Miracle-dz/UniFAR-FTUs huggingface dataset:
A De Novo Designed Trimeric Metalloprotein as a Nip Model of the Acetyl-CoA Synthase

We present a Nip site model of acetyl coenzyme-A synthase (ACS) within a de novo-designed trimer peptide that self-assembles to produce a homoleptic Ni(Cys)3 binding motif. Spectroscopic and kinetic studies of ligand binding demonstrate that Ni binding stabilizes the peptide assembly and produces a terminal NiI-CO complex. When the CO-bound state is reacted with a methyl donor, a new species is quickly produced with new spectral features. While the metal-bound CO is albeit unactivated, the presence of the methyl donor produces an activated metal-CO complex. Selective outer sphere steric modifications demonstrate that the physical properties of the ligand-bound states are altered differently depending on the location of the steric modification above or below the Ni site.
Abnormal Spontaneous Discharges of Primary Sensory Neurons and Pain Behavior in a Rat Model of Vascular Dementia

Patients with vascular dementia experience more pain than healthy elders, potentially due to the presence of central neuropathic pain. However, the mechanisms underlying neuropathic pain in vascular dementia remain poorly understood, and there is currently a lack of effective treatment available. In this study, a rat model of vascular dementia was induced by permanently occluding the common carotid arteries bilaterally (2-VO). The cognitive impairments in the 2-VO rats were evaluated using the Morris Water Maze test, while HE and LBF staining were employed to assess brain tissue lesions in the hippocampal, cerebral cortex, and white matter regions known to be associated with severe memory and learning deficits. Furthermore, pain-related behavioral tests, including mechanical and thermal stimuli assessments, were conducted, and in vivo electrophysiological recordings of primary sensory neurons were performed. Compared to sham-operated and pre-operative rats, rats with vascular dementia exhibited mechanical allodynia and thermal hyperalgesia 30 days after surgery. Furthermore, in vivo electrophysiology revealed a significant increase in the occurrence of spontaneous activity of Aβ- and C-fiber sensory neurons in the rat model of vascular dementia. These results indicate that neuropathic pain behaviors developed in the rat model of vascular dementia, and abnormal spontaneous discharges of primary sensory neurons may play a crucial role in the development of pain after vascular dementia.
Estimates and trends of zero vegetable or fruit consumption among children aged 6–23 months in 64 countries

Children require a diverse diet, that includes vegetables and fruits, to support growth and development and prevent non-communicable diseases. The WHO-UNICEF established a new infant and young child feeding (IYCF) indicator: zero vegetable or fruit (ZVF) consumption among children aged 6–23 months. We estimated the prevalence, trends, and factors associated with ZVF consumption using nationally representative, cross-sectional data on child health and nutrition in low-and-middle-income countries. We examined 125 Demographic and Health Surveys in 64 countries conducted between 2006–2020 with data on whether a child ate vegetables or fruits the previous day. Prevalence of ZVF consumption was calculated by country, region, and globally. Country trends were estimated and tested for statistical significance (p<0.05). Logistic regression analysis was used to examine the relationship between ZVF and child, mother, household, and survey cluster characteristics by world region and globally. Using a pooled estimate of the most recent survey available in each country, we estimate the global prevalence of ZVF consumption as 45.7%, with the highest prevalence in West and Central Africa (56.1%) and the lowest in Latin America and the Caribbean (34.5%). Recent trends in ZVF consumption varied by country (16 decreasing, eight increasing, 14 no change). Country trends in ZVF consumption represented diverse patterns of food consumption over time and may be affected by the timing of surveys. Children from wealthier households and children of mothers who are employed, more educated, and have access to media were less likely to consume ZVF. We find the prevalence of children aged 6–23 months who do not consume any vegetables or fruits is high and is associated with wealth and characteristics of the mother. Areas for future research include generating evidence from low-and-middle-income countries on effective interventions and translating strategies from other contexts to improve vegetable and fruit consumption among young children.
Association between Diabetic Peripheral Neuropathy as Measured Using a Point-of-Care Sural Nerve Conduction Device and Urinary Albumin Excretion in Patients with Type 2 Diabetes

Background: It is not well known whether diabetic peripheral neuropathy diagnosed using a non-invasive point-of-care nerve conduction device called DPN-Check® is associated with diabetic nephropathy. Thus, we aimed to evaluate the association of diabetic peripheral neuropathy with urinary albumin excretion in patients with type 2 diabetes using DPN-Check®. Methods: This retrospective observational study included 323 Japanese patients with type 2 diabetes. The urinary albumin-to-creatinine ratio in a spot urine sample was defined as urinary albumin excretion. Multiple linear regression analysis was used to determine the association of DPN-Check®-determined diabetic peripheral neuropathy with urinary albumin excretion. Results: Patients with DPN-Check®-determined diabetic peripheral neuropathy had significantly higher urinary albumin excretion than those without, while there was no difference in urinary albumin excretion between patients with and without diabetic peripheral neuropathy determined by simplified diagnostic criteria. In the multivariate model, the DPN-Check® determined that diabetic peripheral neuropathy was significantly associated with urinary albumin excretion even after adjustment for covariates (standardized β, 0.123; p = 0.012). Conclusions: Our study found a significant association between diabetic peripheral neuropathy diagnosed using DPN-Check® and urinary albumin excretion in patients with type 2 diabetes.
Longitudinal Changes in Milk Microorganisms in the First Two Months of Lactation of Primiparous and Multiparous Cows

Simple Summary Our results demonstrated the dynamic changes in cow milk microbiota over the first two months of lactation, and the differences in microbial composition between primiparous cows and multiparous cows. The presence and fluctuation of some typically gut-associated microbes in milk indicated that the metabolic changes in dairy cows may influence the microbial structure of cow milk. These changes may potentially be correlated with milk components. Abstract The present experiment was carried out to analyze the longitudinal changes in milk microorganisms. For this purpose, milk samples were collected from 12 healthy cows (n = 96; six primiparous cows and six multiparous cows) at eight different time points. The characteristics and variations in microbial composition were analyzed by 16S rRNA gene high-throughput sequencing. In the primiparous group, higher and more stable alpha diversity was observed in transitional and mature milk compared with the colostrum, with no significant difference in alpha diversity at each time point in the multiparous group. Proteobacteria, Firmicutes, Bacteroidota, and Actinobacteriota were the most dominant phyla, and Pseudomonas, UCG-005, Acinetobacter, Vibrio, Lactobacillus, Bacteroides, Serratia, Staphylococcus, and Glutamicibacter were the most dominant genera in both primiparous and multiparous cow milk. Some typically gut-associated microbes, such as Bacteroides, UCG-005, and Rikenellaceae_RC9_gut_group, etc., were enriched in the two groups. Biomarker taxa with the day in time (DIM) were identified by a random forest algorithm, with Staphylococcus showing the highest degree of interpretation, and the difference in milk microbiota between the two groups was mainly reflected in 0 d–15 d. Additionally, network analysis suggested that there were bacteria associated with the total protein content in milk. Collectively, our results disclosed the longitudinal changes in the milk microbiota of primiparous and multiparous cows, providing further evidence in dairy microbiology.
Targeting the Limbic System: Insights into Its Involvement in Tinnitus

Tinnitus is originally derived from the Latin verb tinnire, which means “to ring”. Tinnitus, a complex disorder, is a result of sentient cognizance of a sound in the absence of an external auditory stimulus. It is reported in children, adults, and older populations. Patients suffering from tinnitus often present with hearing loss, anxiety, depression, and sleep disruption in addition to a hissing and ringing in the ear. Surgical interventions and many other forms of treatment have been only partially effective due to heterogeneity in tinnitus patients and a lack of understanding of the mechanisms of tinnitus. Although researchers across the globe have made significant progress in understanding the underlying mechanisms of tinnitus over the past few decades, tinnitus is still deemed to be a scientific enigma. This review summarises the role of the limbic system in tinnitus development and provides insight into the development of potential target-specific tinnitus therapies.
Morphological and Genetics Support for a Hitherto Undescribed Spotted Cat Species (Genus Leopardus; Felidae, Carnivora) from the Southern Colombian Andes

In 1989, a skin of a small spotted cat, from the Galeras Volcano in southern Colombia (Nariño Department), was donated to the Instituto Alexander von Humboldt (identification, ID 5857) at Villa de Leyva (Boyacá Department, Colombia). Although originally classified as Leopardus tigrinus, its distinctiveness merits a new taxonomic designation. The skin is distinct from all known L. tigrinus holotypes as well as from other Leopardus species. Analysis of the complete mitochondrial genomes from 44 felid specimens (including 18 L. tigrinus and all the current known species of the genus Leopardus), the mtND5 gene from 84 felid specimens (including 30 L. tigrinus and all the species of the genus Leopardus), and six nuclear DNA microsatellites (113 felid specimens of all the current known species of the genus Leopardus) indicate that this specimen does not belong to any previously recognized Leopardus taxon. The mtND5 gene suggests this new lineage (the Nariño cat as we name it) is a sister taxon of Leopardus colocola. The mitogenomic and nuclear DNA microsatellite analyses suggest that this new lineage is the sister taxon to a clade formed by Central American and trans-Andean L. tigrinus + (Leopardus geoffroyi + Leopardus guigna). The temporal split between the ancestor of this new possible species and the most recent ancestor within Leopardus was dated to 1.2–1.9 million years ago. We consider that this new unique lineage is a new species, and we propose the scientific name Leopardus narinensis.
Serum Anti-Thyroglobulin Autoantibodies Are Specific in Predicting the Presence of Papillary-like Nuclear Features and Lymphocytic Infiltrate in the Thyroid Gland

(1) Background: Previous studies have reported a correlation between serum anti-Thyroglobulin-antibodies (TgAb) and papillary thyroid carcinoma. The aim of our study was to evaluate whether serum TgAb and anti-thyroid-peroxidase antibody (TPO) positivity was also related to pre-neoplastic histological changes such as papillary-like nuclear features (PLNF) and with the presence of lymphocytic infiltrate (LI) in thyroid surgical specimens. (2) Methods: The study was retrospectively carried out on 70 consecutively recruited patients who underwent thyroidectomy for benign process and whose TgAb and TPOAb values were retrieved from clinical records. Histological sections of thyroid surgical samples were revised, looking for PLNF and lymphocytic infiltrate. HBME1 expression was assessed by immunohistochemistry. (3) Results: Our results showed a significant association between TgAb, PLNF, and lymphocytic infiltrate. The presence of TgAb was highly specific, but less sensitive, in predicting the presence of PLNF (sensitivity = 0.6, specificity = 0.9; positive predictive value (PPV) = 0.88; negative predictive value (NPV) = 0.63). TgAb positivity showed a good association with the presence of lymphocytic infiltrate (sensitivity = 0.62, specificity = 0.9; PPV = 0.88 and NPV = 0.68). HBME1 immunoreactivity was observed in the colloid of follicles showing PLNF and/or closely associated with LI. (4) Conclusions: The presence of PLNF and LI is associated with serum TgAb positivity. The presence of TgAb and of LI could be triggered by an altered thyroglobulin contained in the HBME1-positive colloid, and could be a first defense mechanism against PLNF that probably represent early dysplastic changes in thyrocytes.
Defining the Characteristics of an e-Health Tool for Suicide Primary Prevention in the General Population: The StopBlues Case in France

With over one million deaths per year in the world, suicide is a major public health problem that could be significantly reduced by effective prevention programs. E-health tools are of particular interest for primary prevention as they can address a broad population including people unaware of their own risk and provide information and help without the fear of stigma. Our main objective was to define the overall characteristics of an e-health tool for suicide primary prevention in the French general population by defining the characteristics of the IT features; the content of the information delivered; the best way to structure it; and how it should be relayed and by whom. The research was carried out through a literature review and a co-construction phase with stakeholders. Four types of strategies may guide the construction of e-health tools for suicide primary prevention: education and awareness, (self-)screening, accessing support, and mental health coping. They should be accessible on different devices to reach the most users, and language and content should be adapted to the target population and to the issue being addressed. Finally, the tool should be consistent with ethical and quality best practices. The e-health tool StopBlues was developed following those recommendations.
Physiological Responses and Fatigue during a Repeated Shuttle-Sprint Running Test in Adolescent Schoolchildren: A Comparison between Sexes and Fatigue Calculation Methods

We examined physiological responses and fatigue in adolescent boys and girls during a repeated shuttle-sprint running test in a school setting. We also compared three calculation methods to assess fatigue during repeated sprints: the fatigue index (FI), the percent sprint decrement (Sdec), and the slope of performance decrement (SlopeD). Twenty-six adolescent students (10 girls and 16 boys, age: 15.3 ± 0.5 y) performed six 30 m sprints with a 180° change of direction at 15 m, interspersed with 10 s of recovery. Blood lactate (BL), heart rate (HR) and countermovement jump performance (CMJ) were measured before and after the sprint test. Boys achieved significantly faster sprint times (11.7% to 14.8% faster than girls in all sprints, p < 0.01), and had higher post-test BL compared with girls (14.0 ± 2.9 vs. 11.3 ± 3.2 mmol/L; p = 0.02; d = 0.93). However, all fatigue indices (FI, Sdec and SlopeD) were similar in boys and girls (FI = 11.5 ± 5.0 vs. 11.5 ± 5.0; SlopeD = 10.6 ± 4.8 vs. 14.5 ± 5.1; Sdec = 5.6 ± 2.2 vs. 7.3 ± 2.2, in boys and girls, respectively, p > 0.05 for all) and were highly correlated with each other (r = 0.86 to 0.97, p < 0.01). CMJ was higher in boys (p < 0.05), but CMJ performance dropped similarly from pre- to post-test in boys and girls (13.7 ± 7.0%, p < 0.01). In conclusion, neuromuscular fatigue during and after repeated shuttle-sprint running is similar in boys and girls, despite the faster sprint times, higher CMJ and higher BL in boys. SlopeD may be used as an alternative index to quantify fatigue during repeated shuttle-sprinting, as it takes into account performance in all sprints and may provide an average sprint-by-sprint performance drop.
Innovation in Radionuclide Therapy for the Treatment of Prostate Cancers: Radiochemical Perspective and Recent Therapeutic Practices

Simple Summary Despite the use of surgery and treatments that inhibit the androgen axis signaling, prostate cancer patients invariably become resistant to castration. In the case of metastatic disease, several alternatives have emerged in the past decade with the development of radionuclide therapies. These treatments may represent an interesting option as they could target either the microenvironment of sclerotic bone metastases or proteins that are specifically expressed at the surface of cancer cells, as it is the case with the prostate-specific membrane antigen. This review summarizes the clinical trials evaluating the efficacy of radionuclide therapies in patients with locally advanced or metastatic prostate tumors. Besides the theragnostic use of radionuclides, it also discusses the recent encouraging results that were obtained with 177Lu-PSMA-617 and the specific requirements for the use of this class of medication. Abstract Prostate cancer represents the second cause of death by cancer in males in western countries. While early-stage diseases are accessible to surgery and/or external radiotherapy, advanced metastatic prostate cancers are primarily treated with androgen deprivation therapy, to which new generation androgen receptor antagonists or taxane-based chemotherapies are added in the case of tumor relapse. Nevertheless, patients become invariably resistant to castration with a median survival that rarely exceeds 3 years. This fostered the search for alternative strategies, independent of the androgen receptor signaling pathway. In this line, radionuclide therapies may represent an interesting option as they could target either the microenvironment of sclerotic bone metastases with the use of radiopharmaceuticals containing samarium-153, strontium-89 or radium-223 or tumor cells expressing the prostate-specific membrane antigen (PSMA), a protein found at the surface of prostate cancer cells. This review gives highlights the chemical properties of radioligands targeting prostate cancer cells and recapitulates the clinical trials evaluating the efficacy of radionuclide therapies, alone or in combination with other approved treatments, in patients with castration-resistant prostate tumors. It discusses some of the encouraging results obtained, especially the benefit on overall survival that was reported with [177Lu]-PSMA-617. It also addresses the specific requirements for the use of this particular class of drugs, both in terms of medical staff coordination and adapted infrastructures for efficient radioprotection.
A Machine Learning Approach for Knee Injury Detection from Magnetic Resonance Imaging

The knee is an essential part of our body, and identifying its injuries is crucial since it can significantly affect quality of life. To date, the preferred way of evaluating knee injuries is through magnetic resonance imaging (MRI), which is an effective imaging technique that accurately identifies injuries. The issue with this method is that the high amount of detail that comes with MRIs is challenging to interpret and time consuming for radiologists to analyze. The issue becomes even more concerning when radiologists are required to analyze a significant number of MRIs in a short period. For this purpose, automated tools may become helpful to radiologists assisting them in the evaluation of these images. Machine learning methods, in being able to extract meaningful information from data, such as images or any other type of data, are promising for modeling the complex patterns of knee MRI and relating it to its interpretation. In this study, using a real-life imaging protocol, a machine-learning model based on convolutional neural networks used for detecting medial meniscus tears, bone marrow edema, and general abnormalities on knee MRI exams is presented. Furthermore, the model’s effectiveness in terms of accuracy, sensitivity, and specificity is evaluated. Based on this evaluation protocol, the explored models reach a maximum accuracy of 83.7%, a maximum sensitivity of 82.2%, and a maximum specificity of 87.99% for meniscus tears. For bone marrow edema, a maximum accuracy of 81.3%, a maximum sensitivity of 93.3%, and a maximum specificity of 78.6% is reached. Finally, for general abnormalities, the explored models reach 83.7%, 90.0% and 84.2% of maximum accuracy, sensitivity and specificity, respectively.
Bayesian fitting of a directional random field with application to precipitation modeling

We propose a Bayesian method for fitting a directional random field based on point observations. The random field W representing the moisture flux direction (MFD), interacts with point observations through the term cos(W A) in the regression equation, where A is the terrain aspect. Our approach extends a similar method for Gaussian Markov random fields, which is a combination of a “smoothness” prior on a rectangular grid and a convolution for o-grid points. A Markov chain Monte Carlo algorithm for fitting W is implemented. As an example, we consider monthly average precipitation data over Taiwan. The random field method helps improve understanding of climatic patterns, as well as estimation and prediction of the average precipitation over the area.
Non-Homologous End-Joining Pathway Genotypes Significantly Associated with Nasopharyngeal Carcinoma Susceptibility

Defects in the non-homologous end-joining (NHEJ) DNA repair pathway lead to genomic instability and carcinogenesis. However, the roles of individual NHEJ genes in nasopharyngeal carcinoma (NPC) etiology are not well-understood. The aim of this study was to assess the contribution of NHEJ genotypes, including XRCC4 (rs6869366, rs3734091, rs28360071, rs28360317, rs1805377), XRCC5 (rs828907, rs11685387, rs9288518), XRCC6 (rs5751129, rs2267437, rs132770, rs132774), XRCC7 rs7003908, and Ligase4 rs1805388, to NPC risk, with 208 NPC patients and 416 controls. Genotype–phenotype correlations were also investigated by measuring mRNA and protein expression in adjacent normal tissues and assessing the NHEJ repair capacity in blood lymphocytes from 43 NPC patients. The results showed significant differences in the distributions of variant genotypes at XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 between the cases and controls. The variant genotypes of these three polymorphisms were associated with significantly increased NPC risks. NPC patients with the risk genotypes at XRCC6 rs2267437 had significantly reduced expression levels of both mRNA and protein, as well as a lower NHEJ repair capacity, than those with the wild-type genotype. In conclusion, XRCC4 rs3734091, rs28360071, and XRCC6 rs2267437 in the NHEJ pathway were associated with NPC susceptibility. XRCC6 rs2267437 can modulate mRNA and protein expression and the NHEJ repair capacity.