bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone Density Distribution in the Cervical Spine
Authors: Lovecchio Francis , Ang Bryan , Louie Philip K. , Chaudary Chirag , Shah Sachin P. , Punyala Ananth , Yao Yu-Cheng , Steinhaus Mike , McCarthy Michael H. , Huang Russel , Lebl Darren , Lafage Virginie , Albert Todd J. , Iyer Sravisht , Qureshi Sheeraz , Kim Han Jo 
Published: April 2022

Study Design Retrospective cohort study Objective Given changes in bone density induced by degenerative disease, general measures of bone health (ie DEXA) are inadequate to evaluate bone density in surgical areas of interest. Regional differences in HU in the cervical spine may influence surgical strategies. The purposes of our study were to determine whether cervical Hounsfield units (HU) vary by level, examine their relationship with age, comorbidities, and alignment, and propose a technique to measure HU in the lateral masses. Methods Two hundred twenty-four patients with degenerative spine pathology with a cervical computed tomography were included (2015-2019). Measurements were performed in each vertebral body (C2-T1; mid-axial, anterior-axial, posterior-axial, mid-coronal, and mid-sagittal) and 2 regions of the lateral masses (C3-C6; mid-cor, mid-sag). To evaluate reliability, 6 observers each measured 355 HU values, inter-relater reliability assessed with intraclass correlation coefficients Correlations of HU with age, BMI, comorbidities, and cervical alignment were evaluated. Results Bone density differed by level, with the lowest HU scores in the lower cervical spine (C6-T1) ( P < .001). No correlations were found between LM HU and age, BMI, CCI, or alignment ( P > .05). Increased kyphosis was weakly correlated with VB HU, while age and CCI showed moderate correlations with VB HU at all levels (P<.001). ICC for HU measurements were good to excellent for the VBs, but poor to moderate for the LMs. Conclusion Bone is least dense in the lower cervical spine. HU scoring is not reliable in the lateral masses. We recommend that a level-specific approach to bone density is considered in surgical planning.
Duty Hours Tracking – Is There an App for That?
Authors: Jorgensen Alexis , Savage Nastassia M. , Sun Xinxin , Domson Gregory 
Published: April 2022

BACKGROUND To monitor duty hour compliance residency programs have used self-report methods which can be skewed by recall bias and data falsification. The purpose of this study was to compare the accuracy of and resident attitudes towards two duty hours tracking tools within our Orthopedic residency. We compared our institution's current self-report method of duty hours tracking via New Innovations (NI) with an automated method utilizing Hours Tracker (HT), a smartphone application which automatically logs work hours via GPS coordinates. The primary outcome measures were number of duty hour violations and survey results on resident perceptions. METHODS The participants were 22 residents of our 25 resident Orthopedic program. Over four weeks, residents tracked duty hours through the standard, selfreport method (NI) and simultaneously through the automated app (HT). Residents also completed an anonymous survey at the end of the study related to perceptions of the methods. RESULTS There was no significant difference in overall number of violations between NI and HT. HT detected more violations of the 8 hours off requirement (12 vs. 5, p = 0.03). Survey data revealed residents found HT significantly easier to use (p = .004) and less burdensome (p < .001) but in greater violation of privacy (p = .001). Residents reported they were more likely to falsify their hours when using NI (p = .002) and that the results of NI would be more likely used against them (p = .042). When analyzing by training year, junior residents indicated HT was overall easier to use than senior residents (p = .048). CONCLUSIONS Our study showed NI and HT are at least equivalent in accuracy with the app being overall better received, particularly by junior level residents. Until we begin accurately tracking duty hours and engaging residents with an easy to use, well-received interface to which report hours, effective developmental program changes will be difficult to achieve. An app-based approach is a starting point for re-thinking duty hours tracking within this digital age.
Early vitrectomy in eyes with non-diabetic vitreous hemorrhage
Authors: Foo Edward , Grassi Piergiacomo , Spiteri-Cornish Kurt 
Published: April 2022

Background: Optimal management of non-diabetic vitreous hemorrhage (NDVH) is controversial, and reliability of B-scan ultrasonography in detecting retinal tears (RTs) has been reported to be highly variable by previous literature. Objectives: To report outcomes of conservative versus surgical management of NDVH and reliability of B-scan ultrasonography in detecting RTs and rhegmatogenous retinal detachment (RRD). Design: Retrospective observational single-center cohort study. Methods: Ninety-six consecutive NDVH from 96 eyes (96 patients) with minimum follow-up duration of 12 months were included. Results: Seventy-two eyes (75%) underwent early pars plana vitrectomy (PPV), 19 (20%) were managed conservatively and 5 (5%) underwent late PPV. Initial mean best corrected visual acuities (BCVAs) were 1.95 ± 1.19, 1.19 ± 1.38, and 1.14 ± 1.04 logMAR respectively, the difference was statistically significant ( p = 0.039). Mean final BCVAs were 0.92 ± 1.19, 0.59 ± 0.87, and 1.25 ± 1.89 logMAR, respectively, the difference was not significant ( p = 0.447). When comparing initial and final BCVAs, the difference was significant only in the early PPV group ( p = 0.00001) and was not significant in the conservative group ( p = 0.066) and in the late PPV group ( p = 0.46). Complications included RRD ( n = 2) and re-bleed in vitrectomized cavity ( n = 1) in the early surgical group, need for additional laser or cryoretinopexy to RTs ( n = 2), retinal detachment ( n = 1), neovascular glaucoma ( n = 1), persistent vitreous hemorrhage ( n = 2) in the conservative group. B-scan ultrasound showed preoperative 11.53% sensitivity and a 60.0% positive predictive value for diagnosing retinal tears (RTs) in NDVH. Conclusion: The benefit of early PPV in NDVH seems to outweigh the risks of surgery, especially in the context of low sensitivity of B-scan in identifying RTs, and significant improvement in final BCVA following surgery may occur. NDVH should be promptly referred to vitreoretinal services, as surgery may be a safer and more advisable option.
Infrared Spectroscopic Analysis in the Differentiation of Epithelial Misplacement From Adenocarcinoma in Sigmoid Colonic Adenomatous Polyps
Authors: Nallala Jayakrupakar , Griggs Rebecca , Lloyd Gavin R , Stone Nick , Shepherd Neil A 
Published: April 2022

Purpose: The differential diagnosis of epithelial misplacement from invasive cancer in the colon is a challenging endeavour, augmented by the introduction of bowel cancer population screening. The main aim of the work is to test, as a proof-of concept study, the ability of the infrared spectroscopic imaging approach to differentiate epithelial misplacement from adenocarcinoma in sigmoid colonic adenomatous polyps. Methods: Ten samples from each of the four diagnostic groups, normal colonic mucosa, adenomatous polyps with low grade dysplasia, epithelial misplacement in adenomatous polyps and adenocarcinoma, were analysed using IR spectroscopic imaging and data processing methods. IR spectral images were subjected to data pre-processing and cluster analysis based segmentation to identify epithelial, connective tissue and stromal regions. Statistical analysis was carried out using principal component analysis and linear discriminant analysis based cross validation, to classify spectral features according to the pathology, and the diagnostic attributes were compared. Results: The combined 4-group classification model on an average showed a sensitivity of 64%, a specificity of 88% and an accuracy of 76% for prediction based on a ‘single spectrum’, whilst a ‘majority-vote’ prediction on an average showed a sensitivity of 73%, a specificity of 90% and an accuracy of 82%. The 2-group model, for the differential diagnosis of epithelial misplacement versus adenocarcinoma, showed an average sensitivity and specificity of 82.5% for prediction based on a ‘single spectrum’ whilst a ‘majority-vote’ classification showed an average sensitivity and specificity of 90%. A 92% area under the curve (AUC) value was obtained when evaluating the classifier using the Receiver Operating Characteristics (ROC) curves. Conclusions: IR spectroscopy shows promise in its ability to differentiate epithelial misplacement from adenocarcinoma in tissue sections, considered as one of the most challenging endeavours in population-wide diagnostic histopathology. Further studies with larger series, including cases with challenging diagnostic features are required to ascertain the capability of this modern digital pathology approach. In the long-term, IR spectroscopy based pathology which is relatively low-cost and rapid, could be a promising endeavour to consider for integration into the existing histopathology pathway, in particular for population based screening programmes where large number of samples are scrutinised.
Mutated SETBP1 activates transcription of Myc programs to accelerate CSF3R-driven myeloproliferative neoplasms
Authors: Carratt Sarah A. , Kong Garth L. , Curtiss Brittany M. , Schonrock Zachary , Maloney Lauren , Maniaci Breanna N. , Blaylock Hunter Z. , Baris Adrian , Druker Brian J. , Braun Theodore P. , Maxson Julia E. 
Published: April 2022

Abstract
Colony stimulating factor 3 receptor (CSF3R) mutations lead to JAK pathway activation and are the molecular hallmark of chronic neutrophilic leukemia (CNL). Approximately half of patients with CNL also have mutations in SET binding protein 1 (SETBP1). In this study, we developed models of SETBP1-mutated leukemia to understand the role that SETBP1 plays in CNL. SETBP1 mutations promote self-renewal of CSF3R-mutated hematopoietic progenitors in vitro and prevent cells from undergoing terminal differentiation. In vivo, SETBP1 mutations accelerate leukemia progression, leading to the rapid development of hepatosplenomegaly and granulocytosis. Through transcriptomic and epigenomic profiling, we found that SETBP1 enhances progenitor-associated programs, most strongly upregulating Myc and Myc target genes. This upregulation of Myc can be reversed by LSD1 inhibitors. In summary, we found that SETBP1 mutations promote aggressive hematopoietic cell expansion when expressed with mutated CSF3R through the upregulation of Myc-associated gene expression programs.
There and back again: the once and current developments in donor-derived platelet products for hemostatic therapy
Authors: Kogler Valery J. , Stolla Moritz 
Published: April 2022

AbstractMore than 100 years ago, Duke transfused whole blood to a patient with thrombocytopenia to raise the platelet count and prevent bleeding. Since then, platelet transfusions have undergone numerous modifications from whole blood–derived platelet-rich plasma to apheresis-derived platelet concentrates. The storage time and temperature have also changed. The mandate to store platelets for a maximum of 5 to 7 days at room temperature has been challenged by recent clinical trial data, ongoing difficulties with transfusion-transmitted infections, and recurring periods of shortages that were further exacerbated by the COVID-19 pandemic. Alternative platelet storage approaches are as old as the first platelet transfusions. Cold-stored platelets may offer increased storage times (days) and improved hemostatic potential at the expense of reduced circulation time. Frozen (cryopreserved) platelets extend the storage time to years but require storage at −80°C and thawing before transfusion. Lyophilized platelets can be powder-stored for years at room temperature and reconstituted within minutes in sterile water but are probably the least explored alternative platelet product to date. Finally, whole blood offers the hemostatic spectrum of all blood components but has challenges such as ABO incompatibility. We know more than ever before about the in vitro properties of these products, and clinical trial data are accumulating. The purpose of this review is to summarize the findings of recent preclinical and clinical studies on alternative, donor-derived platelet products.
Loss of METTL3 attenuates blastic plasmacytoid dendritic cell neoplasm response to PRMT5 inhibition via IFN signaling
Authors: Rethnam Malini , Tan Darren Qiancheng , Tan Shi Hao , Li Jia , Yokomori Rui , Li Ying , Yang Henry , Sanda Takaomi , Suda Toshio 
Published: April 2022

Abstract
Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive hematologic malignancy with poor clinical outcomes. Dysregulated MYC expression, which is associated with protein arginine methyltransferase 5 (PRMT5) dependency, is a recurrent feature of BPDCN. Although recent studies have reported a PRMT5 gene signature in BPDCN patient samples, the role of PRMT5 in BPDCN remains unexplored. Here, we demonstrate that BPDCN is highly sensitive to PRMT5 inhibition. Consistent with the upregulation of PRMT5 in BPDCN, we show that pharmacological inhibition (GSK3326595) of PRMT5 inhibits the growth of the patient-derived BPDCN cell line CAL-1 in vitro and mitigated tumor progression in our mouse xenograft model. Interestingly, RNA-sequencing (RNA-seq) analysis revealed that PRMT5 inhibition increases intron retention in several key RNA methylation genes, including METTL3, which was accompanied by a dose-dependent decrease in METTL3 expression. Notably, the function of cellular m6A RNA modification of METTL3 was also affected by PRMT5 inhibition in CAL-1 cells. Intriguingly, METTL3 depletion in CAL-1 caused a significant increase in interferon (IFN) signaling, which was further elevated upon PRMT5 inhibition. Importantly, we discovered that this increase in IFN signaling attenuated the sensitivity of METTL3-depleted CAL-1 cells to PRMT5 inhibition. Correspondingly, stimulation of IFN signaling via TLR7 agonists weakened CAL-1 cell sensitivity to PRMT5 inhibition. Overall, our findings implicate PRMT5 as a therapeutic target in BPDCN and provide insight into the involvement of METTL3 and the IFN pathway in regulating the response to PRMT5 inhibition.
Distinct clinical and genetic features of hepatitis B virus–associated follicular lymphoma in Chinese patients
Authors: Ren Weicheng , Wang Xianhuo , Yang Mingyu , Wan Hui , Li Xiaobo , Ye Xiaofei , Meng Bing , Li Wei , Yu Jingwei , Lei Mengyue , Xie Fanfan , Jiang Wenqi , Kimby Eva , Huang Huiqiang , Liu Dongbing , Li Zhi-Ming , Wu Kui , Zhang Huilai , Pan-Hammarström Qiang 
Published: April 2022

Abstract
Hepatitis B virus (HBV) infection has been associated with an increased risk for B-cell lymphomas. We previously showed that 20% of diffuse large B-cell lymphoma (DLBCL) patients from China, an endemic area of HBV infection, have chronic HBV infection (surface antigen–positive, HBsAg+) and are characterized by distinct clinical and genetic features. Here, we showed that 24% of follicular lymphoma (FL) Chinese patients are HBsAg+. Compared with the HBsAg− FL patients, HBsAg+ patients are younger, have a higher histological grade at diagnosis, and have a higher incidence of disease progression within 24 months. Moreover, by sequencing the genomes of 109 FL tumors, we observed enhanced mutagenesis and distinct genetic profile in HBsAg+ FLs, with a unique set of preferentially mutated genes (TNFAIP3, FAS, HIST1H1C, KLF2, TP53, PIM1, TMSB4X, DUSP2, TAGAP, LYN, and SETD2) but lack of the hallmark of HBsAg− FLs (ie, IGH/BCL2 translocations and CREBBP mutations). Transcriptomic analyses further showed that HBsAg+ FLs displayed gene-expression signatures resembling the activated B-cell–like subtype of diffuse large B-cell lymphoma, involving IRF4-targeted genes and NF-κB/MYD88 signaling pathways. Finally, we identified an increased infiltration of CD8+ memory T cells, CD4+ Th1 cells, and M1 macrophages and higher T-cell exhaustion gene signature in HBsAg+ FL samples. Taken together, we present new genetic/epigenetic evidence that links chronic HBV infection to B-cell lymphomagenesis, and HBV-associated FL is likely to have a distinct cell-of-origin and represent as a separate subtype of FL. Targetable genetic/epigenetic alterations identified in tumors and their associated tumor microenvironment may provide potential novel therapeutic approaches for this subgroup of patients.
Preinfusion factors impacting relapse immunophenotype following CD19 CAR T cells
Authors: Lamble Adam J. , Myers Regina M. , Taraseviciute Agne , John Samuel , Yates Bonnie , Steinberg Seth M. , Sheppard Jennifer , Kovach Alexandra E. , Wood Brent , Borowitz Michael J. , Stetler-Stevenson Maryalice , Yuan Constance M. , Pillai Vinodh , Foley Toni , Chung Perry , Chen Lee , Lee Daniel W. , Annesley Colleen , DiNofia Amanda , Grupp Stephan A. , Verneris Michael R. , Gore Lia , Laetsch Theodore W. , Bhojwani Deepa , Brown Patrick A. , Pulsipher Michael A. , Rheingold Susan R. , Gardner Rebecca A. , Shah Nirali N. 
Published: April 2022

Abstract
Relapse following chimeric antigen receptor (CAR) T-cell therapy directed against CD19 for relapsed/refractory B-acute lymphoblastic leukemia (r/r B-ALL) remains a significant challenge. Three main patterns of relapse predominate: CD19 positive (CD19pos) relapse, CD19 negative (CD19neg) relapse, and lineage switch (LS). Development and validation of risk factors that predict relapse phenotype could help define potential pre- or post-CAR T-cell infusion interventions aimed at decreasing relapse. Our group sought to extensively characterize preinfusion risk factors associated with the development of each relapse pattern via a multicenter, retrospective review of children and young adults with r/r B-ALL treated with a murine-based CD19-CAR construct. Of 420 patients treated with CAR, 166 (39.5%) relapsed, including 83 (50%) CD19pos, 68 (41%) CD19neg, and 12 (7.2%) LS relapses. A greater cumulative number of prior complete remissions was associated with CD19pos relapses, whereas high preinfusion disease burden, prior blinatumomab nonresponse, older age, and 4-1BB CAR construct were associated with CD19neg relapses. The presence of a KMT2A rearrangement was the only preinfusion risk factor associated with LS. The median overall survival following a post-CAR relapse was 11.9 months (95% CI, 9-17) and was particularly dismal in patients experiencing an LS, with no long-term survivors following this pattern of relapse. Given the poor outcomes for those with post-CAR relapse, study of relapse prevention strategies, such as consolidative hematopoietic stem cell transplantation, is critical and warrants further investigation on prospective clinical trials.
Optimal reperfusion strategy in acute high-risk pulmonary embolism requiring extracorporeal membrane oxygenation support: a systematic review and meta-analysis
Authors: Chopard Romain , Nielsen Peter , Ius Fabio , Cebotari Serghei , Ecarnot Fiona , Pilichowski Hugo , Schmidt Matthieu , Kjaergaard Benedict , Sousa-Casasnovas Iago , Ghoreishi Mehrdad , Narayan Rajeev L. , Lee Su Nam , Piazza Gregory , Meneveau Nicolas 
Published: April 2022

BackgroundThe optimal pulmonary revascularisation strategy in high-risk pulmonary embolism (PE) requiring implantation of extracorporeal membrane oxygenation (ECMO) remains controversial.MethodsWe conducted a systematic review and meta-analysis of evidence comparing mechanical embolectomy and other strategies, including systemic thrombolysis, catheter-directed thrombolysis or ECMO as stand-alone therapy, with regard to mortality and bleeding outcomes.ResultsWe identified 835 studies, 17 of which were included, comprising 327 PE patients. Overall, 32.4% were treated with mechanical pulmonary reperfusion (of whom 85.9% had surgical embolectomy), while 67.6% received other strategies. The mortality rate was 22.6% in the mechanical reperfusion group and 42.8% in the “other strategies” group. The pooled odds ratio for mortality with mechanical reperfusion was 0.439 (95% CI 0.237–0.816) (p=0.009; I2=35.2%)versusother reperfusion strategies and 0.368 (95% CI 0.185–0.733) (p=0.004; I2=32.9%) for surgical embolectomyversusthrombolysis. The rate of bleeding in patients under ECMO was 22.2% in the mechanical reperfusion group and 19.1% in the “other strategies” group (OR 1.27, 95% CI 0.54–2.96; I2=7.7%). The meta-regression model did not identify any relationship between the covariates “more than one pulmonary reperfusion therapy”, “ECMO implantation before pulmonary reperfusion therapy”, “clinical presentation of PE” or “cancer-associated PE” and the associated outcomes.ConclusionsThe results of the present meta-analysis and meta-regression suggest that mechanical reperfusion, notably by surgical embolectomy, may yield favourable results regardless of the timing of ECMO implantation in the reperfusion timeline, independent of thrombolysis administration or cardiac arrest presentation.
Predictors of chronic obstructive pulmonary disease in women who have never smoked: a cohort study
Authors: Engel Roger M. , de Luca Katie , Graham Petra L. , Kaboli Farshchi Masoumeh , Vemulpad Subramanyam , Byles Julie 
Published: April 2022

COPD is responsible for an increasing number of deaths worldwide. Smoking is the most reliable predictor for developing COPD later in life. However, women make up the majority of patients with COPD who have never smoked. There is therefore a need to identify other factors that can predict COPD in women. The aim of this study is to identify factors associated with increasing the risk of developing COPD later in life in women who have never smoked.Data from the Australian Longitudinal Study on Women's Health (ALSWH) cohort born between 1946 and 1951 were used to investigate potential predictors of COPD. Retrospective analyses were performed on data from two of the ALSWH surveys: wave 1 (1996) and wave 9 (2019).There were 3584 women who self-reported as being never-smokers (at waves 1 and 9) and did not have COPD at baseline, of which 109 had developed COPD at wave 9. Logistic regression showed a significant relationship between COPD at wave 9 and baseline breathing difficulties (p<0.001), asthma (p<0.001) and allergies (p=0.026), though significance of asthma and allergies disappeared when included together in a single model, implying that women with these symptoms earlier in life were more likely to be diagnosed with COPD later in life compared to women without these symptoms.Our study supports the inclusion of lung function testing in primary care settings for women over the age of 45 years who have never smoked and have a history of breathing difficulties, asthma or allergies.