Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Untreated Drinking Water at Three Indigenous Yaqui Towns in Mexico: Insights from a Murine Model

Background: Reports in a northwestern Mexico state linked arsenic (As) in drinking water to DNA damage in people from indigenous communities. However, this correlation remains under discussion due to unknown variables related to nutrition, customs, and the potential presence of other metal(oid)s. Methods: To determine this association, we sampled water from three Yaqui towns (Cócorit, Vícam, and Pótam), and analyzed the metals by ICP-OES. We exposed four separate groups, with five male CD-1 mice each, to provide further insight into the potential effects of untreated drinking water. Results: The maximum concentrations of each metal(oid) in µg·L−1 were Sr(819) > Zn(135) > As(75) > Ba(57) > Mo(56) > Cu(17) > Al(14) > Mn(12) > Se(19). Histological studies revealed brain cells with angulation, satellitosis, and reactive gliosis with significant statistical correlation with Mn and As. Furthermore, the liver cells presented hepatocellular degeneration. Despite the early response, there is no occurrence of both statistical and significative changes in hematological parameters. Conclusions: The obtained results provide experimental insights to understand the potential effects of untreated water with low As and Mn contents in murine models. This fact is noteworthy because of the development of histological changes on both the brain and liver at subchronic exposure.
CD73+ CD127high Long-Term Memory CD4 T Cells Are Highly Proliferative in Response to Recall Antigens and Are Early Targets in HIV-1 Infection

HIV-1 infection rapidly leads to a loss of the proliferative response of memory CD4+ T lymphocytes, when cultured with recall antigens. We report here that CD73 expression defines a subset of resting memory CD4+ T cells in peripheral blood, which highly express the α-chain of the IL-7 receptor (CD127), but not CD38 or Ki-67, yet are highly proliferative in response to mitogen and recall antigens, and to IL-7, in vitro. These cells also preferentially express CCR5 and produce IL-2. We reasoned that CD73+ memory CD4+ T cells decrease very early in HIV-1 infection. Indeed, CD73+ memory CD4+ T cells comprised a median of 7.5% (interquartile range: 4.5–10.4%) of CD4+ T cells in peripheral blood from healthy adults, but were decreased in primary HIV-1 infection to a median of 3.7% (IQR: 2.6–6.4%; p = 0.002); and in chronic HIV-1 infection to 1.9% (IQR: 1.1–3%; p < 0.0001), and were not restored by antiretroviral therapy. Moreover, we found that a significant proportion of CD73+ memory CD4+ T cells were skewed to a gut-homing phenotype, expressing integrins α4 and β7, CXCR3, CCR6, CD161 and CD26. Accordingly, 20% of CD4+ T cells present in gut biopsies were CD73+. In HIV+ subjects, purified CD73+ resting memory CD4+ T cells in PBMC were infected with HIV-1 DNA, determined by real-time PCR, to the same level as for purified CD73-negative CD4+ T cells, both in untreated and treated subjects. Therefore, the proliferative CD73+ subset of memory CD4+ T cells is disproportionately reduced in HIV-1 infection, but, unexpectedly, their IL-7 dependent long-term resting phenotype suggests that residual infected cells in this subset may contribute significantly to the very long-lived HIV proviral DNA reservoir in treated subjects.
Healthy cotwins share gut microbiome signatures with their inflammatory bowel disease twins and unrelated patients.

BACKGROUND & AIMS It is currently unclear whether reported changes in the gut microbiome are cause or consequence of inflammatory bowel disease (IBD). Therefore, we studied the gut microbiome of IBD-discordant and -concordant twin pairs, which offers the unique opportunity to assess individuals at increased risk of developing IBD, namely healthy cotwins from IBD-discordant twin pairs. METHODS Fecal samples were obtained from 99 twins (belonging to 51 twin pairs), 495 healthy age-, sex- and BMI-matched controls, and 99 unrelated IBD patients. Whole-genome metagenomic shotgun sequencing was performed. Taxonomic and functional (pathways) composition was compared between healthy-cotwins, IBD-twins, unrelated IBD patients, and healthy controls with multivariable, i.e. adjusted for potential confounding, generalized linear models. RESULTS No significant differences were observed in the relative abundance of species and pathways between healthy cotwins and their IBD-twins (false discovery rate (FDR)<0.10). Compared to healthy controls, 13, 19, and 18 species, and 78, 105, and 153 pathways were found to be differentially abundant in healthy-cotwins, IBD-twins and unrelated IBD patients, respectively (FDR<0.10). Of these, 8/19 (42.1%) and 1/18 (5.6%) species, and 37/105 (35.2%) and 30/153 (19.6%) pathways overlapped between healthy cotwins and IBD-twins, and healthy cotwins and unrelated IBD patients respectively. Many of the shared species and pathways have previously been associated with IBD. The shared pathways include potentially inflammation-related pathways, for example: an increase in propionate degradation and L-arginine degradation pathways. CONCLUSIONS The gut microbiome of healthy cotwins from IBD-discordant twin pairs displays IBD-like signatures. These IBD-like microbiome signatures might precede the onset of IBD. However, longitudinal follow up studies are needed to infer a causal relationship.
Surviving Burn Injury: Drivers of Length of Hospital Stay

With a reduction in the mortality rate of burn patients, length of stay (LOS) has been increasingly adopted as an outcome measure. Some studies have attempted to identify factors that explain a burn patient’s LOS. However, few have investigated the association between LOS and a patient’s mental and socioeconomic status. There is anecdotal evidence for links between these factors; uncovering these will aid in better addressing the specific physical and emotional needs of burn patients and facilitate the planning of scarce hospital resources. Here, we employ machine learning (clustering) and statistical models (regression) to investigate whether segmentation by socioeconomic/mental status can improve the performance and interpretability of an upstream predictive model, relative to a unitary model. Although we found no significant difference in the unitary model’s performance and the segment-specific models, the interpretation of the segment-specific models reveals a reduced impact of burn severity in LOS prediction with increasing adverse socioeconomic and mental status. Furthermore, the socioeconomic segments’ models highlight an increased influence of living circumstances and source of injury on LOS. These findings suggest that in addition to ensuring that patients’ physical needs are met, management of their mental status is crucial for delivering an effective care plan.
Synthesis, characterization, molecular docking and in vitro screening of new metal complexes with coumarin Schiff base as anticholine esterase and antipancreatic cholesterol esterase agents

Abstract In this work, Combining coumarin and thiazole with 3-tertiary butyl salicylaldehyde into in a single molecule, new Schiff base (CTS), and its metal complexes with palladium and platinum were synthesized and characterized by using well-known spectroscopic techniques such as 1H-NMR, 13C-NMR, FT-IR and LC-MS. And also, the formation of these complexes were confirmed by magnetic moment and conductivity measurements. The photophysical properties of CTS were studied and it was observed that the Schiff base has a sensitivity to CN−, F−, and AcO− anions. The quantum chemical calculations based on density functional theory (DFT) were done for explaining some experimental, structural, and spectroscopic data of the dyes. Also, to evaluate the binding interactions between the ligand (CTS) and its metal complexes and enzymes, molecular docking studies were performed and all the compounds tested to determine its inhibition potential against the cholinesterase (AChE and BChE) and pancreatic cholesterol esterase (CEase) enzymes. Both in vitro and in silico the results showed that all of the compounds could act as potent inhibitors of AChE, BChE, and CEase. The Pt (II) complex showed the most potent inhibitory property against all of the enzymes with IC50 values of 12 µM for AChE, 23 µM for BChE, and 21 µM for CEase. Communicated by Ramaswamy H. Sarma
Bioactive Compounds in Wild Nettle (Urtica dioica L.) Leaves and Stalks: Polyphenols and Pigments upon Seasonal and Habitat Variations

This study evaluated the presence of bioactives in wild nettle leaves and stalks during the phenological stage and in the context of natural habitat diversity. Thus, wild nettle samples collected before flowering, during flowering and after flowering from 14 habitats situated in three different regions (continental, mountain and seaside) were analyzed for low molecular weight polyphenols, carotenoids and chlorophylls using UPLC-MS/MS and HPLC analysis, while the ORAC method was performed for the antioxidant capacity measurement. Statistical analysis showed that, when compared to the stalks, nettle leaves contained significantly higher amounts of analyzed compounds which accumulated in the highest yields before flowering (polyphenols) and at the flowering stage (pigments). Moreover, nettle habitat variations greatly influenced the amounts of analyzed bioactives, where samples from the continental area contained higher levels of polyphenols, while seaside region samples were more abundant with pigments. The levels of ORAC followed the same pattern, being higher in leaves samples collected before and during flowering from the continental habitats. Hence, in order to provide the product’s maximum value for consumers’ benefit, a multidisciplinary approach is important for the selection of a plant part as well as its phenological stage with the highest accumulation of bioactive compounds.
Proinflammatory circulating markers: new players for evaluating asymptomatic acute cardiovascular toxicity in breast cancer treatment

Purpose This study aimed to evaluate markers of cardiac damage (total CK, CKMB and CRP), inflammatory markers (free iron, homocysteine and TNF-α) as well as lipidogram in breast cancer patients undergoing acute cycles of doxorubicin (DOX), paclitaxel (PTX) or trastuzumab (TZ) and to verify if there is an association between these markers and the toxicity of the chemotherapeutic treatment. Methods: Included in the study were 120 breast cancer patients and 50 healthy controls. All analyzes were performed on automated systems. For the statistical analysis, each group was compared with the controls according to their normality by Student's t-test and Mann-Whitney test. Results: Our results showed that DOX treatment led to increased hsCRP (4.80 ± 1.23 mg/dL, p = 0.0005), triglycerides (187.6 ± 25.06, p = 0.0231), TNF-α (42.31 ± 17.96 pg/mL, p = 0.01) and Fe levels (138.8 ± 18.6 μg/dL, p = 0.0193). In the meantime, PTX induced changes in CK-MB (8.78 ± 4.2 U/L, p = 0.0361), hsCRP (7.12 ± 1.87 mg/dL, p = 0.0006), cholesterol (201.7 ± 19.54, p = 0.05), triglycerides (201.7 ± 19.54, p = 0.0277), TNF-α (38.27 ± 9.12 pg/mL, p = 0.023), homocysteine (10.95 ± 0, 86 μmol/L, p = 0.005), and free iron (113 ± 18 6 μg/dL, p = 0.045) while TZ augmented CK-MB (6.9 ± 1.97 U/L, p < 0.00), hsPCR (3.12 ± 0.68 mg/dL, p = 0.095), cholesterol (218.3 ± 16.79, p = 0.0317), triglycerides (218.3 ± 16.79, p = 0.0127), TNF-α (89.6 ± 12.11, p = 0.032), homocysteine (9.95 ± 1.15 μmol/L, p = 0.0396), free iron (120.5 ± 4.64 μg/dl, p = 0.0058) as well. Conclusions: Our data demonstrated the existence of a proinflammatory net triggered by breast cancer chemotherapy that could increase cardiomyocytes permeability and allow the leakage of circulating proteins as CK-MB and induce the production of hsCRP.
Inositol phosphates promote HIV-1 assembly and maturation to facilitate viral spread in human CD4+ T cells

Gag polymerization with viral RNA at the plasma membrane initiates HIV-1 assembly. Assembly processes are inefficient in vitro but are stimulated by inositol (1,3,4,5,6) pentakisphosphate (IP5) and inositol hexakisphosphate (IP6) metabolites. Previous studies have shown that depletion of these inositol phosphate species from HEK293T cells reduced HIV-1 particle production but did not alter the infectivity of the resulting progeny virions. Moreover, HIV-1 substitutions bearing Gag/CA mutations ablating IP6 binding are noninfectious with destabilized viral cores. In this study, we analyzed the effects of cellular depletion of IP5 and IP6 on HIV-1 replication in T cells in which we disrupted the genes encoding the kinases required for IP6 generation, IP5 2-kinase (IPPK) and Inositol Polyphosphate Multikinase (IPMK). Knockout (KO) of IPPK from CEM and MT-4 cells depleted cellular IP6 in both T cell lines, and IPMK disruption reduced the levels of both IP5 and IP6. In the KO lines, HIV-1 spread was delayed relative to parental wild-type (WT) cells and was rescued by complementation. Virus release was decreased in all IPPK or IPMK KO lines relative to WT cells. Infected IPMK KO cells exhibited elevated levels of intracellular Gag protein, indicative of impaired particle assembly. IPMK KO compromised virus production to a greater extent than IPPK KO suggesting that IP5 promotes HIV-1 particle assembly in IPPK KO cells. HIV-1 particles released from infected IPPK or IPMK KO cells were less infectious than those from WT cells. These viruses exhibited partially cleaved Gag proteins, decreased virion-associated p24, and higher frequencies of aberrant particles, indicative of a maturation defect. Our data demonstrate that IP6 enhances the quantity and quality of virions produced from T cells, thereby preventing defects in HIV-1 replication.
A Novel In Vitro Culture Model System to Study Merkel Cell Polyomavirus–Associated MCC Using Three-Dimensional Organotypic Raft Equivalents of Human Skin

Merkel cell polyomavirus (MCPyV) is a human polyomavirus causally linked to the development of Merkel cell carcinoma (MCC), an aggressive malignancy that largely arises within the dermis of the skin. In this study, we recapitulate the histopathology of human MCC tumors in vitro using an organotypic (raft) culture system that is traditionally used to recapitulate the dermal and epidermal equivalents of skin in three dimensions (3D). In the optimal culture condition, MCPyV+ MCC cells were embedded in collagen between the epidermal equivalent comprising human keratinocytes and a dermal equivalent containing fibroblasts, resulting in MCC-like lesions arising within the dermal equivalent. The presence and organization of MCC cells within these dermal lesions were characterized through biomarker analyses. Interestingly, co-culture of MCPyV+ MCC together with keratinocytes specifically within the epidermal equivalent of the raft did not reproduce human MCC morphology, nor were any keratinocytes necessary for MCC-like lesions to develop in the dermal equivalent. This 3D tissue culture system provides a novel in vitro platform for studying the role of MCPyV T antigens in MCC oncogenesis, identifying additional factors involved in this process, and for screening potential MCPyV+ MCC therapeutic strategies.
Impella CP Implantation during Cardiopulmonary Resuscitation for Cardiac Arrest: A Multicenter Experience

Background: Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown. Methods: We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival. Results: Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age < 75 years and a time from arrest to CPR ≤ 5 min (p = 0.035 and p = 0.008, respectively). Conclusions: In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.
Framework for the evaluation of new tests for tuberculosis infection

The scale-up of tuberculosis (TB) preventive treatment (TPT) must be accelerated to achieve the targets set by the United Nations High-level Meeting on TB and the End TB Strategy. The scale-up of effective TPT is hampered by concerns about operational challenges to implement the existing tests for TB infection. New simpler tests could facilitate the scale-up of testing for TB infection. We present a framework for evaluation of new immunodiagnostic tests for the detection of TB infection, with an aim to facilitate their standardised evaluation and accelerate adoption into global and national policies and subsequent scale-up. The framework describes the principles to be considered when evaluating new tests for TB infection and provides guidance to manufacturers, researchers, regulators and other users on study designs, populations, reference standards, sample size calculation and data analysis and it is also aligned with the Global Strategy for TB Research and Innovation adopted by the World Health Assembly in 2020. In addition, we briefly describe technical issues that should be considered when evaluating new tests, including the safety for skin tests, costs incurred by patients and the health system, and operational characteristics. The evaluation of new, improved tests for tuberculosis infection should be expedited using standard study protocols to accelerate adoption into policy and subsequent scale-up. A framework for such evaluation is described. https://bit.ly/38ChJbe
The Multifaced Actions of Curcumin in Pregnancy Outcome

Curcumin, also known as diferuloylmethane, is the main polyphenolic substance present in the rhizomes of Curcuma longa L. This plant showed many beneficial effects and has been used since ancient times for both food and pharmaceutical purposes. Due to its pleiotropic functions, curcumin consumption in the human diet has become very common thanks also to the fact that this natural compound is considered quite safe as it does not have serious side effects. Its functions as an anti-inflammatory, anti-oxidant, neuroprotective, immunomodulatory, anti-toxicant, anti-apoptotic, and anti-diabetic compound are already known and widely demonstrated. There are numerous studies concerning its effects on various human pathologies including cancer, diabetes and arthritis while the studies on curcumin during pregnancy have been performed only in animal models. Data concerning the role of curcumin as anti-inflammatory compound suggest a possible use of curcumin in managing pregnancy complications such as Preeclampsia (PE), Gestational Diabetes Mellitus (GDM), Fetal Growth Restriction (FGR), PreTerm Birth (PTB), and exposure to toxic agents and pathogens. The aim of this review is to present data to support the possible use of curcumin in clinical trials on human gestation complications.
Brain blood and cerebrospinal fluid flow dynamics during rhythmic handgrip exercise in young healthy men and women

The cerebral fluid response to exercise, including the arterial and venous cerebral blood flow (CBF) and cerebrospinal fluid (CSF), currently remains unknown. We used time‐resolved phase‐contrast magnetic resonance imaging to assess changes in CBF and CSF flow dynamics during moderate‐intensity rhythmic handgrip (RHG) exercise in young healthy men and women. Our data demonstrated that RHG increases the cerebral arterial inflow and venous outflow while decreasing the pulsatile CSF flow during RHG. Furthermore, changes in blood stroke volume at the measured arteries, veins, and sinuses and CSF stroke volume at the cerebral aqueduct were positively correlated with each other during RHG. Male and female participants exhibited distinct blood pressure responses to RHG, but their cerebral fluid responses were similar. These results collectively suggest that RHG influences both CBF and CSF flow dynamics in a way that is consistent with the Monro–Kellie hypothesis to maintain intracranial volume‐pressure homeostasis in young healthy adults.
Accumulation of metals by naturally growing herbaceous and tree species in iron ore tailings

The aim of the study was to identify pioneering species that naturally colonize Fe tailings and accumulation of heavy metals. Total, bioavailable, acid extractable and water‐soluble fractions were studied. After the second year onwards, along with nine herbaceous pioneering species, four tree species (Teactona grandis, Alstonia scholaris, Azadirachta indica and Peltaphorum) were found growing naturally. The study shows that some species could accumulate relatively high metal concentrations indicating internal detoxification of metals. The study revealed that T. grandis accumulated a higher concentration of metals than A. scholaris in the Fe tailings, but all concentrations were within the normal range. Native naturally colonizing plant species may be used for the bioremediation of iron tailings as initial cover species to stabilize and reduce erosion. The findings concluded that metal content in Fe tailings would not affect the natural establishment and growth of tree species; rather that higher Fe content promotes luxurious growth.
The Grapevine E3 Ubiquitin Ligase VriATL156 Confers Resistance against the Downy Mildew Pathogen Plasmopara viticola

Downy mildew, caused by Plasmopara viticola, is one of the most severe diseases of grapevine (Vitis vinifera L.). Genetic resistance is an effective and sustainable control strategy, but major resistance genes (encoding receptors for specific pathogen effectors) introgressed from wild Vitis species, although effective, may be non-durable because the pathogen can evolve to avoid specific recognition. Previous transcriptomic studies in the resistant species Vitis riparia highlighted the activation of signal transduction components during infection. The transfer of such components to V. vinifera might confer less specific and therefore more durable resistance. Here, we describe the generation of transgenic V. vinifera lines constitutively expressing the V. riparia E3 ubiquitin ligase gene VriATL156. Phenotypic and molecular analysis revealed that the transgenic plants were less susceptible to P. viticola than vector-only controls, confirming the role of this E3 ubiquitin ligase in the innate immune response. Two independent transgenic lines were selected for detailed analysis of the resistance phenotype by RNA-Seq and microscopy, revealing the profound reprogramming of transcription to achieve resistance that operates from the earliest stages of pathogen infection. The introduction of VriATL156 into elite grapevine cultivars could therefore provide an effective and sustainable control measure against downy mildew.