bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of absolute versus relative temperature on health and the role of social care
Authors: Masiero Giuliano , Mazzonna Fabrizio , Santarossa Michael 
Published: April 2022

AbstractWe investigate the effect of extreme temperatures on mortality and emergency hospital admissions, and whether local social care allows to mitigate their adverse effects. We merge monthly administrative data on mortality and hospital discharge from Italian municipalities for the period 2001–2015 with daily data on local weather conditions, and yearly data on disaggregated municipal expenditure. We compare two different measures of temperature shocks, one using the conventional approach based on absolute levels (without accounting for regional heterogeneity) and the other based on deviations from local mean temperatures. The former approach shows noisy evidence of an increase in mortality due to extremely hot days while the latter approach shows a large increase in mortality and hospital admissions for cardiovascular and respiratory diseases due to both cold and hot days. These effects are mostly driven by the oldest age group and partially by young children. Then, we report evidence of a mitigating effect of social expenditure on the impact of extremely hot and cold days on both emergency hospital admission and mortality rates. A back of the envelope calculation suggests that the additional social care expenditure is fully compensated by the benefits arising from the lower impact of temperature shocks.
The prognostic value of adding systemic inflammation response index to Epstein–Barr virus DNA in childhood nasopharyngeal carcinoma: A real‐world study
Authors: Jin Ya‐Nan , Liu Bao‐Qiu , Peng Kun‐Wei , Ou Xue‐Qing , Zeng Wu‐Shuang , Zhang Wang‐Jian , Marks Tia , Yao Ji‐Jin , Xia Liang‐Ping 
Published: April 2022

AbstractBackgroundTo assess the prognostic value of the systemic inflammation response index (SIRI) combined with plasma load of Epstein–Barr virus (EBV) DNA in children and adolescents with locoregionally advanced nasopharyngeal carcinoma (CALANPC).MethodsA total of 205 consecutive patients with CALANPC were enrolled. We used recursive partitioning analysis (RPA) to classify patients into various risk groups, with a primary endpoint of overall survival (OS).ResultsElevated SIRI (≥1.53) and EBV DNA (≥4000 copy/ml) were significantly associated with inferior OS in CALANPC. RPA categorized patients into low‐ and high‐risk groups based on prognostic factors. Survival curves showed excellent discrimination in OS (95.3% vs 77.6%; p < 0.001) between the low‐ and high‐risk groups. A significant improvement was confirmed using the prognostic methods for conventional TNM staging systems (p < 0.05).ConclusionsThe combination of SIRI with EBV DNA provided a more detailed understanding of patient risks, and enhanced risk discrimination in CALANPC.
Identification of hepatic steatosis in living liver donors by machine learning models
Authors: Lim Jihye , Han Seungbong , Lee Danbi , Shim Ju Hyun , Kim Kang Mo , Lim Young‐Suk , Lee Han Chu , Jung Dong Hwan , Lee Sung‐Gyu , Kim Ki‐Hun , Choi Jonggi 
Published: April 2022

Abstract
Selecting an optimal donor for living donor liver transplantation is crucial for the safety of both the donor and recipient, and hepatic steatosis is an important consideration. We aimed to build a prediction model with noninvasive variables to evaluate macrovesicular steatosis in potential donors by using various prediction models. The study population comprised potential living donors who had undergone donation workup, including percutaneous liver biopsy, in the Republic of Korea between 2016 and 2019. Meaningful macrovesicular hepatic steatosis was defined as >5%. Whole data were divided into training (70.5%) and test (29.5%) data sets based on the date of liver biopsy. Random forest, support vector machine, regularized discriminant analysis, mixture discriminant analysis, flexible discriminant analysis, and deep neural network machine learning methods as well as traditional logistic regression were employed. The mean patient age was 31.4 years, and 66.3% of the patients were men. Of the 1652 patients, 518 (31.4%) had >5% macrovesicular steatosis on the liver biopsy specimen. The logistic model had the best prediction power and prediction performances with an accuracy of 80.0% and 80.9% in the training and test data sets, respectively. A cut‐off value of 31.1% for the predicted risk of hepatic steatosis was selected with a sensitivity of 77.7% and specificity of 81.0%. We have provided our model on the website (https://hanseungbong.shinyapps.io/shiny_app_up/) under the name DONATION Model. Our algorithm to predict macrovesicular steatosis using routine parameters is beneficial for identifying optimal potential living donors by avoiding superfluous liver biopsy results.
Analysis of Joule heating and chemical reaction effects in electroosmosis peristaltic transport of couple‐stress and micropolar fluids
Authors: Reddy Kattamreddy Venugopal , Reddy Machireddy Gnaneswara , Makinde Oluwole Daniel 
Published: April 2022

AbstractThis article features the reaction of electroosmosis peristaltic transport of combined couple‐stress and micropolar fluid in an inclined asymmetric channel through a porous medium. Mathematical modeling is given in the presence of Joule heating, thermal radiation, and heat flux effects. The relevant equations are computed subject to long wavelength and small Reynolds number approximation. The coupled system resulting equations have been executed computationally to plot different effects graphically. A detailed analysis of the results is given through graphs. Graphs are plotted for velocity, temperature, concentration, and pumping characteristics. The impact of each significant parameter on flow, species, and thermal characteristics is enumerated in these studies. The influence of couple stress and electroosmosis parameters are also simulated. This problem is very significant to the discussion of chemical separation/fraternization procedures and bio‐microfluidics devices for the resolution of the diagnosis.
Chasing the origin of 23 recurrent BRCA1 mutations in Pakistani breast and ovarian cancer patients
Authors: Rashid Muhammad Usman , Muhammad Noor , Naeemi Humaira , Shehzad Umara , Hamann Ute 
Published: April 2022

AbstractKnowledge of population specific BRCA1/2 founder mutations provides a valuable and cost‐effective genetic testing strategy. Twenty‐three recurrent BRCA1 mutations have been identified previously in 100 Pakistani breast and/or ovarian cancer families. These accounted for 72.5% of all BRCA1 mutations identified. In our study, we investigated whether these mutations (identified in ≥2 unrelated patients) have a common ancestral origin and estimated the ages of these mutations. Haplotype analyses were performed in 188 individuals (100 index patients, 88 relatives) from Pakistani breast/ovarian cancer families, all harboring one of the 23 recurrent BRCA1 mutations, and 90 healthy controls. Six microsatellite markers (D17S800, D17S1801, D17S855, D17S1322, D17S1323, and D17S951) were analyzed. Mutation ages were estimated using DMLE+2.3 software. An identical haplotype of different length was found in families harboring the same BRCA1 mutation and suggested founder effects for all 23 mutations. Sixteen founder mutations were ethnicity‐specific: 15 occurred in families of Punjabi background and one in a family of Pathan background. The remaining seven mutations occurred in families with two ethnic backgrounds. All BRCA1 founder mutations were estimated to have arisen approximately 147 to 159 generations ago. Our findings suggest founder effects for all 23 recurrent BRCA1 mutations. This knowledge allows the design and development of a cost effective local genetic testing strategy in Pakistan.
THP‐1 reference data: Proposal of an in vitro branched evolution model for cancer cell lines
Authors: Kasai Fumio , Hirayama Noriko , Fukushima Makoto , Kohara Arihiro , Nakamura Yukio 
Published: April 2022

AbstractTHP‐1 is a representative leukemia cell line and is registered with four different numbers in JCRB and RIKEN BRC cell banks. However, differences between these four lines remain unclear. In our study, these four THP‐1 cell lines, JCRB0112, JCRB0112.1 (corresponding to ATCC TIB‐202), RCB1189 (DSMZ ACC‐16) and RCB3686, have been compared at chromosome and DNA sequence levels. Our results reveal that ploidy has been changed in JCRB0112 and RCB1189, which are triploid and tetraploid, respectively. Patterns of variant frequencies from target sequencing are unique to each ploidy, estimating whole genomic status based on partial sequence data. SNP microarrays showed four distinct profiles with a large‐scale loss of heterozygosity, reflected in subtle differences in STR genotypes. Transcriptome patterns suggest that JCRB0112.1 has diverged highly from the other three lines. RCB1189 and JCRB0112.1 responded to PMA faster than RCB3686 and JCRB0112. We have identified RCB3686 as the closest to the original THP‐1, which can be an optimal model of AML‐M5. These four THP‐1 genomes and transcriptomes exhibit significant differences, indicating four independent sublines and demonstrating the influence of genetic drift on gene expression. As these cells share the same name, THP‐1 must be accompanied by their registration number of each cell repository. Our data provide genomic features of four THP‐1 sublines and serve as a reference profile to classify widely spread THP‐1 progenies, which could be distinguished by a comparison of 24 STR markers. Multiple sublines can be generated by separate cell cultures, which would be explained by in vitro branched evolution.
Inside Cover
Authors: Yan Min , Wu Mei X. 
Published: April 2022

Exhausting exercise results in hypoxia in muscle cells and impedes myotube differentiation from myoblasts, a process involving active biogenesis of nuclei and mitochondria. The impediment was however substantially mitigated by pretreatment of myoblasts with low‐level light therapy (Pre‐LLL). Pre‐LLL, but not post‐LLL, significantly enhanced glucose uptake, prevented energy metabolic switch from oxidative phosphorylation to glycolysis, suppressed lactate production, and restored myoblast differentiation into myotubes under hypoxic conditions.Further details can be found in the article by Min Yan and Mei X. Wu (e202100246)
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Anti-Mullerian Hormone as Predictor of Future and Ongoing Bone Loss During the Menopause Transition
Authors: Karlamangla Arun S , Shieh Albert , Greendale Gail A , Yu Elaine W , Burnett-Bowie Sherri-Ann M , Sluss Patrick M , Martin Deborah , Morrison Anthony , Finkelstein Joel S 
Published: April 2022

ABSTRACT
The menopause transition in women is a period of significant bone loss, with rapid declines in bone mineral density (BMD) commencing a year before the final menstrual period (FMP). Changes in menstrual bleeding patterns cannot reliably tell us if this rapid bone loss has begun or is imminent. We hypothesized that low circulating levels of anti-Mullerian hormone (AMH), which decline as women approach the FMP, would be associated with future and ongoing rapid bone loss. We used data from The Study of Women's Health Across the Nation, a multisite, multi-ethnic, prospective cohort study of the menopause transition to test this hypothesis. Adjusted for age, body mass index, race/ethnicity, and study site, every 50% decrement in AMH level in premenopause and early perimenopause was associated with 0.14% per year faster decline over the following 3 to 4 years in lumbar spine BMD and 0.11% per year faster decline in femoral neck BMD (p &lt; 0.001 for both). AMH in late perimenopause was not associated with the rate of future BMD decline. AMH was also associated with the magnitude of ongoing bone loss, measured as percent of peak BMD lost by the end of the next 2 to 3 years. Every 50% decrement in AMH level was associated with 0.22% additional loss in spine BMD in premenopause, 0.43% additional loss in early perimenopause, and 0.50% additional loss in late perimenopause (p &lt; 0.001 for all three). If a woman will lose more of her peak BMD than the site-specific least significant change (LSC) at either the lumbar spine or femoral neck by the next 2 to 3 years, then AMH below 100 pg/mL will detect it with sensitivity of 50% in premenopause, 80% in early perimenopause, and 98% in late perimenopause. These findings suggest that AMH measurement can help flag women at the brink of significant bone loss for early intervention. © 2022 American Society for Bone and Mineral Research (ASBMR).
Inhibition of MAC30 exerts antitumor effects in nasopharyngeal carcinoma via affecting the Akt/GSK‐3β/β‐catenin pathway
Authors: Zhang Pengfei , Tian Qi , Gao Huan , Zhao Andi , Shao Yuan , Yang Jin 
Published: April 2022

AbstractMeningioma‐associated protein 30 (MAC30) is a vital modulator of malignant transformation in numerous cancers. Yet, the involvement of MAC30 in nasopharyngeal carcinoma (NPC) is undetermined. This study was devoted to the study of the function of MAC30 in NPC, along with the molecular mechanism of its involvement in disease progression. This study showed an elevated level of MAC30 in NPC tissues and cell lines. MAC30 silencing impeded the proliferation, colony formation, and invasion of NPC cells, while MAC30 upregulation had the opposite effects. MAC30 regulated the Wnt/β‐catenin pathway via affecting the protein kinase B (Akt)/glycogen synthase kinase‐3β axis. Akt inhibition markedly abrogated the MAC30‐mediated activation of the Wnt/β‐catenin pathway. Restoration of β‐catenin reversed MAC30 silencing‐induced tumor‐inhibiting effects. Knockdown of MAC30 weakened the tumorigenic potential of NPC cells in vivo. This study elucidates the fact that inhibition of MAC30 produces antitumor effects in NPC via affecting the Akt/Wnt/β‐catenin pathway.
CO2 trapping of selected N‐heterocyclic vinylidenes with an NBO mechanistic scrutiny by DFT
Authors: Soroudi Shadi , Kassaee Mohamad Zaman 
Published: April 2022

AbstractTrapping of CO2 is probed by a set of three N‐heterocyclic vinylidene minima, from the azole family, including imidazole (1), 1,2,4‐triazole (2), and tetrazole (3), at M06‐2X/6‐311++G** level of theory. Exothermic adsorption of CO2 over 1, 2, and 3 gives the initial CO2‐complex, 1a, 2a, and 3a, with no transition state (TS). Consequently, carbenic π‐additions to CO2 (within 1a, 2a, and 3a) may give reactant‐like, three‐membered cyclic TSs, which lead to the exothermic formation of 1b > 2b > 3b. Alternatively, CO2 intramolecular reactions within 1a, 2a, and 3a may result in the formation of the product‐like, five‐membered cyclic TSs, which lead to the endothermic formation of unstable side products 1c, 2c, and 3c, which revert to 1a, 2a, and 3a, respectively. Hence, this manuscript focuses on the main CO2 trapped products (1b, 2b, and 3b), and takes advantage of the immense potential of the NBO and AIM data in elucidating their formation provisional mechanisms. Unprecedentedly, contributions of different donor‐acceptor interacting orbitals to the formation of each product are assessed on the basis of their second‐order perturbation stabilization energy (E2) values.
Silencing oncogene cell division cycle associated 5 induces apoptosis and G1 phase arrest of non‐small cell lung cancer cells via p53‐p21 signaling pathway
Authors: Shen Wei , Tong Dimin , Chen Jie , Li Hongxiang , Hu Zeyang , Xu Shuguang , He Sufang , Ge Zhen , Zhang Jianan , Mao Qiqi , Chen Hang , Xu Guodong 
Published: April 2022

AbstractBackgroundsAs a regulator of cell cycle, cell division cycle‐associated 5 (CDCA5) is involved in the progression of various malignant tumors. However, the potential relationship between CDCA5 and lung cancer has not been reported.MethodsIn our study, we analyzed the expression of CDCA5 in a variety of malignant tumors, performed Kaplan‐Meier survival analysis of lung adenocarcinoma (LUAD), explored the potential relationship between CDCA5 expression and clinicopathological characteristics, assessed the predictive capability of at different stages of clinicopathological characteristics, revealed the enriched functions and signaling pathways among LUAD paitents with high CDCA5 expression, and investigated the correlation between PD‐1, PD‐L1, and CDCA5 through bioinformatics analyses. Subsequently, we performed quantitative real‐time reverse transcription‐polymerase chain reaction (qRT‐PCR) and western blotting (WB) to demonstrate that CDCA5 mediates the p53‐p21 pathway and regulates the cell cycle.ResultCDCA5 is probably involved in the occurrence and development of NSCLC, and function as a reliable biomarker for predicting the survival outcomes of patients with early stage of patients with LUAD. Furthermore, CDCA5 may be a promising indicator of immunotherapy efficacy. In addition, silencing the expression of CDCA5 significantly increased the proportion of apoptotic NSCLC cells, and caused NSCLC cells to be arrested in the G1 phase.ConslusionIn conclusion, CDCA5 regulated the cell cycle of NSCLC cells by mediating the p53‐p21 signaling pathway, participating in the development and progression of NSCLC patients.
Hsa_circ_0058129 regulates papillary thyroid cancer development via miR‐873‐5p/follistatin‐like 1 axis
Authors: Tan Xiangrong , Zhao Jiazheng , Lou Jianlin , Zheng Wen , Wang Peng 
Published: April 2022

AbstractBackgroundPapillary thyroid cancer (PTC) is an endocrine malignancy with a high incidence. Circular RNAs (circRNAs) participate in regulating PTC. Here, we analyzed the role of hsa_circ_0058129 (circ_0058129) in PTC.MethodsThe expression of circ_0058129, fibronectin 1 (FN1) mRNA, microRNA‐873‐5p (miR‐873‐5p), and follistatin‐like 1 (FSTL1) was detected by qRT‐PCR and western blot. Cell proliferation was analyzed by CCK‐8, EdU, and flow cytometry analysis assays. Cell migration and invasion were evaluated by Transwell assay. The targeting relationship of miR‐873‐5p and circ_0058129 or FSTL1 was identified through dual‐luciferase reporter assay, RIP assay, and RNA pull‐down assay. Xenograft mouse model assay was implemented to determine the effect of circ_0058129 on tumor formation in vivo.ResultsThe circ_0058129 and FSTL1 abundances were increased, while the miR‐873‐5p content was decreased in PTC tissues and cells compared with control groups. Circ_0058129 shortage inhibited PTC cell proliferation, migration, and invasion. Moreover, miR‐873‐5p repressed PTC cell malignancy by binding to FSTL1. Circ_0058129 targeted miR‐873‐5p to regulate FSTL1.ConclusionCirc_0058129 expedited PTC progression through the miR‐873‐5p/FSTL1 pathway.
Evaluation of Lorlatinib Cerebrospinal Fluid Concentrations in Relation to Target Concentrations for Anaplastic Lymphoma Kinase (ALK) Inhibition
Authors: Sun Steven , Pithavala Yazdi K. , Martini Jean‐François , Chen Joseph 
Published: April 2022

AbstractLorlatinib is a third‐generation, brain‐penetrant anaplastic lymphoma kinase (ALK) and c‐ros oncogene 1 (ROS1) tyrosine kinase inhibitor (TKI) with robust intracranial activity in patients with ALK‐ or ROS1‐positive non‐small cell lung cancer (NSCLC). Data from the ongoing open‐label, single‐arm, multicenter, phase‐1/2 study of lorlatinib in patients with metastatic ALK‐ or ROS1‐positive NSCLC were used to further investigate the potential brain penetration of lorlatinib. Patients received escalating lorlatinib doses (10–200 mg once daily or 35–100 mg twice daily) or the approved dosing (100 mg daily). Plasma was collected from all patients, and cerebrospinal fluid (CSF) was collected at baseline and during the study from 5 patients with suspected or confirmed leptomeningeal carcinomatosis or carcinomatous meningitis. For those 5 patients, lorlatinib concentrations ranged from 2.64 to 125 ng/mL in the CSF and from 12.7 to 457 ng/mL in the plasma; free plasma concentrations ranged from 4.318 to 155.385 ng/mL. The CSF/free plasma ratio was 0.77 (R2 = 0.96 and P < .001). Using a post‐hoc population pharmacokinetic model, the average steady‐state unbound plasma concentration of lorlatinib was derived and the CSF concentration was estimated for all patients. Known minimum efficacy concentrations (Ceff) for wild‐type and mutated (L1196M and G1202R) ALK were used to derive central nervous system (CNS) Ceff. Estimated CNS concentrations exceeded the derived CNS Ceff values in all patients for wild‐type ALK and the ALK L1196M mutation, and in 35.8% of patients for the ALK G1202R mutation. Projected lorlatinib CNS concentrations were consistent with the high intracranial response rates reported in clinical trials and provide further evidence of the potent CNS penetration of lorlatinib.
Involvement of Parkin‐mediated mitophagy in the pathogenesis of chronic obstructive pulmonary disease‐related sarcopenia
Authors: Ito Akihiko , Hashimoto Mitsuo , Tanihata Jun , Matsubayashi Sachi , Sasaki Ryoko , Fujimoto Shota , Kawamoto Hironori , Hosaka Yusuke , Ichikawa Akihiro , Kadota Tsukasa , Fujita Yu , Takekoshi Daisuke , Ito Sabro , Minagawa Shunsuke , Numata Takanori , Hara Hiromichi , Matsuoka Tatsuki , Udaka Jun , Araya Jun , Saito Mitsuru , Kuwano Kazuyoshi 
Published: April 2022

AbstractBackgroundSarcopenia is characterized by the loss of skeletal muscle mass and strength and is associated with poor prognosis in patients with chronic obstructive pulmonary disease (COPD). Cigarette smoke (CS) exposure, a major cause for COPD, induces mitochondrial damage, which has been implicated in sarcopenia pathogenesis. The current study sought to examine the involvement of insufficient Parkin‐mediated mitophagy, a mitochondrion‐selective autophagy, in the mechanisms by which dysfunctional mitochondria accumulate with excessive reactive oxygen species (ROS) production in the development of COPD‐related sarcopenia.MethodsThe involvement of Parkin‐mediated mitophagy was examined using in vitro models of myotube formation, in vivo CS‐exposure model using Parkin−/− mice, and human muscle samples from patients with COPD‐related sarcopenia.ResultsCigarette smoke extract (CSE) induced myotube atrophy with concomitant 30% reduction in Parkin expression levels (P < 0.05). Parkin‐mediated mitophagy regulated myotube atrophy by modulating mitochondrial damage and mitochondrial ROS production. Increased mitochondrial ROS was responsible for myotube atrophy by activating Muscle Ring Finger 1 (MuRF‐1)‐mediated myosin heavy chain (MHC) degradation. Parkin−/− mice with prolonged CS exposure showed enhanced limb muscle atrophy with a 31.7% reduction in limb muscle weights (P < 0.01) and 2.3 times greater MuRF‐1 expression (P < 0.01) compared with wild‐type mice with concomitant accumulation of damaged mitochondria and oxidative modifications in 4HNE expression. Patients with COPD‐related sarcopenia exhibited significantly reduced Parkin but increased MuRF‐1 protein levels (35% lower and 2.5 times greater protein levels compared with control patients, P < 0.01 and P < 0.05, respectively) and damaged mitochondria accumulation demonstrated in muscles. Electric pulse stimulation‐induced muscle contraction prevented CSE‐induced MHC reduction by maintaining Parkin levels in myotubes.ConclusionsTaken together, COPD‐related sarcopenia can be attributed to insufficient Parkin‐mediated mitophagy and increased mitochondrial ROS causing enhanced muscle atrophy through MuRF‐1 activation, which may be at least partly preventable through optimal physical exercise.