bluuebunny/crossref_metadata_2025_split huggingface dataset:
Frequent somatic TET2 mutations in chronic NK-LGL leukemia with distinct patterns of cytopenias
Authors: Olson Thomas L. , Cheon HeeJin , Xing Jeffrey C. , Olson Kristine C. , Paila Umadevi , Hamele Cait E. , Neelamraju Yaseswini , Shemo Bryna C. , Schmachtenberg Matt , Sundararaman Shriram K. , Toro Mariella F. , Keller Cheryl A. , Farber Emily A. , Onengut-Gumuscu Suna , Garrett-Bakelman Francine E. , Hardison Ross C. , Feith David J. , Ratan Aakrosh , Loughran Thomas P. 
Published: March 2021

Abstract
Chronic natural killer large granular lymphocyte (NK-LGL) leukemia, also referred to as chronic lymphoproliferative disorder of NK cells, is a rare disorder defined by prolonged expansion of clonal NK cells. Similar prevalence of STAT3 mutations in chronic T-LGL and NK-LGL leukemia is suggestive of common pathogenesis. We undertook whole-genome sequencing to identify mutations unique to NK-LGL leukemia. The results were analyzed to develop a resequencing panel that was applied to 58 patients. Phosphatidylinositol 3-kinase pathway gene mutations (PIK3CD/PIK3AP1) and TNFAIP3 mutations were seen in 5% and 10% of patients, respectively. TET2 was exceptional in that mutations were present in 16 (28%) of 58 patient samples, with evidence that TET2 mutations can be dominant and exclusive to the NK compartment. Reduced-representation bisulfite sequencing revealed that methylation patterns were significantly altered in TET2 mutant samples. The promoter of TET2 and that of PTPRD, a negative regulator of STAT3, were found to be methylated in additional cohort samples, largely confined to the TET2 mutant group. Mutations in STAT3 were observed in 19 (33%) of 58 patient samples, 7 of which had concurrent TET2 mutations. Thrombocytopenia and resistance to immunosuppressive agents were uniquely observed in those patients with only TET2 mutation (Games-Howell post hoc test, P = .0074; Fisher’s exact test, P = .00466). Patients with STAT3 mutation, inclusive of those with TET2 comutation, had lower hematocrit, hemoglobin, and absolute neutrophil count compared with STAT3 wild-type patients (Welch’s t test, P ≤ .015). We present the discovery of TET2 mutations in chronic NK-LGL leukemia and evidence that it identifies a unique molecular subtype.
The characterization of distinct populations of murine skeletal cells that have different roles in B lymphopoiesis
Authors: Green Alanna C. , Tjin Gavin , Lee Samuel C. , Chalk Alistair M. , Straszkowski Lenny , Kwang Diannita , Baker Emma K. , Quach Julie M. , Kimura Takaharu , Wu Joy Y. , Purton Louise E. 
Published: March 2021

AbstractHematopoiesis is extrinsically controlled by cells of the bone marrow microenvironment, including skeletal lineage cells. The identification and subsequent studies of distinct subpopulations of maturing skeletal cells is currently limited because of a lack of methods to isolate these cells. We found that murine Lin–CD31–Sca-1–CD51+ cells can be divided into 4 subpopulations by using flow cytometry based on their expression of the platelet-derived growth factor receptors ⍺ and β (PDGFR⍺ and PDGFRβ). The use of different skeletal lineage reporters confirmed the skeletal origin of the 4 populations. Multiplex immunohistochemistry studies revealed that all 4 populations were localized near the growth plate and trabecular bone and were rarely found near cortical bone regions or in central bone marrow. Functional studies revealed differences in their abundance, colony-forming unit–fibroblast capacity, and potential to differentiate into mineralized osteoblasts or adipocytes in vitro. Furthermore, the 4 populations had distinct gene expression profiles and differential cell surface expression of leptin receptor (LEPR) and vascular cell adhesion molecule 1 (VCAM-1). Interestingly, we discovered that 1 of these 4 different skeletal populations showed the highest expression of genes involved in the extrinsic regulation of B lymphopoiesis. This cell population varied in abundance between distinct hematopoietically active skeletal sites, and significant differences in the proportions of B-lymphocyte precursors were also observed in these distinct skeletal sites. This cell population also supported pre-B lymphopoiesis in culture. Our method of isolating 4 distinct maturing skeletal populations will help elucidate the roles of distinct skeletal niche cells in regulating hematopoiesis and bone.
Outcomes and prognostic factors in angioimmunoblastic T-cell lymphoma: final report from the international T-cell Project
Authors: Advani Ranjana H. , Skrypets Tetiana , Civallero Monica , Spinner Michael A. , Manni Martina , Kim Won Seog , Shustov Andrei R. , Horwitz Steven M. , Hitz Felicitas , Cabrera Maria Elena , Dlouhy Ivan , Vassallo José , Pileri Stefano A. , Inghirami Giorgio , Montoto Silvia , Vitolo Umberto , Radford John , Vose Julie M. , Federico Massimo 
Published: March 2021

Abstract
Angioimmunoblastic T-cell lymphoma (AITL) is a unique subtype of peripheral T-cell lymphoma (PTCL) with distinct clinicopathologic features and poor prognosis. We performed a subset analysis of 282 patients with AITL enrolled between 2006 and 2018 in the international prospective T-cell Project (NCT01142674). The primary and secondary end points were 5-year overall survival (OS) and progression-free survival (PFS), respectively. We analyzed the prognostic impact of clinical covariates and progression of disease within 24 months (POD24) and developed a novel prognostic score. The median age was 64 years, and 90% of patients had advanced-stage disease. Eighty-one percent received anthracycline-based regimens, and 13% underwent consolidative autologous stem cell transplant (ASCT) in first complete remission (CR1). Five-year OS and PFS estimates were 44% and 32%, respectively, with improved outcomes for patients who underwent ASCT in CR1. In multivariate analysis, age ≥60 years, Eastern Cooperative Oncology Group performance status &gt;2, elevated C-reactive protein, and elevated β2 microglobulin were associated with inferior outcomes. A novel prognostic score (AITL score) combining these factors defined low-, intermediate-, and high-risk subgroups with 5-year OS estimates of 63%, 54%, and 21%, respectively, with greater discriminant power than established prognostic indices. Finally, POD24 was a powerful prognostic factor with 5-year OS of 63% for patients without POD24 compared with only 6% for patients with POD24 (P &lt; .0001). These data will require validation in a prospective cohort of homogeneously treated patients. Optimal treatment of AITL continues to be an unmet need, and novel therapeutic approaches are required.
Prediction and analysis of multiple protein lysine modified sites based on conditional wasserstein generative adversarial networks
Authors: Yang Yingxi , Wang Hui , Li Wen , Wang Xiaobo , Wei Shizhao , Liu Yulong , Xu Yan 
Published: March 2021

AbstractBackgroundProtein post-translational modification (PTM) is a key issue to investigate the mechanism of protein’s function. With the rapid development of proteomics technology, a large amount of protein sequence data has been generated, which highlights the importance of the in-depth study and analysis of PTMs in proteins.MethodWe proposed a new multi-classification machine learning pipeline MultiLyGAN to identity seven types of lysine modified sites. Using eight different sequential and five structural construction methods, 1497 valid features were remained after the filtering by Pearson correlation coefficient. To solve the data imbalance problem, Conditional Generative Adversarial Network (CGAN) and Conditional Wasserstein Generative Adversarial Network (CWGAN), two influential deep generative methods were leveraged and compared to generate new samples for the types with fewer samples. Finally, random forest algorithm was utilized to predict seven categories.ResultsIn the tenfold cross-validation, accuracy (Acc) and Matthews correlation coefficient (MCC) were 0.8589 and 0.8376, respectively. In the independent test, Acc and MCC were 0.8549 and 0.8330, respectively. The results indicated that CWGAN better solved the existing data imbalance and stabilized the training error. Alternatively, an accumulated feature importance analysis reported that CKSAAP, PWM and structural features were the three most important feature-encoding schemes. MultiLyGAN can be found athttps://github.com/Lab-Xu/MultiLyGAN.ConclusionsThe CWGAN greatly improved the predictive performance in all experiments. Features derived from CKSAAP, PWM and structure schemes are the most informative and had the greatest contribution to the prediction of PTM.
Ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in mediastinal mass resection by median sternotomy: a randomized, double-blind, placebo-controlled trial
Authors: Chen Hexiang , Song Wenqin , Wang Wei , Peng Yawen , Zhai Chunchun , Yao Lihua , Xia Zhongyuan 
Published: March 2021

AbstractBackgroundUltrasound-guided parasternal intercostal nerve block is rarely used for postoperative analgesia, and its value remains unclear. This study aimed to evaluate the effectiveness of ultrasound-guided parasternal intercostal nerve block for postoperative analgesia in patients undergoing median sternotomy for mediastinal mass resection.MethodsThis randomized, double-blind, placebo-controlled trial performed in Renmin Hospital, Wuhan University, enrolled 41 participants aged 18–65 years. The patients scheduled for mediastinal mass resection by median sternotomy were randomly assigned were randomized into 2 groups, and preoperatively administered 2 injections of ropivacaine (PSI) and saline (control) groups, respectively, in the 3rd and 5th parasternal intercostal spaces with ultrasound-guided (USG) bilateral parasternal intercostal nerve block. Sufentanil via patient-controlled intravenous analgesia (PCIA) was administered to all participants postoperatively. Pain score, total sufentanil consumption, and postoperative adverse events were recorded within the first 24 h.ResultsThere were 20 and 21 patients in the PSI and control group, respectively. The PSI group required 20% less PCIA-sufentanil compared with the control group (54.05 ± 11.14 μg vs. 67.67 ± 8.92 μg,P < 0.001). In addition, pain numerical rating scale (NRS) scores were significantly lower in the PSI group compared with control patients, both at rest and upon coughing within 24 postoperative hours. Postoperative adverse events were generally reduced in the PSI group compared with controls.ConclusionsUSG bilateral parasternal intercostal nerve block effectively reduces postoperative pain and adjuvant analgesic requirement, with good patient satisfaction, therefore constituting a good option for mediastinal mass resection by median sternotomy.
Risk factors for electrocardiographic left ventricular hypertrophy in a young Chinese general population: the Hanzhong adolescent cohort study
Authors: Liao Yue-Yuan , Gao Ke , Fu Bo-Wen , Yang Lei , Zhu Wen-Jing , Ma Qiong , Chu Chao , Yan Yu , Wang Yang , Zheng Wen-Ling , Hu Jia-Wen , Wang Ke-Ke , Sun Yue , Chen Chen , Mu Jian-Jun 
Published: March 2021

Abstract
Background
Electrocardiographic left ventricular hypertrophy (ECG-LVH) is a common manifestation of preclinical cardiovascular disease. The present study aimed to investigate risk factors for ECG-LVH and its prevalence in a cohort of young Chinese individuals.

Methods
(1) A total of 1515 participants aged 36–45 years old from our previously established cohort who were followed up in 2017 were included. Cross-sectional analysis was used to examine risk factors for ECG-LVH and its prevalence. (2) A total of 235 participants were recruited from the same cohort in 2013 and were followed up in 2017. Longitudinal analysis was used to determine the predictors of LVH occurrence over the 4-year period. We used multivariable logistic regression models to calculate OR and 95% CIs and to analyze risk factors for ECG-LVH.

Results
In the cross-sectional analysis, the prevalence of LVH diagnosed by the Cornell voltage-duration product in the overall population and the hypertensive population was 4.6% and 8.8%, respectively. The logistic regression results shown that female sex [2.611 (1.591–4.583)], hypertension [2.638 (1.449–4.803)], systolic blood pressure (SBP) [1.021 (1.007–1.035)], serum uric acid (SUA) [1.004 (1.001–1.006)] and carotid intima-media thickness (CIMT) [67.670 (13.352–342.976)] were significantly associated with the risk of LVH (all P < 0.05). In the longitudinal analysis, fasting glucose [1.377 (1.087–1.754)], SBP [1.046 (1.013–1.080)] and female sex [1.242 (1.069–1.853)] were independent predictors for the occurrence of LVH in the fourth year of follow-up.

Conclusions
Our study suggested that female sex, hypertension, SBP, SUA and CIMT were significantly associated with the risk of LVH in young people. In addition, fasting glucose, SBP and female sex are independent predictors of the occurrence of LVH in a young Chinese general population.
Uncovering unsuspected advanced liver fibrosis in patients referred to alcohol nurse specialists using the ELF test
Authors: Rhodes Freya , Cococcia Sara , Panovska-Griffiths Jasmina , Tanwar Sudeep , Westbrook Rachel H. , Rodger Alison , Rosenberg William M. 
Published: March 2021

Abstract
Background and aims
Alcohol use disorders (AUD) cause 7.2% of UK hospital admissions/year. Most are not managed by hepatologists and liver disease may be missed. We used the Enhanced Liver Fibrosis (ELF) test to investigate prevalence and associations of occult advanced liver fibrosis in AUD patients not known to have liver fibrosis.

Methods
Liver fibrosis was assessed using ELF in prospective patients referred to the Royal Free Hospital Alcohol Specialist Nurse (November 2018–December 2019). Known cases of liver disease were excluded. Patient demographics, blood tests, imaging data and alcohol histories recorded. Advanced fibrosis was categorised as ELF ≥ 10.5.

Results
The study included 99 patients (69% male, mean age 53.1 ± 14.4) with median alcohol intake 140 units/week (IQR 80.9–280), and a mean duration of harmful drinking of 15 years (IQR 10–27.5). The commonest reason for admission was symptomatic alcohol withdrawal (36%). The median ELF score was 9.62, range 6.87–13.78. An ELF score ≥ 10.5 was recorded in 28/99 (29%) patients, of whom 28.6% had normal liver tests. Within previous 5-years, 76% had attended A&E without assessment of liver disease. The ELF score was not associated with recent alcohol intake (p = 0.081), or inflammation (p = 0.574).

Conclusion
Over a quarter of patients with AUD had previously undetected advanced liver fibrosis assessed by ELF testing. ELF was not associated with liver inflammation or recent alcohol intake. The majority had recent missed opportunities for investigating liver disease. We recommend clinicians use non-invasive tests to assess liver fibrosis in patients admitted to hospital with AUD.
Efficacy of quetiapine for delirium prevention in hospitalized older medical patients: a randomized double-blind controlled trial
Authors: Thanapluetiwong Saran , Ruangritchankul Sirasa , Sriwannopas Orapitchaya , Chansirikarnjana Sirintorn , Ittasakul Pichai , Ngamkala Tipanetr , Sukumalin Lalita , Charernwat Piangporn , Saranburut Krittika , Assavapokee Taweevat 
Published: March 2021

Abstract
Background
Delirium is a common disorder among hospitalized older patients and results in increased morbidity and mortality. The prevention of delirium is still challenging in older patient care. The role of antipsychotics in delirium prevention has been limited. Therefore, we conducted a trial to investigate the efficacy of quetiapine use to prevent delirium in hospitalized older medical patients.

Methods
This study was a randomized double-blind controlled trial conducted at Ramathibodi Hospital, Bangkok, Thailand. Patients aged ≥65 years hospitalized in the internal medicine service were randomized to quetiapine 12.5 mg or placebo once daily at bedtime for a maximum 7-day duration. The primary end point was delirium incidence. Secondary end points were delirium duration, length of hospital stay, ICU admission, rehospitalization and mortality within 30 and 90 days.

Results
A total of 122 patients were enrolled in the study. Eight (6.6%) left the trial before receiving the first dose of the intervention, whereas 114 (93.4%) were included in an intention-to-treat analysis allocated to the quetiapine or placebo group (n = 57 each). The delirium incidence rates in the quetiapine and placebo groups were 14.0 and 8.8% (OR = 1.698, 95% CI 0.520–5.545, P = 0.381), respectively. Other endpoints in the quetiapine and placebo groups were the median length of hospital stay, 6 (4–8) days versus 5 (4–8) days (P = 0.133), respectively; delirium duration, 4 (2.3–6.5) versus 3 (1.5–4.0) days (P = 0.557), respectively; ICU admission, 3 (5.3%) patients from both groups (P = 1.000); and mortality in the quetiapine and placebo groups, 1 (1.8%) versus 2 (3.5%) at 30 days (P = 0.566) and 7 (12.3%) versus 9 (15.8%) days at 90 days (P = 0.591). There were no significant differences in other outcomes. None of the participants reported adverse events.

Conclusions
Quetiapine prophylaxis did not reduce delirium incidence in hospitalized older medical patients. The use of quetiapine to prevent delirium in this population group should not be recommended.

Trial registration
This trial was retrospectively registered with the Thai clinical trials registry (TCTR) at clinicaltrials.in.th (TCTR20190927001) on September 26, 2019.
Reduction in unplanned hospitalizations associated with a physician focused intervention to reduce potentially inappropriate medication use among older adults: a population-based cohort study
Authors: Alcusky M. , Thomas R. B. , Jafari N. , Keith S. W. , Kee A. , Del Canale S. , Lombardi M. , Maio V. 
Published: March 2021

Abstract
Background
A multimodal general practitioner-focused intervention in the Local Health Authority (LHA) of Parma, Italy, substantially reduced the prevalence of potentially inappropriate medication (PIM) use among older adults. Our objective was to estimate changes in hospitalization rates associated with the Parma LHA quality improvement initiative that reduced PIM use.

Methods
This population-based longitudinal cohort study was conducted among older residents (> 65 years) using the Parma LHA administrative healthcare database. Crude and adjusted unplanned hospitalization rates were estimated in 3 periods (pre-intervention: 2005–2008, intervention: 2009–2010, post-intervention: 2011–2014). Multivariable negative binomial models estimated trends in quarterly hospitalization rates among individuals at risk during each period using a piecewise linear spline for time, adjusted for time-dependent and time-fixed covariates.

Results
The pre-intervention, intervention, and post-intervention periods included 117,061, 107,347, and 121,871 older adults and had crude hospitalization rates of 146.2 (95% CI: 142.2–150.3), 146.8 (95% CI: 143.6–150.0), and 140.8 (95% CI: 136.9–144.7) per 1000 persons per year, respectively. The adjusted pre-intervention hospitalization rate was declining by 0.7% per quarter (IRR = 0.993; 95% CI: 0.991–0.995). The hospitalization rate declined more than twice as fast during the intervention period (1.8% per quarter, IRR = 0.982; 95% CI: 0.979–0.985) and was nearly constant post-intervention (IRR: 0.999; 95% CI: 0.997–1.001). Contrasting model predictions for the intervention period (Q1 2009 to Q4 2010), the intervention was associated with 1481 avoided hospitalizations.

Conclusion
In a large population of older adults, a multimodal general practitioner-focused intervention to decrease PIM use was associated with a decline in the unplanned hospitalization rate. Such interventions to reduce high risk medication use among older adults warrant consideration by health systems seeking to improve health outcomes and reduce high-cost acute care utilization.
Cross-cultural adaptation and validation of the Finnish version of the central sensitization inventory and its relationship with dizziness and postural control
Authors: Mikkonen Jani , Luomajoki Hannu , Airaksinen Olavi , Neblett Randy , Selander Tuomas , Leinonen Ville 
Published: March 2021

Abstract
Background
Central Sensitization (CS) involves dysfunction in neurophysiological mechanisms that increase neuronal responses to both noxious and non-noxious stimuli in the central nervous system. The Central Sensitization Inventory (CSI) is considered the leading patient-reported outcome measure for assessing CS-related symptoms. The aim of this study was to translate and cross-culturally adapt the CSI into Finnish (CSI-FI) and to evaluate its psychometric properties.

Methods
Translation and cross-cultural validation of the CSI was conducted according to established guidelines. The validation sample was 229 subjects, including 42 pain free controls and 187 subjects with chronic musculoskeletal pain. The CSI-FI was evaluated for internal consistency, test-retest reliability, exploratory factor analysis with maximum likelihood extraction, relationship with subject-reported outcome measures [Tampa scale of kinesiophobia (TSK), the Depression scale (DEPS), 5-level EQ-5D version (EQ-5 L-5D), Roland-Morris Disability Questionnaire (RMDQ), and Pain and Sleep Questionnaire Three-Item Index (PSQ-3)], pain history, subjective symptoms of dizziness, and CS-related diagnoses on CSI part B. Furthermore, we studied the ability of the CSI-FI to distinguish pain free controls, subjects with chronic pain in a single body area, and subjects with multisite chronic pain. In addition, we studied the relationship of CSI-FI scores with postural control on a force plate.

Results
The CSI-FI demonstrated good internal consistency (0.884) and excellent test-retest reliability (0.933) with a 7 ± 1 day gap between test administrations. Exploratory factor analysis with maximum likelihood extraction yielded a one factor solution. Fair to good correlations were found between the CSI-FI and the TSK, DEPS, EQ-5 L-5D, RMDQ, and PSQ-3. Subjective symptoms of dizziness correlated better with CSI-FI scores than any of the CS-related diagnoses on CSI part B. Total CSI-FI scores successfully distinguished between pain free controls, subjects with chronic pain in a single body area, and subjects with multisite chronic pain. The multisite pain group reported significantly more dizziness symptoms than the other two groups. Force plate measurements showed no relationship between postural control and CSI-FI scores.

Conclusion
The CSI-FI translation was successfully cross-culturally adapted and validated into Finnish. CSI-FI psychometric properties and scores were all in acceptable levels and in line with previous CSI validations. The CSI-FI appears to be a valid and reliable instrument for assessing CS-related symptomology in Finnish-speaking populations.