bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of Endotypes of Hospitalized COVID-19 Patients
Authors: Ranard Benjamin L. , Megjhani Murad , Terilli Kalijah , Doyle Kevin , Claassen Jan , Pinsky Michael R. , Clermont Gilles , Vodovotz Yoram , Asgari Shadnaz , Park Soojin 
Published: November 2021

Background: Characterization of coronavirus disease 2019 (COVID-19) endotypes may help explain variable clinical presentations and response to treatments. While risk factors for COVID-19 have been described, COVID-19 endotypes have not been elucidated.Objectives: We sought to identify and describe COVID-19 endotypes of hospitalized patients.Methods: Consensus clustering (using the ensemble method) of patient age and laboratory values during admission identified endotypes. We analyzed data from 528 patients with COVID-19 who were admitted to telemetry capable beds at Columbia University Irving Medical Center and discharged between March 12 to July 15, 2020.Results: Four unique endotypes were identified and described by laboratory values, demographics, outcomes, and treatments. Endotypes 1 and 2 were comprised of low numbers of intubated patients (1 and 6%) and exhibited low mortality (1 and 6%), whereas endotypes 3 and 4 included high numbers of intubated patients (72 and 85%) with elevated mortality (21 and 43%). Endotypes 2 and 4 had the most comorbidities. Endotype 1 patients had low levels of inflammatory markers (ferritin, IL-6, CRP, LDH), low infectious markers (WBC, procalcitonin), and low degree of coagulopathy (PTT, PT), while endotype 4 had higher levels of those markers.Conclusions: Four unique endotypes of hospitalized patients with COVID-19 were identified, which segregated patients based on inflammatory markers, infectious markers, evidence of end-organ dysfunction, comorbidities, and outcomes. High comorbidities did not associate with poor outcome endotypes. Further work is needed to validate these endotypes in other cohorts and to study endotype differences to treatment responses.
Effects of Galvanic Vestibular Stimulation on Visual Verticality and Standing Posture Differ Based on the Polarity of the Stimulation and Hemispheric Lesion Side in Patients With Stroke
Authors: Tohyama Takamichi , Kondo Kunitsugu , Otaka Yohei 
Published: November 2021

Introduction: There is growing evidence supporting the relationship of vertical misperception and poor balance control with asymmetrical standing posture in patients with stroke. Although the vestibular system has been shown to be responsible for vertical misperception and balance disorders, the effect of galvanic vestibular stimulation (GVS) on both vertical misperception and postural asymmetry after stroke remains elusive. The aim of this study was to investigate the effects of GVS on visual verticality and postural asymmetry after stroke and to clarify whether the effects differ depending on the polarity of the stimulation and hemispheric lesion side.Methods: We measured the subjective visual vertical (SVV) and body weight distribution on each foot in an upright stance in 24 patients with a hemispheric stroke (10 with a left hemisphere lesion and 14 with a right hemisphere lesion) and nine age-matched healthy controls. During the measurements, bipolar GVS (1.5 mA) was applied over the bilateral mastoid processes in three stimulation conditions: contralesional-anodal and ipsilesional-cathodal vestibular stimulation, ipsilesional-anodal and contralesional-cathodal vestibular stimulation, and no stimulation. To examine whether GVS modulates visual verticality and standing posture, SVV and weight-bearing in the three conditions were analyzed.Results: During no stimulation, the SVV deviated to the contralesional side in patients with a right hemisphere lesion, while more weight-bearing was observed on the ipsilesional limb than on the contralesional limb in both patient groups than in the controls. The SVV was modulated by reversing the polarity of GVS in all the groups when the cathodal stimulus side was either ipsilateral or contralateral to the lesion while the ipsilesional-cathodal vestibular stimulation reduced weight-bearing asymmetry in only the patients with a right hemisphere lesion.Conclusions: These findings demonstrate that the effects of GVS on the SVV and standing posture differ depending on the polarity of GVS and the hemispheric lesion side. Patients with a right hemisphere lesion have difficulty maintaining their preferred standing posture under visual verticality modulation evoked by GVS. The application of GVS may clarify whether the vestibular system has neural redundancy after stroke to suppress any effects of the stimulation, including modulation of the visual verticality, on balance.
Differential Effects of Pathological Beta Burst Dynamics Between Parkinson’s Disease Phenotypes Across Different Movements
Authors: Neuville Raumin S. , Petrucci Matthew N. , Wilkins Kevin B. , Anderson Ross W. , Hoffman Shannon L. , Parker Jordan E. , Velisar Anca , Bronte-Stewart Helen M. 
Published: November 2021

Background: Resting state beta band (13–30 Hz) oscillations represent pathological neural activity in Parkinson’s disease (PD). It is unknown how the peak frequency or dynamics of beta oscillations may change among fine, limb, and axial movements and different disease phenotypes. This will be critical for the development of personalized closed loop deep brain stimulation (DBS) algorithms during different activity states.Methods: Subthalamic (STN) and local field potentials (LFPs) were recorded from a sensing neurostimulator (Activa® PC + S, Medtronic PLC.) in fourteen PD participants (six tremor-dominant and eight akinetic-rigid) off medication/off STN DBS during 30 s of repetitive alternating finger tapping, wrist-flexion extension, stepping in place, and free walking. Beta power peaks and beta burst dynamics were identified by custom algorithms and were compared among movement tasks and between tremor-dominant and akinetic-rigid groups.Results: Beta power peaks were evident during fine, limb, and axial movements in 98% of movement trials; the peak frequencies were similar during each type of movement. Burst power and duration were significantly larger in the high beta band, but not in the low beta band, in the akinetic-rigid group compared to the tremor-dominant group.Conclusion: The conservation of beta peak frequency during different activity states supports the feasibility of patient-specific closed loop DBS algorithms driven by the dynamics of the same beta band during different activities. Akinetic-rigid participants had greater power and longer burst durations in the high beta band than tremor-dominant participants during movement, which may relate to the difference in underlying pathophysiology between phenotypes.
Fructose Induces Visceral Adipose Tissue Inflammation and Insulin Resistance Even Without Development of Obesity in Adult Female but Not in Male Rats
Authors: Kovačević Sanja , Brkljačić Jelena , Vojnović Milutinović Danijela , Gligorovska Ljupka , Bursać Biljana , Elaković Ivana , Djordjevic Ana 
Published: November 2021

Introduction: Obesity and related metabolic disturbances are frequently related to modern lifestyle and are characterized by excessive fructose intake. Visceral adipose tissue (VAT) inflammation has a central role in the development of insulin resistance, type 2 diabetes (T2D), and metabolic syndrome. Since sex-related differences in susceptibility and progression of metabolic disorders are not yet fully understood, our aim was to examine inflammation and insulin signaling in VAT of fructose-fed female and male adult rats.Methods: We analyzed effects of 9-week 10% fructose-enriched diet on energy intake, VAT mass and histology, and systemic insulin sensitivity. VAT insulin signaling and markers of VAT inflammation, and antioxidative defense status were also evaluated.Results: The fructose diet had no effect on VAT mass and systemic insulin signaling in the female and male rats, while it raised plasma uric acid, increased PPARγ level in the VAT, and initiated the development of a distinctive population of small adipocytes in the females. Also, adipose tissue insulin resistance, evidenced by increased PTP1B and insulin receptor substrate 1 (IRS1) inhibitory phosphorylation and decreased Akt activity, was detected. In addition, fructose stimulated the nuclear accumulation of NFκB, increased expression of proinflammatory cytokines (IL-1β, IL-6, and TNFα), and protein level of macrophage marker F4/80, superoxide dismutase 1, and glutathione reductase. In contrast to the females, the fructose diet had no effect on plasma uric acid and VAT inflammation in the male rats, but less prominent alterations in VAT insulin signaling were observed.Conclusion: Even though dietary fructose did not elicit changes in energy intake and led to obesity in the females, it initiated the proliferation of small-sized adipocytes capable of storing fats further. In contrast to the males, this state of VAT was accompanied with enhanced inflammation, which most likely contributed to the development of insulin resistance. The observed distinction could possibly originate from sex-related differences in uric acid metabolism. Our results suggest that VAT inflammation could precede obesity and start even before the measurable increase in VAT mass, making it a silent risk factor for the development of T2D. Our results emphasize that adipose tissue dysfunction, rather than its simple enlargement, could significantly contribute to the onset and development of obesity and related metabolic disorders.
Long-Term Efficacy of Neoadjuvant Concurrent Chemoradiotherapy for Potentially Resectable Advanced Siewert Type II and III Adenocarcinomas of the Esophagogastric Junction
Authors: Tian Yuan , Wang Jun , Qiao Xueying , Zhang Jun , Li Yong , Fan Liqiao , Zhang Zhidong , Zhao Xuefeng , Tan Bibo , Wang Dong , Yang Peigang , Zhao Qun 
Published: November 2021

BackgroundReports have shown that neoadjuvant concurrent chemoradiotherapy (nCRT) increases the R0 resection rate for patients with Siewert type II or III adenocarcinoma of the gastroesophageal junction (AEG). However, the long-term efficacy of nCRT for AEG patients remains unclear. In this multicenter study, we investigated the long-term results of AEG patients treated with nCRT.MethodsA total of 149 patients with potentially resectable advanced AEG (T3/4, Nany, M0) were randomly divided into two groups: the nCRT-treated group (treated group) (n = 76) and the surgery group (control group) (n = 73). The primary endpoint was disease-free survival (DFS), and the secondary outcome indexes included the R0 resection rate, HER-2 expression, tumor regression grade (TRG), objective response rate (ORR), disease control rate (DCR), overall survival (OS), and adverse events.ResultsIn the treated group, the overall therapeutic efficacy rate was 40.8%, and the pathological complete response (pCR) rate was 16.9%. The rates of patients who underwent R0 resection in the treated and control groups were 97.0% and 87.7%, respectively (p &lt; 0.05). The toxic effects were mainly graded 1–2 in the treated group. The median DFS times in the treated and control groups were 33 and 27 months, respectively (p = 0.08), whereas the median OS times were 39 and 30 months, respectively (p = 0.01). The median DFS times of patients with positive and negative HER-2 expression in the treated group were 13 and 43 months, respectively (p = 0.01), and the median OS times were 27 and 41 months, respectively (p = 0.01).ConclusionSurgery after nCRT improved the efficacy of treatment for AEG patients and thus provided a better prognosis.Clinical Trial RegistrationThe trial is registered with ClinicalTrials.gov (number NCT01962246).
The Positivity Rate of IA-2A and ZnT8A in the Chinese Han Population With Type 1 Diabetes Mellitus: Association With rs1143627 and rs1143643 Polymorphisms in the IL1B Gene
Authors: Li Jiaqi , Sun Xiaoxiao , Luo Shuoming , Lin Jian , Xiao Yang , Yu Haibo , Huang Gan , Li Xia , Xie Zhiguo , Zhou Zhiguang 
Published: November 2021

Objective: To investigate the association between susceptibility to type 1 diabetes mellitus (T1DM) and polymorphisms (rs1143627 and rs1143643) in the interleukin 1 beta (IL1B) gene in the Chinese Han population.Methods: The Meso Scale Discovery (MSD) method was used to detect the concentration of IL-1β in 24 T1DM patients and 27 healthy controls. MassARRAY was used to analyze the polymorphisms in the IL1B gene in 510 patients with classic T1DM and 531 healthy controls. The general data of the T1DM patients and healthy controls were compared by the chi-square test and Mann-Whitney U test. The chi-square test and logistic regression were used to analyze the frequency distributions of alleles and genotypes of polymorphisms in the IL1B gene. The Kruskal-Wallis H test and chi-square test were used for the genotype-phenotype analysis of rs1143627 and rs1143643 in the IL1B gene.Results: ① The concentration of IL-1β in T1DM patients was significantly higher than that in healthy controls. ② rs1143627 and rs1143643 in the IL1B gene were significantly correlated with the positivity rates for IA-2A and ZnT8A; genotype GG at rs1143627 and genotype CC at rs1143643 in the case group showed lower positivity rates for IA-2A and ZnT8A. ③ There was no significant difference in the genotypes or allele frequencies at rs1143627 (GG/GA/AA) or rs1143643 (CC/CT/TT) between the case group and control group (p &gt; 0.05). ④ rs1143627 and rs1143643 were not found to be linked to T1DM susceptibility under different genetic models.Conclusion: rs1143627 and rs1143643 in the IL1B gene correlate with the positivity rate of IA-2A and ZnT8A in Chinese Han individuals with T1DM.
Off-Label Use of Venetoclax in Patients With Acute Myeloid Leukemia: Single Center Experience and Data From Pharmacovigilance Database
Authors: Gozzo Lucia , Vetro Calogero , Brancati Serena , Longo Laura , Vitale Daniela Cristina , Romano Giovanni Luca , Mauro Elisa , Fiumara Paolo Fabio , Maugeri Cinzia , Parisi Marina Silvia , Dulcamare Ilaria , Garibaldi Bruno , Duminuco Andrea , Palumbo Giuseppe Alberto , Di Raimondo Francesco , Drago Filippo 
Published: November 2021

The potent oral inhibitor of BCL2, venetoclax (VEN), used to treat adults with chronic lymphocytic leukaemia, has been approved in US for the treatment of naïve patients with acute myeloid leukemia (AML) unfit for intensive chemotherapy and recently in Europe, too. However, the drug has been used for years in combination with hypomethylating agents (HMAs) in patients not eligible to other treatment option, according to the so-called off-label use. We collected real-world data about patients treated with VEN + HMAs in the context of a pharmacovigilance project focused on the evaluation of the safety and effectiveness of drugs used for unapproved indication in Italian hospitals. From March to December 2020, 24 patients started treatment with VEN combined with HMAs. 21 patients have been assessed for response. Eleven (52%) patients reached complete remission (CR), and three patients (14%) CR with partial hematological recovery (CRh), with a median duration of response of 4.5 months (range 0.5–12.5). 19 patients experienced at least 1 adverse drug reaction (ADR), mostly serious, including 3 deaths (9% of ADRs; 12.5% of patients) in febrile neutropenia. Hematological toxicities and infections (cytopenia, neutropenia, febrile neutropenia, sepsis), were the most reported ADRs (84.4%). In general, neutropenic fever occurred more frequently in patients treated with decitabine (7 out of 9, 78%) compared to azacitidine (5 out of 15, 33%; p = 0.03), whereas response assessment did not differ based on used HMA (p = 0.1). These results confirm the benefit-risk profile of VEN in a real-world setting of patients with no adequate therapeutic options.
Co-Administration of Vonoprazan, Not Tegoprazan, Affects the Pharmacokinetics of Atorvastatin in Healthy Male Subjects
Authors: Hwang Sejung , Ko Jae-Wook , Lee Heechan , Kim Seokuee , Kim Bongtae , Song Geun Seog , Kim Jungryul 
Published: November 2021

Potassium-competitive acid blocker is a new class of drugs inhibiting gastric acid. It is controversial that vonoprazan showed the inhibitory activities of cytochrome P450 3A4. This study aimed to evaluate the pharmacokinetics (PK) of atorvastatin and safety when atorvastatin was administered alone and co-administered with vonoprazan or tegoprazan. An open-label, multiple-dose, 3-intervention, 4-sequence, 4-period, partial replicate crossover study was conducted, and three interventions were; one is orally administered atorvastatin 40 mg alone once daily for 7 days, another is atorvastatin co-administered with vonoprazan 20 mg, and the other is atorvastatin co-administered with tegoprazan 50 mg. PK blood samples were collected up to 24 h after the last dose, and PK parameters for atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were estimated by a non-compartmental method. Safety was evaluated, including adverse events and clinical laboratory tests. A total of 28 subjects completed the study. When atorvastatin was co-administered with vonoprazan, the systemic exposures of atorvastatin and atorvastatin lactone significantly increased, and the metabolic ratio of 2-hydroxyatorvastatin significantly decreased. Hypergastrinemia only occurred when atorvastatin was co-administered with vonoprazan. However, the plasma concentration profiles of atorvastatin, 2-hydroxyatorvastatin and atorvastatin lactone were similar when atorvastatin was administered alone or co-administered with tegoprazan. In conclusion, after multiple doses of atorvastatin co-administered with vonoprazan in healthy subjects, the systemic exposure of atorvastatin and the incidence of hypergastrinemia increased. With tegoprazan, however, those interactions were not observed.
Classification of Fibrillation Organisation Using Electrocardiograms to Guide Mechanism-Directed Treatments
Authors: Li Xinyang , Shi Xili , Handa Balvinder S. , Sau Arunashis , Zhang Bowen , Qureshi Norman A. , Whinnett Zachary I. , Linton Nick W. F. , Lim Phang Boon , Kanagaratnam Prapa , Peters Nicholas S. , Ng Fu Siong 
Published: November 2021

Background: Atrial fibrillation (AF) and ventricular fibrillation (VF) are complex heart rhythm disorders and may be sustained by distinct electrophysiological mechanisms. Disorganised self-perpetuating multiple-wavelets and organised rotational drivers (RDs) localising to specific areas are both possible mechanisms by which fibrillation is sustained. Determining the underlying mechanisms of fibrillation may be helpful in tailoring treatment strategies. We investigated whether global fibrillation organisation, a surrogate for fibrillation mechanism, can be determined from electrocardiograms (ECGs) using band-power (BP) feature analysis and machine learning.Methods: In this study, we proposed a novel ECG classification framework to differentiate fibrillation organisation levels. BP features were derived from surface ECGs and fed to a linear discriminant analysis classifier to predict fibrillation organisation level. Two datasets, single-channel ECGs of rat VF (n = 9) and 12-lead ECGs of human AF (n = 17), were used for model evaluation in a leave-one-out (LOO) manner.Results: The proposed method correctly predicted the organisation level from rat VF ECG with the sensitivity of 75%, specificity of 80%, and accuracy of 78%, and from clinical AF ECG with the sensitivity of 80%, specificity of 92%, and accuracy of 88%.Conclusion: Our proposed method can distinguish between AF/VF of different global organisation levels non-invasively from the ECG alone. This may aid in patient selection and guiding mechanism-directed tailored treatment strategies.
Alterations in Functional Connectivity Measured by Functional Magnetic Resonance Imaging and the Relationship With Heart Rate Variability in Subjects After Performing Orgasmic Meditation: An Exploratory Study
Authors: Newberg Andrew B. , Wintering Nancy A. , Hriso Chloe , Vedaei Faezeh , Stoner Marie , Ross Reneita 
Published: November 2021

Background: We measured changes in resting brain functional connectivity, with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), associated with a creative meditation practice that is augmented by clitoral stimulation and is designed to not only achieve a spiritual experience but to help individuals manage their most intimate personal relationships. Briefly, the meditative state is attained by both the male and female participants while the male stimulates the woman’s clitoris. The goal of this practice, called orgasmic meditation (OM), according to the practitioners is not sexual, but to use the focus on clitoral stimulation to facilitate a meditative state of connectedness and calm alertness between the two participants.Methods: fMRI was acquired on 20 pairs of subjects shortly following one of two states that were randomized in their order – during the OM practice or during a neutral condition. The practice is performed while the female is lying down on pillows with the clitoris exposed. During the practice, the male performs digital stimulation of the clitoris for 15 min. Resting BOLD image acquisition was performed at completion of the practice to assess changes in functional connectivity associated with the performance of the practice.Results: The results demonstrated significant changes (p &lt; 0.05) in functional connectivity associated with the OM compared to the neutral condition. For the entire group there was altered connectivity following the OM practice involving the left superior temporal lobe, the frontal lobe, anterior cingulate, and insula. In female subjects, there was altered connectivity involving the cerebellum, thalamus, inferior frontal lobe posterior parietal lobe, angular gyrus, amygdala and middle temporal gyrus, and prefrontal cortex. In males, functional connectivity changes involved the supramarginal gyrus, cerebellum, and orbitofrontal gyrus, cerebellum, parahippocampus, inferior temporal gyrus, and anterior cingulate.Conclusion: Overall, these findings suggest a complex pattern of functional connectivity changes occurring in both members of the couple pair that result from this unique meditation practice. The changes represent a hybrid of functional connectivity findings with some similarities to meditation based practices and some with sexual stimulation and orgasm. This study has broader implications for understanding the dynamic relationship between sexuality and spirituality.
Trends in Cognitive Function Among Chinese Elderly From 1998 to 2018: An Age-Period-Cohort Analysis
Authors: Hu Xiaoqian , Gu Shuyan , Zhen Xuemei , Sun Xueshan , Gu Yuxuan , Dong Hengjin 
Published: November 2021

Objectives: To investigate the effects of age, period, and cohort (APC) on trends in cognitive function among the Chinese elderly, and to explore how gender gaps in cognitive function change with age, period, and cohort.Methods: This study used data from the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 1998 to 2018, and included 90,432 participants aged above 65 years old. The measurement of cognitive function was the score of the Mini-Mental State Examination (MMSE). Cross-classified random-effect models were used to investigate age, period, and cohort trends in cognitive function.Results: Mini-Mental State Examination scores decreased with age at an increasing rate. While the cohort effect was nearly stable, the period effect demonstrated a downward trend from 1998 to 2002 followed by a nearly flat line. Females were associated with lower MMSE scores than males. When age increased, the gender gaps in MMSE scores further increased. The period-based gender gaps in MMSE scores diverged throughout the 20 years, while the cohort-based gender disparities in MMSE scores converged with successive cohorts.Conclusions: Age, period, and cohort had different and independent effects on cognitive function among the Chinese elderly. The effect of age was stronger than that of period and cohort. Gender disparities in cognitive function increased with age and period, and decreased with successive cohorts.