Miracle-dz/UniFAR-FTUs huggingface dataset:
Pharmacometabolomics Identifies 3-Hydroxyadipic Acid, d-Galactose, Lysophosphatidylcholine (P-16:0), and Tetradecenoyl-l-Carnitine as Potential Predictive Indicators of Gemcitabine Efficacy in Pancreatic Cancer Patients

Gemcitabine (GEM)-based chemotherapy is the standard regimen for the treatment of pancreatic cancer (PC). However, chemoresistance is a major challenge in PC treatment. Reliable biomarkers are urgently needed to predict the response to GEM-based therapies. GEM-sensitive (GEM-S) and GEM-resistant (GEM-R) pancreatic carcinoma xenograft models were established, and GEM monotherapy and GEM plus nanoparticle albumin-bound paclitaxel (nab-PTX) doublet therapy were administered to GEM-S/R tumor-bearing mice. Metabolomic mass spectrometry (MS) analysis of serum, liver, and tumor samples was performed using an ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometer. The results showed that both GEM monotherapy and combination therapy significantly inhibited the tumor growth in GEM-S subgroup. However, in the GEM-R subgroup, tumor growth was not significantly inhibited by GEM monotherapy, but was significantly suppressed by GEM combination therapy. Metabolic profiling analysis by hierarchical cluster analysis and partial least squares discriminant analysis showed that the differences in metabolites were most significant in serum of three types of samples in the GEM-S/R subgroups, regardless of the administration of GEM monotherapy or combination therapy. The differential metabolite analysis of serum samples revealed 38 and 26 differential metabolites between the GEM-R and GEM-S subgroups treated with GEM monotherapy or combination therapy, and four common discriminating metabolites were investigated: 3-hydroxyadipic acid, d-galactose, lysophosphatidylcholine (LysoPC) (P-16:0), and tetradecenoyl-l-carnitine. The relative amounts of the four metabolites changed significantly and consistently after GEM monotherapy or combination therapy. The levels of these four metabolites were significantly different in the GEM-S and GEM-R pancreatic carcinoma xenograft models; thus, these metabolites could be effective predictive indicators of the efficacy of chemotherapy in PC patients, regardless of the administration of GEM alone or GEM plus nab-PTX.
Transcranial Direct Current Stimulation Ameliorates Cognitive Impairment via Modulating Oxidative Stress, Inflammation, and Autophagy in a Rat Model of Vascular Dementia

To investigate the potential applications and the molecular mechanisms of transcranial direct current stimulation (tDCS) on cognitive impairment in a vascular dementia (VD) animal model. Sprague-Dawley rats were used in this study. VD rat model was induced by modified permanent bilateral common carotid artery occlusion (2-VO) approach. Anodal tDCS was applied to the animals. Morris water maze was used to analyze spatial memory and navigation ability. The pathological changes in the hippocampal CA1 region and cerebral cortex were examined via Hematoxylin-Eosin staining. The rats were sacrificed for the measurement of the level of superoxide (SOD), glutathione (GSH), reactive oxidative species (ROS), malondialdehyd (MDA), Interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α level in the hippocampus. Western blot was carried out to measure the hippocampal expression of microtubule-associated protein 1 light chain 3 (LC-3) and p62. Rats with VD have decreased number of neurons in the hippocampus and cerebral cortex, as well as worse cognitive impairment. The proliferation of activated microglia and astroglia, accompanied with attenuation of myelination were observed in the white matter about 1 month after 2-VO operation. These abnormalities were significantly ameliorated by tDCS treatment. Further study revealed that anodal tDCS could suppress the MDA and ROS level, while enhance the SOD and GSH level to reduce the oxidative stress. Anodal tDCS could inhibit hypoperfusion-induced IL-1β, IL-6, and TNF-α expression to attenuate inflammatory response in hippocampus. Moreover, anodal tDCS treatment could alleviate autophagy level. The study has demonstrated a possible therapeutic role of tDCS in the treatment of cognitive impairment in VD.
Examining Ownership Equity as a Psychological Factor on Tourism Business Failure Forecasting

This paper examines ownership equity as a predictor of future business failure within the tourism and hospitality sectors. The main goals of this study were to examine which ratios are the most important for a tourism business failure forecasting model and how significant is the “total percentage of equity ownership by company directors” ratio compared with other ratios associated with the probability of bankruptcy. A stepwise weight assessment ratio analysis (SWARA) was applied, and 12 tourism bankruptcy experts evaluated key ratios. Total percentage of equity ownership by company directors is considered a psychological factor, and it was identified as the fourth most important ratio for a business failure forecasting model. Academicians and practitioners can use the findings of this study whenever developing a forecasting model for tourism and hospitality enterprises.
Iron Metabolism, Ferroptosis, and the Links With Alzheimer’s Disease

Iron is an essential transition metal for numerous biologic processes in mammals. Iron metabolism is regulated via several coordination mechanisms including absorption, utilization, recycling, and storage. Iron dyshomeostasis can result in intracellular iron retention, thereby damaging cells, tissues, and organs through free oxygen radical generation. Numerous studies have shown that brain iron overload is involved in the pathological mechanism of neurodegenerative disease including Alzheimer’s disease (AD). However, the underlying mechanisms have not been fully elucidated. Ferroptosis, a newly defined iron-dependent form of cell death, which is distinct from apoptosis, necrosis, autophagy, and other forms of cell death, may provide us a new viewpoint. Here, we set out to summarize the current knowledge of iron metabolism and ferroptosis, and review the contributions of iron and ferroptosis to AD.
Wetter climates select for higher immune gene diversity in resident, but not migratory, songbirds

Pathogen communities can vary substantially between geographical regions due to different environmental conditions. However, little is known about how host immune systems respond to environmental variation across macro-ecological and evolutionary scales. Here, we select 37 species of songbird that inhabit diverse environments, including African and Palaearctic residents and Afro-Palaearctic migrants, to address how climate and habitat have influenced the evolution of key immune genes, the major histocompatibility complex class I (MHC-I). Resident species living in wetter regions, especially in Africa, had higher MHC-I diversity than species living in drier regions, irrespective of the habitats they occupy. By contrast, no relationship was found between MHC-I diversity and precipitation in migrants. Our results suggest that the immune system of birds has evolved greater pathogen recognition in wetter tropical regions. Furthermore, evolving transcontinental migration appears to have enabled species to escape wet, pathogen-rich areas at key periods of the year, relaxing selection for diversity in immune genes and potentially reducing immune system costs.
Genotypic Diversity and Host-Specificity of Frankia Bacteria Associated with Sympatric Populations of Alnus rubra and Alnus rhombifolia in Oregon

Abstract Biological nitrogen fixation is one of the most critical processes contributing to ecosystem productivity and stability on a global scale. In temperate climates of the northern hemisphere, plant-root associated bacteria of the genus Frankia are the major nitrogen fixers in forest environments. Trees belonging to the genus Alnus are the most widespread hosts of Frankia in the Pacific Northwest, and a myriad of biotic and abiotic factors can influence the robustness of this symbiosis. Host identity and bacterial strain are important features that can impact Alnus-Frankia association, but little is known about the interplay of intrageneric hosts that co-occur in natural settings. In this study we investigated the genetic diversity and host specificity of Frankia bacteria associated with sympatrically occurring populations of Alnus rubra (red alder) and Alnus rhombifolia (white alder) in Oregon. Based on sequence analysis of the nifH gene recovered from root nodules we found low overall bacterial diversity. One dominant Frankia genotype was associated with both host species, indicating a lack of strong host specificity in this system. Our results suggest that certain intrageneric plant hosts with overlapping distributions show cross-compatibility with symbiotic actinorhizal bacteria, and that low strain diversity of these bacteria can persist across mixed host populations.
Impact on Macro-Benthic Communities of Hydraulic Dredging for Razor Clam Ensis minor in the Tyrrhenian Sea

Bivalve molluscs fishery is of great importance along the Italian coasts, both in economic and landing terms, and different edible bivalve species are harvested both in Adriatic and Tyrrhenian Seas. A medium-term assessment of the impact of the hydraulic dredges targeting razor clam Ensis minor on macro-benthic community was made during two surveys carried out in winter 2017 and late spring – summer 2018 in central Tyrrhenian Sea, which represents the main fishing ground for this species. The study area was located between 1 and 4 m depth, within 0.3 nautical miles from the coast. A net sampler (40 cm width, 18 cm height, and 14 mm mesh size) was mounted on a commercial dredge (3 m width) and enabled to collect specimens of the smallest sizes for the entire community present in the areas. A control area was identified where fishing does not occur, in order to compare exploited and not exploited sea bottoms. The results show that benthic assemblages found in dredged areas are characterized by species living in high-energy habitat, due to the closeness to the shore, and thus showing a high resilience at medium-term disturbs. Differences in species richness were not clearly evident both for the entire community and for the mollusc assemblages evaluated over the two surveys, among the control and the impacted areas, with few exceptions mainly depending on local conditions and anthropic pressure. Thus, even if the benthic community is typical of a moderately disturbed environment, the effects of fishing on the community structure are still discernible over and above the natural variation.
Factors associated with Advanced Bone Age in Overweight and Obese Children

Purpose Obese children may often present with advanced bone age. We aimed to evaluate the correlation between factors associated with childhood obesity and advanced bone age. Methods We enrolled 232 overweight or obese children. Anthropometric and laboratory data, and the degree of nonalcoholic fatty liver disease (NAFLD) were measured. We analyzed factors associated with advanced bone age by measuring the differences between bone and chronological ages. Results The normal and advanced bone age groups were comprised of 183 (78.9%) and 49 (21.1%) children, respectively. The prevalence of advanced bone age significantly increased as the percentiles of height, weight, waist circumference, and body mass index (BMI) increased. BMI z-score was higher in the advanced bone age group than in the normal bone age group (2.43±0.52 vs. 2.10±0.46; p<0.001). The levels of insulin (27.80±26.13 μU/mL vs. 18.65±12.33 μU/mL; p=0.034) and homeostatic model assessment–insulin resistance (6.56±6.18 vs. 4.43±2.93; p=0.037) were significantly higher, while high density lipoprotein-cholesterol levels were lower (43.88±9.98 mg/dL vs. 48.95±10.50 mg/dL; p=0.005) in the advanced bone age group compared to those in the normal bone age group, respectively. The prevalence of advanced bone age was higher in obese children with metabolic syndrome than in those without (28.2% vs. 14.7%; p=0.016). The prevalence of advanced bone age was higher in obese children with a more severe degree of NAFLD. Conclusion Advanced bone age is associated with a severe degree of obesity and its complications.
Cerebral microinfarcts affect brain structural network topology in cognitively impaired patients

Cerebral microinfarcts (CMIs), a novel cerebrovascular marker, are prevalent in Alzheimer’s disease (AD) and associated with cognitive impairment. Nonetheless, the underlying mechanism of how CMIs influence cognition remains uncertain. We hypothesized that cortical-CMIs disrupted structural connectivity in the higher-order cognitive networks, leading to cognitive impairment. We analyzed diffusion-MRI data of 92 AD (26 with cortical-CMIs) and 110 cognitive impairment no dementia patients (CIND, 28 with cortical-CMIs). We compared structural network topology between groups with and without cortical-CMIs in AD/CIND, and tested whether structural connectivity mediated the association between cortical-CMIs and cognition. Cortical-CMIs correlated with impaired structural network topology (i.e. lower efficiency/degree centrality in the executive control/dorsal attention networks in CIND, and lower clustering coefficient in the default mode/dorsal attention networks in AD), which mediated the association of cortical-CMIs with visuoconstruction dysfunction. Our findings provide the first in vivo human evidence that cortical-CMIs impair cognition in elderly via disrupting structural connectivity.
Synthesis of Dithiolethiones and Identification of Potential Neuroprotective Agents via Activation of Nrf2-Driven Antioxidant Enzymes.

Oxidative stress is implicated in the pathogenesis of a wide variety of neurodegenerative disorders, and accordingly, dietary supplement of exogenous antioxidants or/and upregulation of endogenous antioxidant defense system is promising for therapeutic intervention or chemoprevention of neurodegenerative diseases. Nrf2, a master regulator of the cellular antioxidant machinery, cardinally participates in the transcription of cytoprotective genes against oxidative/electrophilic stresses. Herein, we report the synthesis of 59 structurally diverse dithiolethiones and evaluation of their neuroprotection against 6-hydroxydopamine- or H2O2-induced oxidative damages in PC12 cells, a neuron-like rat pheochromocytoma cell line. Initial screening identified compounds 10 and 11 having low cytotoxicity but conferring remarkable protection on PC12 cells from oxidative-mediated damages. Further studies demonstrated that both compounds upregulated a battery of antioxidant genes as well as corresponding genes' products. Significantly, silence of Nrf2 expression abolishes cytoprotection of 10 and 11, indicating targeting Nrf2 activation is pivotal for their cellular functions. Taken together, the two lead compounds discovered here with potent neuroprotective functions against oxidative stress via Nrf2 activation merit further development as therapeutic or chemopreventive candidates for neurodegenerative disorders.
Scavenger receptor class A, member 5 is associated with thyroid cancer cell lines progression via epithelial‐mesenchymal transition

Thyroid cancer (TC) has become one of most common endocrine malignancies in recent decades. Due to gene background polymorphism, it's outcome goes quite differently in each patient. For exploring the mechanism, we performed whole transcriptome sequencing of paired papillary thyroid carcinoma (PTC) and adjacent thyroid tissues. As a result, scavenger receptor class A member 5 (SCARA5) might be a crucial anti‐oncogene associated with PTC. By RT‐qPCR, we first detected the expression of SCARA5 in PTC tissue and three type of TC cell lines. Besides, The Cancer Genome Atlas (TCGA) data were gathered to analysis the relationship between SCARA5 and clinical feature. A series of loss‐function experiments in TC cell lines (KTC‐1 and BCPAP) to investigate the function of SCARA5 in PTC. The results showed that SCARA5 expression in PTC was lower than adjacent normal tissue. And, it's consistent with the TCGA database. After analyse the correlation between SCARA5 expression and clinicopathological features in TCGA database, we discovered that downregulated SCARA5 is significantly connected age (P = .04) and tumour size (P = .032). Knockdown of SCARA5 in TC cell line could significantly increase the function of cells proliferation, colony formation, migration, and invasion. Furthermore, we also proved that SCARA5 could modulate the expression of epithelial‐mesenchymal transition‐related proteins, which influence invasion and migration. To best of our knowledge, SCARA5 is a suppressor gene which was associated with PTC and might be a potential therapeutic target in the future.
Multicenter Perioperative Outcomes Group Enhanced Observation Study Postoperative Pain Profiles, Analgesic Use, and Transition to Chronic Pain and Excessive and Prolonged Opioid Use Patterns Methodology

To study the impact of anesthesia opioid-related outcomes and acute and chronic postsurgical pain, we organized a multicenter study that comprehensively combined detailed perioperative data elements from multiple institutions. By combining pre- and postoperative patient-reported outcomes with automatically extracted high-resolution intraoperative data obtained through the Multicenter Perioperative Outcomes Group (MPOG), the authors sought to describe the impact of patient characteristics, preoperative psychological factors, surgical procedure, anesthetic course, postoperative pain management, and postdischarge pain management on postdischarge pain profiles and opioid consumption patterns. This study is unique in that it utilized multicenter prospective data collection using a digital case report form integrated with the MPOG framework and database. Therefore, the study serves as a model for future studies using this innovative method. Full results will be reported in future articles; the purpose of this article is to describe the methods of this study.
Driving simulator experiments to study drowsiness: A systematic review

Abstract Objective: The National Highway Traffic Safety Administration in the USA estimated that the effects of drowsiness while driving led to approximately 72,000 crashes, 44,000 injuries, and 800 deaths in 2013. Keeping this in mind, the risk and injuries of drowsy driving remain a major safety issue that clearly needs to be studied. Our purpose was to conduct a systematic review of international literature including studies on driving behavior associated to drowsy and fatigued drivers. The research focused on the prediction and effects of drowsiness, and particularly on studies based on driving in simulated environments. Additionally, we searched for studies related to driving simulators, in general, to better understand the tool’s efficacy and its advantages and disadvantages. Methods: This review was made in accordance with PRISMA statement guidelines. After conducting in-depth research in targeted databases, 23 studies met the inclusion criteria; the papers were analyzed regarding the type of experiment and procedures and driving performance of 690 participants was studied. Results: Studies revealed that drowsiness have effects on driving performance and these effects become more relevant with time-on-task and in monotonous scenarios and landscapes. In addition, some documents include validations of several technologies to detect and predict sleepiness. Conclusions: Overall, we can conclude that drowsiness and fatigue impair driving performance, resulting in drivers who are more exposed to risky situations.
Reply to Zhou and Wu, “Be Careful with Adverse Events Caused by Cefoperazone-Sulbactam”

aDivision of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan bChang Gung University College of Medicine, Taoyuan, Taiwan cDivision of Infectious Diseases, Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan dCollege of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan eDivision of Infectious Diseases, Department of Internal Medicine, Wan Fang Medical Center, Taipei, Taiwan fDepartment of Internal Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan gDivision of Infectious Diseases and Tropical Medicine, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan hDivision of Infectious Diseases, Department of Internal Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan iGeneral Research Center, Department of Medical Research, Taipei Veterans General Hospital and Institute of Public Health, School of Medicine, National Yang-Ming University, Taipei, Taiwan jDivision of Infectious Diseases, Shuang-Ho Hospital, Taipei Medical University, Taipei, Taiwan kDepartment of Internal Medicine, Chi Mei Hospital, Liouying, Taiwan lDepartment of Medicine, Chi Mei Medical Center, Tainan, Taiwan mDepartment of Health and Nutrition, Chia Nan University of Pharmacy and Science, Tainan, Taiwan nSchool of Medicine, National Yang-Ming University, Taipei, Taiwan oDepartment of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan pDepartment of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan qCollege of Medicine, National Cheng Kung University, Tainan, Taiwan rDepartment of Internal Medicine, China Medical University Hospital, Taichung, Taiwan sDepartment of Microbiology and Immunology, School of Medicine, China Medical University, Taichung, Taiwan tDivision of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan