bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and electrocardiographic outcomes evaluated by telemedicine of outpatients with clinical suspicion of COVID-19 treated with chloroquine compounds in Brazil†
Authors: Nascimento Bruno R. , Paixão Gabriela M. M. , Tonaco Luìs Antônio B. , Alves Ana Carolina D. , Peixoto David C. , Ribeiro Leonardo B. , Mendes Mayara S. , Gomes Paulo R. , Pires Magda C. , Ribeiro Antonio Luiz P. 
Published: February 2023

AimsTo evaluate clinical and electrocardiographic outcomes of patients with COVID-19, comparing those using chloroquine compounds (chloroquine) to individuals without specific treatment.MethodsOutpatients with suspected COVID-19 in Brazil who had at least one tele-electrocardiography (ECG) recorded in a telehealth system were enrolled in two arms (Group 1: chloroquine and Group 2: without specific treatment) and one registry (Group 3: other treatments). Outcomes were assessed through follow-up calls (phone contact, days 3 and 14) and linkage to national mortality and hospitalization databases. The primary outcome was composed of: hospitalization, intensive care admission, mechanical ventilation, and all-cause death, and the ECG outcome was the occurrence of major abnormalities by the Minnesota code. Significant variables in univariable logistic regression were included in 4 models: 1-unadjusted; 2-adjusted for age and sex; 3-model 2 + cardiovascular risk factors and 4-model 3 + COVID-19 symptoms.ResultsIn 303 days, 712 (10.2%) patients were allocated in group 1, 3,623 (52.1%) in group 2 and 2,622 (37.7%) in group 3; 1,969 had successful phone follow-up (G1: 260, G2: 871, and G3: 838). A late follow-up ECG was obtained for 917 (27.2%) patients [group 1: 81 (11.4%), group 2: 512 (14.1%), group 3: 334 (12.7%)]. In adjusted models, chloroquine was independently associated with greater chance of the composite clinical outcome: phone contact (model 4): OR = 3.24 (95% CI 2.31–4.54), p &lt; 0.001. Chloroquine was also independently associated with higher mortality, assessed by phone + administrative data (model 3): OR = 1.67 (95% CI 1.20–2.28). However, chloroquine did not associate with the occurrence of major ECG abnormalities [model 3; OR = 0.80 (95% CI 0.63–1.02, p = 0.07)]. Abstracts with partial results of this work was accepted in the American Heart Association Scientific Sessions, November 2022, in Chicago, IL, USA.ConclusionChloroquine was associated with a higher risk of poor outcomes in patients suspected to have COVID-19 when compared to those who received standard care. Follow-up ECGs were obtained in only 13.2% of patients and did not show any significant differences in major abnormalities amongst the three groups. In the absence of early ECG changes, other side effects, late arrhythmias or deferral of care may be hypothesized to explain the worse outcomes.
Causal relationship between atrial fibrillation and leukocyte telomere length: A two sample, bidirectional Mendelian randomization study
Authors: Sha Zimo , Hou Tianzhichao , Zhou Taojie , Dai Yang , Bao Yangyang , Jin Qi , Ye Jing , Lu Yiming , Wu Liqun 
Published: February 2023

BackgroundAtrial fibrillation (AF) is an age-related disease, while telomeres play a central role in aging. But the relationship between AF and telomere length (LTL) is still controversial. This study aims to examine the potential causal association between AF and LTL by using Mendelian randomization (MR).MethodsBidirectional two-sample MR, expression and protein quantitative trait loci (eQTL and pQTL)-based MR were performed using genetic variants from United Kingdom Biobank, FinnGen, and a meta-analysis study, which comprised nearly 1 million participants in the Atrial Fibrillation Study and 470,000 participants in the Telomere Length Study. Apart from the inverse variance weighted (IVW) approach as the main MR analysis, complementary analysis approaches and sensitivity analysis were applied.ResultsThe forward MR revealed a significant causal estimate for the genetically predicted AF with LTL shortening [IVW: odds ratio (OR) = 0.989, p = 0.007; eQTL-IVW: OR = 0.988, p = 0.005; pQTL-IVW: OR = 0.975, p &lt; 0.005]. But in the reverse MR analysis, genetically predicted LTL has no significant correlation with AF (IVW: OR = 0.995, p = 0.916; eQTL-IVW: OR = 0.999, p = 0.995; pQTL-IVW: OR = 1.055, p = 0.570). The FinnGen replication data yielded similar findings. Sensitivity analysis ensured the stability of the results.ConclusionThe presence of AF leads to LTL shortening rather than the other way around. Aggressive intervention for AF may delay the telomere attrition.
Effects of norepinephrine on plaque hypoxia in atherosclerotic rabbits
Authors: Wang Jia-Yu , Liu Kun , Wang Yu-Bo , Deng You-Bin , Sun Jie 
Published: February 2023

BackgroundHypoxia plays a vital role throughout the whole process of atherosclerotic vulnerable plaque formation, which may be induced by a reduced oxygen supply. The vasa vasorum can be affected by norepinephrine (NE) and cause a reduced oxygen supply, ultimately leading to plaque hypoxia. This study aimed to investigate the effects of norepinephrine, which can increase the tension of the vasa vasorum, on plaque hypoxia, evaluated by contrast-enhanced ultrasound imaging.MethodsAtherosclerosis (AS) was induced in New Zealand white rabbits by a combination of a cholesterol-rich diet and aortic balloon dilation. After the atherosclerotic model was well established, NE was intravenously administered three times per day for 2 weeks. Contrast-enhanced ultrasound (CEUS) and immunohistochemistry staining were performed to evaluate the expression of hypoxia-inducible factor alpha (HIF-α) and vascular endothelial growth factor (VEGF) in atherosclerotic plaques.ResultsThe plaque blood flow decreased after long-term norepinephrine administration. The expression of HIF-α and VEGF in atherosclerotic plaques concentrated in the outer medial layers increased, which indicated that NE might cause plaque hypoxia by contraction of the vasa vasorum.ConclusionApparent hypoxia of atherosclerotic plaques after long-term NE administration was mainly caused by decreased plaque blood flow due to the contraction of the vasa vasorum and high blood pressure.
The association between hemoglobin A1c and all-cause mortality in the ICU: A cross-section study based on MIMIC-IV 2.0
Authors: Liu Chunxia , Pang Ke , Tong Jianbin , Ouyang Wen , Li Liang , Tang Yongzhong 
Published: February 2023

BackgroundHyperglycemia has been reported to be associated with the outcomes of patients in the intensive care unit (ICU). However, the relationship between hemoglobin A1c (HbA1c) and long-term or short-term mortality in the ICU is still unknown. This study used the Medical Information Mart for Intensive Care (MIMIC)-IV database to investigate the relationship between HbA1c and long-term or short-term mortality among ICU patients without a diabetes diagnosis.MethodsA total of 3,154 critically ill patients without a diabetes diagnosis who had HbA1c measurements were extracted and analyzed from the MIMIC-IV. The primary outcome was 1-year mortality, while the secondary outcomes were 30-day mortality and 90-day mortality after ICU discharge. HbA1c levels were classified into four levels according to three HbA1c values (5.0%, 5.7%, and 6.5%). The Cox regression model was used to investigate the relationship between the highest HbA1c measurement and mortality. Finally, this correlation was validated using the XGBoost machine learning model and Cox regression after propensity score matching (PSM).ResultsThe study eventually included 3,154 critically ill patients without diabetes who had HbA1c measurements in the database. HbA1c levels of below 5.0% or above 6.5% were significantly associated with 1-year mortality after adjusting for covariates in Cox regression (HR: 1.37; 95% CI: 1.02–1.84 or HR: 1.62; 95% CI: 1.20–2.18). In addition, HbA1c 6.5% was linked to 30-day mortality (HR: 1.81; 95% CI: 1.21–2.71) and 90-day mortality (HR: 1.62; 95% CI: 1.14–2.29). The restricted cubic spline demonstrated a U-shaped relationship between HbA1c levels and 1-year mortality. The AUCs of the training and testing datasets in the XGBoost model were 0.928 and 0.826, respectively, while the SHAP plot revealed that HbA1c was somewhat important for the 1-year mortality. Higher HbA1c levels in Cox regression were still significantly associated with 1-year mortality after PSM for other factors,ConclusionsThe 1-year mortality, 30-day mortality, and 90-day mortality rates for critically ill patients after discharge from ICU are significantly associated with HbA1c. HbA1c &lt; 5.0% and ≥6.5% would increase 30-day, 90-day, and 1-year mortality, while levels between 5.0% and 6.5% of HbA1c did not significantly affect these outcomes.
Habitat quality evolution characteristics and multi-scenario prediction in Shenzhen based on PLUS and InVEST models
Authors: Wang Jiangbo , Wu Yufan , Gou Aiping 
Published: February 2023

Based on the PLUS model, research proposed a method to adjust the probability of land use transition to reduce the calculation error of the number of pixels. The refined algorithm is applied to simulate Shenzhen land use situation in 2030 under a progressive scenario using three periods of Shenzhen land use data in 2000, 2010 and 2020. Then, InVEST model was employed to evaluate the distribution situation and future trends of habitat quality in Shenzhen during the study period. Following are the conclusions: 1) The construction land in Shenzhen expanded rapidly and the ecological land gradually shrank during the research period. The proportion of artificial surface area increased by about 45.4% (304.98 km2) within 20 years. 2) By simulating the land use situation of Shenzhen in 2030, the results revealed that the land use change of Shenzhen in the future is mainly concentrated in the central and western regions. 3) The overall average habitat quality of Shenzhen was at a medium level, but the habitat quality showed a continuous degradation trend in each year throughout the study period. Spatially, the habitat quality degradation are mainly concentrated in Shenzhen’s central and western region. 4) Under the natural development scenario, Shenzhen’s habitat quality would experience a sharp decline by 2030. The habitat quality of the conservation area is guaranteed to a certain degree, but the artificial surface expansion outside the area will still affect the habitat quality in the boundary constraint scenario; Only in scenario of ecological priority, the habitat quality of Shenzhen has been restored and improved to a large extent. 5) In order to slow down the degradation trend and improve the regional ecological environment. It is necessary not only to strictly implement various protection boundaries delineated in the context of Territorial Spatial Planning, but also to implement the policy of “Clear waters and green mountains are as good as mountains of gold and silver” in the process of urban development. Government should reasonably control the scale of cities, optimize the ecological compensation mechanism, and implement ecological restoration policies such as returning farmland to forests and returning farmland to grassland.
Effects of (S)-ketamine on depression-like behaviors in a chronic variable stress model: a role of brain lipidome
Authors: Zhou Cuihong , Zhao Xinxin , Ma Xinxu , Ma Hongzhe , Li Rui , Hu Guangtao , Wang Huaning , Peng Zhengwu , Cai Min 
Published: February 2023

Introduction: Compelling evidence indicates that a single sub-anesthetic dose of (S)-ketamine elicits rapid and robust antidepressant effects. However, the underlying mechanisms behind the antidepressant effects of (S)-ketamine remain unclear.Methods: Here, using a chronic variable stress (CVS) model in mice, we analyzed changes inthe lipid compositions of the hippocampus and prefrontal cortex (PFC) with a mass spectrometry-based lipidomic approach.Results: Similar to previous research outcomes, the current study also showed that (S)-ketamine reversed depressive-like behaviors in mice produced by CVS procedures. Moreover, CVS induced changes inthe lipid compositions of the hippocampus and PFC, notably in the contents of sphingolipids, glycerolipids, and fatty acyls. With the administration of (S)-ketamine, CVS-induced lipid disturbances were partially normalized, particularly in the hippocampus.Conclusion: Altogether, our results indicated that (S)-ketamine could rescue CVS-induced depressive-like behaviors in mice through region-specific modulation of the brain lipidome, contributing to the understanding of (S)-ketamine’s antidepressant effects.
Motor and cognitive deficits limit the ability to flexibly modulate spatiotemporal gait features in older adults with mild cognitive impairment
Authors: Rosenberg Michael C. , Slusarenko Alexandra , Cao Ke , Lucas McKay J. , Emmery Laura , Kesar Trisha M. , Hackney Madeleine E. 
Published: February 2023

Introduction:Dance-based therapies are an emerging form of movement therapy aiming to improve motor and cognitive function in older adults with mild cognitive impairments (MCIs). Despite the promising effects of dance-based therapies on function, it remains unclear how age-related declines in motor and cognitive function affect movement capacity and influence which movements and rhythms maximize dance therapy efficacy. Here, we evaluated the effects of age and MCI on the ability to accurately modulate spatial (i.e., joint kinematics), temporal (i.e., step timing), and spatiotemporal features of gait to achieve spatial and temporal targets during walking.Methods:We developed novel rhythmic movement sequences—nine spatial, nine temporal, and four spatiotemporal—that deviated from typical spatial and temporal features of walking. Healthy young adults (HYA), healthy older adults (HOA), and adults with MCI were trained on each gait modification before performing the modification overground, with kinematic data recorded using wearable sensors.Results:HOA performed spatial (p= 0.010) and spatiotemporal (p= 0.048) gait modifications less accurately than HYA. Individuals with MCI performed spatiotemporal gait modifications less accurately than HOA (p= 0.017). Spatial modifications to the swing phase of gait (p= 0.006, Cohen’sd= −1.3), and four- and six-stepDuplerhythms during temporal modifications (p≤ 0.030, Cohen’sd≤ 0.9) elicited the largest differences in gait performance in HYA vs. HOA and HOA vs. MCI, respectively.Discussion:These findings suggest that age-related declines in strength and balance reduce the ability to accurately modulate spatial gait features, while declines in working memory in individuals with MCI may reduce the ability to perform longer temporal gait modification sequences. Differences in rhythmic movement sequence performance highlight motor and cognitive factors potentially underlying deficits in gait modulation capacity, which may guide therapy personalization and provide more sensitive indices to track intervention efficacy.
Comparison of oncological outcomes in elderly early-stage cervical cancer patients treated with radical surgery or radiotherapy: A real-world retrospective study with propensity score matching
Authors: Gu Yu , Cheng Hongyan , Cang Wei , Chen Lihua , Yang Junjun , Xiang Yang 
Published: February 2023

ObjectiveTo compare the oncological outcomes of radical surgery and radical radiotherapy in elderly (over 65 years) patients with early-stage cervical cancer (IB-IIA).MethodsElderly patients with stage IB-IIA cervical cancer treated at Peking Union Medical College Hospital from January 2000 to December 2020 were retrospectively reviewed. All patients were divided into the radiotherapy group (RT group) and the operation group (OP group) according to their primary intervention. Propensity score matching (PSM) analysis was performed to balance the biases. The primary outcome was overall survival (OS), and the secondary outcomes were progression-free survival (PFS) and adverse effects.ResultsA total of 116 patients were eligible for the study (47 in the RT group, and 69 in the OP group), and after PSM, 82 patients were suitable for further analysis (37 in the RT group, and 45 in the OP group). In the real-world setting, it was found that compared with radiotherapy, operation was more frequently selected for elderly cervical cancer patients with adenocarcinoma (P &lt; 0.001) and IB1 stage cancer (P &lt; 0.001). The 5-year PFS rates between the RT and OP groups were not significant (82.3% vs. 73.6%, P = 0.659), and the 5-year OS rate of the OP group was significantly better than that in the RT group (100% vs. 76.3%, P = 0.039), especially in patients with squamous cell carcinoma (P = 0.029) and tumor size of 2~4 cm with G2 differentiation (P = 0.046). There was no significant difference in PFS between the two groups (P = 0.659). In the multivariate analysis, compared with operation, radical radiotherapy was an independent risk factor of OS (hazard ratio = 4.970, 95% CI, 1.023~24.140, P = 0.047). No difference was observed in adverse effects between the RT and OP groups (P = 0.154) and in ≥grade 3 adverse effects (P = 0.852).ConclusionThe study found that surgery was more frequently selected for elderly cervical cancer patients with adenocarcinoma and IB1 stage cancer in the real-world setting. After PSM to balance the biases, it showed that compared with radiotherapy, surgery could improve the OS of elderly early-stage cervical cancer patients and was an independent protective factor of OS in elderly early-stage cervical cancer patients.
Diagnostic value of tumor-associated autoantibodies panel in combination with traditional tumor markers for lung cancer
Authors: Xu Yu , Zhang Wenjing , Xia Tingting , Liu Yuliang , Bi Zhoukui , Guo Liang , Xie Weijia , Xiang Ying , Xu Zhi , Yu Zubin , Li Yafei , Bai Li 
Published: February 2023

IntroductionThe diagnostic value of 7 tumor-associated autoantibodies (AABs) including p53, PGP9.5, SOX2, GAGE7, GBU4-5, MEGEA1, and CAGE for the detection of lung cancer has shown inconsistency in several studies. This study aimed to confirm the diagnostic value of 7AABs and to explore whether the diagnostic value would be improved by combining them with 7 traditional tumor-associated antigens (CEA, NSE, CA125, SCC, CA15-3, pro-GRP, and CYFRA21-1) in clinical settings.MethodsThe plasma levels of 7-AABs were detected by enzyme-linked immunosorbent assay (ELISA) in 533 lung cancer cases and 454 controls. The 7 tumor antigens (7-TAs) were measured by Electrochemiluminescence immunoassay with Cobas 6000 (Roche, Basel, Switzerland).ResultsThe positive rate of 7-AABs in the lung cancer group (64.00%) was significantly higher than that of healthy controls (47.90%). The 7-AABs panel was able to discriminate lung cancer from controls with a specificity of 51.50%. After combining the 7-AABs with 7-TAs, the sensitivity showed a significantly enhancement compared with 7AABs panel alone (92.09% vs 63.21%). In patients with resectable lung cancer, the combination of 7-AABs and 7-TAs improved the sensitivity from 63.52% to 97.42%DiscussionIn conclusion, our study found that the diagnostic value of 7-AABs was enhanced when combined with 7-TAs. This combined panel could be used as promising biomarker to detect resectable lung cancer in clinical settings.
Case Report: A novel PHOX2B p.Ala248_Ala266dup variant causing congenital central hypoventilation syndrome
Authors: Artamonova Irina N. , Zlotina Anna M. , Ismagilova Olga R. , Levko Tatyana A. , Kolbina Natalia Yu , Bryzzhin Aleksandr V. , Smorodin Andrey P. , Borodin Alexandr V. , Mamaeva Ekaterina A. , Sukhotskaya Anna A. , Kagantsov Ilya M. , Malysheva Daria A. , Vasichkina Elena S. , Pervunina Tatiana M. , Petrova Natalia A. 
Published: February 2023

IntroductionCongenital central hypoventilation syndrome (CCHS) is a rare disease characterized by central alveolar hypoventilation and impaired autonomic regulation, caused by pathogenic variants of PHOX2B gene. More than 90% of patients have a polyalanine repeat mutation (PARM) in the heterozygous state, characterized by the expansion of GCN repeats and an increase in the number of alanine repeats, so that genotypes 20/24–20/33 are formed (the normal genotype is 20/20). The remaining 10% of patients harbor non-PARMs.Case descriptionWe present a clinical case of a girl with a novel PHOX2B heterozygous genetic variant in the exon 3: NM_003924.4: c.735_791dup, p.Ala248_Ala266dup. The duplication includes 16 GCN (alanine) repeats and 3 adjacent amino acids. Both clinically healthy parents demonstrated a normal PHOX2B sequence. In addition, the girl has a variant of unknown significance in RYR1 gene and a variant of unknown significance in NKX2-5 gene. The child's phenotype is quite special. She needs ventilation during sleep, and has Hirschsprung's disease type I, arteriovenous malformation S4 of the left lung, ventricular and atrium septal defects, coronary right ventricular fistula, hemodynamically nonsignificant, episodes of sick sinus and atrioventricular dissociation with bradycardia, divergent alternating strabismus, and oculus uterque (both eyes) (OU) retinal angiopathy. Two episodes of hypoglycemic seizures were also registered. Severe pulmonary hypertension resolved after appropriate ventilation adjustment. Diagnostic odyssey was quite dramatic.ConclusionDetection of a novel PHOX2B variant expands the understanding of molecular mechanisms of CCHS and genotype–phenotype correlations.
Successful weaning from the invasive respiratory support after nusinersen treatment in a child with SMA type 1: A case report
Authors: Pan Meiling , Shi Jun , Miao Hongjun , Zhang Qin 
Published: February 2023

BackgroundSpinal muscular atrophy (SMA) is an autosomal recessive disease, which can be classified into 4 types according to the symptom onset age and the highest physical developmental milestone. Among them, type 1 SMA is the most severe form that affects infants younger than 6 months. Permanent assisted ventilation is usually needed for infants with type 1 SMA before the age of 2 years due to the rapid progression of disease. Nusinersen can improve the motor function of SMA patients, but its effect on respiratory function varies. In the present study, we reported a case of child with type 1 SMA who was successfully weaned from the invasive respiratory support after nusinersen treatment.Case presentationA girl aged 6 years and 5 months was admitted for SMA in the Children’s Hospital of Nanjing Medical University for 18 times. She received the first administration of nusinersen in November 2020 at the age of 5 years and 1 month. At the age of 6 years and 1 month following 6 loading doses, we tried to wean the child from the invasive ventilation for non-invasive respiratory support using a nasal mask. At present, the patient shows oxygen saturation (SpO2) above 95% without ventilator support during the daytime, and no signs of dyspnea. A non-invasive home ventilator was used at nighttime for the sake of safety. The CHOP INTEND score increased by 11 points from the first loading dose to the sixth. She can now move her limbs against gravity, take in food orally and perform partial vocal function.ConclusionsWe reported a child with type 1 SMA who was successfully weaned from the 2-years invasive ventilation after 6 loading doses, and now only need non-invasive ventilation 12 h per day. It is suggested that even a late nusinersen treatment can improve respiratory and motor function in SMA patients, and wean them from mechanical ventilation, thus improve the quality of life and reduce the medical cost.