bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Molecular Basis of the Effect of Temperature on the Structure and Function of SARS-CoV-2 Spike Protein
Authors: Khan Faez Iqbal , Lobb Kevin A. , Lai Dakun 
Published: March 2022

The remarkable rise of the current COVID-19 pandemic to every part of the globe has raised key concerns for the current public healthcare system. The spike (S) protein of SARS-CoV-2 shows an important part in the cell membrane fusion and receptor recognition. It is a key target for vaccine production. Several researchers studied the nature of this protein under various environmental conditions. In this work, we applied molecular modeling and extensive molecular dynamics simulation approaches at 0°C (273.15 K), 20°C (293.15 K), 40°C (313.15 K), and 60°C (333.15 K) to study the detailed conformational alterations in the SARS-CoV-2 S protein. Our aim is to understand the influence of temperatures on the structure, function, and dynamics of the S protein of SARS-CoV-2. The structural deviations, and atomic and residual fluctuations were least at low (0°C) and high (60°C) temperature. Even the internal residues of the SARS-CoV-2 S protein are not accessible to solvent at high temperature. Furthermore, there was no unfolding of SARS-CoV-2 spike S reported at higher temperature. The most stable conformations of the SARS-CoV-2 S protein were reported at 20°C, but the free energy minimum region of the SARS-CoV-2 S protein was sharper at 40°C than other temperatures. Our findings revealed that higher temperatures have little or no influence on the stability and folding of the SARS-CoV-2 S protein.
Where to From Here?
Authors: Schleif Robert , Espinosa Manuel 
Published: March 2022

The biological-biochemical community has been shocked and delighted by the remarkable progress that has recently been made on a problem that has consumed the attention, energy, and resources of many, if not most of the scientists in the field for the past 50 years. The problem has been to predict the tertiary structure of a protein merely from its amino acid sequence. Nature does it easily enough, but it has been an incredibly difficult problem, often considered intractable, for humankind. The breakthrough has come in the form of two computer-based approaches, AlphaFold2 and RoseTTAFold in conjunction with factors such as the use of vast computing power, the field of artificial intelligence, and the existence of huge protein sequence databases. The advancement of these tools depended upon and was stimulated by the last 50 years of development of smaller and smaller and more and more powerful electronics components, mainly processors and memory. Along with the problem of protein folding, determining the function or mechanism of action of proteins has similarly limped along as did protein folding until the recent breakthroughs. Perhaps AlphaFold2 and RoseTTAFold can substantially aid in protein mechanistic studies. Now it is not completely insane to consider what might be the next grand challenge in biochemistry-biology. We offer several possibilities.
Anodal Transcranial Direct Current Stimulation Could Modulate Cortical Excitability and the Central Cholinergic System in Akinetic Rigid-Type Parkinson's Disease: Pilot Study
Authors: Oh Eungseok , Park Jinse , Youn Jinyoung , Jang Wooyoung 
Published: March 2022

BackgroundTranscranial direct current stimulation (tDCS) is a non-invasive technique that has been widely studied as an alternative treatment for Parkinson's disease (PD). However, its clinical benefit remains unclear. In this study, we aimed to investigate the effect of tDCS on the central cholinergic system and cortical excitability in mainly akinetic rigid-type patients with PD.MethodsIn total, 18 patients with PD were prospectively enrolled and underwent 5 sessions of anodal tDCS on the M1 area, which is on the contralateral side of the dominant hand. We excluded patients with PD who had evident resting tremor of the hand to reduce the artifact of electrophysiologic findings. We compared clinical scales reflecting motor, cognitive, and mood symptoms between pre- and post-tDCS. Additionally, we investigated the changes in electrophysiologic parameters, such as short latency afferent inhibition (SAI) (%), which reflects the central cholinergic system.ResultsThe United Parkinson's Disease Rating Scale Part 3 (UPDRS-III), the Korean-Montreal Cognitive Assessment (MoCA-K), and Beck Depression Inventory (BDI) scores were significantly improved after anodal tDCS (p &lt; 0.01, p &lt; 0.01, and p &lt; 0.01). Moreover, motor evoked potential amplitude ratio (MEPAR) (%) and integrated SAI showed significant improvement after tDCS (p &lt; 0.01 and p &lt; 0.01). The mean values of the change in integrated SAI (%) were significantly correlated with the changes in UPDRS-III scores; however, the MoCA-K and BDI scores did not show differences.ConclusionsAnodal tDCS could influence the central cholinergic system, such as frontal cortical excitability and depression in PD. This mechanism could underlie the clinical benefit of tDCS in patients with PD.
Microvascular Decompression for Trigeminal Neuralgia Caused by Venous Offending on the Ventral Side of the Root Entrance/Exit Zone: Classification and Management Strategy
Authors: Wang Wenhua , Yu Feng , Kwok Sze Chai , Wang Yuhai , Yin Jia 
Published: March 2022

BackgroundTrigeminal neuralgia (TGN) is typically caused by an offending artery (OA) but may also involve an offending vein. Venous offending on the ventral side of the root entrance/exit zone (VO-VREZ) is particularly challenging.ObjectiveTo analyze the rate and pattern of VO-VREZ and propose management strategy accordingly.MethodsVO-VREZ was classified into 3 types based on its anatomical relationship with a nerve root (A, the vein was covered by the nerve root entirely; B, the vein was lateral to the nerve root; and C, the vein penetrated the nerve root) and 3 groups based on the absence/presence of offending artery (I, no OA; II, suspected OA; and III, definitive OA).ResultsThe analysis included 143 cases with complete follow-up. Type A, B, and C accounted for 11.9, 31.5, and 56.6% of the cases, respectively. Group I, II, and III accounted for 24.5, 26.6, and 49.0%, respectively. Most group I VO-VREZ cases (26 out of 31) were managed with coagulation followed by division. Most group II VO-VREZ cases (31 out of 38) were decompressed with shredded Teflon interposition. Group III VO-VREZ was left in place in all 70 cases. Immediate pain relief was achieved in all cases. Temporary hemifacial hypesthesia occurred in 21 patients (14.7%), among which 14 were managed with Teflon decompression. Within the 4.5-year median follow-up, pain recurred in 11 patients (7.7%), but all with lesser intensity.ConclusionVO-VREZ is not uncommon in patients with TGN. Different management strategy should be chosen according to the anatomical feature and the absence/presence of arterial conflict.
Volumetric Brain Loss Correlates With a Relapsing MOGAD Disease Course
Authors: Rechtman Ariel , Brill Livnat , Zveik Omri , Uliel Benjamin , Haham Nitzan , Bick Atira S. , Levin Netta , Vaknin-Dembinsky Adi 
Published: March 2022

BackgroundMyelin oligodendrocyte glycoprotein antibody disorders (MOGAD) have evolved as a distinct group of inflammatory, demyelinating diseases of the CNS. MOGAD can present with a monophasic or relapsing disease course with distinct clinical manifestations.However, data on the disease course and disability outcomes of these patients are scarce. We aim to compare brain volumetric changes for MOGAD patients with different disease phenotypes and HCs.MethodsBrain magnetic resonance imaging (MRI) scans and clinical data were obtained for 22 MOGAD patients and 22 HCs. Volumetric brain information was determined using volBrain and MDbrain platforms.ResultsWe found decreased brain volume in MOGAD patients compared to HCs, as identified in volume of total brain, gray matter, white matter and deep gray matter (DGM) structures. In addition, we found significantly different volumetric changes between patients with relapsing and monophasic disease course, with significantly decreased volume of total brain and DGM, cerebellum and hippocampus in relapsing patients during the first year of diagnosis. A significant negative correlation was found between EDSS and volume of thalamus.ConclusionsBrain MRI analyses revealed volumetric differences between MOGAD patients and HCs, and between patients with different disease phenotypes. Decreased gray matter volume during the first year of diagnosis, especially in the cerebrum and hippocampus of MOGAD patients was associated with relapsing disease course.
Sleep Habits, Quality of Life and Psychosocial Aspects in the Older Age: Before and During COVID-19
Authors: Almondes Katie Moraes de , Castro Eleni de Araujo Sales , Paiva Teresa 
Published: March 2022

AimThis study aimed to describe sleep habits, quality of life and psychosocial aspects in older people and analyze associated differences considering the time before COVID-19 pandemic and during its first wave in Portugal.MethodsOnline survey used for data collection received answers from 914 elderly (age range 65 – 90y), from April to August 2020.ResultsSymptoms of self-perception of depression, anxiety, irritability and economic problems were not prominent in the elderly, except for worries concerning uncertainty about the future. There was no difference in sleep duration before and during the pandemic, although there was a worsening of some aspects related to sleep, such as sleep quality, sleep efficiency, awakening quality, sleep latency and nocturnal awakenings. Gender comparisons showed a higher vulnerability in women. Some morbidities got worse during the pandemic among the elderly, such as Insomnia, Headaches, Depression, Tinnitus, among others.ConclusionEven though our data suggest that the pandemic did not have a great impact on quality of life, sleep quality and psychosocial aspects in the elderly, they were still affected by the worsening of their health conditions, including sleep and morbidities. Some behaviors may act as protective factors in this population, such as walking and keeping contact with others, as well as other aspects like financial stability, high level of education and family support, as they can help them to cope better with difficulties.
Genetic Inhibition of Plppr5 Aggravates Hypoxic-Ischemie-Induced Cortical Damage and Excitotoxic Phenotype
Authors: Sun Yuxiao , Jin Mei-fang , Li Lili , Liu Yueying , Wang Dandan , Ni Hong 
Published: March 2022

Hypoxia-ischemia (HI) is the most common acute brain threat in neonates and a leading cause of neurodevelopmental impairment. Exploring the new molecular mechanism of HI brain injury has important clinical translational significance for the next clinical intervention research. Lipid phosphatase-related proteins (PLPPRs) are regulators of mitochondrial membrane integrity and energy metabolism. We recently found that Plppr5 knockout exacerbated HI impairment in some aspects and partially attenuated the neuroprotective effects of melatonin, suggesting that Plppr5 may be a novel intervention target for HI. The present study aimed to determine the long-term effects of gene knockout of Plppr5 on HI brain injury, focusing on the neuronal excitability phenotype, and to determine the effect of Plppr5 gene silencing on neuronal zinc metabolism and mitochondrial function in vitro. 10-day-old wild type (WT) mice and Plppr5-deficient (Plppr5–/–) mice were subjected to hypoxia-ischemia. Lesion volumes and HI-induced neuroexcitotoxic phenotypes were quantified together with ZnT1 protein expression in hippocampus. In addition, HT22 (mouse hippocampal neuronal cells) cell model was established by oxygen–glucose deprivation/reoxygenation (OGD/R) treatment and was treated with medium containing LV-sh_Plppr5 or control virus. Mitochondrial oxidative stress indicator ROS, mitochondrial ZnT1 protein expression and zinc ion content were detected.ResultsPlppr5-deficient mice subjected to hypoxia-ischemia at postnatal day 10 present significantly higher cerebral infarction. Plppr5-deficient mice were endowed with a more pronounced superexcitability phenotype at 4 weeks after HI, manifested as a reduced seizure threshold. ZnT1 protein was also found reduced in Plppr5-deficient mice as well as in mice subjected to HI excitotoxicity. Plppr5 knockout in vivo exacerbates HI brain injury phenotypes, including infarct volume and seizure threshold. In addition, knockout of the Plppr5 gene reduced the MFS score to some extent. In vitro Plppr5 silencing directly interferes with neuronal zinc metabolism homeostasis and exacerbates hypoxia-induced mitochondrial oxidative stress damage. Taken together, our findings demonstrate for the first time that Plppr5-deficient mouse pups exposed to neuronal hypoxia and ischemia exhibit aggravated acute brain injury and long-term brain excitability compared with the same treated WT pups, which may be related to the disruption of zinc and mitochondria-dependent metabolic pathways in the hippocampus. These data support further investigation into novel approaches targeting Plppr5-mediated zinc and mitochondrial homeostasis in neonatal HIE.
Comparison of the Index of Nutritional Quality in Breast Cancer Patients With Healthy Women
Authors: Behrad Nasab Mojgan , Afsharfar Maryam , Ahmadzadeh Mina , Vahid Farhad , Gholamalizadeh Maryam , Abbastorki Saheb , Davoodi Sayed Hossein , Majidi Nazanin , Akbari Mohammad Esmail , Doaei Saeid 
Published: March 2022

BackgroundThe index of nutritional quality (INQ) is derived from the food frequency questionnaire (FFQ) and is a method of quantitative and qualitative analysis of diet. This study aimed to compare the INQ for different dietary components between breast cancer (BC) patients and healthy control.MethodsThis case-control study was performed on 180 women with BC and 360 healthy women. Data on general characteristics, medical history, anthropometric indices, physical activity, alcohol consumption, reproductive history, smoking, and dietary intake were collected. A valid FFQ was used to assess the intake of nutrients and the INQ was calculated based on the daily intake of the nutrients.ResultsThere was a significant association between BC and INQ of vitamin A (OR = 0.07, 0.01–0.29), vitamin E (OR = 0.43, 0.20–0.93), vitamin B6 (OR = 0.003, 0.000–0.021), riboflavin (OR = 0.25, 0.11–0.59), vitamin K (OR = 0.58, 0.37–0.90), biotin (OR = 0.07, 0.02–0.26), vitamin B12 (OR = 0.32, 0.18–0.56), vitamin C (OR = 0.72, 0.55–0.95), zinc (OR = 0.020, 0.005–0.083), calcium (OR = 0.14, 0.04–0.54) and magnesium (OR = 0.003, 0.000–0.024). Further adjustment for BMI disappeared the association between INQ of vitamin C and BC. The results did not change after further adjustments for waist circumstance and total calorie intakeConclusionA significant association was observed between BC and the INQ of vitamin A, vitamin E, vitamin B6, riboflavin, vitamin K, biotin, vitamin B12, vitamin C, zinc, calcium, and magnesium. The INQ can be used as an indicator in assessing clinical nutrition-related problems. Future longitudinal studies are needed to confirm these results.
Effect of Green Tea Extract and Soy Isoflavones on the Pharmacokinetics of Rosuvastatin in Healthy Volunteers
Authors: Zeng Weiwei , Hu Miao , Lee Hon Kit , Wat Elaine , Lau Clara Bik San , Ho Chung Shun , Wong Chun Kwok , Tomlinson Brian 
Published: March 2022

Background and AimGreen tea and soy products are extensively consumed in daily life. Research has shown that green tea catechins and soy isoflavones may influence the activity of drug metabolizing enzymes and drug transporters. We examined whether regular consumption of green tea extract or soy isoflavones affected the pharmacokinetics of a single dose of rosuvastatin in healthy subjects and whether any interactions were influenced by the polymorphism in the drug transporter ABCG2.Study DesignThis was an open-label, three-phase randomized crossover study with single doses of rosuvastatin.MethodsHealthy Chinese male subjects were given a single dose of rosuvastatin 10 mg on 3 occasions: 1. without herbs; 2. with green tea extract; 3. with soy isoflavone extract. The green tea and soy isoflavone extract were given at a dose containing EGCG 800 mg once daily or soy isoflavones−80 mg once daily for 14 days before statin dosing and at the same time as the statin dosing with at least 4-weeks washout period between phases.ResultsTwenty healthy male subjects completed the study and the intake of green tea extract significantly reduced the systemic exposure to rosuvastatin by about 20% reducing AUC0−24h from [geometric mean (% coefficient of variation)] 108.7 (28.9) h·μg/L to 74.1 (35.3) h·μg/L and Cmax from 13.1 (32.2) μg/L to 7.9 (38.3) μg/L (P &lt; 0.001 for both), without affecting the elimination half-life. The ABCG2 421C&gt;A polymorphism had a significant effect on rosuvastatin exposure but no impact on the interaction with green tea. Soy isoflavones had no significant effect on rosuvastatin pharmacokinetics.ConclusionThis study showed that repeated administration of green tea extract significantly reduced the systemic exposure of rosuvastatin in healthy volunteers. These effects might be predicted to either reduce or increase the lipid-lowering effect of rosuvastatin depending on the mechanism of the effect.
Autophagy-Related Signatures as Prognostic Indicators for Hepatocellular Carcinoma
Authors: Ye Wen , Shi Zhehao , Zhou Yilin , Zhang Zhongjing , Zhou Yi , Chen Bicheng , Zhang Qiyu 
Published: March 2022

BackgroundHepatocellular carcinoma (HCC) is the most common and deadly type of liver cancer. Autophagy is the process of transporting damaged or aging cellular components into lysosomes for digestion and degradation. Accumulating evidence implies that autophagy is a key factor in tumor progression. The aim of this study was to determine a panel of novel autophagy-related prognostic markers for liver cancer.MethodsWe conducted a comprehensive analysis of autophagy-related gene (ARG) expression profiles and corresponding clinical information based on The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) databases. The univariate Cox proportional regression model was used to screen candidate autophagy-related prognostic genes. In addition, a multivariate Cox proportional regression model was used to identify five key prognostic autophagy-related genes (ATIC, BAX, BIRC5, CAPNS1, and FKBP1A), which were used to construct a prognostic signature. Real-time qPCR analysis was used to evaluate the expression levels of ARGs in 20 surgically resected HCC samples and matched tumor-adjacent normal tissue samples. In addition, the effect of FKBP1A on autophagy and tumor progression was determined by performing in vitro and in vivo experiments.ResultsBased on the prognostic signature, patients with liver cancer were significantly divided into high-risk and low-risk groups in terms of overall survival (OS). A subsequent multivariate Cox regression analysis indicated that the prognostic signature remained an independent prognostic factor for OS. The prognostic signature possessing a better area under the curve (AUC) displayed better performance in predicting the survival of patients with HCC than other clinical parameters. Furthermore, FKBP1A was overexpressed in HCC tissues, and knockdown of FKBP1A impaired cell proliferation, migration, and invasion through the PI3K/AKT/mTOR signaling pathway.ConclusionThis study provides a prospective biomarker for monitoring outcomes of patients with HCC.
Bone Metastasis From Gastric Adenocarcinoma—What Are the Risk Factors and Associated Survival? A Large Comprehensive Population-Based Cohort Study
Authors: Huang Lei , Zhao Yajie , Shi Yan , Hu Weiguo , Zhang Jun 
Published: March 2022

BackgroundWhile bone metastasis is not common in gastric adenocarcinoma (GaC), it can have important impacts on prognosis. This large cohort study aimed at exploring factors associated with bone metastasis in GaC and investigating the time-dependent cumulative mortalities and prognostic factors in GaC patients with bone metastasis at the population level.MethodsData on patients with GaC diagnosed in 2010–2016 were retrieved from a large population-based database. We explored factors associated with bone metastasis using the multivariable-adjusted logistic model. We then calculated the time-dependent cancer-specific mortalities in GaC patients with bone metastasis using the cumulative incidence function and compared mortalities across subgroups using Gray’s test. We further assessed factors associated with mortality using the multivariable-adjusted Fine–Gray subdistribution hazard model.ResultsTogether 11,072 eligible patients with metastatic GaC were enrolled, which comprised 1,511 (14%) people with bone metastasis and 9,561 (86%) with other metastasis, encompassing 6,999 person-years of follow-up. Bone metastasis was more frequently detected in 2014 or later, in younger patients, in patients with gastric cardia cancers, in people with signet-ring cell carcinoma, and in those with poorly differentiated/undifferentiated cancers; it was less commonly observed in black patients. Bone metastasis was associated with more frequent brain and lung metastases. The median survival of patients with bone metastasis was 4 months; the 6-month and 3-year cancer-specific cumulative mortalities were 56% and 85%, respectively. In patients receiving chemotherapy, American Indians/Alaskan Natives, patients with gastric antrum/pylorus cancers, and those with positive lymph nodes had higher mortality risks, while those undergoing resection had lower mortality hazards.ConclusionIn GaC patients, bone metastasis was associated with various clinicopathologic factors including age, ethnicity, tumor location, histology, differentiation, and metastasis to other sites. Patients with bone metastasis had poor prognosis which was associated with ethnicity, tumor location, lymph node involvement, and treatment. Our findings provide important hints for tailed patient management and for further mechanistic investigations.
Development and Validation of a Preoperative Nomogram for Predicting Benign and Malignant Gallbladder Polypoid Lesions
Authors: Han Shuai , Liu Yu , Li Xiaohang , Jiang Xiao , Li Baifeng , Zhang Chengshuo , Zhang Jialin 
Published: March 2022

PurposeThe purpose of this study was to develop and validate a preoperative nomogram of differentiating benign and malignant gallbladder polypoid lesions (GPs) combining clinical and radiomics features.MethodsThe clinical and imaging data of 195 GPs patients which were confirmed by pathology from April 2014 to May 2021 were reviewed. All patients were randomly divided into the training and testing cohorts. Radiomics features based on 3 sequences of contrast-enhanced computed tomography were extracted by the Pyradiomics package in python, and the nomogram further combined with clinical parameters was established by multiple logistic regression. The performance of the nomogram was evaluated by discrimination and calibration.ResultsAmong 195 GPs patients, 132 patients were pathologically benign, and 63 patients were malignant. To differentiate benign and malignant GPs, the combined model achieved an area under the curve (AUC) of 0.950 as compared to the radiomics model and clinical model with AUC of 0.929 and 0.925 in the training cohort, respectively. Further validation showed that the combined model contributes to better sensitivity and specificity in the training and testing cohorts by the same cutoff value, although the clinical model had an AUC of 0.943, which was higher than 0.942 of the combined model in the testing cohort.ConclusionThis study develops a nomogram based on the clinical and radiomics features for the highly effective differentiation and prediction of benign and malignant GPs before surgery.