito Takeshi , Yoshii Akira , Yoshimura Michihiro 
Published: June 2021

A 46‐year‐old man who had undergone hematopoietic stem cell transplant twice because of acute lymphoblastic leukemia with recurrence presented with dyspnea, leading to a diagnosis of pulmonary arterial hypertension which was quickly and effectively treated with the phosphodiesterase type 5 inhibitor tadalafil. To our knowledge, pulmonary arterial hypertension related to hematologic malignancies requiring hematopoietic stem cell transplant is rarely reported. Importantly, the present case suggests that early diagnosis and treatment with a pulmonary vasodilator, such as tadalafil, can greatly decrease pulmonary vascular resistance in patients with severe pulmonary arterial hypertension after hematopoietic stem cell transplant and can then improve other symptoms. Accordingly, pulmonary vascular disease should be considered if respiratory symptoms develop following hematopoietic stem cell transplant, because treatment with pulmonary vasodilator may lead to significant improvement in pulmonary arterial hypertension.
What is the content of virtually delivered pain management programmes for people with persistent musculoskeletal pain? A systematic review
Authors: Booth Gregory , Williams Deborah , Patel Hasina , Gilbert Anthony W 
Published: June 2021

Introduction: Virtual consultations (VC) have been embraced by healthcare organisations during the COVID-19 pandemic. VC allows continuation of patient care while adhering to government advised restrictions and social distancing measures. Multidisciplinary pain management programmes (PMPs) are a core element of many pain services and utilising virtual methods to deliver PMPs has allowed them to continue to provide care. This systematic review aimed to explore the content of existing virtually delivered PMPs and discuss if and how these findings can be used to guide clinical delivery. Methods: Eligible studies included adults (aged ⩾18 years) with persistent musculoskeletal pain and any virtually delivered intervention that was described as a PMP or that had components of PMPs. Databases were searched from inception until July 2020. We performed a content analysis comparing existing interventions with established evidence-based clinical guidelines published by the British Pain Society (BPS). Intervention reporting quality was assessed using the Template for Intervention Description and Replication (TIDieR) checklist: an established checklist developed to improve the completeness of the reporting of interventions. Results: Eight studies were included. One intervention included six of the seven components recommended by the BPS; none included all seven. ‘Skills training and activity management’ was present in all eight interventions; ‘education’ and ‘cognitive therapy methods’ were present in six interventions; ‘graded activation’ and ‘methods to enhance acceptance, mindfulness and psychological flexibility’ were present in four interventions; ‘physical exercise’ was present in two interventions and ‘graded exposure’ was present in one intervention. None of the studies described all 12 items of the TIDieR checklist adequately enough for replication. Conclusion: Published virtual PMPs partially meet established clinical guidelines. Future virtual PMPs should be based on evidence-based clinical guidelines, and more research is needed to explore the effectiveness of virtually delivered PMPs and each recommended component.
Telemedicine in Spine Surgery: Global Perspectives and Practices
Authors: Riew Grant J. , Lovecchio Francis , Samartzis Dino , Louie Philip K. , Germscheid Niccole , An Howard , Cheung Jason Pui Yin , Chutkan Norman , Mallow Gary Michael , Neva Marko H. , Phillips Frank M. , Sciubba Daniel , El-Sharkawi Mohammad , Valacco Marcelo , McCarthy Michael H. , Makhni Melvin C. , Iyer Sravisht 
Published: June 2021

Study Design: Cross-sectional, anonymous, international survey. Objectives: The COVID-19 pandemic has resulted in the rapid adoption of telemedicine in spine surgery. This study sought to determine the extent of adoption and global perspectives on telemedicine in spine surgery. Methods: All members of AO Spine International were emailed an anonymous survey covering the participant’s experiences with and perceptions of telemedicine. Descriptive statistics were used to depict responses. Responses were compared among regions. Results: 485 spine surgeons participated in the survey. Telemedicine usage rose from <10.0% to >39.0% of all visits. A majority of providers (60.5%) performed at least one telemedicine visit. The format of “telemedicine” varied widely by region: European (50.0%) and African (45.2%) surgeons were more likely to use phone calls, whereas North (66.7%) and South American (77.0%) surgeons more commonly used video ( P < 0.001). North American providers used telemedicine the most during COVID-19 (>60.0% of all visits). 81.9% of all providers “agreed/strongly agreed” telemedicine was easy to use. Respondents tended to “agree” that imaging review, the initial appointment, and postoperative care could be performed using telemedicine. Almost all (95.4%) surgeons preferred at least one in-person visit prior to the day of surgery. Conclusion: Our study noted significant geographical differences in the rate of telemedicine adoption and the platform of telemedicine utilized. The results suggest a significant increase in telemedicine utilization, particularly in North America. Spine surgeons found telemedicine feasible for imaging review, initial visits, and follow-up visits although the vast majority still preferred at least one in-person preoperative visit.
Temporal Trends and Severity in Injury and Illness Incidence in the National Basketball Association Over 11 Seasons
Authors: Bullock Garrett S. , Ferguson Tyler , Vaughan Jake , Gillespie Desiree , Collins Gary , Kluzek Stefan 
Published: June 2021

Background: There is a paucity of current data describing injuries in professional basketball players. Utilizing publicly available injury data will allow for greater transparency for stakeholders to use the data as a shared resource to create future basketball injury prevention programs. Purpose: To describe injury and illness incidence, severity, and temporal trends in National Basketball Association (NBA) players. Among those who develop time-loss injury or illness, we estimated severity based on games missed because of injury or illness. Study Design: Descriptive epidemiology study. Methods: Publicly available NBA data were extracted through a reproducible computer-programmed process from the 2008 to 2019 seasons. Data were externally validated by 2 independent reviewers through other publicly available data sources. Injury and illness were calculated per 1000 athlete game-exposures (AGEs). Injury severity was calculated as games missed because of injury or illness. Injury and illness data were stratified by body part, position, severity (slight, minor, moderate, or severe), month, and year. Results: A total of 1369 players played a total of 302,018 player-games, with a total of 5375 injuries and illnesses. The overall injury and illness incidence was 17.80 per 1000 AGEs. The median injury severity was 3 games (interquartile range, 0-6 games) missed per injury. Overall, 33% of injuries were classified as slight; 26%, as minor; 26%, as moderate; and 15%, as severe. The ankle (2.57 injuries/1000 AGEs), knee (2.44 injuries/1000 AGEs), groin/hip/thigh (1.99 injuries/1000 AGEs), and illness (1.85 illnesses/1000 AGEs) had the greatest incidence of injury and illness. Neither injury or illness incidence nor severity was different among basketball playing positions. Injury incidence demonstrated increasing incremental trends with season progression. Injuries were similar throughout the 11-year reporting period, except for a substantial increase in the lockout-shortened 2012 season. Conclusion: The ankle and knee had the greatest injury incidence. Injury incidence was similar among basketball positions. Injury incidence increased throughout the season, demonstrating the potential relationship between player load and injury incidence.
Association of Sports Participation With Osteoarthritis: A Systematic Review and Meta-Analysis
Authors: Bestwick-Stevenson Thomas , Ifesemen Onosi S. , Pearson Richard G. , Edwards Kimberley L. 
Published: June 2021

Background: The association between participating in sport and osteoarthritis is not fully understood. Purpose: To investigate the association between osteoarthritis and participating in sports not listed in previous reviews: American football, archery, baseball, bobsleigh, curling, handball, ice hockey, shooting, skeleton, speed skating, and wrestling. Study Design: Systematic review; Level of evidence, 3. Methods: We searched 4 electronic databases and hand searched recent/in-press editions of relevant journals. The criteria for study selection were case-control studies, cohort studies, nested case-control studies, and randomized trials with a control group that included adults to examine the effect of exposure to any of the included sports on the development of osteoarthritis. Results: The search returned 6197 articles after deduplication. Nine studies were included in the final review, covering hip, knee, and ankle osteoarthritis. There were no studies covering archery, baseball, skeleton, speed skating, or curling. The 6 sports included in the review were analyzed as a collective; the results of the meta-analysis indicated that participation in the sports analyzed was associated with an increased risk of developing osteoarthritis of the hip (relative risk [RR] = 1.67 [95% confidence interval (CI), 1.15-2.41]; P = .04), knee (RR = 1.60 [95% CI, 1.23-2.08]; P < .001), and ankle (RR = 7.08 [95% CI, 1.24-40.51]; P = .03) as compared with controls. Meta-analysis suggested a significantly increased likelihood of developing hip osteoarthritis through participating in wrestling (RR = 1.78 [95% CI, 1.20-2.64]; P = .004) and ice hockey (RR = 1.70 [95% CI, 1.27-2.29]; P < .001), while there was no significant difference through participating in handball (RR = 2.50 [95% CI, 0.85-7.36]; P = .10). Likelihood of developing knee osteoarthritis was significantly increased in wrestling (RR = 2.22 [95% CI, 1.59-3.11]) and ice hockey (RR = 1.52 [95% CI, 1.18-1.96]; both P < .002). According to the meta-analysis, shooting did not have a significant effect on the RR of knee osteoarthritis as compared with other sports (RR = 0.43 [95% CI, 0.06-2.99]; P = .39). Conclusion: The likelihood of developing hip and knee osteoarthritis was increased for ice hockey and wrestling athletes, and the risk of developing hip osteoarthritis was increased for handball athletes. The study also found that participation in the sports examined, as a collective, resulted in an increased risk of developing hip, knee, and ankle osteoarthritis.
PRC2 loss of function confers a targetable vulnerability to BET proteins in T-ALL
Authors: Andrieu Guillaume P. , Kohn Milena , Simonin Mathieu , Smith Charlotte L. , Cieslak Agata , Dourthe Marie-Émilie , Charbonnier Guillaume , Graux Carlos , Huguet Françoise , Lhéritier Véronique , Dombret Hervé , Spicuglia Salvatore , Rousselot Philippe , Boissel Nicolas , Asnafi Vahid 
Published: June 2021

Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a group of aggressive hematological cancers with dismal outcomes that are in need of new therapeutic options. Polycomb repressor complex 2 (PRC2) loss-of-function alterations were reported in pediatric T-ALL, yet their clinical relevance and functional consequences remain elusive. Here, we extensively analyzed PRC2 alterations in a large series of 218 adult T-ALL patients. We found that PRC2 genetic lesions are frequent events in T-ALL and are not restricted to early thymic precursor ALL. PRC2 loss of function associates with activating mutations of the IL7R/JAK/STAT pathway. PRC2-altered T-ALL patients respond poorly to prednisone and have low bone marrow blast clearance and persistent minimal residual disease. Furthermore, we identified that PRC2 loss of function profoundly reshapes the genetic and epigenetic landscapes, leading to the reactivation of stem cell programs that cooperate with bromodomain and extraterminal (BET) proteins to sustain T-ALL. This study identifies BET proteins as key mediators of the PRC2 loss of function-induced remodeling. Our data have uncovered a targetable vulnerability to BET inhibition that can be exploited to treat PRC2-altered T-ALL patients.
Clinical relevance of clonal hematopoiesis in persons aged ≥80 years
Authors: Rossi Marianna , Meggendorfer Manja , Zampini Matteo , Tettamanti Mauro , Riva Emma , Travaglino Erica , Bersanelli Matteo , Mandelli Sara , Antonella Galbussera Alessia , Mosca Ettore , Saba Elena , Chiereghin Chiara , Manes Nicla , Milanesi Chiara , Ubezio Marta , Morabito Lucio , Peano Clelia , Soldà Giulia , Asselta Rosanna , Duga Stefano , Selmi Carlo , De Santis Maria , Malik Karolina , Maggioni Giulia , Bicchieri Marilena , Campagna Alessia , Tentori Cristina A. , Russo Antonio , Civilini Efrem , Allavena Paola , Piazza Rocco , Corrao Giovanni , Sala Claudia , Termanini Alberto , Giordano Laura , Detoma Paolo , Malabaila Aurelio , Sala Luca , Rosso Stefano , Zanetti Roberto , Saitta Claudia , Riva Elena , Condorelli Gianluigi , Passamonti Francesco , Santoro Armando , Sole Francesc , Platzbecker Uwe , Fenaux Pierre , Bolli Niccolò , Castellani Gastone , Kern Wolfgang , Vassiliou George S. , Haferlach Torsten , Lucca Ugo , Della Porta Matteo G. 
Published: June 2021

Abstract
Clonal hematopoiesis of indeterminate potential (CHIP) is associated with increased risk of cancers and inflammation-related diseases. This phenomenon becomes common in persons aged ≥80 years, in whom the implications of CHIP are not well defined. We performed a mutational screening in 1794 persons aged ≥80 years and investigated the relationships between CHIP and associated pathologies. Mutations were observed in one-third of persons aged ≥80 years and were associated with reduced survival. Mutations in JAK2 and splicing genes, multiple mutations (DNMT3A, TET2, and ASXL1 with additional genetic lesions), and variant allele frequency ≥0.096 had positive predictive value for myeloid neoplasms. Combining mutation profiles with abnormalities in red blood cell indices improved the ability of myeloid neoplasm prediction. On this basis, we defined a predictive model that identifies 3 risk groups with different probabilities of developing myeloid neoplasms. Mutations in DNMT3A, TET2, ASXL1, or JAK2 were associated with coronary heart disease and rheumatoid arthritis. Cytopenia was common in persons aged ≥80 years, with the underlying cause remaining unexplained in 30% of cases. Among individuals with unexplained cytopenia, the presence of highly specific mutation patterns was associated with myelodysplastic-like phenotype and a probability of survival comparable to that of myeloid neoplasms. Accordingly, 7.5% of subjects aged ≥80 years with cytopenia had presumptive evidence of myeloid neoplasm. In summary, specific mutational patterns define different risk of developing myeloid neoplasms vs inflammatory-associated diseases in persons aged ≥80 years. In individuals with unexplained cytopenia, mutational status may identify those subjects with presumptive evidence of myeloid neoplasms.
RNAseq and quantitative proteomic analysis of Dictyostelium knock-out cells lacking the core autophagy proteins ATG9 and/or ATG16
Authors: Xiong Qiuhong , Song Ning , Li Ping , Fischer Sarah , Konertz Roman , Wagle Prerana , Glöckner Gernot , Wu Changxin , Eichinger Ludwig 
Published: June 2021

Abstract
Background
Autophagy is an evolutionary ancient mechanism that sequesters substrates for degradation within autolysosomes. The process is driven by many autophagy-related (ATG) proteins, including the core members ATG9 and ATG16. However, the functions of these two core ATG proteins still need further elucidation. Here, we applied RNAseq and tandem mass tag (TMT) proteomic approaches to identify differentially expressed genes (DEGs) and proteins (DEPs) in Dictyostelium discoideum ATG9‾, ATG16‾ and ATG9‾/16‾ strains in comparison to AX2 wild-type cells.

Result
In total, we identified 332 (279 up and 53 down), 639 (487 up and 152 down) and 260 (114 up and 146 down) DEGs and 124 (83 up and 41 down), 431 (238 up and 193 down) and 677 (347 up and 330 down) DEPs in ATG9‾, ATG16‾ and ATG9‾/16‾ strains, respectively. Thus, in the single knock-out strains, the number of DEGs was higher than the number of DEPs while in the double knock-out strain the number of DEPs was higher. Comparison of RNAseq and proteomic data further revealed, that only a small proportion of the transcriptional changes were reflected on the protein level. Gene ontology (GO) analysis revealed an enrichment of DEPs involved in lipid metabolism and oxidative phosphorylation. Furthermore, we found increased expression of the anti-oxidant enzymes glutathione reductase (gsr) and catalase A (catA) in ATG16‾ and ATG9‾/16‾ cells, respectively, indicating adaptation to excess reactive oxygen species (ROS).

Conclusions
Our study provides the first combined transcriptome and proteome analysis of ATG9‾, ATG16‾ and ATG9‾/16‾ cells. Our results suggest, that most changes in protein abundance were not caused by transcriptional changes, but were rather due to changes in protein homeostasis. In particular, knock-out of atg9 and/or atg16 appears to cause dysregulation of lipid metabolism and oxidative phosphorylation.