bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insight into genomic organization of pathogenic coronaviruses, SARS-CoV-2: Implication for emergence of new variants, laboratory diagnosis and treatment options
Authors: Bedada Fikru B. , Gorfu Gezahegn , Teng Shaolei , Neita Marguerite E. 
Published: October 2022

SARS-CoV-2 is a novel zoonotic positive-sense RNA virus (ssRNA+) belonging to the genus beta coronaviruses (CoVs) in the Coronaviridae family. It is the causative agent for the outbreak of the disease, COVID-19. It is the third CoV causing pneumonia around the world in the past 2 decades. To date, it has caused significant deaths worldwide. Notably, the emergence of new genetic variants conferring efficient transmission and immune evasion remained a challenge, despite the reduction in the number of death cases, owing to effective vaccination regimen (boosting) and safety protocols. Thus, information harnessed from SARS-CoV-2 genomic organization is indispensable for seeking laboratory diagnosis and treatment options. Here in, we review previously circulating variants of SARS-CoV-2 designated variant of concern (VOC) including the Alpha (United Kingdom), Beta (South Africa), Gamma (Brazil), Delta (India), and recently circulating VOC, Omicron (South Africa) and its divergent subvariants (BA.1, BA.2, BA.3, BA.2.12.1, BA.4 and BA.5) with BA.5 currently becoming dominant and prolonging the COVID pandemic. In addition, we address the role of computational models for mutagenesis analysis which can predict important residues that contribute to transmissibility, virulence, immune evasion, and molecular detections of SARS-CoV-2. Concomitantly, the importance of harnessing the immunobiology of SARS‐CoV‐2 and host interaction for therapeutic purpose; and use of an in slilico based biocomputational approaches to achieve this purpose via predicting novel therapeutic agents targeting PRR such as toll like receptor, design of universal vaccine and chimeric antibodies tailored to the emergent variant have been highlighted.
Association of lower liver function with cognitive impairment in the Shenzhen ageing-related disorder cohort in China
Authors: Wu Kaiyu , Xu Chunyan , Qiu Guozhen , Guo Qiwen , Chen Chunchun , Liu Wei , Liu Jianjun , Liu Kangding , Zhu Feiqi 
Published: October 2022

BackgroundAccumulating evidence suggests that alterations in liver function may play an important role in the pathogenesis of Alzheimer’s disease (AD). However, it remains unclear whether there is any relationship between lower liver function and cognitive impairment among the elderly.MethodsFrom 2017 to 2018, we recruited 7,201 older people (over 60 years old) from 51 community health centers in the Luohu District of Shenzhen City. According to the Mini-Mental State Examination (MMSE) score and education level, participants were divided into a cognitive impairment group (n = 372) and a normal cognitive function group (n = 6,829). Nonparametric test, chi-square tests, and binary logistic regression were used to analyze the data.ResultsCognitive impairment group exhibits older age, more female sex, lower education level, and lower levels of albumin and triglyceride. Additionally, the aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio was mainly distributed in the range of 1.17 to 1.3 in the cognitive impairment group, and 0.85 to 1.00 in the normal cognitive function group (χ2 = 10.02, p = 0.04). Binary logistic regression showed that cognitive impairment was significantly associated with age (OR = 0.934, 95%CI: 0.886–0.985, p = 0.017), female sex (OR = 2.255, 95%CI: 1.761–2.888, p &lt; 0.001), lower education level (less than senior high school) (OR = 11.509, 95%CI: 9.064–14.613, p &lt; 0.001), and lower albumin (OR = 1.023, 95%CI: 1.004–1.043, p = 0.011).ConclusionExcept for age, female sex, and lower education level, lower level of albumin and elevated AST to ALT ratio correlate with cognitive impairment. Whether lower liver function plays a role in AD needs to be further studied.
Subdural hematoma expansion in relation to measured mean and peak systolic blood pressure: A retrospective analysis
Authors: Plowman Keegan , Lindner David , Valle-Giler Edison , Ashkin Alex , Bass Jessica , Ruthman Carl 
Published: October 2022

ObjectiveSubdural hematomas (SDH) account for an estimated 5 to 25% of intracranial hemorrhages. Acute SDH occur secondary to rupture of the bridging veins leading to blood collecting within the dural space. Risk factors associated with SDH expansion are well documented, however, there are no established guidelines regarding blood pressure goals in the management of acute SDH. This study aims to retrospectively evaluate if uncontrolled blood pressure within the first 24 h of hospitalization in patients with acute SDH is linked to hematoma expansion as determined by serial CT imaging.MethodsA single center, retrospective study looked at 1,083 patients with acute SDH, predominantly above age 65. Of these, 469 patients met the inclusion criteria. Blood pressure was measured during the first 24 h of admission along with PT, INR, platelets, blood alcohol level, anticoagulation use and antiplatelet use. Follow-up CT performed within the first 24 h was compared to the initial CT to determine the presence of hematoma expansion. Mean systolic blood pressure (SBP), peak SBP, discharge disposition, length of stay and in hospital mortality were evaluated.ResultsWe found that patients with mean SBP &lt;140 in the first 24 h of admission had a lower rate of hematoma expansion than those with SBP &gt; 140. Patients with peak SBP &gt; 200 had an increased frequency of hematoma expansion with the largest effect seen in patients with SBP &gt; 220. Other risk factors did not contribute to hematoma expansion.ConclusionsThese results suggest that blood pressure is an important factor to consider when treating patients with SDH with medical management. Blood pressure management should be considered in addition to serial neurological exams, repeat radiological imaging, seizure prophylaxis and reversal of anticoagulation.
The pros and cons of multiple puncture in percutaneous balloon compression for treatment of trigeminal neuralgia
Authors: Sun Chenglong , Zheng Wenhao , Zhu Qiang , Du Quan , Yu Wenhua 
Published: October 2022

BackgroundPercutaneous balloon compression (PBC) is an effective and well-established surgery for treating trigeminal neuralgia (TN). However, if the initial attempt fails to produce a distinct pear shape, there is no conventional strategy to follow: repeat a few days later or re-puncture?AimsThis study aimed to analyze the risk and gain of re-puncturation in PBC surgery for TN treatment.MethodsWe reviewed radiographs and medical records from 79 consecutive PBC cases. The complications and surgical outcomes were compared between one-time success pears and multiple re-puncturing pears. Re-puncturing methods included selecting a more appropriate entry point, a more possible entry angle, finding a stretchy spot around the margin of foramen ovale (FO) with a trocar, and exploring the direction with more resistance using a thinner guiding needle.ResultsIn 50% of cases, satisfactory pears were obtained after the first puncture, and in 35% of cases, satisfactory pears were obtained following re-puncturation. Except for hemihypogeusia, which was significantly more in multiple punctures cases (p &lt; 0.05), no additional adverse effects were statistically different between the two groups. There are very few rare complications associated with re-puncturation. Log-Rank test of pain-free rate revealed no statistically significant differences between the two groups (p = 0.129).ConclusionThis study establishes the safety of re-puncturation in PBC surgery for TN treatment. The operation increases pears and does not cause any serious complications. The surgical outcomes of re-puncturation pears are almost identical to those one-time success pears.
Vestibular dysfunction in pediatric patients with cochlear implantation: A systematic review and meta-analysis
Authors: Wu Qiong , Zhang Qin , Xiao Qianwen , Zhang Yuzhong , Chen Zichen , Liu Shuyun , Wang Xueyan , Xu Yong , Xu Xin-Da , Lv Jingrong , Jin Yulian , Yang Jun , Zhang Qing 
Published: October 2022

ObjectiveVestibular dysfunction may delay the achievement of balance and perception milestones in pediatric patients after cochlear implantation (CIM).MethodsA strategic literature search was done following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched the PubMed, Medline, Embase, Web of Science, and Cochrane Library databases from inception to July 2022. Studies were included on the otoliths, semicircular canals, and balance function changes in children after CIM. Two reviewers independently assessed the level of evidence, methodological limitations, risk of bias, and characteristics of the cases. Matched pre- and postoperative vestibular functional test data, including ocular and cervical vestibular-evoked myogenic potential (oVEMP and cVEMP), caloric test, video head impulse test (vHIT), and Bruininks-Oseretsky Test 2 (BOT-2), were used to calculate the relative risk of vestibular disorders. Subgroup analyses were performed according to surgical approach, CIM device status, and etiology.ResultsTwenty studies that met the inclusion criteria were selected for the meta-analysis. We observed significant vestibular dysfunction in pediatric patients with CIM. The results showed a statistically significant increase in abnormal cVEMP response (RR = 2.20, 95% CI = 1.87, 2.58, P &lt; 0.0001), abnormal oVEMP response (RR = 2.10, 95% CI = 1.50, 2.94, P &lt; 0.0001), and abnormal caloric test results (RR = 1.62, 95% CI = 1.20, 2.19, P = 0.0018) after implantation. Statistically significant differences were not found in the vHIT test results of all three semicircular canals before and after the operation (P &gt; 0.05). Regarding static and dynamic balance, we found significantly poorer BOT-2 scores in children with CIM than in the normal group (mean difference = −7.26, 95% CI = −10.82, −3.70, P &lt; 0.0001).ConclusionThe results showed that vestibular dysfunction might occur after CIM in pediatric patients. Some children experience difficulties with postural control and balance. Our results suggest that a comprehensive evaluation of vestibular function should be performed before and after CIM.
Effect of the interaction between alcohol and meat consumption on the hyperlipidaemia risk among elderly individuals: Evidence from Shanghai, China
Authors: Huang Xiaojing , Hui Hong , Zhu Wenqing , Chen Ning , Wei Yan , Wang Zhaoxin , Shi Jianwei 
Published: October 2022

BackgroundDiet and other lifestyle habits may have an increased effect on blood lipids in older people. This study aimed to examine the associations between diet (meat, fish, and egg), alcohol consumption and blood lipids.MethodsSurveillance data on chronic diseases and their risk factors were collected from Shanghai during 2017–2018. A Kish table was used for sampling 438 older adults, of whom 71 consumed alcohol. Logistic regression was used to test the relationships between diet, alcohol consumption and blood lipid levels in elderly individuals, and the marginal effects (MEs) were estimated.ResultsDyslipidaemia was more common among drinkers than among nondrinkers (P &lt; 0.01). Alcohol consumption was associated with dyslipidaemia (OR = 2.667, P &lt; 0.01 for TC; OR = 1.919, P &lt; 0.05 for LDL; OR = 3.412, P &lt; 0.01 for TG), and consumption of more than 50 g of meat per day showed similar associations (OR = 3.227, P &lt; 0.01 for TC; OR = 3.263, P &lt; 0.01, for LDL; OR = 2.329, P &lt; 0.01 for TG). The MEs of alcohol drinking and excessive meat consumption on the rate of dyslipidaemia were 0.324 for TC (P &lt; 0.01), 0.255 for LDL (P &lt; 0.05), and 0.174 for TG (P &lt; 0.01).DiscussionThe risk of hyperlipidaemia was increased among elderly individuals with excessive meat and alcohol consumption, which also had an interactive effect.
Pembrolizumab-combination therapy for previously untreated metastatic nonsquamous NSCLC: Real-world outcomes at US oncology practices
Authors: Liu Stephen V. , Hu Xiaohan , Li Yeran , Zhao Bin , Burke Thomas , Velcheti Vamsidhar 
Published: October 2022

ObjectivesThe availability of immunotherapies has expanded the options for treating metastatic NSCLC, but information is needed regarding outcomes of immunotherapy for patients treated outside of clinical trials. The aim of this retrospective study was to evaluate the outcomes of therapy with first-line pembrolizumab plus pemetrexed and carboplatin (pembrolizumab-combination) for patients with metastatic nonsquamous NSCLC in the real-world setting of oncology clinics in the United States (US).MethodsUsing deidentified, longitudinal patient records from a nationwide, electronic health record-derived US database, we identified patients with metastatic nonsquamous NSCLC, without EGFR/ALK/ROS1 genomic alterations, who had received no previous systemic anticancer therapy. Eligible patients had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 and initiated first-line pembrolizumab-combination therapy from 11-May-2017 to 31-January-2019; data cutoff was 31-August-2020. Patients treated in a clinical trial were excluded. Manual chart review supplemented technology-enabled abstraction to identify disease progression and tumor response. Time-to-event endpoints from initiation of pembrolizumab-combination therapy were determined using Kaplan-Meier.ResultsOf 377 patients with metastatic nonsquamous NSCLC, 105 (28%), 104 (28%), and 103 (27%) had programmed death-ligand 1 (PD-L1) expression ≥50%, 1–49%, and &lt;1%, respectively; PD-L1 expression was not documented for 65 patients (17%). Median age was 66 years, and 227 patients (60%) were men. Median follow-up time from first-line therapy initiation to data cutoff was 31.2 months (range, 19.0-39.6 months). Median pembrolizumab real-world time on treatment (rwToT) was 5.8 months (95% CI, 5.0-6.7); 12- and 24-month on-treatment rates for pembrolizumab were 28.0% and 14.9%, respectively. Median overall survival (OS) was 17.2 months (95% CI, 13.6-19.9). For patients in PD-L1 expression ≥50%, 1-49%, &lt;1%, and unknown cohorts, the 12-month survival rates were 66.0%, 58.5%, 54.5%, and 58.3%, respectively, and 24-month survival rates were 43.1%, 37.2%, 35.6%, and 42.0%, respectively. Median real-world progression-free survival was 6.2 months (95% CI, 5.5-7.1); and the real-world response rate was 39.3%, with median duration of response of 13.1 months (95% CI, 10.5-16.8).ConclusionsThese findings demonstrate the benefits of first-line pembrolizumab-combination therapy for patients with EGFR/ALK-wild-type, metastatic nonsquamous NSCLC and good performance status who are treated at US community oncology clinics.
Machine learning advances the integration of covariates in population pharmacokinetic models: Valproic acid as an example
Authors: Zhu Xiuqing , Zhang Ming , Wen Yuguan , Shang Dewei 
Published: October 2022

Background and Aim: Many studies associated with the combination of machine learning (ML) and pharmacometrics have appeared in recent years. ML can be used as an initial step for fast screening of covariates in population pharmacokinetic (popPK) models. The present study aimed to integrate covariates derived from different popPK models using ML.Methods: Two published popPK models of valproic acid (VPA) in Chinese epileptic patients were used, where the population parameters were influenced by some covariates. Based on the covariates and a one-compartment model that describes the pharmacokinetics of VPA, a dataset was constructed using Monte Carlo simulation, to develop an XGBoost model to estimate the steady-state concentrations (Css) of VPA. We utilized SHapley Additive exPlanation (SHAP) values to interpret the prediction model, and calculated estimates of VPA exposure in four assumed scenarios involving different combinations of CYP2C19 genotypes and co-administered antiepileptic drugs. To develop an easy-to-use model in the clinic, we built a simplified model by using CYP2C19 genotypes and some noninvasive clinical parameters, and omitting several features that were infrequently measured or whose clinically available values were inaccurate, and verified it on our independent external dataset.Results: After data preprocessing, the finally generated combined dataset was divided into a derivation cohort and a validation cohort (8:2). The XGBoost model was developed in the derivation cohort and yielded excellent performance in the validation cohort with a mean absolute error of 2.4 mg/L, root-mean-squared error of 3.3 mg/L, mean relative error of 0%, and percentages within ±20% of actual values of 98.85%. The SHAP analysis revealed that daily dose, time, CYP2C19*2 and/or *3 variants, albumin, body weight, single dose, and CYP2C19*1*1 genotype were the top seven confounding factors influencing the Css of VPA. Under the simulated dosage regimen of 500 mg/bid, the VPA exposure in patients who had CYP2C19*2 and/or *3 variants and no carbamazepine, phenytoin, or phenobarbital treatment, was approximately 1.74-fold compared to those with CYP2C19*1/*1 genotype and co-administered carbamazepine + phenytoin + phenobarbital. The feasibility of the simplified model was fully illustrated by its performance in our external dataset. Conclusion: This study highlighted the bridging role of ML in big data and pharmacometrics, by integrating covariates derived from different popPK models.
Failure quantitative assessment approach to MOSFET power device by detecting parasitic parameters
Authors: Yun Minghui , Yang Daoguo , He Siliang , Cai Miao , Xiao Jing , Zhang Kailin , Zhang Guo-Qi 
Published: October 2022

With the emerging wide bandgap (WBG) semiconductor development, the increasing power density and efficiency of power electronic converters may cause more switching oscillation, electromagnetic interference noise, and additional power loss, further increasing the probability of device failure. Therefore, determining and quantifying the failure of a metal-oxide-semiconductor-field-effect transistor (MOSFET), which assembled using WBG semiconductor in some applications, is crucial to improving the reliability of a power converter. This study proposes a novel failure quantitative assessment approach based on MOSFET parasitic parameters. According to the two-port network theory, MOSFET is equivalent to some second-order RLC circuits composed of independent inductances, capacitances, and resistances in series. Then, the frequency-domain impedance associated with the physical failure of MOSFET is identified through frequency domain reflectometry. Accelerated aging and bond wires cut-off experiments are employed to obtain various quality states of the MOSFET device. Result shows that the MOSFET quality level and its number of bond wire lift-offs can be quantified effectively. Drain-to-source on-resistance (RDS(on)) that normally represents the MOSFET quality shows a positive linear function relationship on drain-to-source parasitic resistance (RD + RS) during the quality degradation proceeding. This finding matches with the correlation established between RDS (on) and RD + RS in theory. Meanwhile, source parasitic inductance (LS) increases with the severity of bond wires faults, and even the slight fault shows a high sensitivity. The proposed approach would be an effective quality screening technology for power semiconductor devices without power on treatment, which can effectively avoid the impact of junction temperature and test conditions (current and voltage) on test results, and does not need to design additional test circuits. The test frequency range we used in this approach was 10–300 MHz, which to some extent is suitable for providing an on-line quality monitoring technology for high-frequency WBG power devices manufacturing.
The impact of an exercise intervention using low-cost equipment on functional fitness in the community-dwelling older adults: A pilot study
Authors: Rodrigues Filipe , Amaro Nuno , Matos Rui , Mendes Diogo , Monteiro Diogo , Morouço Pedro 
Published: October 2022

Exercise interventions have shown significant improvements in the older adult population regarding functional and cognitive capacity. However, much research has applied exercise protocols that are expensive both for research and participation. Thus, high investments that are made are currently not ecologically efficient. The aim of the study was to determine whether the impact of a 20-week multicomponent exercise intervention using low-cost material could improve physical fitness in community-dwelling older adults. We tested the feasibility of this three times per week exercise protocol using an inclusive approach. Eligibility criteria included age ≥65 years, the ability to stand and walk with or without assistive devices, being physically inactive; medical clearance, and living in the community. Outcomes were muscle resistance measured using the chair-stand test for lower limbs, cardiorespiratory capacity measured using the 6-min walk test, and agility and balance using the Timed-up and Go test. Flexibility was measured using the chair sit and reach for lower limbs and the back scratch for upper limbs using the dominant leg and arm, respectively. Hand grip strength was measured using a dynamometer. Thirty participants (n = 30) were recruited and included in the intention-to-treat analysis. The mean age of participants was 70 years (±3.62 years), 100% were Caucasians, and 50% were female. There was a significant trend toward a clinically important improvement in the chair-stand (t = −5.23; p &lt; 0.001; d = 0.36), arm curl (t = −5.21; p &lt; 0.001; d = 0.74), 6-min walk test (t = −4.69; p = &lt;0.001; d = 0.77), timed-up and go test (t = 8.788; p &lt; 0.001; d = 1.18), and hand grip strength (t = 2.846; p = 0.009; d = 0.23). There were also differences in the back scratch (t = 2.243; p = 0.035; d = 0.29) and chair sit and reach test (t = −3.380; p &lt; 0.001; d = 0.15). This pilot study has provided preliminary evidence that a 20-week community-based low-cost exercise program may be effective in improving overall functional fitness in older people. The pilot trial has provided the necessary data to design future randomized-controlled trials that can be implemented in the community in an ecological feasible manner.
Histological characteristics, cell wall hydrolytic enzyme activity, and transcriptome analysis with seed shattering of Stylosanthes accessions
Authors: Li Xinyong , Zhang Jingwen , Zhang Jingxue , Sheng Wei , Huang Rui , Dong Rongshu , Ding Xipeng , Liu Pandao , Liu Guodao 
Published: October 2022

Stylosanthes spp. (stylo) are annual or perennial legume forages that are widely grown as forage and cover crops in tropical and subtropical regions. However, the seed yield of stylo is very low due to serious seed shattering. In the present study, we found that, although seed shattering was common among the stylo accessions, the shattering rates were genetically different. Therefore, we first synthesized the morphological, histological characteristic, physiochemical, and transcriptome analyses to determine the seed shattering mechanism in stylo. In general, the stylo germplasm with shorter lobules and thicker stems had a lower seed shattering rate and a higher seed weight. The seed and seed stalk joint is the abscission zone in stylo. Multiplex histology and hydrolytic enzyme activity analysis showed that the tearing of the abscission zone occurs due to the intense enzymatic degradation of polygalacturonase and cellulase in the seed shattering-susceptible accession TF0275. cDNA libraries from the abscission zone tissues of TF0041 and TF0275 at 14, 21, and 28 days after flowering were constructed and sequenced. A total of 47,606 unigenes were annotated and 18,606 differentially expressed genes (DEGs) were detected, including 9,140 upregulated and 9,446 downregulated unigenes. Furthermore, the 26 candidate DEGs involved in lignin biosynthesis, cellulase synthesis, and plant hormone signal transduction were found at all three developmental stages. This study provides valuable insights for future mechanistic studies of seed shattering in stylo.