Miracle-dz/UniFAR-FTUs huggingface dataset:
FKBP51 in the Oval Bed Nucleus of the Stria Terminalis Regulates Anxiety-Like Behavior

Visual Abstract The cochaperone FKBP51, encoded by the Fkbp5 gene, has been identified as central risk factor for anxiety-related disorders and stress system dysregulation. In the brain, the oval bed nucleus of the stria terminalis (ovBNST) has been implicated in stress-induced anxiety. However, the role of Fkbp5 in the ovBNST and its impact on anxiety-like behavior have remained unknown. Here, we show in mice that Fkbp5 in the ovBNST is reactive to acute stress and coexpressed with the stress-regulated neuropeptides Tac2 and Crh. Subsequently, results obtained from viral-mediated manipulation indicate that Fkbp5 overexpression (OE) in the ovBNST results in an anxiolytic-like tendency regarding behavior and endocrinology, whereas a Fkbp5 knock-out (KO) exposed a clear anxiogenic phenotype, indicating that native ovBNST expression and regulation is necessary for normal anxiety-related behavior. Notably, our data suggests that a stress-induced increase of Fkbp5 in the ovBNST may in fact have a protective role, leading to a transient decrease in anxiety and suppression of a future stress-induced hypothalamic-pituitary-adrenal (HPA) axis activation. Together, our findings provide a first insight into the previously unknown relationship and effects of Fkbp5 and the ovBNST on anxiety-like behavior and HPA axis functioning.
Stress Signal ULBP4, an NKG2D Ligand, Is Upregulated in Multiple Sclerosis and Shapes CD8+ T-Cell Behaviors

Background and Objectives We posit the involvement of the natural killer group 2D (NKG2D) pathway in multiple sclerosis (MS) pathology via the presence of specific NKG2D ligands (NKG2DLs). We aim to evaluate the expression of NKG2DLs in the CNS and CSF of patients with MS and to identify cellular stressors inducing the expression of UL16-binding protein 4 (ULBP4), the only detectable NKG2DL. Finally, we evaluate the impact of ULBP4 on functions such as cytokine production and motility by CD8+ T lymphocytes, a subset largely expressing NKG2D, the cognate receptor. Methods Human postmortem brain samples and CSF from patients with MS and controls were used to evaluate NKG2DL expression. In vitro assays using primary cultures of human astrocytes and neurons were performed to identify stressors inducing ULBP4 expression. Human CD8+ T lymphocytes from MS donors and age/sex-matched healthy controls were isolated to evaluate the functional impact of soluble ULBP4. Results We detected mRNA coding for the 8 identified human NKG2DLs in brain samples from patients with MS and controls, but only ULBP4 protein expression was detectable by Western blot. ULBP4 levels were greater in patients with MS, particularly in active and chronic active lesions and normal-appearing white matter, compared with normal-appearing gray matter from MS donors and white and gray matter from controls. Soluble ULBP4 was also detected in CSF of patients with MS and controls, but a smaller shed/soluble form of 25 kDa was significantly elevated in CSF from female patients with MS compared with controls and male patients with MS. Our data indicate that soluble ULBP4 affects various functions of CD8+ T lymphocytes. First, it enhanced the production of the proinflammatory cytokines GM-CSF and interferon-γ (IFNγ). Second, it increased CD8+ T lymphocyte motility and favored a kinapse-like behavior when cultured in the presence of human astrocytes. CD8+ T lymphocytes from patients with MS were especially altered by the presence of soluble ULBP4 compared with healthy controls. Discussion Our study provides new evidence for the involvement of NKG2D and its ligand ULBP4 in MS pathology. Our results point to ULBP4 as a viable target to specifically block 1 component of the NKG2D pathway without altering immune surveillance involving other NKG2DL.
Statin use and risk of dementia or Alzheimer's disease: a systematic review and meta-analysis of observational studies.

AIMS As the potential impact of statins on cognitive decline and dementia is still debated, we conducted a meta-analysis of observational studies to examine the effect of statin use on the risk of Alzheimer's disease (AD) and dementia. METHODS AND RESULTS PubMed, Cochrane, and EMBASE were searched since inception to January 2021. Inclusion criteria were: (i) cohort or case-control studies; (ii) statin users compared to non-users; and (iii) AD and/or dementia risk as outcome. Estimates from original studies were pooled using restricted maximum-likelihood random-effect model. Measure of effects were reported as odds ratio (OR) and 95% confidence intervals (CIs). In the pooled analyses, statins were associated with a decreased risk of dementia [36 studies, OR 0.80 (CI 0.75-0.86)] and of AD [21 studies, OR 0.68 (CI 0.56-0.81)]. In the stratified analysis by sex, no difference was observed in the risk reduction of dementia between men [OR 0.86 (CI 0.81-0.92)] and women [OR 0.86 (CI 0.81-0.92)]. Similar risks were observed for lipophilic and hydrophilic statins for both dementia and AD, while high-potency statins showed a 20% reduction of dementia risk compared with a 16% risk reduction associated with low-potency statins, suggesting a greater efficacy of the former, although a borderline statistical significance (P = 0.05) for the heterogeneity between estimates. CONCLUSION These results confirm the absence of a neurocognitive risk associated with statin treatment and suggest a potential favourable role of statins. Randomized clinical trials with an ad hoc design are needed to explore this potential neuroprotective effect.
STUDY OF REED-BED OF AN URBAN WASTEWATER IN A NIGERIAN COMMUNITY

The need for treatment of municipal wastewater prior to its disposal is important. One method used for treating wastewater is that of a constructed wetland system (CW). The use of a CW has attracted interest in developing nations due to its operational efficiency and cost effectiveness. This paper examines an existing CW in order to determine its effectiveness in the removal of pollutants from a sewer that feeds into a major river system in Nigeria. The CW, which employs hydrophytes to degrade the wastewater from a facility of nearly 10,000 people, is comprised of six cement-block tanks. Samples were collected from the entry and exit points of the CW’s cells and analysed for dissolved oxygen, conductivity, pH and temperature. The pH remained constant (6.8 - 6.9) at ambient temperature of 270C. Conductivity ranged from 700 to 840 ppm. The dissolved oxygen (DO) ranged from 0.9mg/l at the entrance to 0.1 mg/l at the final exit point. Analysis of the data suggests that the CW is not efficient, and steps -- like aeration and an increase in the resident times of the wastewater in each cell of the CW -- need to be taken to improve its performance.
mTOR inhibitor improves testosterone-induced myocardial hypertrophy in hypertensive rats

Objective: Compelling evidence have described the incidence of hypertension and left ventricular hypertrophy (LVH) in postmenopausal women is significantly increased worldwide. Our team’s previous research identified that androgen was an underlying factor contributing to increased blood pressure and LVH in postmenopausal women. However, little is known about how androgens affect LVH in postmenopausal hypertensive women. The purpose of this study was to evaluate the role of mTOR signaling pathway in myocardial hypertrophy in androgen-induced postmenopausal hypertension and whether mTOR inhibitors can protect the myocardium from androgen-induced interference to prevent and treat cardiac hypertrophy. Design and method: For that, ovariectomized (OVX) spontaneously hypertensive rats (SHR) aged 12 weeks were used to study the effects of testosterone (T 2.85 mg/kg/weekly im) on blood pressure and myocardial tissue. On the basis of antihypertensive therapy (chlorthalidone 8 mg/kg/day ig), the improvement of blood pressure and myocardial hypertrophy in rats treated with different dose gradients of rapamycin (0.8 mg/kg/day Vs 1.5 mg/kg/day Vs 2 mg/kg/day ip) in OVX+ estrogens (E 9.6 mg/Kg/day, ig)+T group was further evaluated. Results: After T intervention, the OVX female rats exhibited significant increments in the heart weight / tibial length (TL), cross-sectional area of cardiomyocytes and the mRNA expressions of atrial natriuretic peptide, B- myosin heavy chain and matrix metalloproteinase 9 accompanied by a significant reduction in the uterine weight/TL and issue inhibitor of metalloproteinase 1. Mammalian rapamycin receptor (mTOR), ribosomal protein S6 kinase (S6K1), 4E-bindiong protein 1(4EBP1) and eukaryotic translation initiation factor 4E in myocardial tissue of OVX+E+T group were expressed at higher levels than those of the other four groups. On the other hand, rapamycin abolished the effects of T-induced cardiac hypertrophy, decreased the systolic and diastolic blood pressure of SHR, and inhibited the activation of mTOR/ S6K1/4EBP1 signaling pathway in a concentration-dependent manner. Conclusions: Collectively, these data suggest that the mTOR/S6K1/4EBP1 pathway is an important therapeutic target for the prevention of LVH in postmenopausal hypertensive women with high T levels. Our findings also support the standpoint that the mTOR inhibitor, rapamycin, can eliminate T-induced cardiomyocyte hypertrophy.
Trajectory and Predictors of Mental Health Symptoms and Wellbeing in Newly Admitted Nursing Home Residents

ABSTRACT Objectives This study determined changes in multiple aspects of mental health and wellbeing in newly admitted nursing home residents, and identified risk and protective factors. Methods Participants were 204 residents recently admitted to one of 42 nursing homes in Melbourne, Australia. A subgroup of 82 participants were followed up eight months post-admission. Depression, anxiety, stress, adjustment, and quality of life were assessed at baseline and follow-up. Predictive factors (demographics, health, transition factors, nursing home characteristics) were examined in multiple regression analyses. Results Rates of depression and anxiety were high at both baseline and follow-up. Low self-rated health and medical comorbidity predicted poor wellbeing at baseline. Higher perceived control in the relocation to the nursing home and engagement in meaningful activities were associated with better post-admission outcomes. Baseline psychotropic medication use predicted lower anxiety at follow-up but did not impact depressive symptoms. Conclusions There were no significant changes in mental health and wellbeing from one to eight months post-admission. The negative effect of residing in a for-profit nursing home requires further investigation. Clinical Implications Individual activity scheduling and an opportunity to participate in relocation decision-making and planning may support resident wellbeing post-admission.
Conflict monitoring and attentional adjustment during binocular rivalry

To make sense of ambiguous and, at times, fragmentary sensory input, the brain must rely on a process of active interpretation. At any given moment, only one of several possible perceptual representations prevails in our conscious experience. Our hypothesis is that the competition between alternative representations induces a pattern of neural activation resembling cognitive conflict, eventually leading to fluctuations between different perceptual outcomes in the case of steep competition. To test this hypothesis, we probed changes in perceptual awareness between competing images using binocular rivalry. We drew our predictions from the conflict monitoring theory, which holds that cognitive control is invoked by the detection of conflict during information processing. Our results show that fronto‐medial theta oscillations (5–7 Hz), an established electroencephalography (EEG) marker of conflict, increases right before perceptual alternations and decreases thereafter, suggesting that conflict monitoring occurs during perceptual competition. Furthermore, to investigate conflict resolution via attentional engagement, we looked for a neural marker of perceptual switches as by parieto‐occipital alpha oscillations (8–12 Hz). The power of parieto‐occipital alpha displayed an inverse pattern to that of fronto‐medial theta, reflecting periods of high interocular inhibition during stable perception, and low inhibition around moments of perceptual change. Our findings aim to elucidate the relationship between conflict monitoring mechanisms and perceptual awareness.
Mismatch repair deficiency in early‐onset duodenal, ampullary, and pancreatic carcinomas is a strong indicator for a hereditary defect

Mismatch repair deficiency (dMMR) is a hallmark of Lynch syndrome (LS), but its prevalence in early‐onset (diagnosed under the age of 50 years) duodenal, ampullary, and pancreatic carcinomas (DC, AC, and PC, respectively) is largely unknown. We explored the prevalence of dMMR and the underlying molecular mechanisms in a retrospectively collected cohort of 90 early‐onset carcinomas of duodenal, ampullary, and pancreatic origin. dMMR was most prevalent in early‐onset DCs (47.8%); more than half of those were associated with hereditary cancer syndromes (LS or constitutional mismatch repair deficiency syndrome). All dMMR AC and PC were due to LS. Concordance of dMMR with underlying hereditary condition warrants ubiquitous dMMR testing in all early‐onset DC, AC, and PC.
Ultrasound-Guided Treatments for the Painful Shoulder.

Shoulder pain is an extremely common condition. The painful shoulder may be the result of a wide spectrum of underlying pathological conditions, including calcific tendinopathy of the rotator cuff, subacromial-subdeltoid bursitis, acromioclavicular or glenohumeral arthritis, tenosynovitis of the long biceps tendon, rotator cuff lesions, and many other less common conditions. Ultrasound imaging is an effective tool for the diagnosis and also for the image guidance of treatment of the majority of these conditions. Several ultrasound-guided procedures are effective for pain relief, such as percutaneous irrigation, intra-bursal or intra-articular drugs injection, fluid aspiration, neural block. This review article aims to summarize and discuss the most common treatment possibilities with ultrasound guidance for the painful shoulder.
Accuracy of Estimated Reference Crop Evapotranspiration

Evapotranspiration from cool‐season grasses is used as the reference for ET0. The requirements for local calibration for three equations for ET0 recommended by the Food and Agriculture Organization of the United Nations (FAO) are shown for different climatic regions of California. Data from measured coolseason‐grass evapotranspiration and Class A pan evaporation from sites located in large well‐watered, irrigated grass pastures in three distinct climatic conditions are used to evaluate a method for estimating ET0 that requires only measured values of maximum and minimum air temperatures. Mean temperature, minimum relative humidity, and solar radiation can all be estimated from maximum and minimum air temperatures. The equation for ET0 that requires only temperature measurements may seem to be quite simple, but it is in reality a very comprehensive procedure incorporating most of the climatic interactions that influence the evaporative potential. The analysis of data from four lysimeter and Class A pan sit.
Femoral antetorsion after calcar‐guided short‐stem total hip arthroplasty: A cadaver study

Calcar‐guided short stems in total hip arthroplasty (THA) permit surgeons to successfully reconstruct postoperative femoroacetabular offset, accurately restore leg length, and adequately re‐establish a wide range of caput‐collum‐diaphyseal angles. However, their effect on femoral antetorsion is less known. Indeed, controlling antetorsion of the femoral stem can be challenging because of the differences in individual femoral geometry and curvature. Therefore, we investigated if calcar‐guided short‐stem THA alters femoral antetorsion and compared it with conventional‐stem THA. Using 12 Thiel‐fixed, full‐body cadaver specimens from donors without known hip disorders, we compared an uncemented calcar‐guided femoral short‐stem prosthesis with an uncemented conventional straight‐stem prosthesis. In a paired study setup, each specimen received a calcar‐guided short stem on one side and a conventional stem on the other. On the acetabular side, all specimens received a press‐fit, monobloc acetabular cup. Femoral antetorsion angles were measured using the Waidelich method, and pre‐ and post‐operative angles of both sides were recorded. The mean preoperative femoral antetorsion angles were similar in both groups (24.8° ± 7.5° vs. 23.8° ± 6.1°, p = 0.313). Mean postoperative femoral antetorsion angles were 23.0° ± 5.5° in short‐stem and 13.5° ± 7.1° in conventional‐stem hips. Short‐stem hips had a small but nonsignificant difference in femoral antetorsion angles pre‐ and post‐operatively (1.8° ± 3.2°, p = 0.109), while the difference for conventional‐stem hips was much larger and highly significant (10.3° ± 5.8°, p < 0.001). Calcar‐guided short‐stem THA effectively restores femoral antetorsion. However, how this affects long‐term clinical outcomes and complications warrants further exploration.
Prosurvival IL-7–Stimulated Weak Strength of mTORC1-S6K Controls T Cell Memory via Transcriptional FOXO1–TCF1–Id3 and Metabolic AMPKα1–ULK1–ATG7 Pathways

Key Points IL-2 and IL-7 induce S6Kstrong and S6Kweak signals, leading to forming TE and TM cells. IL-7–stimulated S6Kweak signaling controls T cell memory via FOXO1 and AMPK pathways. CD8+ memory T (TM) cells play a critical role in immune defense against infection. Two common γ-chain family cytokines, IL-2 and IL-7, although triggering the same mTORC1–S6K pathway, distinctly induce effector T (TE) cells and TM cells, respectively, but the underlying mechanism(s) remains elusive. In this study, we generated IL-7R-/and AMPKα1-knockout (KO)/OTI mice. By using genetic and pharmaceutical tools, we demonstrate that IL-7 deficiency represses expression of FOXO1, TCF1, p-AMPKα1 (T172), and p-ULK1 (S555) and abolishes T cell memory differentiation in IL-7R KO T cells after Listeria monocytogenesis rLmOVA infection. IL-2– and IL-7–stimulated strong and weak S6K (IL-2/S6Kstrong and IL-7/S6Kweak) signals control short-lived IL-7R−CD62L−KLRG1+ TE and long-term IL-7R+CD62L+KLRG1− TM cell formations, respectively. To assess underlying molecular pathway(s), we performed flow cytometry, Western blotting, confocal microscopy, and Seahorse assay analyses by using the IL-7/S6Kweak–stimulated TM (IL-7/TM) and the control IL-2/S6Kstrong–stimulated TE (IL-2/TE) cells. We determine that the IL-7/S6Kweak signal activates transcriptional FOXO1, TCF1, and Id3 and metabolic p-AMPKα1, p-ULK1, and ATG7 molecules in IL-7/TM cells. IL-7/TM cells upregulate IL-7R and CD62L, promote mitochondria biogenesis and fatty acid oxidation metabolism, and show long-term cell survival and functional recall responses. Interestingly, AMPKα1 deficiency abolishes the AMPKα1 but maintains the FOXO1 pathway and induces a metabolic switch from fatty acid oxidation to glycolysis in AMPKα1 KO IL-7/TM cells, leading to loss of cell survival and recall responses. Taken together, our data demonstrate that IL-7–stimulated weak strength of mTORC1–S6K signaling controls T cell memory via activation of transcriptional FOXO1–TCF1–Id3 and metabolic AMPKα1–ULK1–ATG7 pathways. This (to our knowledge) novel finding provides a new mechanism for a distinct IL-2/IL-7 stimulation model in T cell memory and greatly impacts vaccine development.
Pathogenic investigations of Streptococcus pasteurianus, an underreported zoonotic pathogen, isolated from a diseased piglet with meningitis.

Streptococcus pasteurianus, an underreported opportunistic pathogen, is considered an increasingly recognized cause of meningitis and bacteremia in many animals and humans worldwide. However, except for some epidemiological studies, there is no report about the gene-deletion mutagenesis, virulence factors, reservoir niches, or animal infection models for this pathogen. In this study, we first isolated an S. pasteurianus strain from a newly weaned piglet's brain with meningitis. The genomic sequence of this swine isolate WUSP067 shared high homology with that of two human strains. The comparative genome analysis showed that strain WUSP067 contained a fucose utilization cluster absent in human strains, and it shared 91% identity with that of an integrative and conjugative element (ICE) ICEssuZJ20091101-2 from Streptococcus suis, another important swine bacterial pathogen. Strain WUSP067 was resistant to erythromycin, tulathromycin, lincomycin, clindamycin, doxycycline, and gentamycin, and ICEs are vehicles for harboring antimicrobial resistance genes. The infection model was established using the three-week-old newly weaned ICR mice. The 50% lethal dose value of strain WUSP067 was 4.0×107 colony-forming units per mouse. The infected mice showed severe signs of meningitis and pathological changes in brains. Furthermore, the capsule-deficient mutant was generated using natural transformation, and we showed that capsule was an essential virulence factor for S. pasteurianus. In addition, we found that tonsils and hilar lymph nodes of healthy pigs may be reservoir niches for this bacterium. Thus, our study provided valuable information about the pathogenetic characteristics and antimicrobial resistance of S. pasteurianus and paved the way for studying its pathogenesis. This article is protected by copyright. All rights reserved.
The effect of body mass index on blood loss and complications in simultaneous bilateral total hip arthroplasty: A multicenter retrospective study

Background The effect of body mass index (BMI) on blood loss in simultaneous bilateral total hip arthroplasty (SBTHA) was still undetermined. The purpose of the study was to evaluate the blood loss, transfusion and incidence of complications in normal, overweight, and obese patients undergoing SBTHA. Methods A total of 344 patients following SBTHA were enrolled into this study. The patients were assigned into three groups on the basis of their BMI, including normal (BMI 18.0–24.9 kg/ m 2 ), overweight (BMI 25.0–29.9 kg/ m 2 ), or obese group (BMI ≥ 30.0 kg/ m 2 ). The primary outcome was total blood loss (TBL), and secondary outcomes were intraoperative blood loss, drain volume, ratio of TBL and patient’s blood volume (PBV), transfusion rate and volume, hemoglobin and hematocrit drop, length of stay, expenses, and complications. Results The PBV and TBL increased significantly along with the elevated BMI (p < 0.001; p = 0.019, respectively). There was no significant difference in intraoperative blood loss, drain volume, transfusion volume, length of stay, expenses, or incidence of complications among the three groups. In addition, the transfusion rate in normal group was higher than that in overweight (58.3% vs 39.6%, p = 0.001) and obese group (58.3% vs 31.9%, p = 0.001). The maximum hemoglobin drop in obese group was the highest (p = 0.001). Conclusion Obesity could increase perioperative blood loss but not increase transfusion risk in the setting of SBTHA. Conversely, obese and overweight patients maybe have lower transfusion need compared with normal patients because of more blood volume. In addition, obesity did not affect the incidence of complications.
Design of omni-directional underwater robotic vehicle

Underwater robotic vehicles have been attractive to many applications. Among potential applications of these vehicles include fishery, underwater pollution monitoring, and waste cleaning and handling in the ocean as well as nuclear sites. Over the last decade, there has been increasing R&D effort toward more advanced and intelligent underwater vehicles in support of a variety of applications. In the Autonomous Systems Laboratory, an omni-directional intelligent navigator (ODIN) which has dual (autonomous/remote) operational modes and a mechanical manipulator, was designed as a part of the research in developing a real-time 3D graphic, integrated test platform for advanced vehicle technologies. RSI Research Ltd. manufactured the first model which is described in this paper. <<ETX>>