bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tumor suppressor function of Gata2 in acute promyelocytic leukemia
Authors: Katerndahl Casey D. S. , Rogers Olivia R. S. , Day Ryan B. , Cai Michelle A. , Rooney Timothy P. , Helton Nichole M. , Hoock Mieke , Ramakrishnan Sai Mukund , Nonavinkere Srivatsan Sridhar , Wartman Lukas D. , Miller Christopher A. , Ley Timothy J. 
Published: June 2021

Abstract
Most patients with acute promyelocytic leukemia (APL) can be cured with combined all-trans retinoic acid (ATRA) and arsenic trioxide therapy, which induces the destruction of PML-RARA, the initiating fusion protein for this disease. However, the underlying mechanisms by which PML-RARA initiates and maintains APL cells are still not clear. Therefore, we identified genes that are dysregulated by PML-RARA in mouse and human APL cells and prioritized GATA2 for functional studies because it is highly expressed in preleukemic cells expressing PML-RARA, its high expression persists in transformed APL cells, and spontaneous somatic mutations of GATA2 occur during APL progression in mice and humans. These and other findings suggested that GATA2 may be upregulated to thwart the proliferative signal generated by PML-RARA and that its inactivation by mutation (and/or epigenetic silencing) may accelerate disease progression in APL and other forms of acute myeloid leukemia (AML). Indeed, biallelic knockout of Gata2 with CRISPR/Cas9-mediated gene editing increased the serial replating efficiency of PML-RARA–expressing myeloid progenitors (as well as progenitors expressing RUNX1-RUNX1T1, or deficient for Cebpa), increased mouse APL penetrance, and decreased latency. Restoration of Gata2 expression suppressed PML-RARA–driven aberrant self-renewal and leukemogenesis. Conversely, addback of a mutant GATA2R362G protein associated with APL and AML minimally suppressed PML-RARA–induced aberrant self-renewal, suggesting that it is a loss-of-function mutation. These studies reveal a potential role for Gata2 as a tumor suppressor in AML and suggest that restoration of its function (when inactivated) may provide benefit for AML patients.
Laparoscopic uterosacral ligament suspension versus sacrospinous ligament fixation for apical prolapse: perioperative outcomes
Authors: Gabra Martina G. , Winget Veronica , Torabi Mohammad T. , Addis Ilana , Hatch Kenneth , Heusinkveld John 
Published: June 2021

Abstract
Background
Pelvic organ prolapse can be repaired vaginally or laparoscopically. Studies comparing vaginal repair with sacrospinous ligament fixation (SSLF) or uterosacral ligament suspension (V-USLS) have found no difference in functional or adverse outcomes. Laparoscopic USLS (L-USLS) is becoming a popular treatment for pelvic organ prolapse because it has a low rate of ureteral compromise. To date, no studies have compared perioperative outcomes between L-USLS and SSLF. The objective of this study is to compare the rates of perioperative complications between these two methods.

Methods
This was a retrospective chart review of 243 consecutive patients who underwent L-USLS or SSLF at one institution between March 2017 and August 2019 for apical pelvic organ prolapse. Descriptive data was analyzed as appropriate with Student’s t tests and chi-square. Univariable logistic regression analysis was performed to assess predictors of perioperative complications.

Results
Preoperative Pelvic Organ Prolapse Quantification Stage (POP-Q) was similar between the two cohorts (p = 0.23). After adjusting for confounding factors, L-USLS was associated with a longer operative time (118 vs 142 min, p < 0.01) and shorter length of hospitalization (0.68 vs 1.06 days, p < 0.01). The estimated blood loss between the procedures was not statistically significant after adjusting for confounding factors. There was no difference in perioperative complication rates between L-USLS and SSLF (5% vs 7%, p = 0.55). No clinical risk factors were significantly associated with perioperative complications.

Conclusion
We did not find a difference in complications between L-USLS and SSLF.
Identification of genomic regions affecting production traits in pigs divergently selected for feed efficiency
Authors: Delpuech Emilie , Aliakbari Amir , Labrune Yann , Fève Katia , Billon Yvon , Gilbert Hélène , Riquet Juliette 
Published: June 2021

Abstract
Background
Feed efficiency is a major driver of the sustainability of pig production systems. Understanding the biological mechanisms that underlie these agronomic traits is an important issue for environment questions and farms' economy. This study aimed at identifying genomic regions that affect residual feed intake (RFI) and other production traits in two pig lines divergently selected for RFI during nine generations (LRFI, low RFI; HRFI, high RFI).

Results
We built a whole dataset of 570,447 single nucleotide polymorphisms (SNPs) in 2426 pigs with records for 24 production traits after both imputation and prediction of genotypes using pedigree information. Genome-wide association studies (GWAS) were performed including both lines (global-GWAS) or each line independently (LRFI-GWAS and HRFI-GWAS). Forty-five chromosomal regions were detected in the global-GWAS, whereas 28 and 42 regions were detected in the HRFI-GWAS and LRFI-GWAS, respectively. Among these 45 regions, only 13 were shared between at least two analyses, and only one was common between the three GWAS but it affects different traits. Among the five quantitative trait loci (QTL) detected for RFI, two were close to QTL for meat quality traits and two pinpointed novel genomic regions that harbor candidate genes involved in cell proliferation and differentiation processes of gastrointestinal tissues or in lipid metabolism-related signaling pathways. In most cases, different QTL regions were detected between the three designs, which suggests a strong impact of the dataset structure on the detection power and could be due to the changes in allelic frequencies during the establishment of lines.

Conclusions
In addition to efficiently detecting known and new QTL regions for feed efficiency, the combination of GWAS carried out per line or simultaneously using all individuals highlighted chromosomal regions that affect production traits and presented significant changes in allelic frequencies across generations. Further analyses are needed to estimate whether these regions correspond to traces of selection or result from genetic drift.
Correlation between white blood cell count at admission and mortality in COVID-19 patients: a retrospective study
Authors: Zhu Bin , Feng Xiaokai , Jiang Chunguo , Mi Song , Yang Liya , Zhao Zhigang , Zhang Yong , Zhang Liming 
Published: June 2021

Abstract
Background
Coronavirus disease-19 (COVID-19) has become a world health threaten. Its risk factors with death were still not known. White blood cells (WBC) count as a reflection of inflammation has played a vital role in COVID-19, however its level with death is not yet investigated.

Methods
In this retrospective, single-center study, all confirmed patients with COVID-19 at West Branch of Union Hospital from Jan 29 to Feb 28, 2020 were collected and analyzed. Demographic and clinical data including laboratory examinations were analyzed and compared between recovery and death patients.

Results
A total of 163 patients including 33 death cases were included in this study. Significant association was found between WBC count and death (HR = 1.14, 95%CI: 1.09–1.20, p < 0.001). The regression analysis results showed there was a significant association between WBC count and death (HR = 5.72, 95%CI: 2.21–14.82, p < 0.001) when use the second quartile as a cutoff value (> 6.16 × 10^9/L). The difference was still exist after adjusting for confounding factors (HR = 6.26, 95%CI: 1.72–22.77, p = 0.005). In addition, Kaplan-meier survival analysis showed that there was a significant decline of the cumulative survival rate (p < 0.001) in those with WBC count ≥6.16 × 10^9/L.

Conclusion
WBC count at admission is significantly corelated with death in COVID-19 patients. Higher level of WBC count should be given more attention in the treatment of COVID-19.
AFP and eGFR are related to early and late recurrence of HCC following antiviral therapy
Authors: Watanabe Takao , Tokumoto Yoshio , Joko Kouji , Michitaka Kojiro , Horiike Norio , Tanaka Yoshinori , Tada Fujimasa , Kisaka Yoshiyasu , Nakanishi Seiji , Yamauchi Kazuhiko , Ochi Hironori , Hiraoka Atsushi , Yagi Sen , Yukimoto Atsushi , Hirooka Masashi , Abe Masanori , Hiasa Yoichi 
Published: June 2021

Abstract
Background
An unexpected recurrence of hepatocellular carcinoma (HCC) sometimes occurs in patients with hepatitis C virus (HCV) after treatment with direct-acting antivirals (DAAs). However, the characteristics of patients with HCC recurrence may differ depending on time after DAA treatment. We aimed to identify risk factors related to HCC recurrence according to time after DAA treatment.

Methods
Of 1663 patients with HCV treated with a DAA, 199 patients had a previous history of HCC. We defined HCC recurrence within 1 year after DAA treatment as ‘early recurrence’, and recurrence more than 1 year after as ‘late recurrence’. The different risk factors between the early and late phases of HCC recurrence after the end of DAA therapy were investigated.

Results
Ninety-seven patients experienced HCC recurrence during the study period. Incidences of recurrence were 29.8, 41.0, and 53.4% at 1, 2, and 3 years, respectively, after the end of DAA therapy. Multivariate analysis identified post-treatment α-fetoprotein (AFP) as an independent factor contributing to HCC recurrence in the early phase (hazard ratio, 1.056; 95% confidence interval, 1.026–1.087, p < 0.001) and post-treatment estimated glomerular filtration rate (eGFR) (hazard ratio, 0.98; 95% confidence interval, 0.96–0.99, p = 0.032) as a predictor of HCC recurrence in the late phase.

Conclusion
Patients with higher post-treatment AFP in the early phase and those with lower post-treatment eGFR in the late phase had a high risk of HCC recurrence. The risk factors associated with HCC recurrence after DAA treatment were different between the early and late phases.
Pretreatment systemic inflammation response index is predictive of pathological complete response in patients with breast cancer receiving neoadjuvant chemotherapy
Authors: Dong Jie , Sun Qingqing , Pan Yueyin , Lu Nannan , Han Xinghua , Zhou Qiong 
Published: June 2021

Abstract
Background
Inflammation plays an important role in tumor proliferation, metastasis, and resistance to chemotherapy. The systemic inflammation response index (SIRI), has been reported to be closely related to prognosis in many tumors, such as breast and gastric cancers. However, the predictive value of pretreatment SIRI on pathological complete response (pCR) rates in patients with breast cancer treated with neoadjuvant chemotherapy (NAC) is unknown. This study examined the correlation between SIRI and pCR in patients with breast cancer receiving NAC and identified convenient and accurate predictive indicators for pCR.

Methods
We retrospectively analyzed the clinicopathological parameters and pretreatment peripheral blood characteristics of the 241 patients with breast cancer who received NAC between June 2015 and June 2020. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff of SIRI. ROC curves were also plotted to verify the accuracy of inflammatory markers for pCR prediction. The chi-squared test was used to explore the relationships of SIRI with pCR and other clinicopathological parameters. Multivariate analyses were performed using a logistic regression model.

Results
Among the 241 patients, 48 (19.92%) achieved pCR. pCR was significantly related to SIRI, the neutrophil-lymphocyte ratio (NLR), the lymphocyte-monocyte ratio (LMR), molecular subtypes and other clinicopathological parameters, such as BMI, clinical T and N staging, and histological grade. Multivariate analyses indicated that the clinical T and N staging, SIRI, and NLR were independent prognostic factors for pCR in patients with breast cancer. The area under the ROC curve for SIRI was larger than that for NLR. Compared to patients with SIRI ≥0.72, patients with SIRI < 0.72 had a nearly 5-fold higher chance of obtaining pCR (odds ratio = 4.999, 95% confidence interval = 1.510–16.551, p = 0.000).

Conclusions
Pretreatment SIRI is predictive of pCR in patients with breast cancer receiving NAC, and the index can assist physicians in formulating personalized treatment strategies.
Evaluation of patients admitted with musculoskeletal tuberculosis: sixteen years’ experience from a single center in Turkey
Authors: Ozdemir Mikail , Ozdemir H. Gulnihal 
Published: June 2021

AbstractBackgroundThe aim of our study was to describe musculoskeletal system tuberculosis (TB) as a single-center experience.MethodsThis is a retrospective observational study conducted at a TB Dispensary in the east Mediterranean part of Turkey between 2004 and 2020. The clinical and demographic characteristics including age, gender, involvement location and duration of illness, presenting complaint, local examination findings, treatment outcome were retrieved and analyzed from the case files. Statistical analyses were performed using SPSS Statistics version 17.0 (IBM). The normality of data analysed by using Kolmogorov-Smirnov. The descriptive statistics were reported as mean ± standard deviation, medians, and ranges (min-max).ResultsOverall, 31 patients (3.2 % of all TB cases) with a mean age of 44.2 ± 16.7 years had musculoskeletal tuberculosis. The mean duration of treatment was 12.9 ± 5.5 months. Of the 31 patients, six (19.4 %) had concomitant pulmonary TB. One of the patients was in the pediatrics age group, and two of them were in the geriatric group. The most affected area was the vertebra. The most common complaint of the patients was back pain and seen in 22 patients (70.9 %).ConclusionsThe physicians should be suspicious about the diagnosis of musculoskeletal TB disease. If the diagnosis and treatment are delayed, spinal damage and other consequences might be incurable.
The engineered expression of secreted HSPB5-Fc in CHO cells exhibits cytoprotection in vitro
Authors: Li Jing , Yu Jingjing , Xue Wenxian , Huang Huili , Yan Longjun , Sang Fan , An Shuangshuang , Zhang Jing , Wang Mingli , Zhang Jun , Li Hui , Cui Xiukun , He Jiang , Hu Yanzhong 
Published: June 2021

AbstractBackgroundHSPB5 is an ATP-independent molecular chaperone that is induced by heat shock or other proteotoxic stresses. HSPB5 is cytoprotective against stress both intracellularly and extracellularly. It acts as a potential therapeutic candidate in ischemia-reperfusion and neurodegenerative diseases.ResultsIn this paper, we constructed a recombinant plasmid that expresses and extracellularly secrets a HSPB5-Fc fusion protein (sHSPB5-Fc) at 0.42 μg/ml in CHO-K1 cells. This sHSPB5-Fc protein contains a Fc-tag at the C-terminal extension of HSPB5, facilitating protein-affinity purification. Our study shows that sHSPB5-Fc inhibits heat-induced aggregation of citrate synthase in a time and dose dependent manner in vitro. Administration of sHSPB5-Fc protects lens epithelial cells against cisplatin- or UVB-induced cell apoptosis. It also decreases GFP-Httex1-Q74 insolubility, and reduces the size and cytotoxicity of GFP-Httex1-Q74 aggregates in PC-12 cells.ConclusionThis recombinant sHSPB5-Fc exhibits chaperone activity to protect cells against proteotoxicity.
A cross-sectional study clarifying profiles of patients with diabetes who discontinued pharmacotherapy: reasons and consequences
Authors: Tominaga Yoshiko , Morisky Donald E. , Mochizuki Mayumi 
Published: June 2021

Abstract
Background
Although diabetes is one of the fastest increasing diseases in prevalence worldwide and demands significant medical resources, more than half of all patients with diabetes do not achieve the expected target level of blood glucose. As a potential cause of poor glycemic control, insufficient adherence to medication has long been discussed and variably studied. However, dropout from treatment as another plausible cause has not been fully examined. The aim of this study was to clarify profiles of patients with diabetes who discontinued pharmacotherapy (Discont group) by extracting reasons of their decisions and by comparing with those who continued (Cont group) in terms of the related factors to glycemic control.

Methods
A cross-sectional, internet-based survey was conducted among Japanese with diabetes registered in a database. A self-administered questionnaire consisting of the 8-item version of the Morisky Medication Adherence Scale (MMAS-8), glycosylated haemoglobin (HbA1c) level, and demographic and disease characteristics was completed by all participants. Reasons for medication discontinuation and resumption were also received retrospectively from participants in the Discont group. To examine the risk of uncontrolled HbA1c, logistic regression analysis was conducted in each group.

Results
In the Discont group (148 cases), older age at resumption of pharmacotherapy and current smoking habit increased the probability of uncontrolled HbA1c, whereas in the Cont group (146 cases), a familial history of diabetes and better medication adherence in MMAS-8 scores decreased the probability of uncontrolled HbA1c. A relationship between medication adherence and HbA1c level was seen in the Cont but not in the Discont group. About 70 % of those in the Discont group made their decision to terminate diabetes treatment without consulting physicians and half of them perceived their situations inappropriately.

Conclusions
Those who discontinued pharmacotherapy were less adherent to medication than those who did not discontinue. Risk factors for glycemic control also differed between those who discontinued and those who did not. More than one-third of participants with diabetes who discontinued pharmacotherapy had inappropriate perceptions of their disease, which medical professionals should be aware of for better interventions.
Radiofrequency ablation versus repeat hepatectomy in the treatment of recurrent hepatocellular carcinoma in subcapsular location: a retrospective cohort study
Authors: Wei Fuqun , Huang Qizhen , Zhou Yang , Luo Liuping , Zeng Yongyi 
Published: June 2021

Abstract
Background
Repeat hepatectomy and radiofrequency ablation (RFA) are widely used to treat early recurrent hepatocellular carcinoma (RHCC) located in the subcapsular region, but the optimal treatment strategy remains to be controversial.

Methods
A total of 126 RHCC patients in the subcapsular location after initial radical hepatectomy were included in this study between Dec 2014 and Jan 2018. These patients were divided into the RFA group (46 cases) and the repeat hepatectomy group (80 cases). The primary endpoints include repeat recurrence-free survival (rRFS) and overall survival (OS), and the secondary endpoint was complications. The propensity-score matching (PSM) was conducted to minimize the bias. Complications were evaluated using the Clavien-Dindo classification, and severe complications were defined as classification of complications of ≥grade 3.

Results
There were no significant differences in the incidence of severe complications were observed between RFA group and repeat hepatectomy group in rRFS and OS both before (1-, 2-, and 3-year rRFS rates were 65.2%, 47.5%, and 33.3% vs 72.5%, 51.2%, and 39.2%, respectively, P = 0.48; 1-, 2-, and 3-year OS rates were 93.5%, 80.2%, and 67.9% vs 93.7%, 75.8%, and 64.2%, respectively, P = 0.92) and after PSM (1-, 2-, and 3-year rRFS rates were 68.6%, 51.0%, and 34.0% vs 71.4%, 42.9%, and 32.3%, respectively, P = 0.78; 1-, 2-, and 3-year OS rates were 94.3%, 82.9%, and 71.4% vs 88.6%, 73.8%, and 59.0%, respectively, P = 0.36). Moreover, no significant differences in the incidence of severe complications were observed between the RFA group and repeat hepatectomy group.

Conclusion
Both repeat hepatectomy and RFA are shown to be effective and safe for the treatment of RHCC located in the subcapsular region.
MiR-194-5p enhances the sensitivity of nonsmall-cell lung cancer to doxorubicin through targeted inhibition of hypoxia-inducible factor-1
Authors: Xia Mengning , Sheng Lili , Qu Wei , Xue Xue , Chen Hucheng , Zheng Guoyan , Chen Weigang 
Published: June 2021

AbstractBackgroundDespite chemotherapy being a common treatment, an increase in chemoresistance over time is unavoidable. We therefore investigated the role of miR-194-5p in regulating chordoma cell behavior and examined the downstream effectors of miR-194-5p.MethodsIn this study, NSCLC cell lines A549 and H460 were cultured under hypoxic conditions for 1 week to induce drug resistance to doxorubicin (DOX). The connection between miR-194-5p and HIF-1 was revealed by reverse transcription and real-time polymerase chain reaction (RT-qPCR), western blot, and dual-luciferase assays. We used TUNEL staining and the CCK-8 test to assess the sensitivity of NSCLC cells to DOX.ResultsWe found that hypoxia-induced NSCLC cells enhanced resistance to DOX. MiR-194-5p was substantially reduced, and HIF-1 was increased in hypoxia-induced drug-resistant NSCLC cells. Moreover, miR-194-5p successfully induced NSCLC cell apoptosis by directly inhibiting HIF-1, thereby enhancing DOX sensitivity.ConclusionsMiR-194-5p enhanced the sensitivity of NSCLC cells to DOX by directly inhibiting HIF-1. This work provides insights into underlying treatments for drug-resistant NSCLC.
Hospital utilization rates for influenza and RSV: a novel approach and critical assessment
Authors: Johnson Emily K. , Sylte Dillon , Chaves Sandra S. , Li You , Mahe Cedric , Nair Harish , Paget John , van Pomeren Tayma , Shi Ting , Viboud Cecile , James Spencer L. 
Published: June 2021

AbstractBackgroundInfluenza and respiratory syncytial virus (RSV) contribute significantly to the burden of acute lower respiratory infection (ALRI) inpatient care, but heterogeneous coding practices and availability of inpatient data make it difficult to estimate global hospital utilization for either disease based on coded diagnoses alone.MethodsThis study estimates rates of influenza and RSV hospitalization by calculating the proportion of ALRI due to influenza and RSV and applying this proportion to inpatient admissions with ALRI coded as primary diagnosis. Proportions of ALRI attributed to influenza and RSV were extracted from a meta-analysis of 360 total sources describing inpatient hospital admissions which were input to a Bayesian mixed effects model over age with random effects over location. Results of this model were applied to inpatient admission datasets for 44 countries to produce rates of hospital utilization for influenza and RSV respectively, and rates were compared to raw coded admissions for each disease.ResultsFor most age groups, these methods estimated a higher national admission rate than the rate of directly coded influenza or RSV admissions in the same inpatient sources. In many inpatient sources, International Classification of Disease (ICD) coding detail was insufficient to estimate RSV burden directly. The influenza inpatient burden estimates in older adults appear to be substantially underestimated using this method on primary diagnoses alone. Application of the mixed effects model reduced heterogeneity between countries in influenza and RSV which was biased by coding practices and between-country variation.ConclusionsThis new method presents the opportunity of estimating hospital utilization rates for influenza and RSV using a wide range of clinical databases. Estimates generally seem promising for influenza and RSV associated hospitalization, but influenza estimates from primary diagnosis seem highly underestimated among older adults. Considerable heterogeneity remains between countries in ALRI coding (i.e., primary vs non-primary cause), and in the age profile of proportion positive for influenza and RSV across studies. While this analysis is interesting because of its wide data utilization and applicability in locations without laboratory-confirmed admission data, understanding the sources of variability and data quality will be essential in future applications of these methods.