Miracle-dz/UniFAR-FTUs huggingface dataset:
Natural Fibre-Reinforced Biofoams

Starches and polylactic acids (PLAs) represent the main biobased and biodegradable polymers with potential industrial availability in the next decades for “bio” foams applications. This paper investigates the improvement of their morphology and properties through processing and materials parameters. Starch foams were obtained by melt extrusion in which water is used as blowing agent. The incorporation of natural fibres (hemp, cellulose, cotton linter, sugarcane, coconut) in the starch foam induced a density reduction up to 33%, a decrease in water absorption, and an increase in mechanical properties according to the fibre content and nature. PLA foams were obtained through single-screw extrusion using of a chemical blowing agent that decomposed at the PLA melting temperature. A void content of 48% for PLA and 25% for cellulose fibre-reinforced PLA foams and an improvement in mechanical properties were achieved. The influence of a fibre surface treatment was investigated for both foams.
Changes in the Physiological Processes During Training and Official Competitions in Young Karate Athletes / Promjene u fiziološkim procesima za vrijeme treninga i zvaničnih takmičenja kod mladih karatista

It was conducted functional and anthropological tests on a sample of ten male karate athletes aged between 15-18 years, with long training experience, and who are candidates for the National Team of the Republic of Macedonia. The research was conducted so that the dynamics and changes in the heart rate and blood lactate levels of the karate athletes can be determined during training and during official competition. The differences in the values of blood lactates and the heart rate which emerged during training and official competition are determined by using the T-test. The resulting values for the blood lactate level show a statistically significant difference during training and official competition in all measurements at the level p <0.00. The same conclusion applies to the heart rate values, where we can also register a statistically significant difference in the values gathered during training and during official competition (p <0.00) as well as after warm up and after the measurements in all three fights.
Toxicity of Zinc Phosphide-Based Rodenticide Formulated and Sold in Nigeria

The toxicity of zinc phosphide-based rodenticide formulated and sold in Nigeria was investigated. Preliminary toxicity study was conducted using 24 rats and based results a dosage of zinc phosphide-based rodenticides 1 g to 200 g feed was adopted for this study. A further batch of 30 albino rats was procured for the main study. The rats were observed for period of 3 and 6 hours. At the end of the time interval, the animals were euthanized under chloroform anesthesia, blood samples were collected into sterile ethylene diaminetetraacetic acid and heparin sample bottles. Kidney and liver organs were collected and stored in 40% formaldehyde. Biochemical parameters, ALT, AST, Creatinine, urea, uric acid and potassium concentrations were enhanced 3 and 6 hours after administration of the rodenticide to the albino rats. There were also elevations for total WBC and PLT values. The enhancement of most of the biochemical and hematological parameters investigated suggest the possible failures of several organs of the rats studied. Histological slides indicated breakdown of cellular matrix compared to the slide obtained for the control. Also, there was congestion of liver sinusoids. The sinusoidal congestion found after 6 hours of ZP administration in this study may be the reason for the markedly elevated ALT and AST levels.
Spectroscopically Identified Intermediate Age Stars at 0.5 - 3 pc Distance from Sgr A*

Nuclear star clusters (NSCs) at the dynamical center of galaxies appear to have a complex star formation history. This suggests repeated star formation even in the influence of the strong tidal field from supermassive black holes. In our previous study, we have detected 31 so far unknown early-type star candidates throughout the Galactic NSC (at 0.5 - 3 pc from Sgr A*; Nishiyama and Schoedel 2013). The aim of this study is a confirmation of the spectral type for the candidates. We have carried out NIR spectroscopic observations of the candidates using Subaru/IRCS/AO188/LGS. K-band spectra for 20 out of the 31 candidates were obtained. By determining an equivalent width, EW(CO), of the 12CO absorption feature at 2.294 um, we have derived an effective temperature and a bolometric magnitude for each candidate, and then constructed an HR diagram. No young (~ Myr), massive stars are included in the 20 candidates we observed; however, 13 candidates are most likely intermediate-age giants (50 - 500 Myr). Two other sources have ages of ~1 Gyr, and the remaining five sources are old (> 1 Gyr), late-type giants. Although none of the early-type star candidates from our previous narrow-band imaging observations can be confirmed as a young star, we find that the photometric technique is sensitive to distinguish old, late-type giants from young and intermediate-age populations. The intermediate-age stars could be so far unknown members of a population formed in a starburst ~100 Myr ago. Finding no young (~ a few Myr) stars at R = 0.5 - 3 pc favors the in-situ formation scenario for the presence of the young stars at R < 0.5 pc. Furthermore, the different spatial distributions of the young and the intermediate-age stars imply that the Galactic NSC is an aggregate of stars born in different places and under different physical conditions.
Welfare and pregnancy rate of ewes undergoing transcervical artificial insemination with ketamine subarachnoid anesthesia

This study aimed to evaluate the impact of subarachnoid anesthesia with ketamine during transcervical artificial insemination (TCAI) on the welfare of ewes and on subsequent pregnancy rates. Ninety Suffolk adult ewes were randomized into three treatment groups: control group (CG), which underwent the TCAI procedure as established by cervical traction (CG; n = 30) and two groups that received subarachnoid anesthesia with ketamine at a dose of either 0.75mg/kg (KE0.75; n = 30) or 1.5 mg/kg (KE1.5; n = 30) 5 min before the cervical traction procedure. Intrauterine insemination was performed using frozen semen from three males previously analyzed and approved for fertility. The use of subarachnoid anesthesia decreased ewes’ vocalizations (P = 0.0001) and abdominal contraction (P= 0.0150) during cervical manipulations. The CG had more groans and vocalizations at the moment of cervix clamping and applicator passage through the cervix (P = 0.001). The cervix traction was facilitated by anesthesia. For the control group, most of the cervical traction was done just up to the middle of the vagina (P = 0.0021). Pregnancy rates increased significantly with anesthesia (P = 0.04) as shown by the rates of 40.0%, 56.7%, and 66.7% for CG, KE1.5, and KE0.75, respectively. The CG showed behaviors associated with absolute immobility, which is suggestive of distress. In brief, the use of ketamine in subarachnoid anesthesia for transcervical artificial insemination in ewes facilitated cervical traction, increased the pregnancy rate, and improved animal welfare.
Potential off-target effects of beta-blockers on gut hormone receptors: In silico study including GUT-DOCK—A web service for small-molecule docking

The prolonged use of many currently available drugs results in the severe side effect of the disruption of glucose metabolism leading to type 2 diabetes mellitus (T2DM. Gut hormone receptors including glucagon receptor (GCGR) and the incretin hormone receptors: glucagon-like peptide 1 receptor (GLP1R) and gastric inhibitory polypeptide receptor (GIPR) are important drug targets for the treatment of T2DM, as they play roles in the regulation of glucose and insulin levels and of food intake. In this study, we hypothesized that we could compensate for the negative influences of specific drugs on glucose metabolism by the positive incretin effect enhanced by the off-target interactions with incretin GPCR receptors. As a test case, we chose to examine beta-blockers because beta-adrenergic receptors and incretin receptors are expressed in a similar location, making off-target interactions possible. The binding affinity of drugs for incretin receptors was approximated by using two docking scoring functions of Autodock VINA (GUT-DOCK) and Glide (Schrodinger) and juxtaposing these values with the medical information on drug-induced T2DM. We observed that beta-blockers with the highest theoretical binding affinities for gut hormone receptors were reported as the least harmful to glucose homeostasis in clinical trials. Notably, a recently discovered beta-blocker compound 15 ([4-((2S)-3-(((S)-3-(3-bromophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-2-(2-cyclohexyl-2-phenylacetamido)-3-oxopropyl)benzamide was among the top-scoring drugs, potentially supporting its use in the treatment of hypertension in diabetic patients. Our recently developed web service GUT-DOCK (gut-dock.miningmembrane.com) allows for the execution of similar studies for any drug-like molecule. Specifically, users can compute the binding affinities for various class B GPCRs, gut hormone receptors, VIPR1 and PAC1R.
Cells exhibiting strong p16INK4a promoter activation in vivo display features of senescence

Significance The accumulation of senescent cells over a lifetime causes age-related pathologies; however, the inability to reliably identify senescent cells in vivo has hindered clinical efforts to employ this knowledge as a means to ameliorate or reverse aging. Here, we describe a reporter allele, p16tdTom, enabling the in vivo identification and isolation of cells featuring high-level activation of the p16INK4a promoter. Our findings provide an insight into the functional and molecular characteristics of p16INK4a-activated cells in vitro and in vivo. We show that such cells accumulate with aging or other models of injury, and that they exhibit clinically targetable features of cellular senescence. The activation of cellular senescence throughout the lifespan promotes tumor suppression, whereas the persistence of senescent cells contributes to aspects of aging. This theory has been limited, however, by an inability to identify and isolate individual senescent cells within an intact organism. Toward that end, we generated a murine reporter strain by “knocking-in” a fluorochrome, tandem-dimer Tomato (tdTom), into exon 1α of the p16INK4a locus. We used this allele (p16tdTom) for the enumeration, isolation, and characterization of individual p16INK4a-expressing cells (tdTom+). The half-life of the knocked-in transcript was shorter than that of the endogenous p16INK4a mRNA, and therefore reporter expression better correlated with p16INK4a promoter activation than p16INK4a transcript abundance. The frequency of tdTom+ cells increased with serial passage in cultured murine embryo fibroblasts from p16tdTom/+ mice. In adult mice, tdTom+ cells could be readily detected at low frequency in many tissues, and the frequency of these cells increased with aging. Using an in vivo model of peritoneal inflammation, we compared the phenotype of cells with or without activation of p16INK4a and found that tdTom+ macrophages exhibited some features of senescence, including reduced proliferation, senescence-associated β-galactosidase (SA-β-gal) activation, and increased mRNA expression of a subset of transcripts encoding factors involved in SA-secretory phenotype (SASP). These results indicate that cells harboring activation of the p16INK4a promoter accumulate with aging and inflammation in vivo, and display characteristics of senescence.
Incidence and treatment of mediastinal leakage after esophagectomy: Insights from the multicenter study on mediastinal leaks

BACKGROUND Mediastinal leakage (ML) is one of the most feared complications of esophagectomy. A standard strategy for its diagnosis and treatment has been difficult to establish because of the great variability in their incidence and mortality rates reported in the existing series. AIM To assess the incidence, predictive factors, treatment, and associated mortality rate of mediastinal leakage using the standardized definition of mediastinal leaks recently proposed by the Esophagectomy Complications Consensus Group (ECCG). METHODS Seven Italian surgical centers (five high-volume, two low-volume) affiliated with the Italian Society for the Study of Esophageal Diseases designed and implemented a retrospective study including all esophagectomies (n = 501) with intrathoracic esophagogastric anastomosis performed from 2014 to 2017. Anastomotic MLs were defined according to the classification recently proposed by the ECCG. RESULTS Fifty-nine cases of ML were recorded, yielding an overall incidence of 11.8% (95%CI: 9.1%-14.9%). The surgical approach significantly influenced the occurrence of ML: the proportion of leakage was 10.5% and 9% after open and hybrid esophagectomy (HE), respectively, and doubled (20%) after totally minimally invasive esophagectomy (TMIE) (P = 0.016). No other predictive factors were found. The 30- and 90-d overall mortality rates were 1.4% and 3.2%, respectively; the 30- and 90-d leak-related mortality rates were 5.1% and 10.2%, respectively; the 90-d mortality rates for TMIE and HE were 5.9% and 1.8%, respectively. Endoscopy was the first-line treatment in 49% of ML cases, with the need for retreatment in 17.2% of cases. Surgery was needed in 44.1% of ML cases. Endoscopic treatment had the lowest mortality rate (6.9%). Removal of the gastric tube with stoma formation was necessary in 8 (13.6%) cases. CONCLUSION The incidence of ML after esophagectomy was high mainly in the TMIE group. However, the general and specific (leak-related) mortality rates were low. Early treatment (surgical or endoscopic) of severe leaks is mandatory to limit related mortality.
Elastography-based screening for esophageal varices in patients with advanced chronic liver disease

Elastography-based liver stiffness measurement (LSM) is a non-invasive tool for estimating liver fibrosis but also provides an estimate for the severity of portal hypertension in patients with advanced chronic liver disease (ACLD). The presence of varices and especially of varices needing treatment (VNT) indicates distinct prognostic stages in patients with compensated ACLD (cACLD). The Baveno VI guidelines suggested a simple algorithm based on LSM < 20 kPa (by transient elastography, TE) and platelet count > 150 G/L for ruling-out VNT in patients with cACLD. These (and other) TE-based LSM cut-offs have been evaluated for VNT screening in different liver disease etiologies. Novel point shear-wave elastography (pSWE) and two-dimensional shear wave elastography (2D-SWE) methodologies for LSM have also been evaluated for their ability to screen for “any” varices and for VNT. Finally, the measurement of spleen stiffness (SSM) by elastography (mainly by pSWE and 2D-SWE) may represent another valuable screening tool for varices. Here, we summarize the current literature on elastography-based prediction of “any” varices and VNT. Finally, we have summarized the published LSM and SSM cut-offs in clinically useful scale cards.
Repetitive switching between DNA-binding modes enables target finding by the glucocorticoid receptor

ABSTRACT Transcription factor mobility is a determining factor in the regulation of gene expression. Here, we have studied the intranuclear dynamics of the glucocorticoid receptor (GR) by using fluorescence recovery after photobleaching and single-molecule microscopy. First, we have described the dynamic states in which the GR occurs. Second, we have analyzed the transitions between these states by using a continuous-time Markov chain model and functionally investigated these states by making specific mutations in the DNA-binding domain. This analysis revealed that the GR diffuses freely through the nucleus and, once it leaves this free diffusion state, most often enters a repetitive switching mode. In this mode it alternates between slow diffusion as a result of brief nonspecific DNA-binding events, and a state of stable binding to specific DNA target sites. This repetitive switching mechanism results in a compact search strategy that facilitates finding of DNA target sites by the GR. This article has an associated First Person interview with the first author of the paper. Summary: Analysis of the intranuclear mobility pattern of the glucocorticoid receptor by using FRAP and single-molecule microscopy (SMM) shows that the receptor is in a ‘repetitive switching’ mode most of the time.
Circulating androgens and postmenopausal ovarian cancer risk in the Women's Health Initiative Observational Study

Our knowledge of epidemiologic risk factors for ovarian cancer supports a role for androgens in the pathogenesis of this disease; however, few studies have examined associations between circulating androgens and ovarian cancer risk. Using highly sensitive LC–MS/MS assays, we evaluated associations between pre‐diagnostic serum levels of 12 androgens, including novel androgen metabolites that reflect androgen activity in tissues, and ovarian cancer risk among postmenopausal women in a nested case–control study in the Women's Health Initiative (WHI) Observational Study (OS). We frequency‐matched 169 ovarian cancer cases to 410 controls from women enrolled in WHI‐OS who were not using menopausal hormones at enrollment/blood draw. We estimated associations overall and by subtype (n = 102 serous/67 non‐serous) using multivariable adjusted logistic regression. Androgen/androgen metabolite levels were not associated with overall ovarian cancer risk. In analyses by subtype, women with increased levels of androsterone‐glucuronide (ADT‐G) and total 5‐α reduced glucuronide metabolites (markers of tissue‐level androgenic activity) were at increased risk of developing non‐serous ovarian cancer: ADT‐G tertile (T)3 versus T1 odds ratio [OR] (95% confidence interval [CI]) 4.36 (1.68–11.32), p‐heterogeneity 0.002; total glucuronide metabolites 3.63 (1.47–8.95), 0.002. Risk of developing serous tumors was unrelated to these markers. ADT‐G and total glucuronide metabolites, better markers of tissue‐level androgenic activity in women than testosterone, were associated with an increased risk of developing non‐serous ovarian cancer. Our work demonstrates that sex steroid metabolism is important in the etiology of non‐serous ovarian cancers and supports a heterogeneous hormonal etiology across histologic subtypes of ovarian cancer.
Intraperitoneal α-Emitting Radioimmunotherapy with 211At in Relapsed Ovarian Cancer: Long-Term Follow-up with Individual Absorbed Dose Estimations

Eliminating microscopic residual disease with α-particle radiation is theoretically appealing. After extensive preclinical work with α-particle–emitting 211At, we performed a phase I trial with intraperitoneal α-particle therapy in epithelial ovarian cancer using 211At conjugated to MX35, the antigen-binding fragments—F(ab′)2—of a mouse monoclonal antibody. We now present clinical outcome data and toxicity in a long-term follow-up with individual absorbed dose estimations. Methods: Twelve patients with relapsed epithelial ovarian cancer, achieving a second complete or nearly complete response with chemotherapy, received intraperitoneal treatment with escalating (20–215 MBq/L) activity concentrations of 211At-MX35 F(ab′)2. Results: The activity concentration was escalated to 215 MBq/L without any dose-limiting toxicities. Most toxicities were low-grade and likely related to the treatment procedure, not clearly linked to the α-particle irradiation, with no observed hematologic toxicity. One grade 3 fatigue and 1 grade 4 intestinal perforation during catheter implantation were observed. Four patients had a survival of more than 6 y, one of whom did not relapse. At progression, chemotherapy was given without signs of reduced tolerability. Overall median survival was 35 mo, with a 1-, 2-, 5-, and 10-y survival of 100%, 83%, 50%, and 25%, respectively. Calculations of the absorbed doses showed that a lower specific activity is associated with a lower single-cell dose, whereas a high specific activity may result in a lower central dose in microtumors. Individual differences in absorbed dose to possible microtumors were due to variations in administered activity and the specific activity. Conclusion: No apparent signs of radiation-induced toxicity or decreased tolerance to relapse therapy were observed. The dosimetric calculations show that further optimization is advisable to increase the efficacy and reduce possible long-term toxicity.
Patients’ experiences on accessing health care services for management of hypertension in rural Bangladesh, Pakistan and Sri Lanka: A qualitative study

Hypertension is the leading risk factor for cardiovascular disease and leading cause of premature death globally. In 2008, approximately 40% of adults were diagnosed with hypertension, with more than 1.5 billion people estimated to be affected globally by 2025. Hypertension disproportionally affects low- and middle-income countries, where the prevalence is higher and where the health systems are more fragile. This qualitative study explored patients’ experiences on the management and control of hypertension in rural Bangladesh, Sri Lanka and Pakistan. We conducted sixty semi-structured interviews, with 20 participants in each country. Hypertensive individuals were recruited based on age, gender and hypertensive status. Overall, patients’ reported symptoms across the three countries were quite similar, although perceptions of hypertension were mixed. The majority of patients reported low knowledge on how to prevent or treat hypertension. The main barriers to accessing health services, as reported by participants, were inadequate services and poor quality of existing facilities, shortage of medicine supplies, busyness of doctors due to high patient load, long travel distance to facilities, and long waiting times once facilities were reached. Patients also mentioned that cost was a barrier to accessing services and adhering to medication. Many patients, when asked for areas of improvement, reported on the importance of the provider-patient relationship and mentioned valuing doctors who spent time with them, provided advice, and could be trusted. However, most patients reported that, especially at primary health care level and in government hospitals, the experience with their doctor did not meet their expectations. Patients in the three countries reported desire for good quality local medical services, the need for access to doctors, medicine and diagnostics and decreased cost for medication and medical services. Patients also described welcoming health care outreach activities near their homes. Areas of improvement could focus on reorienting community health workers’ activities; involving family members in comprehensive counseling for medication adherence; providing appropriate training for health care staff to deliver effective information and services for controlling hypertension to patients; enhancing primary health care and specialist services; improving supplies of hypertensive medication in public facilities; taking into account patients’ cultural and social background when providing services; and facilitating access and treatment to those who are most vulnerable.