Miracle-dz/UniFAR-FTUs huggingface dataset:
Seeding Activity of Skin Misfolded Tau as a Biomarker for Tauopathies

Background Tauopathies are a group of age-related neurodegenerative diseases characterized by the accumulation of pathologically phosphorylated tau protein in the brain, leading to prion-like propagation and aggregation. They include Alzheimer’s disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and Pick’s disease (PiD). Currently, reliable diagnostic biomarkers that directly reflect the capability of propagation and spreading of misfolded tau aggregates in peripheral tissues and body fluids are lacking. Methods We utilized the seed-amplification assay (SAA) employing ultrasensitive real-time quaking-induced conversion (RT-QuIC) to assess the prion-like seeding activity of pathological tau in the skin of cadavers with neuropathologically confirmed tauopathies, including AD, PSP, CBD, and PiD, compared to normal controls. Results We found that the skin prion-SAA demonstrated a significantly higher sensitivity (75–80%) and specificity (95–100%) for detecting tauopathy, depending on the tau substrates used. Moreover, increased tau-seeding activity was also observed in biopsy skin samples from living AD and PSP patients examined. Analysis of the end products of skin-tau SAA confirmed that the increased seeding activity was accompanied by the formation of tau aggregates with different physicochemical properties related to two different tau substrates used. Conclusions Overall, our study provides proof-of-concept that the skin tau-SAA can differentiate tauopathies from normal controls, suggesting that the seeding activity of misfolded tau in the skin could serve as a diagnostic biomarker for tauopathies.
Changes in ghrelin, GLP-1, and PYY levels after diet and exercise in obese individuals

SUMMARY OBJECTIVE: Diet and exercise, which are the building blocks of obesity management, provide weight loss by creating a negative energy balance. However, the effect of energy deficit induced by long-term diet and exercise on appetite hormones remains unclear. The study was designed to determine the effect of a 12-week diet and exercise program applied to obese individuals on the levels of appetite hormones, namely, ghrelin, GLP-1, and PYY. METHODS: A total of 62 obese individuals (BMI≥30) and 48 healthy controls (BMI 18.50–29.99) participated in the study. Appropriate diet (1000–1500 kcal/day) and exercise (at least 5000 steps/day) programs were applied to obese individuals according to age, gender, and BMI. The ghrelin, GLP-1, and PYY values of the participants were analyzed by the ELISA method and commercial kit by taking venous blood samples before and after 12 weeks of treatment. RESULTS: While ghrelin levels of individuals decreased significantly after diet and exercise, PYY levels increased significantly. However, despite the treatment applied, the GLP-1 and PYY levels of the case group did not reach the levels of the control group. CONCLUSION: Long-term diet and exercise intervention had a positive effect on appetite regulation hormones. It reduced ghrelin levels after treatment. Associated weight loss was facilitated. In the case group, increased satiety hormones after combined treatment supported the maintenance of body weight by increasing satiety.
Correlates of post-traumatic growth among persons bereaved from cancer: A systematic review and meta-analysis

Background Recent research identified that cancer bereavement can lead to post-traumatic growth (PTG). Although PTG and its correlates are well explored in cancer patients and survivors, persons bereaved from cancer have received scant attention. Therefore, the present review attempts to identify the correlates of PTG among persons bereaved from cancer. Methods A systematic search in PubMed, Web of Science, APA PsycNet, Science Direct, Scopus, and Wiley was conducted to identify quantitative studies published in English, resulting in 12 eligible reports being included in the final analysis. JBI critical checklists were employed to appraise the risk of bias. Results The review identified 17 correlates, which were classified into four categories: demographic factors (age, gender, religious status, level of education), loss-related factors (time since death, quality of death, prolonged grief symptoms), interpersonal factors (relationship to the deceased, social support, attachment style, bereavement behaviours) and intrapersonal factors (resilience, coping, rumination, benevolence, meaningfulness, self-worth). Random effects meta-analyses on six correlates revealed correlation coefficients of age = -0.02 (95% CI: -0.35–0.31), gender = 0.27 (95% CI: 0.08–0.45), time since death = 0.09 (95% CI: -0.02–0.20), quality of death = 0.29 (95% CI: -0.01–0.54), prolonged grief symptoms = 0.22 (95% CI: 0.08–0.35) and relationship to the deceased = 0.13 (95% CI: -0.03–0.29). Fixed effects meta-analysis was performed for social support (r = 0.13, 95% CI: 0.04–0.21). However, PTG was found to be significantly associated with gender, prolonged grief symptoms, and social support. Conclusions Very few studies examined PTG among persons bereaved from cancer, highlighting the need for increased attention, understanding, and conceptualisation of PTG in the population.
Resolving the slip-rate inconsistency of the northern Dead Sea fault

Reported fault slip rates, a key quantity for earthquake hazard and risk analyses, have been inconsistent for the northern Dead Sea fault (DSF). Studies of offset geological and archeological structures suggest a slip rate of 4 to 6 millimeters per year, consistent with the southern DSF, whereas geodetic slip-rate estimates are only 2 to 3 millimeters per year. To resolve this inconsistency and overcome limited access to the northern DSF in Syria, we here use burst-overlap interferometric time-series analysis of satellite radar images to provide an independent slip-rate estimate of ~2.8 millimeters per year. We also show that the high geologic slip rate could, by chance, be inflated by earthquake clustering and suggest that the slip-rate decrease from the southern to northern DSF can be explained by splay faults and diffuse offshore deformation. These results suggest a microplate west of the northern DSF and a lower earthquake hazard for that part of the fault.
Integrating and optimizing tonabersat in standard glioblastoma therapy: A preclinical study

Glioblastoma (GB), a highly aggressive primary brain tumor, presents a poor prognosis despite the current standard therapy, including radiotherapy and temozolomide (TMZ) chemotherapy. Tumor microtubes involving connexin 43 (Cx43) contribute to glioma progression and therapy resistance, suggesting Cx43 inhibition as a potential treatment strategy. This research aims to explore the adjuvant potential of tonabersat, a Cx43 gap junction modulator and blood-brain barrier-penetrating compound, in combination with the standard of care for GB. In addition, different administration schedules and timings to optimize tonabersat’s therapeutic window are investigated. The F98 Fischer rat model will be utilized to investigate tonabersat’s impact in a clinically relevant setting, by incorporating fractionated radiotherapy (three fractions of 9 Gy) and TMZ chemotherapy (29 mg/kg). This study will evaluate tonabersat’s impact on tumor growth, survival, and treatment response through advanced imaging (CE T1-w MRI) and histological analysis. Results show extended survival in rats receiving tonabersat with standard care, highlighting its adjuvant potential. Daily tonabersat administration, both preceding and following radiotherapy, emerges as a promising approach for maximizing survival outcomes. The study suggests tonabersat’s potential to reduce tumor invasiveness, providing a new avenue for GB treatment. In conclusion, this preclinical investigation highlights tonabersat’s potential as an effective adjuvant treatment for GB, and its established safety profile from clinical trials in migraine treatment presents a promising foundation for further exploration.
Temperature difference and systemic risk: Evidence from LASSO-VAR-DY based on China’s pan-financial market

Climate change-induced pan-financial market and the contagion of systemic financial risks are becoming important issues in the financial sector. The paper measures the temperature difference in terms of the degree and direction of deviation of the actual temperature relative to the average temperature of the same historical period. Based on the high-dimensional time-series variable LASSO-VAR-DY framework, we construct a pan-financial market volatility correlation network consisting of 112 Chinese listed companies in banking, insurance, securities, real estate, traditional energy, and new energy, use eigenvector centrality to measure the systematic risk of each firm, and then empirically test the effect of temperature difference on systematic risk under pan-financial market scenario. The results of the study show that (ⅰ) There is a significant difference among the systemic risk of financial sectors such as banking, insurance, and securities in the financial market pan-financial market scenario and the systemic risk when the financial market pan-financial market is not taken into account;(ⅱ) Higher temperature significantly exacerbates systemic financial risk, while colder temperature significantly mitigates systemic risk, but both have an asymmetric effect on systemic risk, and there is sectoral heterogeneity. (ⅲ) From the dynamic evolutionary characteristics, there are significant differences in the response of systemic financial risk to positive and negative temperature shocks;(iv) The results of the systemic risk variance decomposition indicate that the temperature change contributes more to the variance of systemic risk in the banking and securities sectors in pan-financial market;(ⅴ) The contagion source of financial systemic risk shows an obvious path of leaping and changing characteristics, and the contagion source of systemic risk (source of impact) shows the evolution law of "bank → real estate → new energy → temperature difference," which means that the temperature difference has become the contagion source of systemic financial risk. This study provides a reference for preventing and resolving systemic risks under pan-financial market scenario and provides a basis for improving the current macroprudential regulatory framework.
Applying the Theory of Reliability to the Assessment of Hazard, Risk and Safety in a Hydrologic System: A Case Study in the Upper Sola River Catchment, Poland

River basin safety issues and hazards arising from extreme hydrological and meteorological events pose significant risks to human life and can entail economic and financial losses. In this study, the practical aspects of reliability theory linked to reliability engineering, and the associated mathematical tools used to describe technical systems, were applied to explore the structural reliability of a quasi-natural system—a portion of the Upper Sola River catchment in Poland. As part of this study, methods such as the Fault Tree Method (FTM), Event Tree Method (ETM), Risk Matrix and Ranking Method for assessing hazard, risk and losses connected with the occurrence of such events are suggested to improve flood risk management and enhance the capacity to safeguard against such events by improving current flood protection protocols in accordance with EC Flood Directives.
Brain dynamics reflecting an intra-network brain state is associated with increased posttraumatic stress symptoms in the early aftermath of trauma

This study examines the association between brain dynamic functional network connectivity (dFNC) and current/future posttraumatic stress (PTS) symptom severity, and the impact of sex on this relationship. By analyzing 275 participants’ dFNC data obtained ~2 weeks after trauma exposure, we noted that brain dynamics of an inter-network brain state link negatively with current (r=−0.179, pcorrected= 0.021) and future (r=−0.166, pcorrected= 0.029) PTS symptom severity. Also, dynamics of an intra-network brain state correlated with future symptom intensity (r = 0.192, pcorrected = 0.021). We additionally observed that the association between the network dynamics of the inter-network brain state with symptom severity is more pronounced in females (r=−0.244, pcorrected = 0.014). Our findings highlight a potential link between brain network dynamics in the aftermath of trauma with current and future PTSD outcomes, with a stronger protective effect of inter-network brain states against symptom severity in females, underscoring the importance of sex differences.
Efficacy of Acupuncture in Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis

Purpose The effect of acupuncture as adjunctive therapy for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) was controversial. Thus, we aimed to evaluate the effects of acupuncture for treating AECOPD. Methods Eight databases were searched from database inception to July 30, 2023. All RCTs compared acupuncture plus conventional western medicine with conventional western medicine alone were included. Outcomes were quality of life, lung function, blood oxygen condition, exercise capacity, daily symptoms, duration of hospitalization, and adverse events. The statistical analyses were conducted using Stata 17.0, and methodological quality was measured by the Cochrane bias risk assessment tool. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess the quality of evidence. Results Twelve studies including 915 patients were included. Compared with conventional western medicine alone, acupuncture combined with conventional western therapy significantly improved quality of life (CAT: MD: −3.25; 95% CI: −3.73 to −2.78, P<0.001) and arterial blood gas (PaCO2: MD: −1.85; 95% CI: −2.74 to −0.95, P<0.001; PaO2: MD: 5.15; 95% CI: 1.22 to 9.07, P = 0.01). And for lung function, statistical benefits were found in FEV1/FVC (MD: 4.66; 95% CI: 2.21 to 7.12, P<0.001), but no difference was seen for FEV1% (MD: 1.83; 95% CI: −0.17 to 3.83, P = 0.073). There was no significant improvement in exercise capacity (6MWD: MD: 96.69; 95% CI: −0.60 to 193.98, P = 0.051), hospitalization duration (MD: −5.70; 95% CI: −11.97 to 0.58, P = 0.075), and dyspnea (mMRC: MD: −0.19; 95% CI: −0.61 to 0.63, P = 0.376) between two groups. Overall bias for CAT and mMRC was in “high” risk, FEV1%, FEV1/FVC, PaCO2, and PaO2 was in “some concern” and 1 RCT assessing hospitalization duration was in “low” risk. And the overall assessments were either moderate, low or very low certainty. Seven trials performed safety assessment of acupuncture, and no serious adverse events were reported. Conclusion Acupuncture might have auxiliary effects on AECOPD. However, the quality of the evidence is limited, and more high-quality RCTs are needed to be performed in the future.
A P2RY12 Deficiency Results in Sex-specific Cellular Perturbations and Sexually Dimorphic Behavioral Anomalies

Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature of microglial-neuronal interactions, but seldom consider how this dynamism varies with microglial sex differences, leaving a significant gap in our knowledge. This study focuses on P2RY12, a highly expressed microglial signature gene that mediates microglial-neuronal interactions, we show that adult females have a significantly higher expression of the receptor than adult male microglia. We further demonstrate that a genetic deletion of P2RY12 induces sex-specific cellular perturbations with microglia and neurons in females more significantly affected. Correspondingly, female mice lacking P2RY12 exhibit unique behavioral anomalies not observed in male counterparts. These findings underscore the critical, sex-specific roles of P2RY12 in microglial-neuronal interactions, offering new insights into basal interactions and potential implications for CNS disease mechanisms.
Soil-tool interaction of a simple tillage tool in sand

This study was focused to experimentally evaluate the draft force on a simple tillage tool operating in different conditions in sand. The soil-tool interaction was evaluated in controlled laboratory conditions in a soil bin. A full multilevel factorial experiment was used with one response variable and four experimental factors. The selected design 3 tools × 3 tillage depth × 3 rake angle × 3 forward speed with two replications had a total of 243 runs. Influence of four independent variables including tillage depth (15, 20, 25 cm), rake angle (25, 35, 50 degrees), forward speed (0.67, 0.98, 1.39 m/s) and cutting-edge angle of the tool (30, 45 and 60 degrees) on draft force as the dependent variable was evaluated.
Statistical determination of service quality gaps in primary health care in Guayas, Ecuador

The present work determines the gaps between expectations and perceptions about the quality of the service that patients and families receive in primary health care (PHC) in Guayas, Ecuador. A descriptive, cross-sectional and non-experimental study was carried out, primarily prospective with respect to expectations and retrospective with respect to perceptions of service quality. For its development, a random sample of 533 users from the northern and southern urban sectors of the city of Guayaquil was determined, who were asked to answer a questionnaire. Their responses were collected using a seven-point scale intended to determine magnitudes of gaps, which were confirmed using the Wilcoxon test. The results reveal a significant gap between women, specifically those over 21 years of age who have studied at the technological and university level, and those who work. In general, the five dimensions of quality present significant gaps, highlighting that the lowest gap occurs when the medical professional listens attentively and treats the patient with kindness. Instead, the largest gap occurs because there are no available or easily accessible times for medical appointments. Finally, the dimension that indicates the gaps that service providers best resolve are the empathy items, recording the smallest deviations; On the contrary, the reliability dimension presents the greatest deviation, thus showing higher degrees of dissatisfaction, in both cases significant.
Dietary Perceptions among Patients with Crohn’s Disease in Clinical Remission: Comparison with an Era Preceding the Availability of Biologic Therapy

Abstract Introduction Dietary temperance significantly affects the quality of life of patients with Crohn’s disease (CD) and remains a major concern. However, perceptions of diet in remission may have changed from the era when treatment options were limited. Therefore, we compared the dietary perceptions and treatment of patients with CD in remission with previously published data from the time biologic therapy was not introduced. Methods We compared the data of 254 patients with CD in remission who completed a questionnaire survey in 2022 with those of 76 patients with CD in remission collected in 2003, when biologics were not used for maintenance therapy in Japan. Remission was defined as a CD activity index of 150 or less in both studies. Perceptions of diet (degree of eating whatever one likes) were assessed using single-item nominal scale responses. Results The percentage of patients receiving enteral nutrition therapy had decreased (past vs. present: 43.4 vs. 12.6%), while the proportion of patients receiving biologic therapy increased (0 vs. 88.6%, respectively). The percentages of patients who responded “not at all,” “sometimes,” and “mostly” when asked if they could eat whatever they liked had changed, respectively, from 9.2%, 46.1%, and 44.7% in the past to 4.3%, 25.2%, and 70.5% in the present. Conclusion The proportion of those who ate whatever they liked and the mean body mass index increased in comparison with the corresponding values 20 years ago. With the advent of biologic therapies, the number of patients with CD who can enjoy eating has increased.
Evaluating synergistic effects of metformin and simvastatin on ovarian cancer cells

Background Ovarian Cancer (OC) stands as the most lethal gynecological malignancy, presenting an urgent clinical challenge in the quest to improve response rates. One approach to address this challenge is through drug repurposing, exemplified by the investigation of metabolic-modulating drugs such as Metformin (MTF) and Simvastatin (SIM). This study aims to explore the molecular mechanisms contributing to the potential synergistic anti-cancer effects between MTF and SIM on ovarian cancer cells. Methods We assessed the effects of the combination on the proliferation and viability of two cell lines OVCAR-3 and SKOV-3. IC50 concentrations of MTF and SIM were determined using a proliferation assay, followed by subtoxic concentrations to explore the potential synergistic effects on the viability of both cell lines. Transcriptomic analysis was conducted on OVCAR-3 treated cells, and the findings were validated by assessing the expression levels of differentially expressed genes (DEGs) through real-time PCR in both cell lines SK-OV-3 and OVCAR-3. Results Cytotoxicity analysis guided the selection of treatment concentrations as such MTF 10 mM and SIM 5 μM. The combined treatment of MTF and SIM demonstrated a synergistic inhibition of proliferation and viability in both cell lines. In OVCAR-3, exclusive identification of 507 DEGs was seen in the combination arm. Upregulation of FOXO3, RhoA, and TNFα, along with downregulation of PIK3R1, SKP2, and ATP6V1D levels, was observed in OVCAR-3 treated cells. Real-time PCR validation confirmed the consistency of expression levels for the mentioned DEGs. Conclusion Our data strongly supports the presence of synergy between MTF and SIM in OC cells. The combination’s effect is associated with the dysregulation of genes in the key regulators AMPK and mTOR alongside other interconnected pathways.
Lanthanide transport in angstrom-scale MoS2-based two-dimensional channels

Rare earth elements (REEs), critical to modern industry, are difficult to separate and purify, given their similar physicochemical properties originating from the lanthanide contraction. Here, we systematically study the transport of lanthanide ions (Ln3+) in artificially confined angstrom-scale two-dimensional channels using MoS2-based building blocks in an aqueous environment. The results show that the uptake and permeability of Ln3+ assume a well-defined volcano shape peaked at Sm3+. This transport behavior is rooted from the tradeoff between the barrier for dehydration and the strength of interactions of lanthanide ions in the confinement channels, reminiscent of the Sabatier principle. Molecular dynamics simulations reveal that Sm3+, with moderate hydration free energy and intermediate affinity for channel interaction, exhibit the smallest dehydration degree, consequently resulting in the highest permeability. Our work not only highlights the distinct mass transport properties under extreme confinement but also demonstrates the potential of dialing confinement dimension and chemistry for greener REEs separation.