Miracle-dz/UniFAR-FTUs huggingface dataset:
Diagnostic performance of CSF biomarkers in a well-characterized Australian cohort of sporadic Creutzfeldt-Jakob disease

The most frequently utilized biomarkers to support a pre-mortem clinical diagnosis of sporadic Creutzfeldt–Jakob disease (sCJD) include concentrations of the 14-3-3 and total tau (T-tau) proteins, as well as the application of protein amplification techniques, such as the real time quaking-induced conversion (RT-QuIC) assay, in cerebrospinal fluid (CSF). Utilizing CSF from a cohort of neuropathologically confirmed (definite) sCJD (n = 50) and non-CJD controls (n = 48), we established the optimal cutpoints for the fully automated Roche Elecsys® immunoassay for T-tau and the CircuLexTM 14-3-3 Gamma ELISA and compared these to T-tau protein measured using a commercially available assay (INNOTEST hTAU Ag) and 14-3-3 protein detection by western immunoblot (WB). These CSF specimens were also assessed for presence of misfolded prion protein using the RT-QuIC assay. T-tau showed similar diagnostic performance irrespective of the assay utilized, with ~90% sensitivity and specificity. The 14-3-3 protein detection by western blot (WB) has 87.5% sensitivity and 66.7% specificity. The 14-3-3 ELISA demonstrated 81.3% sensitivity and 84.4% specificity. RT-QuIC was the single best performing assay, with a sensitivity of 92.7% and 100% specificity. Our study indicates that a combination of all three CSF biomarkers increases sensitivity and offers the best chance of case detection pre-mortem. Only a single sCJD case in our cohort was negative across the three biomarkers, emphasizing the value of autopsy brain examination on all suspected CJD cases to ensure maximal case ascertainment.
Effect of galvanic vestibular stimulation applied at the onset of stance on muscular activity and gait cycle duration in healthy individuals

Locomotion requires the complex involvement of the spinal and supraspinal systems. So far, the role of vestibular input in gait has been assessed mainly with respect to gait stability. The noninvasive technique of galvanic vestibular stimulation (GVS) has been reported to decrease gait variability and increase gait speed, but the extent of its effect on spatiotemporal gait parameters is not fully known. Objective: Characterize vestibular responses during gait and determine the influence of GVS on cycle duration in healthy young participants. Methods: Fifteen right-handed individuals participated in the study. Electromyography (EMG) recordings of the bilateral soleus (SOL) and tibialis anterior muscles (TA) were performed. First, to determine stimulation intensity, an accelerometer placed on the vertex recorded the amplitude of the head tilts evoked by the GVS (1–4 mA, 200 ms) to establish a motor threshold (T). Second, while participants walked on a treadmill, GVS was applied at the onset of the stance phase during the treadmill gait with an intensity of 1 and 1.5 T with the cathode behind the right (RCathode) or left ear (LCathode). EMG traces were rectified, averaged (n = 30 stimuli), and analyzed. Latency, duration, and amplitude of vestibular responses as well as the mean duration of the gait cycles were measured. Results: GVS mainly induced long-latency responses in the right SOL, right TA and left TA. Only short-latency responses were triggered in the left SOL. Responses in the right SOL, left SOL and left TA were polarity dependent, being facilitatory with RCathode and inhibitory with LCathode, whereas responses in the right TA remained facilitatory regardless of the polarity. With the RCathode configuration, the stimulated cycle was prolonged compared with the control cycle at both 1 and 1.5 T, due to prolonged left SOL and TA EMG bursts, but no change was observed in right SOL and TA. With LCathode, GVS did not modify the cycle duration. Conclusion: During gait, a brief, low-intensity GVS pulse delivered at the right stance onset induced mainly long-latency polarity-dependent responses. Furthermore, a RCathode configuration increased the duration of the stimulated gait cycle by prolonging EMG activity on the anodic side. A similar approach could be explored to influence gait symmetry in individuals with neurological impairment.
Trends in using of antihypertensive medication among US CKD adults, NHANES 2001–2018

Objective Blood pressure (BP) control rates among adult patients taking antihypertensive medications in the United States have not improved over the last decade. Many CKD adults require more than one class of antihypertensive agent to reach the BP target recommended by the guidelines. However, no study has quantified the proportion of adult CKD patients taking antihypertensive medication who are on monotherapy or combination therapy. Methods National Health and Nutrition Examination Survey data during 2001-2018 was used, including adults with CKD taking antihypertensive medication (age ≥ 20 years, n = 4,453). BP control rates were investigated under the BP targets recommended by the 2021 KDIGO, the 2012 KDIGO, and the 2017 ACC/AHA guidelines. Results The percentages of uncontrolled BP among US adults with CKD taking antihypertensive medication were 81.4% in 2001-2006 and 78.2% in 2013-2018. The proportion of monotherapy of antihypertensive regimen were 38.6, 33.3, and 34.6% from 2001 to 2006, 2007-2012, and 2013-2018, with no obvious difference. Similarly, there was no significant change in percentages of dual-therapy, triple-therapy, and quadruple-therapy. Although proportion of CKD adults not treated with ACEi/ARB decreased from 43.5% in 2001-2006 to 32.7% in 2013-2018, treatment of ACEi/ARB among patients with ACR > 300 mg/g had no significant change. Conclusion The BP control rates among US adult CKD patients taking antihypertensive medications have not improved from 2001 to 2018. Mono-therapy accounted for about one third of adult CKD patients taking antihypertensive medication and not changed. Increasing antihypertensive medication combination therapy may help improve BP control in CKD adults in the United States.
A refined protocol for the isolation and monoculture of primary mouse renal peritubular endothelial cells

During an episode of acute kidney injury (AKI), a sudden and rapid decline in renal function is often accompanied by a persistent reduction in mitochondrial function, microvasculature dysfunction/rarefaction, and tubular epithelial injury/necrosis. Additionally, patients who have experienced an AKI are at an elevated risk of developing other progressive renal, cardiovascular, and cardiorenal related diseases. While restoration of the microvasculature is imperative for oxygen and nutrient delivery/transport during proper renal repair processes, the mechanism(s) by which neovascularization and/or inhibition of microvascular dysfunction improves renal recovery remain understudied. Interestingly, pharmacological stimulation of mitochondrial biogenesis (MB) post-AKI has been shown to restore mitochondrial and renal function in mice. Thus, targeting MB pathways in microvasculature endothelial cell (MV-EC) may provide a novel strategy to improve renal vascular function and repair processes post-AKI. However, limitations to studying such mechanisms include a lack of commercially available primary renal peritubular MV-ECs, the variability in both purity and outgrowth of primary renal MV-EC in monoculture, the tendency of primary renal MV-ECs to undergo phenotypic loss in primary monoculture, and a limited quantity of published protocols to obtain primary renal peritubular MV-ECs. Thus, we focused on refining the isolation and phenotypic retention of mouse renal peritubular endothelial cells (MRPEC) for future physiological and pharmacological based studies. Here, we present a refined isolation method that augments the purity, outgrowth, and phenotypic retention of primary MRPEC monocultures by utilizing a collagenase type I enzymatic digestion, CD326+ (EPCAM) magnetic microbead epithelial cell depletion, and two CD146+ (MCAM) magnetic microbead purification cycles to achieve a monoculture MRPEC purity of ≅ 91–99% by all markers evaluated.
GPX3 expression was down-regulated but positively correlated with poor outcome in human cancers

Introduction Cancer is a crucial public health problem and one of the leading causes of death worldwide. Previous studies have suggested that GPX3 may be involved in cancer metastasis and chemotherapy resistance. However, how GPX3 affects cancer patients’ outcomes and the underlying mechanism remains unclear. Methods Sequencing data and clinical data from TCGA, GTEx, HPA, and CPTAC were used to explore the relationship between GPX3 expression and clinical features. Immunoinfiltration scores were used to assess the relationship between GPX3 and the tumor immune microenvironment. Functional enrichment analysis was used to predict the role of GPX3 in tumors. Gene mutation frequency, methylation level, and histone modification were used to predict the GPX3 expression regulation method. Breast, ovarian, colon, and gastric cancer cells were used to investigate the relationship between GPX3 expression and cancer cell metastasis, proliferation, and chemotherapy sensitivity. Results GPX3 is down-regulated in various tumor tissues, and GPX3 expression level can be used as a marker for cancer diagnosis. However, GPX3 expression is associated with higher stage and lymph node metastasis, as well as poorer prognosis. GPX3 is closely related to thyroid function and antioxidant function, and its expression may be regulated by epigenetic inheritance such as methylation modification or histone modification. In vitro experiments, GPX3 expression is associated with cancer cell sensitivity to oxidant and platinum-based chemotherapy and is involved in tumor metastasis in oxidative environments. Discussion We explored the relationship between GPX3 and clinical features, immune infiltration characteristics, migration and metastasis, and chemotherapy sensitivities of human cancers. We further investigated the potential genetic and epigenetic regulation of GPX3 in cancer. Our results suggested that GPX3 plays a complicated role in the tumor microenvironment, simultaneously promoting metastasis and chemotherapy resistance in human cancers.
Spatiotemporal trends in neonatal, infant, and child mortality (1990–2019) based on Bayesian spatiotemporal modeling

Background Neonatal mortality rate (NMR), infant mortality rate (IMR), and child mortality rate (CMR) show a huge difference across countries, which has been posing challenges for public health policies and medical resource allocation. Methods Bayesian spatiotemporal model is applied to assess the detailed spatiotemporal evolution of NMR, IMR, and CMR from a global perspective. Panel data from 185 countries from 1990 to 2019 are collected. Results The continuously decreasing trend of NMR, IMR, and CMR indicated a great improvement in neonatal, infant, and child mortality worldwide. Further, huge differences in the NMR, IMR, and CMR still exist across countries. In addition, the gap of NMR, IMR, and CMR across the countries presented a widening trend from the perspective of dispersion degree and kernel densities. The spatiotemporal heterogeneities demonstrated that the decline degree among these three indicators could be observed as CMR > IMR > NMR. Countries such as Brazil, Sweden, Libya, Myanmar, Thailand, Uzbekistan, Greece, and Zimbabwe showed the highest values of b1i, indicating a weaker downward trend compared to the overall downward trend in the world. Conclusions This study revealed the spatiotemporal patterns and trends in the levels and improvement of NMR, IMR, and CMR across countries. Further, NMR, IMR, and CMR show a continuously decreasing trend, but the differences in improvement degree present a widening trend across countries. This study provides further implications for policy in newborns, infants, and children's health to reduce health inequality worldwide.
Effect of botulinum toxin type A on non-motor symptoms and quality of life in Meige syndrome

Background It has been shown in previous studies that botulinum toxin type A (BTX-A) can effectively relieve the motor symptoms of Meige syndrome. However, its effect on non-motor symptoms (NMS) and quality of life (QoL) has not been comprehensively studied. This study aimed to explore the effects of BTX-A on NMS and QoL and to clarify the relationship between changes in motor symptoms, NMS, and QoL after BTX-A. Methods Seventy-five patients were recruited for the study. All patients were assessed by a series of clinical assessments before, one, and 3 months after BTX-A treatment. Dystonic symptoms, psychiatric disturbances, sleep disorders, and QoL were evaluated. Results After 1 and 3 months of BTX-A treatment, the scores of motor symptoms, anxiety, and depression were significantly decreased (P < 0.05). Except for general health, the scores of the other 36-item short-form health survey QoL subitems were significantly improved after BTX-A (P < 0.05). After 1 month of treatment, the changes in anxiety and depression were not correlated with changes in motor symptoms (P > 0.05). Still, they were negatively correlated with changes in physical functioning, role-physical and mental component summary QoL (P < 0.05). Conclusions BTX-A effectively improved motor symptoms, anxiety, depression, and QoL. Anxiety and depression improvement did not correlate with motor symptom changes after BTX-A, and QoL improvements were strongly associated with psychiatric disturbances.
Risk factors for post-transplant relapse and survival in younger adult patients with t(8;21)(q22;q22) acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation: A multicenter retrospective study

Background Outcomes of patients with t(8;21)(q22;q22) acute myeloid leukemia (AML) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) remain heterogeneous. Methods To identify the risk factors for relapse and survival after allo-HSCT in t(8;21) AML patients, we retrospectively evaluated the clinical and prognostic information of 142 patients with t(8;21) AML undergoing allo-HSCT between January 2002 and September 2018 at 15 hematology research centers in China. Results Twenty-nine patients (20%) relapsed after undergoing allo-HSCT. A > 1-log reduction in RUNX1/RUNX1T1-based minimal residual disease (MRD) directly before allo-HSCT and a > 3-log reduction within the first 3 months after allo-HSCT were associated with a significantly lower post-transplant 3-year cumulative incidence of relapse (CIR, 9% vs. 62% and 10% vs. 47%,all P < 0.001), whereas transplantation during the second complete remission (CR2, 39% vs. 17% during CR1, P = 0.022), during relapse (62% vs. 17% during CR1, P < 0.001) and KIT D816 mutations at diagnosis (49% vs. 18%, P = 0.039) were related to a significantly higher 3-year CIR. Multivariate analysis demonstrated that a > 1-log reduction in MRD directly before transplantation (CIR: hazard ratio(HR), 0.21 [0.03–0.71], P = 0.029; overall survival (OS): HR = 0.27 [0.08–0.93], P = 0.038) and a > 3-log reduction in post-transplant MRD within the first 3 months (CIR: HR = 0.25 [0.07–0.89], P = 0.019; OS: HR = 0.38 [0.15–0.96], P = 0.040) were independent favorable prognostic factors, and transplantation during relapse (CIR: HR = 5.55 [1.23–11.56], P = 0.041; OS: HR = 4.07 [1.82–20.12], P = 0.045) were independent adverse prognostic factors for post-transplant relapse and survival in patients with t(8;21) AML. Conclusion Our study suggests that for patients with t(8;21) AML undergoing allo-HSCT, it would be better to receive transplantation during CR1 with a MRD directly before transplantation achieving at least 1-log reduction. MRD monitoring in the first 3 months after allo-HSCT might be robust in predicting relapse and adverse survival after allo-HSCT.
Development of a feasible and acceptable digital prehabilitation pathway to improve elective surgical outcomes

Objective(s) To codesign and assess the feasibility, acceptability, and appropriateness of a hospital-initiated, community delivered approach to health optimization (prehab) prior to planned surgery. Design Participatory codesign combined with a prospective, observational cohort study (April–July 2022). Setting A large metropolitan tertiary referral service with 2 participating hospitals. Participants All people referred for orthopaedic assessment for joint replacement surgery (hip or knee) triaged as category 2 or 3. Exclusions: category 1; no mobile number. Response rate 80%. Intervention My PreHab Program is a digitally enabled pathway that screens participants for modifiable risk factors for post-operative complications and provides tailored information to enable health optimization prior to surgery with the help of their regular doctor. Outcome measures Acceptability, feasibility, appropriateness, and engagement with the program. Results 36/45 (80%) registered for the program (ages 45–85 yrs.), completed the health-screening survey and had ≥1 modifiable risk factor. Eighteen responded to the consumer experience questionnaire: 11 had already seen or scheduled an appointment with their General Practitioner and 5 planned to. 10 had commenced prehab and, 7 planned to. Half indicated they were likely (n = 7) or very likely (n = 2) to recommend My PreHab Program to others. The My PreHab Program scored an average 3.4 (SD 0.78) for acceptability, 3.5 (SD 0.62) for appropriateness, and 3.6 (SD 0.61) for feasibility, out of a score of 5. Conclusion(s) This digitally delivered intervention is acceptable, appropriate, and feasible to support a hospital-initiated, community-based prehab program.
Identification of groundwater potential zones in the Rabigh-Yanbu area on the western coast of Saudi Arabia using remote sensing (RS) and geographic information system (GIS)

The groundwater potential zones in the Rapigh-Yanbu area, on the west coast of Saudi Arabia, were evaluated using remote sensing and geographic information system data leading to the establishment of major watershed development and management strategies. Many factors, including slope, drainage density, land use, geology, lineament density, elevation, yearly precipitation, and soil type distribution, affect the hydrogeological characteristics of coastal aquifers. The Rabigh-Yanbu coastline groundwater potential zones were located and mapped using these characteristics. The annual precipitation rate is categorized into 2–28 mm, 29–52 mm, 53–76 mm,77–107 mm, and 108–164 mm within the study area. The highest elevation was ordered with the lowest rank of 1, while the lowest elevation was given the highest rank of 5. Slopes of 0°–9° were present in the majority of the study region, while slopes of 9°–63° were present in the northwest. Based on the slope, the research area was separated into five classes; 0-3o; 4-9o; 10–16o; 17–25o; 26–63o. Based on the drainage density map; 0–0.36 km2, 0.37–0.53 km2, 0.54–0.73 km2, 0.74–1.32 km2, 1.33–3.31 km2. The majority of the fractures trended NE–SW and NW–SE. A map of lineament density was made using the line density method. This map makes it obvious that the region was divided into five classes; 0–0.02 km2, 0.03–0.08 km2, 0.09–0.13 km2, 0.14–0.2 km2, and 0.21–0.34 km2. The classification of soil types in the study region into four classes such as clay loam, clay, sandy clay, and loam. Accordingly, the clay soil was ranked 1, while the loam soil was given the highest rank of 4. The Precambrian rocks had low groundwater potential because of their reduced porosity and were ranked 1, while Quaternary deposits had a high porosity and good groundwater potential and were given a high rank of 3. According to the likelihood of groundwater supply, the area is divided into four categories: very good, good, moderate, and poor. The area with very good groundwater potential covered 1,384 km2, while the area with good groundwater potential covered 30,498 km2, according to the findings. The study area had 34,412 km2 of somewhat appropriate land for groundwater development. In contrast, 1,734 km2 of the study area is scarce. The best zones featured the lowest slopes, the least number of lineaments, and the most drainage. The lineaments, which serve as the main conduits for groundwater flow and storage, have significant levels of groundwater recharge capacity in the study area. Managing groundwater according to these identified potential zones will maximize their benefits and increase the groundwater yield. This will help in creating new agricultural, urban, and industrial communities in this strategic area and contribute toward achieving the goals of Saudi Vision 2030.
Walking at the edge: How tempo-spatial nexus forms HRM practices in project-based organizations

Introduction Research has scrutinized the role of different HRM practices in Project-based Organizations (PBOs) mostly in terms of project success and articulated the challenges of traditional HRM to reconcile with the project context. Nevertheless, HRM practices have been addressed less in PBOs with a practice-based research lens. Particularly, the role of tempo-spatial nexus in shaping such practices in this organizational form has been under-researched, although PBOs provide a very suitable context for doing so. Methods Drawing upon a comparative case study in the oil and gas industry of Scotland and adopting a practice-based approach, this research aims to shed light on how HRM practices are shaped and re-shaped in the project-based context. The study, specifically, scrutinizes the role of temporality and space in the formation, adoption and adaptation of HRM practices in these organizational forms. Results and discussion The findings reveal that project characteristics, specifically their duration, size and technical properties, induce different temporalities that along with different work locations and inter-organizational relationships, impact HRM practices as a threefold structure.
Adaptive neuroplasticity in the default mode network contributing to absence of central sensitization in primary dysmenorrhea

Introduction Primary dysmenorrhea (PDM), the most prevalent gynecological problem among women of reproductive age, presents as a regular pattern of cyclic menstrual pain. The presence or absence of central sensitization (i.e., pain hypersensitivity) in cases of PDM is a contentious issue. Among Caucasians, the presence of dysmenorrhea is associated with pain hypersensitivity throughout the menstrual cycle, indicating pain amplification mediated by the central nervous system. We previously reported on the absence of central sensitization to thermal pain among Asian PDM females. In this study, functional magnetic resonance imaging was used to reveal mechanisms underlying pain processing with the aim of explaining the absence of central sensitization in this population. Methods Brain responses to noxious heat applied to the left inner forearm of 31 Asian PDM females and 32 controls during their menstrual and periovulatory phases were analyzed. Results and discussion Among PDM females experiencing acute menstrual pain, we observed a blunted evoked response and de-coupling of the default mode network from the noxious heat stimulus. The fact that a similar response was not observed in the non-painful periovulatory phase indicates an adaptive mechanism aimed at reducing the impact of menstrual pain on the brain with an inhibitory effect on central sensitization. Here we propose that adaptive pain responses in the default mode network may contribute to the absence of central sensitization among Asian PDM females. Variations in clinical manifestations among different PDM populations can be attributed to differences in central pain processing.