bluuebunny/crossref_metadata_2025_split huggingface dataset:
Investigating the Clinico-Molecular and Immunological Evolution of Lung Adenocarcinoma Using Pseudotime Analysis
Authors: Lee Hyunjong , Choi Hongyoon 
Published: March 2022

IntroductionAs the molecular features of lung adenocarcinoma (LUAD) have been evaluated as a cross-sectional study, the course of tumor characteristics has not been modeled. The temporal evolution of the tumor immune microenvironment (TIME), as well as the clinico-molecular features of LUAD, could provide a precise strategy for immunotherapy and surrogate biomarkers for the course of LUAD.MethodsA pseudotime trajectory was constructed in patients with LUAD from the Cancer Genome Atlas and non-small cell lung cancer radiogenomics datasets. Correlation analyses were performed between clinical features and pseudotime. Genes associated with pseudotime were selected, and gene ontology analysis was performed. F-18 fluorodeoxyglucose positron emission tomography images of subjects were collected, and imaging parameters, including standardized uptake value (SUV), were obtained. Correlation analyses were performed between imaging parameters and pseudotime. Correlation analyses were performed between the enrichment scores of various immune cell types and pseudotime. In addition, correlation analyses were performed between the expression of PD-L1, tumor mutation burden, and pseudotime.ResultsPseudotime trajectories of LUAD corresponded to clinical stages. Molecular profiles related to cell division and natural killer cell activity were changed along the pseudotime. The maximal SUV of LUAD tumors showed a positive correlation with pseudotime. Type 1 helper T (Th1) cells showed a positive correlation, whereas M2 macrophages showed a negative correlation with pseudotime. PD-L1 expression showed a negative correlation, whereas tumor mutation burden showed a positive correlation with pseudotime.ConclusionThe estimated pseudotime associated with the stage suggested that it could reflect the clinico-molecular evolution of LUAD. Specific immune cell types in the TIME as well as cell division and glucose metabolism were dynamically changed according to the progression of the pseudotime. As a molecular progression of LUAD, different cellular targets should be considered for immunotherapy.
Prognostic Significance of Neutrophil-to-Lymphocyte Ratio and C-Reactive Protein/Albumin Ratio in Luminal Breast Cancers With HER2-Negativity
Authors: Chen Fei , Chen Danzhi , Jin Lidan , Xu Chenpu , Zhao Wenhe , Hu Wenxian 
Published: March 2022

PurposeThis study was determined to evaluate the prognostic value of neutrophil-to-lymphocyte ratio (NLR) and C-reactive protein/albumin ratio (CAR) prior to surgery in luminal breast cancers (BC) with HER2-negativity.MethodsThe clinical data of 708 HER2-negative luminal BC patients from January 2013 to December 2016 were retrospectively collected and analyzed. The optimal cut-off value of NLR and CAR were determined via receiver operating characteristic (ROC) curve. The disease-free survival (DFS) and cancer specific survival (CSS) rates were estimated using the Kaplan−Meier method. Cox univariate and multivariate proportional hazards regression models were performed to identify significant predictors of DFS and CSS simultaneously.ResultsThe mean age of the patients diagnosed was 52.43 years (range, 15–95 years), and the median follow-up was 62.71 months (range, 12-92 months). Univariate and multivariate analysis confirmed that NLR ≥2.2 was significantly associated with worse DFS (HR=2.886, 95%CI=1.756-4.745, p&lt;0.001), and same results were obtained in terms of CSS (HR=3.999, 95%CI=2.002-7.987, p&lt;0.001). Similarly, CAR ≥0.07 was independently and significantly associated with poor DFS (HR=3.858, 95%CI=2.346-6.345, p&lt;0.001) and CSS (HR=6.563, 95%CI=3.558-12.106, p&lt;0.001).ConclusionPreoperative evaluation of NLR and CAR were significant and independent prognostic indicators for luminal breast cancers with HER2-negativity.
SDK1-ALK Fusion in a Lung Adenocarcinoma Patient With Excellent Response to ALK Inhibitor Treatment: A Case Report
Authors: Ma Lin , Xiao Junjuan , Guan Yaping , Wu Dongfang , Gu Tiantian , Wang Jun 
Published: March 2022

BackgroundRearrangements of Anaplastic lymphoma kinase (ALK) have been discovered as a novel driver mutation in patients with non–small-cell lung cancer (NSCLC). Patients’ responses to ALK tyrosine kinase inhibitors (TKIs) may vary depending on the variations of ALK rearrangements they have. It is imperative for clinicians to identify druggable ALK fusions in routine practice.Case PresentationIn this study, we discovered a rare ALK rearrangement type (SDK1–ALK) in a Chinese lung adenocarcinoma patient who responded well to ALK inhibitor SAF-189s. The positive expression of ALK in lung biopsy tissue was verified by IHC analysis. A new SDK1-ALK fusion was discovered using NGS. The patient was treated with SAF-189s (160 mg per day) as a first-line therapy and went into continuous remission, with a 12 months progression-free survival at the last follow-up.ConclusionThis is the first case of SDK1-ALK fusion with an excellent response to an ALK inhibitor, which will provide better understanding of ALK-TKI applications for NSCLC patients with ALK fusion in the future.
Impact of Umbilical Cord Milking on Hematological Parameters in Preterm Neonates With Placental Insufficiency
Authors: Nagy Mohammed , Nasef Nehad , Gibreel Ahmed , Sarhan Mohamed , Aldomiaty Hoda , Darwish Mohammed , Nour Islam 
Published: March 2022

BackgroundData is still lacking about the expediency of umbilical cord milking (UCM) in preterm neonates born to mothers with placental insufficiency (PI).ObjectiveTo study the effect of UCM in preterm neonates who had ante-natal evidence of placental insufficiency on peripheral blood cluster of differentiation 34 (CD34) percentage, hematological indices, and clinical outcomes.MethodsPreterm neonates, &lt;34 weeks' gestation, born to mothers with evidence of placental insufficiency that underwent UCM (PI+UCM group) were compared with historical controls whose umbilical stumps were immediately clamped [PI+ICC (immediate cord clamping) group] in a case-control study. Peripheral blood CD34 percentage as a measure of hematopoietic stem cell transfusion was the primary outcome. Early and late-onset anemia; polycythemia; frequency of packed red blood cells (PRBCs) transfusion during NICU stay; peak total serum bilirubin (TSB); incidence of phototherapy, admission rectal temperature; first 24 h hypothermia and hypoglycemia; episodes of hypotension and need for volume expander boluses and inotropic support during the first 24 h of age; duration of oxygen therapy; bronchopulmonary dysplasia (BPD); severe intra-ventricular hemorrhage (IVH); necrotizing enterocolitis (NEC); culture-proven late-onset sepsis; length of hospital stay; and in-hospital mortality were secondary outcomes.ResultsIn preterm infants with placental insufficiency, umbilical cord milking was associated with greater peripheral blood CD34 percentage, hemoglobin levels initially and at postnatal age of 2 months, alongside significantly shorter duration of oxygen therapy compared with ICC group. Frequency of packed RBCs transfusion during hospital stay was comparable. Neonates in UCM group had a greater peak TSB level during admission with significantly higher need for phototherapy initiation compared with ICC. Logistic regression, adjusted for gestational age, revealed that UCM resulted in greater CD34 percentage, higher initial hemoglobin level, higher peak serum bilirubin, significant increase of phototherapy initiation, and higher hemoglobin level at 2 months.ConclusionsUCM in preterm neonates born to mothers with placental insufficiency was feasible and resulted in greater CD34 percentage, higher initial hemoglobin level, higher peak serum bilirubin, significant increase of phototherapy initiation, and higher hemoglobin level at 2 months.
Elucidation of the Mechanisms and Effective Substances of Paeoniae Radix Rubra Against Toxic Heat and Blood Stasis Syndrome With a Stage-Oriented Strategy
Authors: Xu Jing-Jing , Xu Feng , Wang Wei , Zhang Yi-Fan , Hao Bei-Quan , Shang Ming-Ying , Liu Guang-Xue , Li Yao-Li , Yang Shu-Bin , Wang Xuan , Cai Shao-Qing 
Published: March 2022

In the clinical practice of traditional Chinese medicine, toxic heat and blood stasis syndrome (THBSS) is a common syndrome observed in various critical diseases. Paeoniae Radix Rubra (PRR) has known therapeutic effects on THBSS. However, its pharmacodynamic mechanisms and effective substances in the treatment of THBSS still need further elucidation. Our previous study indicated that THBSS had three stages of progression, and the abnormal biochemical indices of each stage were different. Therefore, this study aimed to elucidate the pharmacodynamic mechanisms and effective substances of PRR for the treatment of THBSS with a stage-oriented strategy. Specifically, research was performed separately in two stable stages of THBSS: the excessive heat and little blood stasis (EHLBS) and blood stasis (BS) stages. THBSS model rats, at different time periods after syndrome initiation (first 5 h for EHLBS and 24 h later for BS), were used to conduct the two-stage investigation. Targeted metabonomics analysis was performed to elucidate the pharmacodynamic mechanisms of PRR in the treatment of EHLBS or BS. Based on the relationship between the individual differences in blood drug concentrations and pharmacodynamic effects, partial least squares regression analysis was employed to screen for the effective substances from the original constituents and metabolites of PRR. We found that PRR could upregulate primary bile acid biosynthesis, glycerophospholipid metabolism, ether lipid metabolism, and five amino acid metabolic pathways (e.g., arginine and proline metabolism) to treat EHLBS. Meanwhile, PRR alleviated BS by upregulating primary bile acid biosynthesis and downregulating glycerophospholipid metabolism. But PRR had no obvious effects on ether lipid metabolism and amino acid metabolism in this stage. In total, 17 and 9 potential effective substances were found in the EHLBS and BS stages, respectively, among which there were only five common compounds between the two stages. To our knowledge, sixteen compounds were regarded as potential effective substances of PRR for the first time. Therefore, the pharmacodynamic mechanisms and effective substances of PRR in the treatment of EHLBS and BS were partly different. Overall, this stage-oriented strategy provides a new way to study the pharmacodynamic mechanisms and effective substances of traditional Chinese drugs.
Drug Transporters ABCB1 (P-gp) and OATP, but not Drug-Metabolizing Enzyme CYP3A4, Affect the Pharmacokinetics of the Psychoactive Alkaloid Ibogaine and its Metabolites
Authors: F. Martins Margarida L. , Heydari Paniz , Li Wenlong , Martínez-Chávez Alejandra , Venekamp Nikkie , Lebre Maria C. , Lucas Luc , Beijnen Jos H. , Schinkel Alfred H. 
Published: March 2022

The psychedelic alkaloid ibogaine is increasingly used as an oral treatment for substance use disorders, despite being unlicensed in most countries and having reported adverse events. Using wild-type and genetically modified mice, we investigated the impact of mouse (m)Abcb1a/1b and Abcg2 drug efflux transporters, human and mouse OATP drug uptake transporters, and the CYP3A drug-metabolizing complex on the pharmacokinetics of ibogaine and its main metabolites. Following oral ibogaine administration (10 mg/kg) to mice, we observed a rapid and extensive conversion of ibogaine to noribogaine (active metabolite) and noribogaine glucuronide. Mouse Abcb1a/1b, in combination with mAbcg2, modestly restricted the systemic exposure (plasma AUC) and peak plasma concentration (Cmax) of ibogaine. Accordingly, we found a ∼2-fold decrease in the relative recovery of ibogaine in the small intestine with fecal content in the absence of both transporters compared to the wild-type situation. Ibogaine presented good intrinsic brain penetration even in wild-type mice (brain-to-plasma ratio of 3.4). However, this was further increased by 1.5-fold in Abcb1a/1b;Abcg2−/− mice, but not in Abcg2−/− mice, revealing a stronger effect of mAbcb1a/1b in restricting ibogaine brain penetration. The studied human OATP transporters showed no major impact on ibogaine plasma and tissue disposition, but the mOatp1a/1b proteins modestly affected the plasma exposure of ibogaine metabolites and the tissue disposition of noribogaine glucuronide. No considerable role of mouse Cyp3a knockout or transgenic human CYP3A4 overexpression was observed in the pharmacokinetics of ibogaine and its metabolites. In summary, ABCB1, in combination with ABCG2, limits the oral availability of ibogaine, possibly by mediating its hepatobiliary and/or direct intestinal excretion. Moreover, ABCB1 restricts ibogaine brain penetration. Variation in ABCB1/ABCG2 activity due to genetic variation and/or pharmacologic inhibition might therefore affect ibogaine exposure in patients, but only to a limited extent. The insignificant impact of human CYP3A4 and OATP1B1/1B3 transporters may be clinically advantageous for ibogaine and noribogaine use, as it decreases the risks of undesirable drug interactions or interindividual variation related to CYP3A4 and/or OATP activity.
Thermoelectric Conversion From Interface Thermophoresis and Piezoelectric Effects
Authors: Zeng Yu-Jia , Liu Yue-Yang , Pan Hui , Ding Zhong-Ke , Zhou Wu-Xing , Tang Li-Ming , Li Baowen , Chen Ke-Qiu 
Published: March 2022

Piezoelectric effect has proved itself to be a promising energy conversion mechanism that can convert mechanical energy into electricity. Here, we propose an indirect thermoelectric conversion mechanism based on a combination of the thermophoresis and piezoelectric effects. We first analyze this thermally driven mechanism using a simplified theoretical model and then numerically analyze a molecular dynamics (MD) simulation of a hybrid system constructed of a single-layer MoS2 nanoribbon and a concentric carbon nanotube. We show that the thermophoresis-induced piezoelectric output voltage can reach 3.5 V, and this value can be tuned using a temperature difference. The output voltage obtained using this mechanism is significantly higher than that obtained by heating piezoelectric materials directly. Given the generality of the thermophoresis effect in Van der Waals structures, this mechanism has potential applications in the conversion of thermal energy into electrical energy at the nanoscale level.
The Interaction of Central Nervous System and Acute Kidney Injury: Pathophysiology and Clinical Perspectives
Authors: Wang Yiru , Liu Siyang , Liu Qingquan , Lv Yongman 
Published: March 2022

Acute kidney injury (AKI) is a common disorder in critically ill hospitalized patients. Its main pathological feature is the activation of the sympathetic nervous system and the renin-angiotensin system (RAS). This disease shows a high fatality rate. The reason is that only renal replacement therapy and supportive care can reduce the impact of the disease, but those measures cannot significantly improve the mortality. This review focused on a generalization of the interaction between acute kidney injury and the central nervous system (CNS). It was found that the CNS further contributes to kidney injury by regulating sympathetic outflow and oxidative stress in response to activation of the RAS and increased pro-inflammatory factors. Experimental studies suggested that inhibiting sympathetic activity and RAS activation in the CNS and blocking oxidative stress could effectively reduce the damage caused by AKI. Therefore, it is of significant interest to specify the mechanism on how the CNS affects AKI, as we could use such mechanism as a target for clinical interventions to further reduce the mortality and improve the complications of AKI.Systematic Review Registration: [www.ClinicalTrials.gov], identifier [registration number].
Effects of Cardiorespiratory Fitness on Cerebral Oxygenation in Healthy Adults: A Systematic Review
Authors: Salzman Talia , Dupuy Olivier , Fraser Sarah Anne 
Published: March 2022

IntroductionExercise is known to improve cognitive functioning and the cardiorespiratory hypothesis suggests that this is due to the relationship between cardiorespiratory fitness (CRF) level and cerebral oxygenation. The purpose of this systematic review is to consolidate findings from functional near-infrared spectroscopy (fNIRS) studies that examined the effect of CRF level on cerebral oxygenation during exercise and cognitive tasks.MethodsMedline, Embase, SPORTDiscus, and Web of Science were systematically searched. Studies categorizing CRF level using direct or estimated measures of V̇O2max and studies measuring cerebral oxygenation using oxyhemoglobin ([HbO2]) and deoxyhemoglobin ([HHb]) were included. Healthy young, middle-aged, and older adults were included whereas patient populations and people with neurological disorders were excluded.ResultsFollowing PRISMA guidelines, 14 studies were retained following abstract and full-text screening. Cycle ergometer or treadmill tests were used as direct measures of CRF, and one study provided an estimated value using a questionnaire. Seven studies examined the effects of CRF on cerebral oxygenation during exercise and the remaining seven evaluated it during cognitive tasks. Increased [HbO2] in the prefrontal cortex (PFC) was observed during cognitive tasks in higher compared to lower fit individuals. Only one study demonstrated increased [HHb] in the higher fit group. Exercise at submaximal intensities revealed increased [HbO2] in the PFC in higher compared to lower fit groups. Greater PFC [HHb] was also observed in long- vs. short-term trained males but not in females. Primary motor cortex (M1) activation did not differ between groups during a static handgrip test but [HHb] increased beyond maximal intensity in a lower compared to higher fit group.ConclusionConsistent with the cardiorespiratory hypothesis, higher fit young, middle-aged, and older adults demonstrated increased cerebral oxygenation compared to lower fit groups. Future research should implement randomized controlled trials to evaluate the effectiveness of interventions that improve CRF and cerebral oxygenation longitudinally.
Burnout and Quality of Life in Professionals Working in Nursing Homes: The Moderating Effect of Stereotypes
Authors: López-Frutos Patricia , Pérez-Rojo Gema , Noriega Cristina , Velasco Cristina , Carretero Isabel , Martínez-Huertas José Ángel , Galarraga Leyre , López Javier 
Published: March 2022

ObjectiveThis study aimed to analyse how stereotypes towards older people moderate the relationship between burnout and quality of life (QoL) of professionals working in nursing homes.MethodA total of 312 professionals were asked to complete questionnaires of burnout Maslach Burnout Inventory quality of Life (QPL-35) and aging stereotypes (CENVE). The moderation effects were tested using linear regression models.ResultsA negative association was observed between burnout and QoL. It was also found a statistically significant moderator effect of the total score of stereotypes and the health stereotypes, besides a marginally statistically significant moderator effect for motivational stereotypes. The moderator effects were different for people with low and high negative stereotypes. QoL was more affected under conditions of high burnout, in which people with more negative stereotypes tended to present higher QoL than people with lower negative stereotypes.ConclusionHighly burned-out professionals in nursing homes may avoid their negative feelings projecting them to residents through stereotypes, as a way of coping with burnout and increasing their QoL. However, this mechanism is an “aggressive reaction” and may have negative effects for both the older adult and the professional. The comprehension of these variables is essential for developing adequate intervention programs.
An Instrumental Measure of Hand and Facial Movement Abnormalities in Patients With Schizophrenia
Authors: Wang Shu-Mei , Ouyang Wen-Chen , Hsu Hsiao-Man , Hsu Li-Ta 
Published: March 2022

IntroductionMovement disorders have been suggested to be a cardinal component of schizophrenia. With increased research interests in this area, instrumental measures are needed. This study was to examine if the motion capture system was reliable in measuring hand and facial bradykinesia and dyskinesia and more sensitive to detecting movement differences between schizophrenia patients and healthy people than traditional rating scales.MethodsSixteen schizophrenia patients and 20 control subjects were recruited. Hand and facial bradykinesia and dyskinesia were measured using the motion capture system and rated using the Extrapyramidal Symptom Rating Scale and the Abnormal Involuntary Movement Scale.ResultsThe system showed strong test–retest reliability and generated larger effect sizes of group differences than did the rating scales.ConclusionsThe results may support researchers and clinical practitioners to apply the system to sensitively measuring the hand and facial movement symptoms in schizophrenia patients, which contributes to gaining a deep understanding of movement issues in schizophrenia.
Trends in the Incidence and DALYs of Urolithiasis From 1990 to 2019: Results From the Global Burden of Disease Study 2019
Authors: Li Shasha , Huang Xueying , Liu Jie , Yue Suru , Hou Xuefei , Hu Liren , Wu Jiayuan 
Published: March 2022

ObjectivesTo provide a comprehensive assessment of the estimated burden and trend of urolithiasis at the global, regional, and national levels.MethodsThe age-standardized rates (ASRs) of the incidence and disability-adjusted life years (DALYs) of urolithiasis from 1990 to 2019 were obtained from the Global Burden of Disease Study 2019 database. Estimated annual percentage changes (EAPCs) were calculated to quantify the temporal trends in urolithiasis burden.ResultsIn 2019, the ASRs of the incidence and DALYs were 1,394.03/100,000 and 7.35/100,000, respectively. The ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019 with EAPCs of −0.83 and −1.77, respectively. Males had a higher burden of urolithiasis than females. In 2019, the highest burden of urolithiasis was observed in regions with high–middle sociodemographic index (SDI), particularly in Eastern Europe, Central Asia, and Southeast Asia. The burden of urolithiasis increased in most countries or territories. The burden of urolithiasis and SDI had a non-linear relationship, and the estimated value of urolithiasis burden was the highest when the SDI value was ~0.7.ConclusionGlobally, the ASRs of the incidence and DALYs of urolithiasis decreased from 1990 to 2019, but an increasing trend was observed among many countries. More effective and appropriate medical and health policies are needed to prevent and early intervene in urolithiasis.