Miracle-dz/UniFAR-FTUs huggingface dataset:
Contribution of hypoxia inducible factor-1 during viral infections

ABSTRACT Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that plays critical roles during the cellular response to hypoxia. Under normoxic conditions, its function is tightly regulated by the degradation of its alpha subunit (HIF-1α), which impairs the formation of an active heterodimer in the nucleus that otherwise regulates the expression of numerous genes. Importantly, HIF-1 participates in both cancer and infectious diseases unveiling new therapeutic targets for those ailments. Here, we discuss aspects related to the activation of HIF-1, the effects of this transcription factor over immune system components, as well as the involvement of HIF-1 activity in response to viral infections in humans. Although HIF-1 is currently being assessed in numerous clinical settings as a potential therapy for different diseases, up to date, there are no clinical studies evaluating the pharmacological modulation of this transcription factor as a possible new antiviral treatment. However, based on the available evidence, clinical trials targeting this molecule are likely to occur soon. In this review we discuss the role of HIF-1 in viral immunity, the modulation of HIF-1 by different types of viruses, as well as the effects of HIF-1 over their life cycle and the potential use of HIF-1 as a new target for the treatment of viral infections.
Evolution of crystallographic texture and mechanical properties of single- and polycrystalline Mg (99.85 wt.%) subjected to high-pressure torsion (HPT) deformation

Die plastische Verformung mittels Hochdrucktorsion („High Pressure Torsion – HPT“) ist eine Methode, mit der man nanostrukturierte Materialien mit ausergewohnlichen physikalischen Eigenschaften in massiver Form herstellen kann. Die Methode steht derzeit im Zentrum der internationalen wenden. Nur wenig ist von den Merkmalen der HPT Verformung hexagonaler Metalle und Legierungen bekannt, auf die die vorliegende Dissertation abzielt, indem sie die Entwicklung der kristallografischen Textur wahrend und nach der HPT Verformung von ein- und vielkristallinem Mg mit Reinheit 99.85 Gew. % untersuchte und mit Messungen der mechanischen Eigenschaften korrelierte. Die Analysen zeigten zunachst, dass sowohl beim einkristallinen wie auch beim polykristallinem Material die Strukturparameter der Ausgangsmaterialien, wie z.B. die Orientierung und die Grose der Kristallite, auf die Charakteristik der Endtextur bzw. Mikrostruktur auch von hochsten HPT Verformungsgraden keinen Einfluss haben. Diese sind einerseits gekennzeichnet von Komponenten der Scherung, die von der HPT Verformung stammen, andererseits aber auch von Komponenten, die vom hydrostatischen Druck bzw. der der Entlastung folgenden Lagerung bei Raumtemperatur abhangen. Diese Abhangigkeiten konnen durch spezifische Beitrage der dynamischen (“DRX”, wahrend der HPT Verformung) und der statischen (“SRX”, nach HPT Verformung) Erholung bzw. Rekristallisation erklart werden. Um zwischen diesen Beitragen zu unterscheiden, wurden spezielle Experimente durchgefuhrt, bei denen die Proben unmittelbar nach HPT Verformung bzw. vor den Untersuchungen in Flussig-Stickstoff “eingefroren” wurden (Proben Typ „F“); diese wurden mit Proben verglichen (Proben Typ “RX”), die nach der HPT Verformung bei Raumtemperatur gelagert und erst dann untersucht wurden. Auser den speziellen Merkmalen der Textur zeigten die “RX” Proben eine hohere Festigkeit, wahrend dagegen die “F” Proben eine hohere Plastizitat aufwiesen. Intensive Untersuchungen mit verschiedenen Methoden der Elektronenmikroskopie zeigten eine bimodale Mikrostruktur, bestehend sowohl aus kleinen, verformungsinduzierten Kristalliten (Korngrosse unter 0.3μm), als auch aus rekristallisierten, wesentlich groseren Kristalliten (Korngrose uber 5 μm). Analog zu den Texturuntersuchungen nahm der Anteil an erholten bzw. rekristallisierten Kristalliten mit zunehmendem hydrostatischem Druck bzw. zunehmender Auslagerungszeit bei Raumtemperatur zu.
Whole genome resequencing reveals genomic regions associated with thermal adaptation in redband trout

Adaptation to local environments involves evolution of ecologically important traits and underlying physiological processes. Here, we used low coverage whole‐genome resequencing (lcWGR) on individuals to identify genome regions involved in thermal adaptation in wild redband trout Oncorhynchus mykiss gairdneri, a subspecies of rainbow trout that inhabits ecosystems ranging from cold montane forests to high elevation deserts. This study includes allele frequency‐based analyses for selective sweeps among populations, followed by multiple association tests for specific sets of phenotypes measured under thermal stress (acute and chronic survival/mortality; high or low cardiac performance groups). Depending on the groups in each set of analyses, sequencing reads covered 43%–75% of the genome at ≥15× and each analysis included millions of SNPs across the genome. In tests for selective sweeps among populations, a total of six chromosomal regions were significant. The further association tests for specific phenotypes revealed that the region on chromosome 4 was consistently the most significant and contains the cerk gene (ceramide kinase). This study provides insight into a potential genetic mechanism of local thermal adaptation and suggests cerk may be an important candidate gene. However, further validation of this cerk gene is necessary to determine if the association with cardiac performance results in a functional role to influence thermal performance when exposed to high water temperatures and hypoxic conditions.
Proteomic profiling of bladder cancer for precision medicine in the clinical setting: A review for the busy urologist

At present, proteomic methods have successfully identified potential biomarkers of urological malignancies, such as prostate cancer (PC), bladder cancer (BC), and renal cell carcinoma (RCC), reflecting different numbers of key cellular processes, including extracellular environment modification, invasion and metastasis, chemotaxis, differentiation, metabolite transport, and apoptosis. The potential application of proteomics in the detection of clinical markers of urological malignancies can help improve patient assessment through early cancer detection, prognosis, and treatment response prediction. A variety of proteomic studies have already been carried out to find prognostic BC biomarkers, and a large number of potential biomarkers have been reported. It is worth noting that proteomics research has not been applied to the study of predictive markers; this may be due to the incompatibility between the number of measured variables and the available sample size, which has become particularly evident in the study of therapeutic response. On the contrary, prognostic correlation is more common, which is also reflected in existing research. We are now entering an era of clinical proteomics. Driven by proteomic-based workflows, computing tools, and the applicability of cross-correlation of proteomic data, it is now feasible to use proteomic analysis to support personalized medicine. In this paper, we will summarize the current emerging technologies for advanced discovery, targeted proteomics, and proteomic applications in BC, particularly in discovery of human-based biomarkers.
Comparing Pain Neuroscience Education Followed by Motor Control Exercises With Group‐Based Exercises for Chronic Low Back Pain: A Randomized Controlled Trial

Different individualized interventions have been used to improve chronic low back pain (CLBP). However, their superiority over group‐based interventions has yet to be elucidated. We compared an individualized treatment involving pain neuroscience education (PNE) plus motor control exercise (MCE) with group‐based exercise (GE) in patients with CLBP.
Does Etanercept Biosimilar Prescription in a Rheumatology Center Bend the Medication Cost Curve?

Objective The market entry of biosimilars is expected to bring budgetary relief. Our objective was to determine how the introduction of biosimilars influences medication costs in patients with rheumatoid arthritis (RA) and which patients gain access to biologics due to the availability of biosimilars. Methods Using hospital data of patients with RA between 2014 and 2018, an interrupted time series was performed. The interruption in the time series was placed at June 2016 (i.e., the introduction of the etanercept biosimilar). The changes in trends for rheumatic medication costs before and after the interruption were measured. Secondary analyses focused on explaining these trends. Results In the first quarter after the interruption, there was a decrease in total costs for biologic users of –€63,020 (95% CI –€96,487 to –€29,553, P = 0.001). The postinterruption trend did not differ from the preinterruption trend (95% CI –€6695 to €6715, P = 0.998) and after 3 quarters, the medication costs were back at the interruption level. After the interruption, the average cost per biologic user decreased by –€370 (95% CI –€602 to –€138, P = 0.005), followed by a quarterly decrease (relative to the preinterruption trend; 95% CI –€86 to –€14, P = 0.010), bending the average cost curve. The percentage of patients being treated with biologics increased in postinterruption by 0.50 percentage points quarterly (95% CI 0.38–0.62, P < 0.001). Also, the average age at the start of the first biologic increased after the interruption (P = 0.057). Conclusion The average cost per patient treated with biologics decreased after the introduction of biosimilars with a persistent trend. However, the budgetary relief due to market entry of biosimilars vanished quickly due to an increase in patients treated with biologics.
Comparing cytomegalovirus diagnostics by cell culture and quantitative nucleic acid testing in broncho‐alveolar lavage fluids

Many clinical laboratories have replaced virus isolation in cell‐culture (VIC) for cytomegalovirus (CMV) by quantitative‐nucleic‐acid testing (QNAT), rendering clinically relevant CMV‐replication difficult to distinguish from CMV‐shedding or latent infection. We compared direct VIC in 1109 consecutive bronchoalveolar lavage fluids (BALFs) and a well‐validated CMV‐QNAT (Basel‐CMV‐UL111a‐77bp). In the retrospective Group 1 (N = 694) and Group 2 (N = 303), CMV‐QNAT was performed within 48 h from 2‐fold and 10‐fold concentrated total nucleic acid (TNA) eluates, respectively. In Group 3 (N = 112), 2‐fold and 10‐fold concentrated TNA eluates were prospectively analyzed in parallel to VIC. CMV was detected by VIC in 79 of 694 (11%) and 26 of 303 (9%) of Groups 1 and 2, but in 114 of 694 (16%) and 57 of 303 (17%) by CMV‐QNAT, respectively. Median CMV loads were significantly higher in VIC‐positive than in VIC‐negative BALF. The likelihood for CMV detection by VIC was 85% for BALF CMV‐ loads >4 log10 copies/ml. In the prospective Group 3, CMV was detected by VIC in 10 of 112 (9%), and in 14 of 112 (13%) and 20 of 112 (18%) by CMV‐QNAT, when using 2‐fold and 10‐fold concentrated TNA eluates, respectively. Notably, CMV was undetectable by CMV‐QNAT in 10 VIC‐positive cases of Groups 1 and 2, but in none of Group 3. We conclude that CMV‐QNAT can be adopted to BALF diagnostics but requires several careful steps in validation. CMV‐QNAT loads >10 000 copies/ml in BALF may indicate significant CMV replication as defined by VIC, if short shipment and processing procedures can be guaranteed. Discordance of detecting CMV in time‐matched plasma samples emphasises the role of local pulmonary CMV replication, for which histopathology remains the gold standard of proven CMV pneumonia.
Optimisation conjointe de l'adhérence des couches d'oxydes et des cinétiques d'oxydation thermique sur aciers inoxydables

L'utilisation d'aciers inoxydables a 18%Cr dans la partie chaude des lignes d'echappement automobile necessite que ces materiaux aient une cinetique d'oxydation cyclique lente et que la couche d'oxyde qui se forme a leur surface soit adherente. Dans l'optique d'optimiser la composition des nuances actuelles, cette etude s'est interessee a l'influence des elements stabilisants (Ti, Nb) sur le comportement de nuances ferritiques et austenitiques. L'analyse des cinetiques d'oxydation isothermes et cycliques a permis de mettre en evidence l'effet accelerateur de Ti sur les cinetiques paraboliques des nuances ferritiques. Par ailleurs, une forte sensibilite vis-a-vis de l'oxydation catastrophique a ete observee sur les nuances austenitiques et notamment sur celles ne contenant pas de niobium. Les differences de diffusivite du chrome dans le metal semblent pouvoir justifier la difference entre les nuances ferritiques et austenitiques d'une part, et celle entre les nuances austenitiques avec et sans niobium d'autre part. La quantification de l'adherence des couches d'oxyde a ete entreprise via des essais de gonflement-decollement inverse, de flexion trois points, et de traction sous MEB, ce dernier ayant ete adapte au systeme metal/oxyde dans le cadre de cette these. L'ensemble de ces essais a notamment pu mettre en evidence l'effet benefique de Ti sur l'adherence et la difficulte de comparer des valeurs d'energies obtenues par des essais differents.
Differential sensitivities of triple‐negative breast cancer stem cell towards various doses of vitamin C: An insight into the internal antioxidant systems

Cancer stem cells (CSCs) are quiescent and self‐renewing, having low levels of reactive oxygen species (ROS), and are responsible for cancer recurrence after chemotherapy and radiotherapy. However, the interplay between the ROS production and scavenging from the oxidative stress has never been studied in breast CSCs. In this present study, we have investigated the cellular energetics of two triple‐negative breast cancer stem cells (MDA‐MB‐231 and MDA‐MB‐468) treated with two pharmacological doses of vitamin C (10 and 20 mM) that generated ROS. Our results indicate a differential behavior of ROS scavenging by both the CSCs. MDA‐MB‐468 CSCs exhibited higher resistance to ROS induced damage owing to the higher antioxidant activity, lower mitochondrial damage, and less decrease in membrane potential (ΔΨm) as compared with MDA‐MB‐231 CSCs. Moreover, MDA‐MB‐231 CSCs exhibited an intrinsic apoptosis pathway by activating the cytochrome c, caspase‐9, 3, 7, and cleaved PARP upon treatment with vitamin C. This data suggests a possible strategy for targeting breast CSCs using vitamin C. Taken together, the CSCs from MDA‐MB‐231 could be easily targeted by high/pharmacological doses of vitamin C (≥20 mM) thereby indicating a less robust internal antioxidant machinery.
Rendimiento y calidad de semilla de ‘mijo Perla’ con uso de micorrizas Glomus intraradices y fertilizantes químicos

El objetivo de esta investigación fue determinar el efecto de las micorrizas, fertilización química y su combinación en área foliar, composición morfológica, producción y calidad de semilla de mijo perla (Pennisetum glaucum Br.). La evaluación se realizó en primavera-verano 2013 en el Campo Experimental San Luis del INIFAP, se utilizaron micorrizas INIFAP y Azo-Fer, así como 120-60-00 y combinación de micorrizas con 60-30-00 y un testigo (sin ningún fertilizante). Las variables evaluadas fueron altura de planta, índice de área foliar, composición morfológica, producción de semilla, peso de mil semillas, peso hectolítrico, pureza, contenido de humedad, número de semillas por kg y eficiencia en el uso de agua. Se usó un diseño experimental completamente al azar (Tukey, 0.05). No se observaron diferencias (p> 0.05) en índice de altura de planta, área foliar, pureza, humedad, peso hectolítrico y peso de mil semillas. La producción de semilla fue similar (p> 0.05, kg ha-1) con uso de biofertilizantes y fertilizantes (micorriza INIFAP=2 221; micorriza INIFAP + 60-30-00= 1 811, micorriza Azo-Fer = 1 783; micorriza Azo-Fer + 60-30-00 = 1 754) y nutrición mineral (2 685); sin embargo, diferentes al testigo (p≤ 0.05; 1 631). En composición morfológica tanto en antesis como estado lechoso-masoso, no hubo diferencia en biomasa de tallos entre las fuentes de nutrición (p≤ 0.05) y fueron diferentes al testigo.
Acid adaptation of Escherichia coli O157:H7 in fermented goat milk

This study was undertaken to determine the effect of acid adaptation on the survival and growth of Escherichia coli in broth and fermented goat milk. In the first phase of the study, acid resistance of E. coli O157:H7 strain UT 10 and E. coli ATCC 25922 was determined in brain heart infusion broth at pH 7.4, 4.5 and 2.5. Variations due to acid stress in the counts of both strains were determined. Alterations in the fatty acid profile due to acid adaptation were also determined. Acid adaptation enhanced the survival of both strains at pH 4.5, but neither strain could survive after 4 h at pH 2.5. At optimum growth conditions (pH 7.4), E. coli ATCC 25922 exhibited increased viability over E. coli UT 10. At pH 4.5, E. coli UT 10 was more tolerant to low pH than E. coli ATCC 25922. An increase in saturated fatty acids (SAFAs) of both AA strains was observed, indicating the importance of lipid modification in enhancing survival at low pH. In the second phase of the study, acid resistance of E. coli O157:H7 strains UT 10 and UT 15 were determined in commercial fermented at 30 °C for 24 h and stored at 7 °C for 2 days and traditional Amasi fermented for 3 days at ambient temperature (ca 30 °C). E. coli O157:H7 counts in traditional Amasi could not be detected after 3 days of challenge while those in commercial Amasi were detected at 2.7 log10 cfu/ml after the same period. The survival of acid adapted (AA) and non-adapted (NA) strains was similar in traditional Amasi while in commercial Amasi, the NA strain survived significantly better than the AA strain. The results of this study indicate that E. coli O157:H7 can survive during fermentation and storage of fermented goat milk Amasi. They also show that survival of the pathogen in a broth model differs from that in a food system. Survival of E. coli O157:H7 in fermented milk is affected by fermentation time, pH and storage temperature. The food industry should therefore adapt their processing/ preservation procedures by taking the most acid tolerant pathogenic E. coli strains into consideration in order to ensure the safety of their products.
Identification of risk factors of 30-day readmission and 180-day in-hospital mortality, and its corresponding relative importance in patients with Ischemic heart disease: a machine learning approach

ABSTRACT Background: The primary objective of this study is to identify non-laboratory predictors for 30-day hospital readmission and 180-day in-hospital mortality rates among patients hospitalized with ischemic heart disease (IHD). Research design and methods: This is a retrospective cohort study of hospitalized patients (≥ 40 years) with a primary diagnosis of IHD. Data were extracted from the Florida Agency for Health Care Administration dataset from 2006 to 2016. A machine learning approach was used to identify predictors of 30-day hospital readmission and 180-day in-hospital mortality. Results: 346,390 patient records for incident IHD cases were identified. The top two predictors of 30-day readmission were the length of stay and the Elixhauser comorbidity index for readmission [ECI] (Area Under the Curve [AUC]=88%) using decision tree algorithms. For in-hospital mortality, the top two predictors were LOS and ECI (AUC=92%) using gradient boosting regressors. The cumulative 30-day readmission and the 180-day probability of mortality rates were 9.82% and 4.6% respectively. Conclusions: Risk factors of 30-day readmission and 180-day mortality in hospitalized IHD patients identified by machine learning and their relative importance (value) will help pharmacists and other health care providers to prioritize their disease management strategies as they improve the care provided to IHD patients.
Bone Anchored Hearing Aids for the Treatment of Asymmetric Hearing Loss.

OBJECTIVES Asymmetric hearing loss is generally defined as a moderate-to-profound hearing loss in the poorer ear and a mild-to-moderate hearing loss in the better ear. Application of a bone conduction hearing aid is one of the possible treatments for the poorer ear in asymmetric hearing loss. However, the device essentially stimulates the contralateral better ear, precluding true binaural hearing. The aim of this paper is to evaluate the application and utility of bone-anchored hearing aids in the treatment of asymmetric hearing loss. MATERIALS AND METHODS We retrospectively evaluated 215 implanted subjects in our clinic and extracted a series of 27 patients affected by asymmetric hearing loss and treated with bone-anchored hearing aids. All 27 subjects had a mixed hearing loss after middle ear surgery. The preoperative and postoperative audiological data of these patients were collected and analyzed. RESULTS The audiological tests showed an improvement in the performance of hearing perception of sound and speech in quiet and noise. Moreover, the subjects have positively answered the questionnaires administered to evaluate subjective benefits. All subscales of the abbreviated profile of hearing aid benefit and speech, spatial, and qualities of hearing scale showed a significant improvement with the device. CONCLUSION Bone-anchored hearing aids are a suitable treatment for asymmetric hearing loss. When other devices cannot be utilized or are not indicated, the bone conduction devices may allow good audiological results.
Assessment of Heterogeneity in Heart Failure–Related Meta-Analyses

Supplemental Digital Content is available in the text. Background: Assessment of heterogeneity in meta-analyses is critical to ensure the consistency of pooled results. Therefore, we sought to assess the evaluation and reporting of heterogeneity in heart failure (HF) meta-analyses. Methods: Study level meta-analyses pertaining to HF were selected from January 2009 to July 2019, published in 11 high impact factor journals. We tabulated the overall proportion of the meta-analyses reporting statistical heterogeneity and specific metrics and methods employed to quantify and explore heterogeneity. Results: Of 126 HF meta-analyses (612 outcomes), heterogeneity was reported for 422 outcomes (68.9 %) in 108 meta-analyses. Out of the 422 outcomes reporting statistical heterogeneity, 137 outcomes (32.5%) had no observable heterogeneity: (I2=0%), 40 outcomes (9.5%) had low heterogeneity (I2<25%), 76 outcomes (18%) had moderate heterogeneity (I2=25%–50%), and 169 outcomes (40%) had high heterogeneity (I2>50%). Reporting of statistical heterogeneity was not significantly associated with year of publication, funding source, disclosure information, or the type of studies pooled. Sensitivity analysis (n=68) was the most common statistical technique employed to evaluate the source of heterogeneity followed by subgroup analyses (n=59) and meta-regression (n=40). Conclusions: Despite being an essential component of meta-analyses, heterogeneity was not reported for nearly 30% of outcomes and variably handled in contemporary HF meta-analyses. As meta-analyses increase across HF science, interpreting and handling of heterogeneity should be standardized.