Miracle-dz/UniFAR-FTUs huggingface dataset:
Observational Study on Variation of Longitudinal Platelet Counts in Calves over the First 14 Days of Life and Reference Intervals from Cross-Sectional Platelet and Leukocyte Counts in Dairy Calves up to Two Months of Age

Simple Summary To define a healthy animal in an experimental setting or to differentiate and backup a diagnosis in cattle practice, reference intervals (RIs) in haematology diagnostics are necessary. The RIs in calves for blood cell counts, such as platelets and white blood cells, differ from RIs in adult cattle and are not widely studied. Blood results from dairy calves in the Netherlands were used to study the variation in platelet counts in young calves and to calculate an RI for platelet and white blood cell counts. In new-born calves up to six days of age, platelet counts were lower than in calves older than five days. From six days of age until 60 days of age we propose an RI platelet count of 287–1372 × 109/L and for the first 60 days of life an RI for leukocyte count of 4.0–18.9 × 109/L. Abstract Platelet and leukocyte count reference intervals (RIs) for cattle differ by age and while adult RIs are known, RIs for calves are studied less. The aims of this observational study are to evaluate variation of platelet counts of Holstein Friesian calves over the first 14 days of life and to propose RIs for platelet and leukocyte counts of Holstein Friesian calves aged 0–60 days. In a longitudinal study, 19 calves were blood sampled 17 times, in the first 14 days of their lives. Blood was collected in a citrate blood tube and platelet counts were determined. We assessed the course of platelet counts. In a field study, 457 healthy calves were blood sampled once. Blood was collected in an EDTA blood tube and platelet and leukocyte counts were determined. The RIs were calculated by the 2.5 and 97.5 percentiles. Platelet counts started to increase 24 h after birth (mean platelet count 381 × 109/L ± 138 × 109/L) and stabilized after five days (mean platelet count 642 × 109/L ± 265 × 109/L). In calves up to six days of age, platelet counts were lower than in calves older than five days. In conclusion, the RIs of platelet and leukocyte counts in calves were wider in range than the RIs for adult cattle, therefore, calf specific RIs for platelet and leukocyte counts should be used. From 6 until 60 days of age, we propose an RI for platelet counts of 287–1372 × 109/L and for the first 60 days of life an RI for leukocyte counts of 4.0–18.9 × 109/L.
In Vitro and In Vivo Efficacy of a Novel Glucose–Methotrexate Conjugate in Targeted Cancer Treatment

Methotrexate (MTX) is a commonly used antimetabolite, which inhibits folate and DNA synthesis to be effective in the treatment of various malignancies. However, MTX therapy is hindered by the lack of target tumor selectivity. We have designed, synthesized and evaluated a novel glucose–methotrexate conjugate (GLU–MTX) both in vitro and in vivo, in which a cleavable linkage allows intracellular MTX release after selective uptake through glucose transporter−1 (GLUT1). GLU–MTX inhibited the growth of colorectal (DLD-1), breast (MCF-7) and lung (A427) adenocarcinomas, squamous cell carcinoma (SCC-25), osteosarcoma (MG63) cell lines, but not in WI-38 healthy fibroblasts. In tumor cells, GLU–MTX uptake increased 17-fold compared to unconjugated MTX. 4,6-O-ethylidene-α-D-glucose (EDG), a GLUT1 inhibitor, significantly interfered with GLU–MTX induced growth inhibition, suggesting a glucose-mediated drug uptake. Glu-MTX also caused significant tumor growth delay in vivo in breast cancer-bearing mice. These results show that our GLUT-MTX conjugate can be selectively uptake by a range of tumor cells to cause their significant growth inhibition in vitro, which was also confirmed in a breast cancer model in vivo. GLUT1 inhibitor EDG interfered with these effects verifying the selective drug uptake. Accordingly, GLU–MTX offers a considerable tumor selectivity and may offer cancer growth inhibition at reduced toxicity.
Extraneous E-Cadherin Engages the Deterministic Process of Somatic Reprogramming through Modulating STAT3 and Erk1/2 Activity

Although several modes of reprogramming have been reported in different cell types during iPSC induction, the molecular mechanism regarding the selection of different modes of action is still mostly unknown. The present study examined the molecular events that participate in the selection of such processes at the onset of somatic reprogramming. The activity of STAT3 versus that of Erk1/2 reversibly determines the reprogramming mode entered; a lower activity ratio favors the deterministic process and vice versa. Additionally, extraneous E-cadherin facilitates the early events of somatic reprogramming, potentially by stabilizing the LIF/gp130 and EGFR/ErbB2 complexes to promote entry into the deterministic process. Our current findings demonstrated that manipulating the pSTAT3/pErk1/2 activity ratio in the surrounding milieu can drive different modes of action toward either the deterministic or the stochastic process in the context of OSKM-mediated somatic reprogramming.
From Green Technology to Functional Olive Oils: Assessing the Best Combination of Olive Tree-Related Extracts with Complementary Bioactivities

Our aim was to assess the combination of olive tree-related extracts with the most favorable profile of in vitro bioactive properties. We tested the antioxidant (increment of low-density lipoprotein resistance against oxidation), vasoactive (promotion of nitric oxide release and decrease of endothelin-1 production in human umbilical vein endothelial cells), anti-inflammatory (decrease of the endothelial production of vascular cell adhesion molecule-1), and antithrombotic (reduction of the endothelial release of plasminogen activator inhibitor-1) capacities of six phenolic extracts and three triterpenic acid solutions (Ps and Ts, respectively). We tested extracts alone and in combination, at nutritional (Ps: 0.05–0.5 μmol/L; Ts: 0.001–0.1 μmol/L) and nutraceutical doses (Ps: 1–10 μmol/L; Ts: 0.25–10 μmol/L). The combination of Ps rich in 3,4-dihydroxyphenylglycol (76%, P2), hydroxytyrosol (95%, P3), and oleuropein (70%, P4) (final nutritional concentration: 0.15 μmol/L; final nutraceutical concentration: 3 μmol/L) was the best in order to prepare functional products and nutraceuticals with cardioprotective properties, despite the fact that the isolated extract with the greatest in vitro properties was P5 (75% oleocanthal), suggesting a potential synergistic effect among different olive components.
Rosa canina L. Can Restore Endoplasmic Reticulum Alterations, Protein Trafficking and Membrane Integrity in a Dextran Sulfate Sodium-Induced Inflammatory Bowel Disease Phenotype

Rosa canina L. is a natural polyphenol-rich medicinal plant that exhibits antioxidant and anti-inflammatory activities. Recent in vivo studies have demonstrated that a methanol extract of Rosa canina L. (RCME) has reversed an inflammatory bowel disease (IBD)-like phenotype that has been triggered by dextran sulfate sodium (DSS) in mice. In the current study, we investigated the effects of RCME on perturbations of cellular mechanisms induced by DSS-treatment of intestinal Caco-2 cells, including stress response in the endoplasmic reticulum (ER), protein trafficking and sorting as well as lipid rafts integrity and functional capacities of an intestinal enzyme. 6 days post-confluent cells were treated for 24 h with DSS (3%) or simultaneously with DSS (3%) and RCME (100 µg/mL) or exclusively with RCME (100 µg/mL) or not treated. The results obtained demonstrate the ability of RCME to counteract the substantial increase in the expression levels of several ER stress markers in DSS-treated cells. Concomitantly, the delayed trafficking of intestinal membrane glycoproteins sucrase-isomaltase (SI) and dipeptidyl peptidase 4 (DPP4) induced by DSS between the ER and the Golgi has been compromised by RCME. Furthermore, RCME restored the partially impaired polarized sorting of SI and DPP4 to the brush border membrane. An efficient sorting mechanism of SI and DPP4 is tightly associated with intact lipid rafts structures in the trans-Golgi network (TGN), which have been distorted by DSS and normalized by RCME. Finally, the enzymatic activities of SI are enhanced in the presence of RCME. Altogether, DSS treatment has triggered ER stress, impaired trafficking and function of membrane glycoproteins and distorted lipid rafts, all of which can be compromised by RCME. These findings indicate that the antioxidants in RCME act at two major sites in Caco-2 cells, the ER and the TGN and are thus capable of maintaining the membrane integrity by correcting the sorting of membrane-associated proteins.
The mediation role of SOCS3 methylation in the effect of serum testosterone on type 2 diabetes

Previous studies reported that testosterone and DNA methylation of suppressor of cytokine signaling‐3 (SOCS3) were associated with type 2 diabetes (T2D). Testosterone affects SOCS3 gene expression. Therefore, we aimed to investigate how the SOCS3 methylation mediates the relationship between testosterone and T2D among Chinese rural adults.
Water intake and progression of chronic kidney disease: the CKD-REIN cohort study.

BACKGROUND Optimal daily water intake to prevent chronic kidney disease (CKD) progression is unknown. Taking kidney urine-concentrating ability into account, we studied the relation of kidney outcomes in patients with CKD to total and plain water intake and urine volume. METHODS Including 1265 CKD patients (median age, 69 years; mean estimated glomerular filtration rate [eGFR], 32 ml/min per 1.73 m2) from the CKD-REIN cohort (2013-2019), we assessed fluid intake at baseline interviews, collected 24-h urine volumes, and estimated urine osmolarity (eUosm). Using Cox and then linear mixed models, we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney failure and eGFR decline associated with hydration markers, adjusting for CKD progression risk factors and eUosm. RESULTS Patients' median daily intake was 2.0 (interquartile range: 1.6-2.6) L total water and 1.5 (1-1.7) L plain water; median urine volume was 1.9 (1.6-2.4) L/24 h, and mean eUosm, 374 ± 104 mosm/L. Neither total water intake nor urine volume was associated with either kidney outcome. Kidney failure risk increased significantly with decreasing eUosm below 292 mosm/L. Adjusted HRs for kidney failure associated with plain water intake were 1.88 (95%CI 1.02; 3.47), 1.59 (1.06; 2.38), 1.76 (0.95; 3.24), and 1.55 (1.03; 2.32) in patients drinking <0.5, 0.6-1.0, 1.6-2.0, and >2.0 L/day, compared with those drinking 1.0-1.5 L/day. High plain water intake was also significantly associated with faster eGFR decline. CONCLUSION In patients with CKD, the relation between plain water intake and progression to kidney failure appears to be U-shaped. Both low and high intake may not be beneficial in CKD.
Identification of Novel phoP-phoQ Regulated Genes that Contribute to Polymyxin B Tolerance in Pseudomonas aeruginosa

Polymyxin B and E (colistin) are the last resorts to treat multidrug-resistant Gram-negative pathogens. Pseudomonas aeruginosa is intrinsically resistant to a variety of antibiotics. The PhoP-PhoQ two-component regulatory system contributes to the resistance to polymyxins by regulating an arnBCADTEF-pmrE operon that encodes lipopolysaccharide modification enzymes. To identify additional PhoP-regulated genes that contribute to the tolerance to polymyxin B, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) assay and found novel PhoP binding sites on the chromosome. We further verified that PhoP directly controls the expression of PA14_46900, PA14_50740 and PA14_52340, and the operons of PA14_11970-PA14_11960 and PA14_52350-PA14_52370. Our results demonstrated that mutation of PA14_46900 increased the bacterial binding and susceptibility to polymyxin B. Meanwhile, mutation of PA14_11960 (papP), PA14_11970 (mpl), PA14_50740 (slyB), PA14_52350 (ppgS), and PA14_52370 (ppgH) reduced the bacterial survival rates and increased ethidium bromide influx under polymyxin B or Sodium dodecyl sulfate (SDS) treatment, indicating roles of these genes in maintaining membrane integrity in response to the stresses. By 1-N-phenylnaphthylamine (NPN) and propidium iodide (PI) staining assay, we found that papP and slyB are involved in maintaining outer membrane integrity, and mpl and ppgS-ppgH are involved in maintaining inner membrane integrity. Overall, our results reveal novel PhoP-PhoQ regulated genes that contribute to polymyxin B tolerance.
Tauvid™: The First FDA-Approved PET Tracer for Imaging Tau Pathology in Alzheimer’s Disease

Tauvid has been approved by the U.S. Food and Drug Administration (FDA) in 2020 for positron emission tomography (PET) imaging of adult patients with cognitive impairments undergoing evaluation for Alzheimer’s disease (AD) based on tau pathology. Abnormal aggregation of tau proteins is one of the main pathologies present in AD and is receiving increasing attention as a diagnostic and therapeutic target. In this review, we summarised the production and quality control of Tauvid, its clinical application, pharmacology and pharmacokinetics, as well as its limitation due to off-target binding. Moreover, a brief overview on the second-generation of Tau PET tracers is provided. The approval of Tauvid marks a step forward in the field of AD research and opens up opportunities for second-generation tau tracers to advance tau PET imaging in the clinic.
Exogenous nitric oxide stimulates early egress of Eimeria tenella sporozoites from primary chicken kidney cells in vitro

Egress plays a vital role in the life cycle of apicomplexan parasites including Eimeria tenella, which has been attracting attention from various research groups. Many recent studies have focused on early egress induced by immune molecules to develop a new method of apicomplexan parasite elimination. In this study, we investigated whether nitric oxide (NO), an immune molecule produced by different types of cells in response to cytokine stimulation, could induce early egress of eimerian sporozoites in vitro. Eimeria tenella sporozoites were extracted and cultured in primary chicken kidney cells. The number of sporozoites egressed from infected cells was analyzed by flow cytometry after treatment with NO released by sodium nitroferricyanide (II) dihydrate. The results showed that exogenous NO stimulated the rapid egress of E. tenella sporozoites from primary chicken kidney cells before replication of the parasite. We also found that egress was dependent on intra-parasitic calcium ion (Ca2+) levels and no damage occurred to host cells after egress. The virulence of egressed sporozoites was significantly lower than that of fresh sporozoites. The results of this study contribute to a novel field examining the interactions between apicomplexan parasites and their host cells, as well as that of the clearance of intracellular pathogens by the host immune system.
Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease—Current Knowledge, Mechanisms and Perspectives

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut–liver–brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.
Quality of Life and Its Correlates in People Serving Prison Sentences in Penitentiary Institutions

Background: The aim of the study was to analyze the determinants of prison inmates’ quality of life (QoL). Methods: 390 men imprisoned in penitentiary institutions were assessed. Data were collected by means of the Sense of Quality of Life Questionnaire (SQLQ), general self-efficacy scale (GSES), resilience assessment scale (RAS-25), social support scale (SSS), intensity of religious attitude scale (IRA), SPI/TPI, and COPE Inventory, measures that have high validity and reliability. All models were specified in a path analysis using Mplus version 8.2. Results: The positive correlates of QoL are: self-efficacy, social support, intensity of religious attitude, trait and state depression, resilience, and the following coping strategies, which are at the same time mediators between the variables mentioned above and QoL: behavioral disengagement, turning to religion, planning, and seeking social support for instrumental reasons. Conclusions: In penitentiary practice, attention should be devoted to depressive individuals, and support should be provided to them in the first place because depressiveness is the strongest negative correlate of important aspects of prisoners’ QoL. All the remaining significant factors, namely: self-efficacy, social support, intensity of religious attitude, and the following coping strategies: turning to religion, planning, and seeking social support for instrumental reasons, should be taken into account in rehabilitation programs.
Are Smoke and Aerosols Generated During Laparoscopic Surgery a Biohazard? A Systematic Evidence-Based Review

Background. Laparoscopic surgery generates end products that can have potentially harmful effects for the surgical team from short- or long-time exposure. In view of the current SARS-CoV-2 circumstances, controversy has risen concerning the safety of surgical smoke (SS) and aerosols and the perception of an increased risk of exposure during laparoscopic surgery. Methods. The present qualitative systematic review was conducted according to Meta-Analyses and Systematic Reviews of Observational Studies (MOOSE). A literature search was performed from March 2020 up to May 10, 2020, using the PubMed database, Cochrane, and Google Scholar to assess the risk of airborne transmission of viruses and the potential health risk of surgical smoke- and aerosol-generating procedures produced during laparoscopic surgery. The keywords were introduced in combination to obtain better search results. Application of the inclusion and exclusion criteria identified 44 relevant articles. Results. Genetic material from certain viruses, or the virus itself, has been detected in SS and aerosols. However, in the current SARS-CoV-2, as in other coronavirus situations, studies analyzing the presence of airborne transmission of viruses in surgical smoke are lacking. Conclusion. Despite the lack of clear evidence regarding the risk of diseases as the result of smoke- and aerosol-generating procedures during laparoscopic surgery, further investigation is needed. Meanwhile, all available precautions must be taken.
Influences of Recreational Tennis-Playing Exercise Time on Cardiometabolic Health Parameters in Healthy Elderly: The ExAMIN AGE Study

Background: Aging and chronic degeneration are the primary threats to cardiometabolic health in elderly populations. Regular appropriate exercise would benefit the advanced aging population. Purpose: This study investigates whether the degree of weekly tennis participation exhibits differences in primary cardiometabolic parameters, including arterial stiffness, inflammation, and metabolic biomarkers in elderly tennis players. Methods: One hundred thirty-five long-term participants in elder tennis (>50 years old) were initially screened. Twenty-six eligible and voluntary subjects were divided into high tennis time group (HT) (14 ± 1.3 h/week) and low tennis time group (LT) (4.5 ± 0.7 h/week) by stratification analysis based on the amount of tennis playing activity time. The brachial-ankle pulse wave velocity (baPWV), blood pressure, ankle-brachial index (ABI), blood metabolic biomarkers, and insulin resistance were measured to compare the difference between HT and LT groups. Results: The baPWV was significantly lower in the HT group than that in the LT group (1283.92 ± 37.01 vs. 1403.69 ± 53.71 cm/s, p < 0.05). We also found that the HT insulin-resistant homeostasis model assessment (HOMA-IR) was significantly lower than that of LT (1.41 ± 0.11 vs. 2.27 ± 0.48 μIU/mL, p < 0.05). However, the blood lipid biomarkers (glucose, cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglyceride) were not statistical different between HT and LT groups (p > 0.05). Conclusion: We demonstrated that under the condition of similar daily physical activity level, elderly with a higher time of tennis-playing (HT group) exhibited relatively lower arterial stiffness (lower PWV) and lower insulin resistance compared to those with lower time tennis-playing (LT).
Impact of the COVID-19 Pandemic on Oncologists: Results of an International Study

PURPOSE As frontline workers facing the COVID-19 pandemic, healthcare providers should be well-prepared to fight the disease and prevent harm to their patients and themselves. Our study aimed to evaluate the knowledge, attitude, and practice of oncologists in response to the COVID-19 pandemic and its impact on them. METHODS A cross-sectional study was conducted using a validated questionnaire disseminated to oncologists by SurveyMonkey. The tool had 42 questions that captured participants’ knowledge, attitude, and practice; their experiences; and the pandemic’s impact on various aspects of their lives. Participants from Middle East and North African countries, Brazil, and the Philippines completed the electronic survey between April 24 and May 15, 2020. RESULTS Of the 1,010 physicians who participated in the study, 54.75% were male and 64.95% were medical or clinical oncologists. The level of knowledge regarding the prevention and transmission of the virus was good in 52% of participants. The majority (92%) were worried about contracting the virus either extremely (30%) or mildly (62%), and 84.85% were worried about transmitting the virus to their families. Approximately 76.93% reported they would take the COVID 19 vaccine once available, with oncologists practicing in Brazil having the highest odds ratio of intention to receive the COVID-19 vaccine (odds ratio, 11.8, 95% CI, 5.96 to 23.38, P < .001). Participants reported a negative impact of the pandemic on relations with coworkers (15.84%), relations with family (27.84%), their emotional and mental well-being (48.51%), research productivity (34.26%), and financial income (52.28%). CONCLUSION The COVID-19 pandemic has adverse effects on various personal and professional aspects of oncologists’ lives. Interventions should be implemented to mitigate the negative impact and prepare oncologists to manage future crises with more efficiency and resilience.