Miracle-dz/UniFAR-FTUs huggingface dataset:
Bitter Taste Disrupts Spatial Discrimination of Piperine-Evoked Burning Sensations: A Pilot Study

Simple Summary The chemical senses smell, taste, and trigeminal sense enable us to interact with the environment and play an essential role in protecting us from hazardous events. It is theorized that capsaicin and piperine not only elicit burning, but also bitter sensations through bitter taste-responding gustatory receptor cells that possess special channels. Similar psychophysiological responses to capsaicin and piperine suggest that bitter taste might also disrupt the spatial discrimination to piperine-induced burning sensations. Results showed that bitter taste disrupted the spatial discrimination of piperine-evoked burning sensations, providing further evidence for a qualitative similarity between burning and bitter sensations and the usefulness of chemical irritants in spatial discrimination tasks. Abstract This study aimed to investigate the perceptual similarity between piperine-induced burning sensations and bitter taste using piperine-impregnated taste strips (PTS). This pilot study included 42 healthy participants. PTS of six ascending concentrations (1 mg, 5 mg, 10 mg, 15 mg, 20 mg, and 25 mg piperine/dL 96% ethanol) were presented at the anterior tongue, and participants rated perceived intensity and duration. Then, participants performed a spatial discrimination task in which they had to report which of the two strips presented to the anterior tongue contained an irritating stimulus when one strip was always a PTS while the other strip was impregnated with either a single taste quality (sweet or bitter) or a blank strip. Repeated measures one-way ANOVA revealed that burning sensations of higher concentrated PTS were perceived more intense and more prolonged compared to lower concentrated PTS. McNemar’s test showed that PTS were identified correctly significantly less often when presented with bitter strips compared to when presented with blank (p = 0.002) or sweet strips (p = 0.017). Our results showed that bitter taste disrupts the spatial discrimination of piperine-evoked burning sensations. PTS might serve as a basis for further studies on disease-specific patterns in chemosensory disorders.
High-Level Expression of Palmitoylated MPP1 Recombinant Protein in Mammalian Cells

Our recent studies have pointed to an important role of the MAGUK family member, MPP1, as a crucial molecule interacting with flotillins and involved in the lateral organization of the erythroid plasma membrane. The palmitoylation of MPP1 seems to be an important element in this process; however, studies on the direct effect of palmitoylation on protein–protein or protein–membrane interactions in vitro are still challenging due to the difficulties in obtaining functional post-translationally modified recombinant proteins and the lack of comprehensive protocols for the purification of palmitoylated proteins. In this work, we present an optimized approach for the high-yield overexpression and purification of palmitoylated recombinant MPP1 protein in mammalian HEK-293F cells. The presented approach facilitates further studies on the molecular mechanism of lateral membrane organization and the functional impact of the palmitoylation of MPP1, which could also be carried out for other palmitoylated proteins.
The Cytoskeleton and Its Roles in Self-Organization Phenomena: Insights from Xenopus Egg Extracts

Self-organization of and by the cytoskeleton is central to the biology of the cell. Since their introduction in the early 1980s, cytoplasmic extracts derived from the eggs of the African clawed-frog, Xenopus laevis, have flourished as a major experimental system to study the various facets of cytoskeleton-dependent self-organization. Over the years, the many investigations that have used these extracts uniquely benefited from their simplified cell cycle, large experimental volumes, biochemical tractability and cell-free nature. Here, we review the contributions of egg extracts to our understanding of the cytoplasmic aspects of self-organization by the microtubule and the actomyosin cytoskeletons as well as the importance of cytoskeletal filaments in organizing nuclear structure and function.
Pretreatment Neutrophil-to-Lymphocyte Ratio Associated with Tumor Recurrence and Survival in Patients Achieving a Pathological Complete Response Following Neoadjuvant Chemoradiotherapy for Rectal Cancer

Simple Summary Patients with locally advanced rectal cancer who achieve a pathological complete response to neoadjuvant chemoradiotherapy have been associated with excellent long-term prognosis. However, approximately 9% to 12% of patients with a pathological complete response have been reported to experience tumor recurrence and thereby experience poor outcomes. Identifying predictors of recurrence in patients with a pathological complete response is crucial for precise medicine. The neutrophil-to-lymphocyte ratio is a widely available biomarker of systemic inflammation and affects colorectal prognosis. The study aimed to assess the association between neutrophil-to-lymphocyte ratio and oncological outcomes in rectal cancer patients exhibiting a pCR. We found that a pretreatment high neutrophil-to-lymphocyte ratio (≥3.2) was an independent predictor of reduced overall survival and disease-free survival in patients with locally advanced rectal cancer who achieved a pathological complete response to neoadjuvant chemoradiotherapy. Our findings demonstrate that the neutrophil-to-lymphocyte ratio helps identify patients with a pathological complete response who are at high risk of tumor relapse and might facilitate patient selection for precise medicine. Abstract The clinical influence of the neutrophil-to-lymphocyte ratio (NLR) in predicting outcomes in patients with locally advanced rectal cancer (LARC) who achieve a pathological complete response (pCR) to neoadjuvant chemoradiotherapy (NACRT) has seldom been investigated. We retrospectively recruited 102 patients with LARC who achieved a pCR to NACRT and the association of NLR status with survival and tumor recurrence in the patients was analyzed. Thirteen patients (12.7%) developed tumor recurrence. A high NLR (≥3.2) was significantly associated with tumor recurrence (p = 0.039). The 5-year OS rates in patients with a low NLR and patients with a high NLR were 95.1% and 77.7%, respectively (p = 0.014); the 5-year DFS rates in patients with low NLR and patients with a high NLR were 90.6% and 71.3%, respectively (p = 0.031). The Cox proportional hazards model indicated that an NLR of ≥3.2 was an independent poor prognostic factor for DFS (hazard ratio [HR] = 3.12, 95% confidence interval [CI] = 1.06–9.46, p = 0.048) and OS (HR = 6.96, 95% CI = 1.53–35.51, p = 0.013). A pretreatment high NLR (≥3.2) was a promising predictor of reduced OS and DFS in patients with LARC who achieved a pCR to NACRT.
Amino Acids and the Early Mammalian Embryo: Origin, Fate, Function and Life-Long Legacy

Amino acids are now recognised as having multiple cellular functions in addition to their traditional role as constituents of proteins. This is well-illustrated in the early mammalian embryo where amino acids are now known to be involved in intermediary metabolism, as energy substrates, in signal transduction, osmoregulation and as intermediaries in numerous pathways which involve nitrogen metabolism, e.g., the biosynthesis of purines, pyrimidines, creatine and glutathione. The amino acid derivative S-adenosylmethionine has emerged as a universal methylating agent with a fundamental role in epigenetic regulation. Amino acids are now added routinely to preimplantation embryo culture media. This review examines the routes by which amino acids are supplied to the early embryo, focusing on the role of the oviduct epithelium, followed by an outline of their general fate and function within the embryo. Functions specific to individual amino acids are then considered. The importance of amino acids during the preimplantation period for maternal health and that of the conceptus long term, which has come from the developmental origins of health and disease concept of David Barker, is discussed and the review concludes by considering the potential utility of amino acid profiles as diagnostic of embryo health.
Effect of Nutritional Supplementation on Oxidative Stress and Hormonal and Lipid Profiles in PCOS-Affected Females

Polycystic ovary syndrome (PCOS) affects several reproductive and endocrine features in females and has a poorly understood etiology. Treatment strategies for PCOS are limited and are based primarily on diet and nutrient supplementation. Recent studies have recommended some nutrients such as vitamins, minerals and vitamin-like nutrients for the therapy for PCOS. Therefore, it is claimed that the cause of PCOS could be vitamin or mineral deficiency. This review provides a narrative on the effect of nutritional supplementation on oxidative stress induced in PCOS. Oxidative stress plays a formative role in PCOS pathophysiology. This article reviews oxidative stress, its markers, nutritional supplementation and clinical studies. We also aim to show the effect of nutritional supplementation on genes affecting hormonal and glucose-mediated pathways.
Initial Pro Re Nata Brolucizumab for Exudative AMD: The PROBE Study

The present study aimed to determine the efficacy and safety of pro re nata (PRN) intravitreal brolucizumab therapy for neovascular age-related macular degeneration (AMD) without a loading dose in the real-world setting. The PROBE study (Pro Re Nata Brolucizumab for Exudative AMD) is a retrospective, observational, multicentric study that included 27 treatment-naïve patients (27 eyes) with neovascular AMD who received PRN brolucizumab therapy with the treatment interval being at least 8 weeks, should the need for a second consecutive injection arise. The primary outcome measure was changed to best-corrected visual acuity (BCVA) over time. Secondary outcome measures included the determination of change in central subfield thickness (CST) and complications. The mean follow-up was 11.2 ± 1.2 months. The mean baseline and final BCVA were 57.4 ± 4.5 letters and 65.3 ± 3.12 letters, respectively (p = 0.014). The mean gain in letters at the end of follow-up was 7.8 ± 3.5 letters. There was a significant decrease in CST at the end of the follow-up period (p = 0.013). Patients received a mean of 2.2 ± 0.9 injections (in addition to the first mandatory injection) during the follow-up period. There were no adverse events noted. In conclusion, initial PRN brolucizumab for exudative AMD without a loading dose demonstrated significant visual improvement and no adverse events.
Acute and Chronic Effects of Interval Training on the Immune System: A Systematic Review with Meta-Analysis

Simple Summary Interval training (IT) is a popular training strategy recognized by its positive effects on metabolic and cardiovascular system. However, there seems no consensus regarding the effects of IT on immune system parameters. Therefore, we aimed to summarize the evidence regarding the effects of IT on the immune system. As our many findings, an IT acutely promote a transitory change on immune cell count followed by reduced function. The magnitude of these changes seems to vary in accordance with IT type. On the other hand, the regular practice of IT might contribute to improve immune function without apparent change on immune cell count. Abstract Purpose: To summarize the evidence regarding the acute and chronic effects of interval training (IT) in the immune system through a systematic review with meta-analysis. Design: Systematic review with meta-analysis. Data source: English, Portuguese and Spanish languages search of the electronic databases Pubmed/Medline, Scopus, and SciELO. Eligibility criteria: Studies such as clinical trials, randomized cross-over trials and randomized clinical trials, investigating the acute and chronic effects of IT on the immune outcomes in humans. Results: Of the 175 studies retrieved, 35 were included in the qualitative analysis and 18 in a meta-analysis. Within-group analysis detected significant acute decrease after IT on immunoglobulin A (IgA) secretory rate (n = 115; MD = −15.46 µg·min−1; 95%CI, −28.3 to 2.66; p = 0.02), total leucocyte count increase (n = 137; MD = 2.58 × 103 µL−1; 95%CI, 1.79 to 3.38; p < 0.001), increase in lymphocyte count immediately after exercise (n = 125; MD = 1.3 × 103 µL−1; 95%CI, 0.86 to 1.75; p < 0.001), and decrease during recovery (30 to 180 min post-exercise) (n = 125; MD = −0.36 × 103 µL−1;−0.57 to −0.15; p < 0.001). No effect was detected on absolute IgA (n = 127; MD = 47.5 µg·mL−1; 95%CI, −10.6 to 105.6; p = 0.11). Overall, IT might acutely reduce leucocyte function. Regarding chronic effects IT improved immune function without change leucocyte count. Conclusion: IT might provide a transient disturbance on the immune system, followed by reduced immune function. However, regular IT performance induces favorable adaptations on immune function.
TEG® and ROTEM® Traces: Clinical Applications of Viscoelastic Coagulation Monitoring in Neonatal Intensive Care Unit

The concentration of the majority of hemostatic proteins differs considerably in early life, especially in neonates compared to adulthood. Knowledge of the concept of developmental hemostasis is an essential prerequisite for the proper interpretation of conventional coagulation tests (CCT) and is critical to ensure the optimal diagnosis and treatment of hemorrhagic and thrombotic diseases in neonatal age. Viscoelastic tests (VETs) provide a point-of-care, real-time, global, and dynamic assessment of the mechanical properties of the coagulation system with the examination of both cellular and plasma protein contributions to the initiation, formation, and lysis of clots. In this work, we provide a narrative review of the basic principles of VETs and summarize current evidence regarding the two most studied point-of-care VETs, thromboelastography (TEG®) and rotational thromboelastometry (ROTEM®), in the field of neonatal care. A literature analysis shows that viscoelastic hemostatic monitoring appears to be a useful additive technique to CCT, allowing targeted therapy to be delivered quickly. These tools may allow researchers to determine the neonatal coagulation profile and detect neonatal patients at risk for postoperative bleeding, coagulation abnormalities in neonatal sepsis, and other bleeding events in a timely manner, guiding transfusion therapies using the goal-oriented transfusion algorithm. However, diagnosis and treatment algorithms incorporating VETs for neonatal patients in a variety of clinical situations should be developed and applied to improve clinical outcomes. Further studies should be performed to make routinary diagnostic and therapeutic application possible for the neonatal population.
Can the Addition of NT-proBNP and Glucose Measurements Improve the Prognostication of High-Sensitivity Cardiac Troponin Measurements for Patients with Suspected Acute Coronary Syndrome?

Guidelines published in 2021 have supported natriuretic peptide (NP) testing for the prognostication in patients with acute coronary syndrome (ACS) and for the diagnosis of chronic and acute heart failure (HF). Our objective was to determine if the addition of N-terminal pro B-type NP (NT-proBNP) and glucose to high-sensitivity cardiac troponin (hs-cTn) could better identify emergency department (ED) patients with potential ACS at low- and high-risk for a serious cardiovascular outcome over the next 72 h. The presentation sample in two different ED cohorts which enrolled patients with symptoms suggestive of ACS within six hours of pain onset (Cohort-1, n = 126 and Cohort-2, n = 143) that had Abbott hs-cTnI, Roche hs-cTnT, NT-proBNP and glucose were evaluated for NT-proBNP alone and combined with hs-cTn and glucose for the primary outcome (composite which included death, myocardial infarction, HF, serious arrhythmia and refractory angina) via receiver-operating characteristic (ROC) curve analyses with area under the curve (AUC) and diagnostic estimates derived. The AUC for NT-proBNP for the primary outcome was 0.68 (95% confidence interval (CI): 0.59–0.76) and 0.75 (95%CI: 0.67–0.82) in Cohort-1 and 2, respectively, with the 125 ng/L cutoff yielding a higher sensitivity (≥75%) as compared to the 300 ng/L cutoff (≥58%). Using the 125 ng/L cutoff for NT-proBNP with the published glucose and hs-cTn cutoffs for risk-stratification produced a new score (GuIDER score for Glucose, Injury and Dysfunction in the Emergency-setting for cardiovascular-Risk) and yielded higher AUCs as compared to NT-proBNP (p < 0.05). GuIDER scores of 0 and 5 using either hs-cTnI/T yielded sensitivity estimates of 100% and specificity estimates > 92% for the primary outcome. A secondary analysis assessing MI alone in the overall population (combined Cohorts 1 and 2) also achieved 100% sensitivity for MI with a GuIDER cutoff ≥ 2, ruling-out 48% (Roche) and 38% (Abbott) of the population at presentation for MI. Additional studies are needed for the GuIDER score in both the acute and ambulatory setting to further refine the utility, however, the preliminary findings reported here may present a pathway forward for inclusion of NP testing for ruling-out serious cardiac events and MI in the emergency setting.
First-Year Healthcare Resource Utilization Costs of Five Major Cancers in Japan

Reports on the expenditure of cancer treatments per patient using comprehensive data remain unavailable in Japan. This study aimed to use Japan’s cancer registry data and health service utilization data for evaluating the disease-specific, per-patient costs of five major cancers—stomach, lung, colorectal, liver, and breast cancers. We used a database linking the 2017 data from a hospital-based cancer registry and the health service utilization data from the Diagnosis Procedure Combination survey. All patients who started their first treatment course at each hospital were included. The costs were calculated using the total volume of the health services provided and the unit fee information included in the data. We analyzed 304,698 patients. Lung cancer had the highest healthcare cost per-patient for the first year of diagnosis and the longest median hospitalization duration. Conversely, breast cancer showed the lowest cost and the shortest median hospitalization duration. However, in the first month after diagnosis, colorectal cancer showed the highest cost. Subsequently, the gaps between the costs of the five common cancers drastically diminished. The cancer type having the longest hospitalization duration had the highest overall healthcare resource utilization costs. This information is essential for care planning and research studies.
Hepatitis E Virus Immunopathogenesis

Hepatitis E virus is an important emerging pathogen producing a lethal impact on the pregnant population and immunocompromised patients. Starting in 1983, it has been described as the cause for acute hepatitis transmitted via the fecal–oral route. However, zoonotic and blood transfusion transmission of HEV have been reported in the past few decades, leading to the detailed research of HEV pathogenesis. The reason behind HEV being highly virulent to the pregnant population particularly during the third trimester, leading to maternal and fetal death, remains unknown. Various host factors (immunological, nutritional, hormonal) and viral factors have been studied to define the key determinants assisting HEV to be virulent in pregnant and immunocompromised patients. Similarly, chronic hepatitis is seen particularly in solid organ transplant patients, resulting in fatal conditions. This review describes recent advances in the immunopathophysiology of HEV infections in general, pregnant, and immunocompromised populations, and further elucidates the in vitro and in vivo models utilized to understand HEV pathogenesis.
Association between Carbohydrate Intake and the Prevalence of Metabolic Syndrome in Korean Women

Carbohydrates consist of a large proportion of calories in the Asian diet. Therefore, we aimed to investigate the association between carbohydrate intake and metabolic syndrome in Korean women. A cross-sectional analysis was conducted with a total of 4294 Korean women aged 40–69 years from the Korean Genomic and Epidemiology Study (KoGES). Carbohydrate intake was calculated based on a validated food frequency questionnaire. Metabolic syndrome was defined by using the National Cholesterol Education Program, Adult Treatment Panel III (NCEPIII). Logistic regression was used to estimate the association of carbohydrate intake with metabolic syndrome and its components. In this study, high carbohydrate intake seemed to be associated with low socioeconomic status and an imbalanced diet. After adjusting for confounding factors, subjects with higher carbohydrate intake showed an increased risk of metabolic syndrome (odds ratio (OR) 1.34, 95% confidence interval (CI) 1.08–1.66, p-trend = 0.004, highest vs. lowest quartile [≥75.2 vs. <67.0% of energy]), particularly elevated waist circumference. This association was stronger among those with low levels of C-reactive protein (CRP) and those with low dairy intake. In conclusion, higher carbohydrate intake is associated with a higher risk of metabolic syndrome, particularly abdominal obesity, in Korean women. This association may differ according to individuals’ CRP level and dairy intake.
Offline Victimization, Psychological Morbidity, and Problematic Online Behavior among Chinese Secondary School Students

Despite the rise of child victimization in different societies, few researchers have examined its consequences in terms of psychological morbidity (such as depression and anxiety) and problematic online behavior (such as Internet addiction and cyberbullying) in a single study. Moreover, no study has investigated the role of psychological morbidity in mediating the impact of victimization on problematic online behavior (indexed by Internet addiction and cyberbullying) in a single model. Based on a survey of 2843 Chinese secondary students (49.3% male; Mage = 13.97) from six public secondary schools in Fujian, China, we found that experience of victimization was positively associated with depression and anxiety, as well as Internet addiction and cyberbullying. Depression mediated the links between victimization and both Internet addiction and cyberbullying, with the mediating effect on Internet addiction found to be stronger for girls. While anxiety did not mediate the association between victimization and cyberbullying, it mediated the relationship between victimization and Internet addiction in boys. These findings enrich our understanding of the negative outcomes of victimization, as well as directions for intervention.
Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) Decoction Improves the Hypercholesterolemia and Alters the Expression of LXRs in Rat Liver and Hypothalamus

Chronic high-fat diet consumption induces hypercholesterolemia. The effect of Tessaria absinthioides (Hook. & Arn.) DC. (Asteraceae) was studied on the levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), and triglycerides, and on the expression of liver X receptors (LXRs) in a hypercholesterolemic model. Adult male rats received a normal diet (ND) or a high-fat diet (HFD; normal diet + bovine fat + cholesterol). After 14 days, rats received water (W) or a decoction of the aerial parts of T. absinthioides (Ta; 10% w/v) for 2, 4, or 6 weeks. Four and six weeks of Ta improved the levels of TC and HDL-c in HFD. After 6 weeks of Ta, the expression of LXRs in HFD was the same as that in ND in both tissues. The Ta chemical profile was studied with an ultrahigh resolution liquid chromatography Orbitrap MS analysis (UHPLC–PDA–OT-MS/MS). Fifty-one compounds were identified, of which twelve are reported for the first time. Among these compounds, caffeoylquinic acid and its derivatives could modify the lipid profile and the expression of LXRs. This is the first in vivo report of T. absinthioides, which may be a potential candidate against hypercholesterolemia.