bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical characteristics and gene mutation profiles of chronic obstructive pulmonary disease in non-small cell lung cancer
Authors: Yuan Lin , Guo Ting , Hu Chengping , Yang Wei , Tang Xiaoli , Cheng Hao , Xiang Yang , Qu Xiangping , Liu Huijun , Qin Xiaoqun , Qin Ling , Liu Chi 
Published: October 2022

PurposeThe coexistence of chronic obstructive pulmonary disease (COPD) often leads to a worse prognosis in patients with non-small cell lung cancer (NSCLC). Meanwhile, approaches targeting specific genetic alterations have been shown to significantly improve the diagnosis and treatment outcomes of patients with NSCLC. Herein, we sought to evaluate the impact of COPD on the clinical manifestations and gene mutation profiles of NSCLC patients with both circulating tumor (ctDNA) and tumor DNA (tDNA).Materials and methodsThe influence of COPD on clinical features was observed in 285 NSCLC cohorts suffering from NSCLC alone, NSCLC coexisting with COPD, or NSCLC coexisting with prodromal changes in COPD (with emphysema, bullae, or chronic bronchitis). The gene mutation profiles of specific 168 NSCLC-related genes were further analyzed in the NSCLC sub-cohorts with formalin-fixed and paraffin-embedded tumor DNA (FFPE tDNA) samples and plasma circulating tumor DNA (PLA ctDNA) samples. Moreover, mutation concordance was assessed in tDNA and paired ctDNA of 110 NSCLC patients.ResultsRelative to patients with NSCLC alone, patients with NSCLC coexisting with COPD and prodromal changes presented with worse lung functions, more clinical symptoms, signs and comorbidities, and inconsistent gene mutation profiles. In addition, patients in the latter two groups exhibited a higher average frequency of gene mutation. Lastly, mutation concordance between tDNA and ctDNA samples was significantly reduced in NSCLC patients coexisting with COPD.ConclusionsCollectively, our findings revealed that coexistence of COPD leads to worse clinical manifestations and altered gene mutation profiles in patients with NSCLC. Additionally, for NSCLC patients with COPD, the use of ctDNA instead of tDNA may not be the most efficient approach to identifying gene mutations.
A novel association of pyroptosis-related gene signature with the prognosis of hepatocellular carcinoma
Authors: Li Yuyao , Li Yue , Zhang Xuemei , Duan Xiangjuan , Feng Hai , Yu Zhuo , Gao Yueqiu 
Published: October 2022

BackgroundHepatocellular carcinoma (HCC) is one of the global leading lethal tumors. Pyroptosis has recently been defined as an inflammatory programmed cell death, which is closely linked to cancer progression. However, the significance of pyroptosis-related genes (PRGs) in the prognosis of HCC remains elusive.MethodsRNA sequencing (RNA-seq) data of HCC cases and their corresponding clinical information were collected from the Cancer Genome Atlas (TCGA) database, and differential PRGs were explored. The prognostic PRGs were analyzed with univariate COX regression and the least absolute shrinkage and selection operator (LASSO) Cox regression analysis to build a prognostic model in the TCGA training cohort. The predictive model was further validated in the TCGA test cohort and ICGC validation cohort. Differential gene function and associated pathway analysis were performed by Gene ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG). Single-sample gene set enrichment analysis (ssGSEA) was used to identify distinct immune cell infiltration. The mRNA and protein expression of prognostic PRGs was examined by quantitative RT-qPCR and immunohistochemistry.ResultsWe identified 46 PRGs that were differentially expressed between normal and HCC tissues in a TCGA cohort, and HCC patients could be well categorized into two clusters associated with distinct survival rates based on expression levels of the PRGs. A three-PRG prognostic model comprising CHMP4A, HMGB1 and PLK1 was constructed in the training cohort, and HCC patients could be classified into the high- and low-risk subgroups based on the median risk score. High-risk patients exhibited shorter overall survival (OS) than low-risk ones, which was validated in the test cohort and ICGC validation cohort. The risk score of this model was confirmed as an independent prognostic factor to predict OS of HCC patients. GO, KEGG and ssGSEA demonstrated the differential immune cell infiltrations were associated with the risk scores. The higher expression of CHMP4A, HMGB1 and PLK1 were validated in HCC compared to normal in vivo and in vitro.ConclusionThe three-PRG signature (CHMP4A, HMGB1, and PLK1) could act as an independent factor to predict the prognosis of HCC patients, which would shed light upon a potent therapeutic strategy for HCC treatment.
Clinical efficacy of avatrombopag and recombinant human thrombopoietin in the treatment of chronic liver disease-associated severe thrombocytopenia: A real-world study
Authors: Wang Yong-Shuai , Wang Wei , Zhang Sai , Zhang Shen-Yu , Shen Ai-Zong , Wang Wei , Song Hua-Chuan , Yao Huan-Zhang , Song Rui-Peng , Meng Fan-Zheng , Li Lei , Nashan Bjoern , Wang Ji-Zhou , Liu Lian-Xin 
Published: October 2022

Purpose: To investigate the clinical efficacy of avatrombopag, an oral thrombopoietin receptor agonist, versus subcutaneous recombinant human thrombopoietin (rh-TPO) in the treatment of severe thrombocytopenia (TCP) associated with chronic liver disease (CLD).Methods: Clinical data of 250 patients with severe TCP associated with CLD were collected in a single hospital from January 2019 to January 2022. The main parameters measured were the therapeutic response rate, changes in platelets (PLTs), and adverse events. Propensity score matching (PSM) was used to avoid possible selection bias.Results: After PSM, a total of 154 patients were enrolled in the study: 77 in the avatrombopag group and 77 in the rh-TPO group. There was no statistically significant difference between the two groups in the effect of increasing the PLT count (Waldχ2 = 1.659, p = 0.198; Waldχ2 = 0.220, p = 0.639). In addition, no interaction between time and different medications was found (Waldχ2 = 0.540, p = 0.910; Waldχ2 = 1.273, p = 0.736). Interestingly, in the subgroup analysis, both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A (88.89% vs. 63.41%, p =0.003; 81.33% vs. 61.76%, p = 0.043). Fewer patients reported dizziness in the avatrombopag group than in the rh-TPO group both before and after PSM (7.8% vs. 25.0%; 7.8% vs. 24.7%, p &lt; 0.05).Conclusion: Both before and after PSM, avatrombopag showed better clinical efficacy than rh-TPO in the treatment of TCP associated with CLD in Child‒Pugh Class A and showed a lower incidence of dizziness in all patients.
Design and evaluation of rufinamide nanocrystals loaded thermoresponsive nasal in situ gelling system for improved drug distribution to brain
Authors: Dalvi Avantika , Ravi Punna Rao , Uppuluri Chandra Teja 
Published: October 2022

Rufinamide (Rufi) is an antiepileptic drug used to manage Lennox-Gastaut Syndrome and partial seizures. The oral bioavailability of Rufi is less due to its poor solubility and low dissolution rate in the gastrointestinal fluids. This results in less amount of drug reaching the brain following the oral administration of drug. Oral formulations of Rufi are prescribed at a high dose and dosing frequency to increase its distribution to the brain. A Rufi loaded thermoresponsive nasal in situ gel which showed significantly high brain concentrations compared to aqueous suspension of Rufi administered through nasal route was developed by our research group and published. In the current work, we have formulated nanocrystals of Rufi and suspended them in a xyloglucan based thermoresponsive gel to improve the nose-to-brain distribution. The particle size, polydispersity index, and yield (%) of the optimized Rufi nanocrystals were 261.2 ± 2.1 nm, 0.28 ± 0.08, and 89.6 ± 2.0 respectively. The narrow PDI indicates that the manufacturing process is reproducible and reliable. Higher % yield suggested that the method of preparation is efficient. The sol-to-gel transition of in situ gel loaded with Rufi nanocrystals was at 32°C which suggested that the formulation transforms into gel at nasal epithelial temperatures. The nasal pharmacokinetic studies showed that Rufi nanocrystals loaded in situ gel produced higher concentration of the drug in brain (higher brain Cmax) and maintained the drug concentrations for longer duration (higher mean residence time) compared to aqueous suspension of Rufi nanocrystals as well aqueous suspension of Rufi and Rufi loaded in situ gel, reported previously. Nanometric size of the Rufi nanocrystals combined with the in situ gelling properties helped the optimized formulation achieve higher brain distribution and also sustain the drug concentrations in brain for longer duration compared to any of the formulations studied by our research group.
NLRP3 neuroinflammatory factors may be involved in atopic dermatitis mental disorders: an animal study
Authors: Yuan Huimin , Sun Yan , Zhang Shujing , Feng Jing , Tian Zijiao , Liu Jingang , Wang Hang , Gao Yushan , Tang Yang , Zheng Fengjie 
Published: October 2022

Background: Numerous clinical studies have shown that atopic dermatitis (AD) is often associated with mental disorders. This could contribute to the overall burden of atopic dermatitis. However, the underlying mechanism of mental health symptoms in AD has not been fully elucidated.Methods: An AD mouse was induced by 2,4-dinitrofluorobenzene (DNFB), which was repeatedly applied to the back skin of the BALB/C mice to establish an atopic dermatitis mental disorder model. The role of neuroinflammation in the pathogenesis of atopic dermatitis mental disorders was then explored.Results: After the stimulation of DNFB for 35 days, the skin lesions, the HE staining of skin lesions, and the behavioral experiments (including elevated plus maze assay and tail suspension test) suggested that the AD mental disorder mouse model was successfully replicated. The expression of neuroinflammatory factors in the hippocampus was then investigated through Western blotting. The results showed a significant increase in the protein expression of NLRP3, caspase-1, and IL-1β.Conclusion: Mental disorders in AD might be related to the neuroinflammatory response in the hippocampus. An alternative yet essential approach to promoting AD recovery could be through reducing neuroinflammation and improving mental disorders.
Dexmedetomidine postconditioning provides renal protection in patients undergoing laparoscopic partial nephrectomy: A randomized controlled trial
Authors: Jiang Lingling , Zhang Tao , Zhang Yang , Yu Dexin , Zhang Ye 
Published: October 2022

Background: For localized disease, partial nephrectomy of small tumors continues to be the gold-standard treatment. However, temporary clamping is routinely performed during this process to control renal blood flow, which can cause renal ischemic/reperfusion injury. We evaluated whether dexmedetomidine postconditioning (DPOC) can reduce renal ischemic/reperfusion injury for patients receiving laparoscopic partial nephrectomy (LPN).Methods: This randomized double-blind controlled trial included 77 patients who were scheduled for LPN at our hospital. Patients were randomly allocated to the DPOC or control group. DPOC was performed via intravenous administration of dexmedetomidine at 0.6 μg kg−1 for 10 min immediately after unclamping the renal artery. In the control group, saline was administered in place of dexmedetomidine under the same protocol. All participants underwent a 6-month follow-up. The primary outcome were the values of 99mTc-DTPA-GFR in the affected kidney at one and 6 months post-LPN.Result: The GFR values in the DPOC group (35.65 ± 4.89 ml min−1.1.73 m−2) were significantly higher than those the control group (33.10 ± 5.41 ml min−1.1.73 m−2; p = 0.022) at 1 month after LPN. There was no statistically significant difference in GFR value between the two groups at 6 months after LPN.Conclusion: DPOC provides therapeutic benefits to LPN patients, at least on a short-term basis, by alleviating renal ischemic/reperfusion injury.Clinical Trial Registration: Chinese Clinical Trial Registry, identifier [ChiCTR-TRC-14004766].
Assigning quantum labels and improving accuracy for the ro-vibrational eigenstates of H3+ calculated using ScalIT
Authors: Sarka János , Poirier Bill 
Published: October 2022

In a recent article [AIP Adv. 11, 045033 (2021)], we carried out exact quantum dynamical calculations and computed ro-vibrational energy levels and wave functions for the H3+ molecular ion up to the dissociation threshold (at J = 46) using a recently developed potential energy surface (PES) [Mol. Phys. 117, 1663 (2019)]—arguably, the most accurate to date —together with the ScalIT suite of parallel codes. In this work, we further improved the convergence accuracy and range of our ScalIT calculations for all J values up to J = 20 to a few 10–5 cm−1 (or better). In addition, we performed an ab initio assignment of the ro-vibrational energy levels, providing vibrational ‘v1, v2, |l|’ and rotational ‘J, G, U, K’ quantum labels for more than 2,200 ro-vibrational states, including every single 0 ≤ J ≤ 20 state up to and above the barrier to linearity at 10,000 cm−1. The main underlying motivation of our work is to provide a list of reliably labeled, spectroscopically accurate energy levels in a format that can be used in spectroscopic line lists, which are based on both experimental and theoretical levels. Such line lists are of huge importance in various astrochemical and astrophysical contexts.
A deep 96-well plate RBC storage platform for high-throughput screening of novel storage solutions
Authors: Nikulina Maria , Nemkov Travis , D'Alessandro Angelo , Gaccione Peter , Yoshida Tatsuro 
Published: October 2022

Background: Red blood cell (RBC) storage solutions, also known as additive solutions (ASs), first developed in the 1970s, enable extended storage of RBCs. Unfortunately, the advancements in this field have been limited, due to labor intensive and time-consuming serial in vitro and in vivo testing, coupled with very high commercialization hurdles. This study examines the utility of deep 96-well plates for preliminary screenings of novel ASs through comparison of RBC storage with the standard PVC bags in terms of hemolysis and ATP levels, under both normoxic (N) and hypoxic/hypocapnic (H) storage conditions. The necessity for the presence of DEHP, normally provided by PVC bags, is also examined.Materials and methods: A pool of 2 ABO compatible RBC units was split between a bag and a plate. Each plate well contained either 1, 2 or 0 PVC strips cut from standard storage bags to supply DEHP. The H bags and plates were processed in an anaerobic glovebox and stored in O2 barrier bags. Hemolysis and ATP were measured bi-weekly using standard methods.Results: Final ATP and hemolysis values for the plate-stored RBCs were comparable to the typical values observed for 6-week storage of leukoreduced AS-3 RBCs in PVC bags under both N and H conditions. Hemolysis was below FDA and EU benchmarks of 1% and 0.8%, respectively, and excluding DEHP from plates during storage, resulted in an inconsequential increase when compared to bag samples.Discussion: In combination with high-throughput metabolomics workflow, this platform provides a highly efficient preliminary screening platform to accelerate the initial testing and consequent development of novel RBC ASs.
Acute ethanol-induced liver injury is prevented by betaine administration
Authors: Arumugam Madan Kumar , Chava Srinivas , Perumal Sathish Kumar , Paal Matthew C. , Rasineni Karuna , Ganesan Murali , Donohue Terrence M. , Osna Natalia A. , Kharbanda Kusum K. 
Published: October 2022

Binge drinking is the most common form of excessive alcohol use. Repeated episodes of binge drinking cause multiple organ injuries, including liver damage. We previously demonstrated that chronic ethanol administration causes a decline in the intrahepatic ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH). This decline causes impairments in essential methylation reactions that result in alcohol-induced fatty liver (steatosis) and other features of alcohol-associated liver disease (ALD). Co-treatment with betaine during chronic ethanol feeding, normalizes hepatocellular SAM:SAH ratio and alleviates many features of liver damage including steatosis. Here, we sought to examine whether betaine treatment similarly protects against liver injury in an alcohol binge-drinking model. We hypothesized that ethanol binge with prior or simultaneous betaine administration would prevent or attenuate acute alcohol-induced liver damage. Male C57Bl/6 mice were gavaged twice, 12 h apart, with either 6 g ethanol/kg BW or with an equal volume/kg BW of 0.9% NaCl. Two separate groups of mice (n = 5/group) were gavaged with 4 g betaine/kg BW, either 2 h before or simultaneously with the ethanol or saline gavages. All mice were sacrificed 8 h after the last gavage and serum and liver parameters were quantified. Ethanol binges caused a 50% decrease in hepatic SAM:SAH ratio and a &gt;3-fold rise in liver triglycerides (p ≤ 0.05). These latter changes were accompanied by elevated serum AST and ALT activities and blood alcohol concentrations (BAC) that were ∼three-times higher than the legal limit of intoxication in humans. Mice that were treated with betaine 2 h before or simultaneously with the ethanol binges exhibited similar BAC as in mice given ethanol-alone. Both betaine treatments significantly elevated hepatic SAM levels thereby normalizing the SAM:SAH ratio and attenuating hepatic steatosis and other injury parameters, compared with mice given ethanol alone. Simultaneous betaine co-administration with ethanol was more effective in preventing or attenuating liver injury than betaine given before ethanol gavage. Our findings confirm the potential therapeutic value of betaine administration in preventing liver injury after binge drinking in an animal model.
Polycystin-2 (TRPP2) regulates primary cilium length in LLC-PK1 renal epithelial cells
Authors: Scarinci Noelia , Perez Paula L. , Cantiello Horacio F. , Cantero María del Rocío 
Published: October 2022

Polycystin-2 (PC2, TRPP2) is a Ca2+ permeable nonselective cation channel whose dysfunction generates autosomal dominant polycystic kidney disease (ADPKD). PC2 is present in different cell locations, including the primary cilium of renal epithelial cells. However, little is known as to whether PC2 contributes to the primary cilium structure. Here, we explored the effect(s) of external Ca2+, PC2 channel blockers, and PKD2 gene silencing on the length of primary cilia in wild-type LLC-PK1 renal epithelial cells. Confluent cell monolayers were fixed and immuno-labeled with an anti-acetylated α-tubulin antibody to identify primary cilia and measure their length. Although primary cilia length measurements did not follow a Normal distribution, the data were normalized by Box-Cox transformation rendering statistical differences under all experimental conditions. Cells exposed to high external Ca2+ (6.2 mM) decreased a 13.5% (p &lt; 0.001) primary cilia length as compared to controls (1.2 mM Ca2+). In contrast, the PC2 inhibitors amiloride (200 μM) and LiCl (10 mM), both increased primary ciliary length by 33.2% (p &lt; 0.001), and 17.4% (p &lt; 0.001), respectively. PKD2 gene silencing by siRNA elicited a statistically significant, 10.3% (p &lt; 0.001) increase in primary cilia length compared to their respective scrambled RNA transfected cells. The data indicate that conditions that regulate PC2 function or gene expression modify the length of primary cilia in renal epithelial cells. Blocking of PC2 mitigates the effects of elevated external Ca2+ concentration on primary cilia length. Proper regulation of PC2 function in the primary cilium may be essential in the onset of mechanisms that trigger cyst formation in ADPKD.
Combination of physical activity and screen time on life satisfaction in adults: A cross-sectional survey
Authors: Chen Zhenhuai , Sun Jiangang , Zhuang Wei 
Published: October 2022

BackgroundSufficient physical activity (PA) and limited screen time (ST) have been shown to be positively associated with a variety of mental health outcomes. It has been known that PA and ST are independently associated with life satisfaction. Whereas, little is known about the association between combinations of PA and ST with life satisfaction in adults. This study aimed to explore the associations between PA and ST (in insolation or combination) and life satisfaction in adults.MethodsData from the 2014 European Social Survey (ESS) round 7 consisting of 22 countries were analyzed in this study. In total, self-reported data from 40,185 adults were included in the final analysis. The self-administered method was used to collect demographic information, PA, ST, and life satisfaction. The prevalence of meeting PA guidelines (at least 150 min per week) and ST guidelines (no more than 3 h per day) was calculated according to Canadian 24-h Movement Guidelines for Adults.ResultsAdults who were engaged in sufficient PA and limited ST were more likely to report a higher level of life satisfaction. Meeting PA or ST guidelines was more likely to report higher life satisfaction scores [odds ratio (OR) = 1.31, 95% CI: 1.16–1.47]. Compared with not meeting any guidelines, those who met both PA and ST guidelines had a higher OR (OR = 1.55, 95% CI: 1.37–1.76).ConclusionThis study found that participating PA while limiting ST concurrently was linked with better life satisfaction. Creating an active lifestyle is important to population’s well-being.
Medical use and costs for native fathers and children from transnational marriage families in Taiwan from 2004 to 2017
Authors: Chen Yi-Lung 
Published: October 2022

ObjectivesThis is the first study to examine health care utilization in terms of medical use and costs in native fathers and children from transnational families.MethodsTaiwan National Health Insurance Research Database was used to compare the annual medical use and inflation-adjusted medical cost for ambulatory care from 2004 to 2017 between native fathers and children from transnational and native families.ResultsNative fathers from transnational families had lower annual medical use (−0.23 visits) but higher total medical costs (New Taiwan dollars, NT$, 966), especially in dialysis and psychiatry, compared with those from native families. Unlike fathers from transnational families, their children were observed to consistently have lower medical use (−1.35 visits) and costs (NT$ −636), compared with those from native families.ConclusionsThere was different medical use and costs in transnational marriage families, possibly as a result of features in transnational marriage families. These findings provide insight for future health care policies to address the different health care utilization by exploring the unmet needs and barriers relating to children and fathers from transnational families.