bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fragmented QRS Is Independently Predictive of Long-Term Adverse Clinical Outcomes in Asian Patients Hospitalized for Heart Failure: A Retrospective Cohort Study
Authors: Chan Jeffrey Shi Kai , Zhou Jiandong , Lee Sharen , Li Andrew , Tan Martin , Leung Keith Sai Kit , Jeevaratnam Kamalan , Liu Tong , Roever Leonardo , Liu Ying , Tse Gary , Zhang Qingpeng 
Published: November 2021

Background: Fragmented QRS (fQRS) results from myocardial scarring and predicts cardiovascular mortality and ventricular arrhythmia (VA). We evaluated the prevalence and prognostic value of fQRS in Asian patients hospitalized for heart failure.Methods and Results: This was a retrospective cohort study of adult patients hospitalized for heart failure between 1st January 2010 and 31st December 2016 at a tertiary center in Hong Kong. The baseline ECG was analyzed. QRS complexes (&lt;120 ms) with fragmented morphology in ≥2 contiguous leads were defined as fQRS. The primary outcome was a composite of cardiovascular mortality, VA, and sudden cardiac death (SCD). The secondary outcomes were the components of the primary outcome, myocardial infarction, and new-onset atrial fibrillation. In total, 2,182 patients were included, of whom 179 (8.20%) had fQRS. The follow-up duration was 5.63 ± 4.09 years. fQRS in any leads was associated with a higher risk of the primary outcome (adjusted hazard ratio (HR) 1.428 [1.097, 1.859], p = 0.001), but not myocardial infarction or new-onset atrial fibrillation. fQRS in &gt;2 contiguous leads was an independent predictor of SCD (HR 2.679 [1.252, 5.729], p = 0.011). In patients without ischaemic heart disease (N = 1,396), fQRS in any leads remained predictive of VA and SCD (adjusted HR 3.526 [1.399, 8.887], p = 0.008, and 1.873 [1.103, 3.181], p = 0.020, respectively), but not cardiovascular mortality (adjusted HR 1.064 [0.671, 1.686], p = 0.792).Conclusion: fQRS is an independent predictor of cardiovascular mortality, VA, and SCD. Higher fQRS burden increased SCD risk. The implications of fQRS in heart failure patients without ischaemic heart disease require further studies.
Motor Ability and Mental Health of Young Children: A Longitudinal Study
Authors: Hirata Shogo , Kita Yosuke , Suzuki Kota , Kitamura Yuzuki , Okuzumi Hideyuki , Kokubun Mitsuru 
Published: November 2021

This study used a longitudinal method to investigate relations between motor abilities and mental health in young children. We analyzed longitudinal data of 38 Japanese children who were 3–6 years old. We administered the Movement Assessment Battery for Children–Second edition (MABC2) and Strength and Difficulties Questionnaire (SDQ) at 3–4 years and 5–6 years of age: MABC2 was used to evaluate each child’s motor ability; SDQ was used to assess the degree of their mental health difficulties and prosocial behavior. Logistic regression results indicated that the MABC2 score at 3–4 years can predict the risk of motor skill impairments at 5–6 years (adjusted odds ratio was 0.354). Motor ability assessed at 3–4 years, however, did not predict the risk of mental health problems at 5–6 years. Analyses of longitudinal quantitative changes in motor ability and mental health confirmed these results. Mental health problems that occurred at 5–6 years were related only to individual SDQ score differences at 3–4 years. The MABC2 total score at 3–4 years was not related to later prosocial behavior. Boys tended to obtain a lower MABC2 score at 5–6 years. Girls tended to obtain a higher SDQ prosocial score at 5–6 years. Results of this study suggest that motor skill impairment and SDQ-measured mental health are independent characteristics in young Japanese children aged 3–6 years.
A Prospective Comparative Study on Cardiac Alterations After Surgery and Drug Treatment of Primary Aldosteronism
Authors: Chen Yi-Lin , Xu Ting-Yan , Xu Jian-Zhong , Zhu Li-Min , Li Yan , Wang Ji-Guang 
Published: November 2021

BackgroundCurrent guideline recommends both surgery and drug treatment for primary aldosteronism. Treatment effects on the cardiac structure and function remain under investigation.ObjectiveWe performed a prospective study in patients with primary aldosteronism to compare effects of surgery and drug treatment on the cardiac structure and function as assessed by the left ventricular (LV) pressure-strain loop, a novel echocardiographic technique that incorporates myocardial deformation and LV pressure.MethodsOur study included 39 and 28 patients treated with surgery and a mineralocorticoid antagonist, respectively. We performed conventional and speckle tracking echocardiography at baseline and 3 and 6 months of follow-up.ResultsDuring follow-up, both surgery and drug treatment normalized serum potassium concentration and significantly reduced blood pressure. Both treatments significantly and similarly decreased LV mass index and left atrial volume index. However, only in the surgery group did global wasted work significantly decrease (200.8 ± 86.7 at baseline vs. 142.1 ± 58.1 mmHg% at 6 months) and global work efficiency (91.5 ± 3.1 vs. 93.6 ± 2.3%) and global longitudinal strain (−18.3 ± 2.7 vs. −19.2 ± 1.9%) significantly (p &lt; 0.01) increase at 6 months of follow-up. The corresponding differences from the changes in the drug treatment group were 39.5 mmHg% (95% CI, 17.1, 62.0 mmHg%), −1.64% (95% CI, −2.56, −0.71%), and −0.85% (95% CI, −1.51, −0.20%), respectively. In addition, the changes in global wasted work at 6 months of follow-up was significantly correlated with that in 24-h urinary aldosterone excretion in the drug treatment group (r = 0.54) and two groups combined (r = 0.55), but not the surgery group.ConclusionIn spite of similar serum potassium normalization and blood pressure control, surgical removal of an adrenal gland, but not mineralocorticoid receptor antagonism, showed early improvement in cardiac function.
Sarcopenia Is Associated With a Risk of Mortality in People With Type 2 Diabetes Mellitus
Authors: Takahashi Fuyuko , Hashimoto Yoshitaka , Kaji Ayumi , Sakai Ryosuke , Okamura Takuro , Kitagawa Noriyuki , Okada Hiroshi , Nakanishi Naoko , Majima Saori , Senmaru Takafumi , Ushigome Emi , Hamaguchi Masahide , Asano Mai , Yamazaki Masahiro , Fukui Michiaki 
Published: November 2021

BackgroundSarcopenia has reportedly been associated with increased risk of mortality in general populations. However, few studies have investigated the association between sarcopenia and mortality in older people with type 2 diabetes mellitus (T2D). This study aimed to investigate the effect of sarcopenia on incident all-cause mortality in older people with T2D.MethodsLow muscle strength were set at handgrip strength &lt;28 kg for men and &lt;18 kg for women, and low skeletal muscle mass index (SMI), evaluated using the impedance body composition analyzer, were set at SMI &lt;7.0 kg/m2 for men and &lt;5.7 kg/m2 for women. People who had both low muscle strength and low SMI were diagnosed with sarcopenia. Due to a low incidence of all-cause mortality, the propensity score was used. The propensity score was evaluated using multivariable logistic regression models with the following parameters: age, sex, duration of diabetes, history of heart disease, history of cancer, smoking, exercise, alcohol, sodium-glucose cotransporter-2 inhibitor, glucagon-like peptide-1 receptor agonist, insulin, corticosteroid, hypertension, body mass index, glycosylated hemoglobin A1c, triglycerides, and creatinine, and the C-statistic was 0.89.ResultsIn this prospective cohort study, 396 people with an average age and duration of diabetes of 71.3 (6.3) years and 16.3 (11.3) years, respectively, were included. Of those included, 14.6% had sarcopenia. During the average 40.5 (16.5) months of follow-up, 13 people (6 out of the 338 without sarcopenia and 7 out of the 58 with sarcopenia) died. Incident rate were 5.1/1000 person years of follow-up in people without sarcopenia and 41.3/1000 person years of follow-up in people with sarcopenia. According to Cox regression analysis, sarcopenia was associated with all-cause mortality (adjusted hazard ratio: 6.12, 95% confidence interval: 1.52–24.7, p = 0.011).ConclusionSarcopenia is associated with incident all-cause mortality in older outpatients with T2D.
Converging Effects of Three Different Endocrine Disrupters on Sox and Pou Gene Expression in Developing Rat Hippocampus: Possible Role of microRNA in Sex Differences
Authors: Lichtensteiger Walter , Bassetti-Gaille Catherine , Rehrauer Hubert , Georgijevic Jelena Kühn , Tresguerres Jesus A.F. , Schlumpf Margret 
Published: November 2021

Endocrine disrupting chemicals (EDCs) can impair hippocampus-dependent behaviors in rat offspring and in children. In search for key processes underlying this effect, we compared the transcriptomes of rat hippocampus on postnatal day 6 after gestational and lactational exposure to three different EDCs at doses known to impair development of learning and memory. Aroclor 1254, a commercial PCB mixture (5 mg/kg or 0.5 mg/kg), or bisphenol A (5 mg/kg or 0.5 mg/kg) were administered in chow, chlorpyrifos (3 mg/kg or 1 mg/kg) was injected subcutaneously. Male hippocampus exhibited a common effect of all three chemicals on genes involved in cell-autonomous processes, Sox6, Sox11, Pou2f2/Oct2, and Pou3f2/Brn2, all upregulated at the high dose. Additional genes of the Sox and Pou families were affected by only one or two of the chemicals. Real time RT PCR showed a comparable expression change for bisphenol A also at the lower dose. Female hippocampus exhibited much fewer genes with expression changes (almost none with false discovery rate &lt;0.05), and none of the genes of the Sox and Pou families was affected. Since gene network analyses in male hippocampus suggested a link between Sox6 and miR-24, known to be repressed by activation of ER-alpha and to repress Sox6 in other tissues, this microRNA was measured. miR-24 was downregulated by all chemicals at the high dose in males. Values of Sox6 mRNA and miR-24 were inversely correlated in individual male hippocampus samples, supporting the hypothesis that the change in Sox6 expression resulted from an action of miR-24. In contrast, miR-24 levels remained unchanged in hippocampus of females. A sexually dimorphic response of miR-24 may thus be at the basis of the sex difference in Sox6 expression changes following exposure to the three chemicals. ER-alpha expression was also sex-dependent, but the expression changes did not parallel those of potential downstream genes such as Sox6. Sox6 is known to suppress differentiation of Parvalbumin (Pvalb)-expressing interneurons. Individual Sox6 levels (FPKM) were inversely correlated with levels of Pvalb, but not with markers of Sox6-independent interneuron subpopulations, Nos1 and 5HT3aR. Effects on interneuron development are further suggested, in males, by expression changes of Nrg1 and its receptor Erbb4, controlling interneuron migration. Our study disclosed new types of EDC-responsive morphogenetic genes, and illustrated the potential relevance of microRNAs in sexually dimorphic EDC actions.
LBX2-AS1 Activates FSTL3 by Binding to Transcription Factor RARα to Foster Proliferation, Migration, and Invasion of Thyroid Cancer
Authors: Li Jia , Shen Jie , Qin Lan , Lu Dongyan , Ding Enci 
Published: November 2021

Background: Thyroid cancer is a frequent endocrine tumor in women. It is of great significance to investigate the molecular mechanism of progression of thyroid cancer.Methods: Gene expression data set and clinical data were downloaded from The Cancer Genome Atlas database for differential expression analysis. The triplet of downstream transcription factors (TFs) and modulatory genes of target lncRNA in thyroid cancer was predicted by the lncMAP database. mRNA and protein expression of lncRNA LBX2-AS1, RARα, and FSTL3 were detected by qRT-PCR and western blot. The localization of lncRNA LBX2-AS1 in cells was tested by Fluorescence in situ hybridization assay. The RNA immunoprecipitation assay was applied to verify the binding relationship between lncRNA LBX2-AS1 and FSTL3. ChIP and dual-luciferase assays were used to prove the binding relationship between RARα and FSTL3. Cell function experiments were used to test cell proliferation, migration and invasion in each treatment group. The role of lncRNA LBX2-AS1 in thyroid cancer progression was also confirmed in nude mice.Results: Bioinformatics analysis indicated that lncRNA LBX2-AS1, RARα, FSTL3 were remarkably fostered in thyroid cancer tissue, and LBX2-AS1 was evidently correlated with clinical features. The LncMAP triplet prediction showed that LBX2-AS1 recruited TF RARα to modulate FSTL3. RIP assay confirmed that LBX2-AS1 was prominently enriched on RARα. ChIP and dual-luciferase report assays unveiled that RARα bound to the promoter region of FSTL3 and functioned as a TF. Cell function experiments uncovered that LBX2-AS1 boosted the progression of thyroid cancer. The rescue experiments showed that LBX2-AS1 recruited the TF RARα to hasten the transcription activity of FSTL3 and thus promoted the development of thyroid cancer.Conclusion: The integrative results demonstrated that LBX2-AS1 activated FSTL3 by binding to TF RARα to hasten proliferation, migration and invasion of thyroid cancer.
Overt Acute Hepatitis B Deteriorates in Females: Destructive Immunity With an Exaggerated Interleukin-17 Pathway
Authors: Chang Ming-Ling , Yeh Chau-Ting , Chien Rong-Nan , Liaw Yun-Fan 
Published: November 2021

Background and AimsWe previously showed that overt acute hepatitis B (AHB) was more severe in female patients. Using the same cohort and AHB mouse model, we examined the underlying mechanism.MethodsBaseline biochemistry, virological and cytokine assays, and T helper (Th)1 and Th2 immune markers of 118 consecutive patients were analyzed. The decompensated livers of AHB and chronic hepatitis B (CHB) patients who underwent liver transplantation were analyzed immunohistochemically. B6 mice were hydrodynamically injected with pHBV1.3 plasmids.ResultsDecompensated AHB patients (n=41) were older, more often female, and had higher alanine aminotransferase (ALT), soluble programmed cell death protein 1 (sPD-1) levels, and neutrophil-lymphocyte ratios but lower rates of HBeAg positivity and quantitative HBsAg, interferon (IFN)-γ-inducible protein 10 (IP-10), IFN-γ, and interleukin-4 (IL-4) levels than the compensated patients. Female sex (95% CI OR=1.07~54.9), age (1.06~1.40), and ALT levels (1.001~1.004) were associated with hepatic decompensation. Higher sPD-1 but lower IFN-γ and IL-4 levels were observed in female patients. Compared to CHB, decompensated AHB livers had more IL-17-positive cells but fewer HBsAg-positive cells and lower CD4/CD8 ratios. Higher serum IL-17 levels were noted in the female AHB mice than those in the males.ConclusionsFemales predominated in decompensated AHB, in which downregulated IFN-γ and IL-4 with augmented hepatic IL-17-positive cell development indicated accelerating destructive immunity to enhance viral clearance. The early surge of serum IL-17 was confirmed in the female AHB mice. Targeting the pathway involving IFN-γ, IL-4, and IL-17 might prevent liver transplantation or fatality in decompensated AHB.
Real-Life Indications of Interleukin-1 Blocking Agents in Hereditary Recurrent Fevers: Data From the JIRcohort and a Literature Review
Authors: Vinit Caroline , Georgin-Lavialle Sophie , Theodoropoulou Aikaterini , Barbier Catherine , Belot Alexandre , Mejbri Manel , Pillet Pascal , Pachlopnik Jana , Poignant Sylvaine , Rebelle Charlotte , Woerner Andreas , Koné-Paut Isabelle , Hentgen Véronique 
Published: November 2021

BackgroundInterleukin (IL)-1 inhibitors represent the main treatment in patients with colchicine-resistant/intolerant familial Mediterranean fever (crFMF), mevalonate kinase deficiency (MKD), and tumor necrosis factor receptor-associated periodic syndrome (TRAPS). However, the reasons for the use of IL-1 inhibitors in these diseases are still not completely clarified.ObjectiveIdentify real-life situations that led to initiating anakinra or canakinumab treatment in hereditary recurrent fevers (HRFs), combining data from an international registry and an up-to-date literature review.Patients and MethodsData were extracted from the JIRcohort, in which clinical information (demographic data, treatment, disease activity, and quality of life) on patients with FMF, MKD, and TRAPS was retrospectively collected. A literature search was conducted using Medline, EMBASE, and Cochrane databases.ResultsComplete data of 93 patients with HRF (53.8% FMF, 31.2% MKD, and 15.1% TRAPS) were analyzed. Data from both the registry and the literature review confirmed that the main reasons for use of IL-1 blockers were the following: failure of previous treatment (n = 57, 61.3% and n = 964, 75.3%, respectively), persistence of disease activity with frequent attacks (n = 44, 47.3% and n = 1,023, 79.9%) and/or uncontrolled inflammatory syndrome (n = 46, 49.5% and n = 398, 31.1%), severe disease complication or associated comorbidities (n = 38, 40.9% and n = 390, 30.4%), and worsening of patients’ quality of life (n = 36, 38.7% and n = 100, 7,8%). No reasons were specified for 12 (16.4%) JIRcohort patients and 154 (12%) patients in the literature.ConclusionIn the absence of standardized indications for IL-1 inhibitors in crFMF, MKD, and TRAPS, these results could serve as a basis for developing a treat-to-target strategy that would help clinicians codify the therapeutic escalation with IL-1 inhibitors.
Combination of HLA-DR on Mycobacterium tuberculosis-Specific Cells and Tuberculosis Antigen/Phytohemagglutinin Ratio for Discriminating Active Tuberculosis From Latent Tuberculosis Infection
Authors: Luo Ying , Xue Ying , Tang Guoxing , Lin Qun , Song Huijuan , Liu Wei , Yin Botao , Huang Jin , Wei Wei , Mao Liyan , Wang Feng , Sun Ziyong 
Published: November 2021

BackgroundNovel approaches for tuberculosis (TB) diagnosis, especially for distinguishing active TB (ATB) from latent TB infection (LTBI), are urgently warranted. The present study aims to determine whether the combination of HLA-DR on Mycobacterium tuberculosis (MTB)-specific cells and TB antigen/phytohemagglutinin (TBAg/PHA) ratio could facilitate MTB infection status discrimination.MethodsBetween June 2020 and June 2021, participants with ATB and LTBI were recruited from Tongji Hospital (Qiaokou cohort) and Sino-French New City Hospital (Caidian cohort), respectively. The detection of HLA-DR on MTB-specific cells upon TB antigen stimulation and T-SPOT assay were simultaneously performed on all subjects.ResultsA total of 116 (54 ATB and 62 LTBI) and another 84 (43 ATB and 41 LTBI) cases were respectively enrolled from Qiaokou cohort and Caidian cohort. Both HLA-DR on IFN-γ+TNF-α+ cells and TBAg/PHA ratio showed discriminatory value in distinguishing between ATB and LTBI. Receiver operator characteristic (ROC) curve analysis showed that HLA-DR on IFN-γ+TNF-α+ cells produced an area under the ROC curve (AUC) of 0.886. Besides, TBAg/PHA ratio yield an AUC of 0.736. Furthermore, the combination of these two indicators resulted in the accurate discrimination with an AUC of 0.937. When the threshold was set as 0.36, the diagnostic model could differentiate ATB from LTBI with a sensitivity of 92.00% and a specificity of 81.82%. The performance obtained in Qiaokou cohort was further validated in Caidian cohort.ConclusionsThe combination of HLA-DR on MTB-specific cells and TBAg/PHA ratio could serve as a robust tool to determine TB disease states.
Association Between Platelet Levels on Admission and 90-day Mortality in Patients With Exertional Heatstroke, a 10 Years Cohort Study
Authors: Zhong Li , Wu Ming , Ji Jingjing , Wang Conglin , Liu Zhifeng 
Published: November 2021

Background: Heatstroke is a common clinical symptom in summer with high mortality requiring identification of appropriate and rapid methods of assessment.Method: This is a retrospective study that included the recent 10 years clinical data of heatstroke patients. A total of n = 186 patients were included in this study and grouped based on platelet (PLT) abnormality observed on admission.Results: In the study group, n = 120 patients (64.5%) patients had normal PLT and n = 66 patients (35.5%) had abnormal PLT. Compared with PLT-normal group, PLT-abnormal group had higher Acute Physiology and Chronic Health Evaluation II (APACHE II) scores [median 15.0 (IQR 11.5–21.5) vs. 9.0 (IQR 7.0–12.5)] and SOFA scores [median 6.0 (IQR 4.0–10.0) vs. 2.0 (IQR 2.0–4.0)], lower Sequential Organ Failure Assessment (GCS)[median 8.0 (IQR 5.0–12.0) vs. 13.0 (IQR 9.0–14.0)]. The PLT-abnormal group had severe organ damage, including damage to the coagulation system, liver, and kidney (all p &lt; 0.05). Significant differences were noted in 90-day survival between the two groups even after correction for Age, GCS, White blood cell count (WBC), Neutrophil, International normalized ratio (INR), Activated partial thromboplastin time (APTT), Procalcitonin (PCT), Alanine aminotransferase (ALT), Creatine (CR), D-Dime (D-D) (Before correction P &lt; 0.001; After correction P = 0.009).The area under the ROC curve for the prediction of mortality based on PLT was 80.7% (95% CI 0.726–0.888, P &lt; 0.001), the optimal cutoff value was 94, the sensitivity was 77.3%, and the specificity was 82.6%.Conclusion: Patients with heatstroke with platelet abnormalities during admission have more severe organ impairment and a lower 90-day survival rate even when adjusted for other factors.
The COVID-19 Pandemic and the Incidence of the Non-COVID-19 Pneumonia in Adults
Authors: Huang Chienhsiu 
Published: November 2021

Introduction: The coronavirus disease 2019 (COVID-19) lockdown strategies were associated with a significant decrease in the common respiratory viral diseases and decreased the need for hospitalization among children in the COVID-19 outbreak. However, the trend of non-COVID-19 pneumonia in adult people remains uncertain. Our aim is to assess the impact of the COVID-19 pandemic on the incidence of the non-COVID-19 pneumonia in adult people and understand whether the substantial decrease in pneumonia cases is the same as the decline in the incidence of respiratory viral disease activity.Methods: We conducted a retrospective analysis of adult patients presenting with pneumonia from January 2019 to December 2020. Details on all the demographics of the patient of pneumonia, hospital course details, prior admission history within 3 months, respiratory culture, and antibiotics sensitivity test were also obtained.Results: The number of adult patients with community-acquired pneumonia in 2020 was lower than that in 2019, which decreased by 74 patients in 2020. The decreasing number of patients with community-acquired pneumonia between 2019 and 2020 was from −13.9% in January to March 2020 to −39.7% in October to December 2020. The decreasing number of patients with community-acquired pneumonia between 2019 and 2020 was from −14.8% in the youngest cohort to −28.7% in those aged ≥85 years. The number of reduced patients with community-acquired pneumonia is greater in late seasons and older age, respectively. The number of adult patients with hospital-acquired pneumonia in 2020 was lower than that in 2019, which decreased by 23 patients in 2020. The decreasing number of patients with hospital-acquired pneumonia between 2019 and 2020 was from −20.0% in January to March 2020 to −52.4% in October to December 2020. The decreasing number of patients with hospital-acquired pneumonia between 2019 and 2020 was from 0% in the youngest cohort to −45.6% in those aged ≥ 85 years. The number of reduced patients with hospital-acquired pneumonia is greater in late seasons and older age, respectively.Conclusion: Interventions applied to control the COVID-19 pandemic were effective not only in substantial changes in the seasonal influenza activity, but also in decreasing adult pneumonia cases.