Electrical characterization and modeling of 1T-1R RRAM arrays with amorphous and poly-crystalline HfO2

In this work, a comparison between 1T-1R RRAM arrays, manufactured either with amorphous or poly-crystalline Metal–Insulator–Metal cells, is reported in terms of performance, reliability, Set/Reset operations energy requirements, intra-cell and inter-cell variability during 10k endurance cycles and 100k read disturb cycles. The modeling of the 1T-1R RRAM array cells has been performed with two different approaches: (i) a physical model like the Quantum Point Contact (QPC) model was used to find the relationship between the reliability properties observed during the endurance and the read disturb tests with the conductive filament properties; (ii) a compact model to be exploited in circuit simulations tools which models the I–V characteristics of each memory cells technology

Evolution in the use of natural building stone in Madrid, Spain

Many types of stone have been used for construction in Madrid. In historical times, their use was determined by the proximity of the geological resources, the ease of quarrying and transportation links to the city. More recently, as transport connections and quarrying techniques have improved, quality and durability have become key determinants of building stone selection. Local flint was used intensively from the ninth to the eleventh century, when it was replaced by Redueña dolostone, used in turn until the seventeenth century. Granitic rocks from the Guadarrama Mountain Range that crop out in the northern and western area of the province increasingly began to be used in the city from the sixteenth century. Traditionally known as Berroqueña stone, this building stone was quarried in a number of areas; the primary point of supply was Zarzalejo, and from the eighteenth century the granite used was mainly quarried in the Alpedrete area. Eighteenth century advances in underground quarrying made it possible to extract a limestone (Colmenar stone) located in the southeastern part of the region. Together with Berroqueña stone, this limestone became one of Madrid's traditional building stones, and both, highly esteemed for their excellent petrophysical properties and durability, are still used today

A case report on choledochoduodenal fistula: how to suspect this unusual entity?

A choledochoduodenal fistula is an abnormal connection between the common bile duct and the duodenum, which are associated with a history of problems in the common bile duct. It has appeared in 0.74% of patients submitted for biliary tract surgery. The most frequent symptoms of non-obstructive enteric biliary fistulas are: epigastric pain, cholangitis (80.91%), jaundice (54,.26%), fever (50.69%), nausea and/or vomiting (10.30%), abdominal distension (0.39%), asymptomatic (0.11%), and diarrhea (0.11%). Diagnostic imaging methods provide the data of greatest interest in revealing the presence of air in the bile duct. This method, as well as barium reflux under the biliary tree in contrasted studies and in ERCP, reveal the fistulous tract and its location. Neither the prevalence, nor the clinical characteristics that pertain to its presentation, are well known among our population. Possible treatments for this illness include conservative treatment with medication, endoscopic sphincterotomy, and surgical therapy

A Randomized, Controlled Study on the Safety and Efficacy of Maraviroc and/or Favipiravir vs Currently Used Therapy in Severe COVID-19 Adults. “COMVIVIR” Trial.

Multiple studies have established that hyperinflammatory response induced by SARS CoV-2 is a main cause of complications and death in infected subjects. Such dysfunctional immune response has been described as a dysregulated and exacerbated production of cytokines and chemokines that attracts and activates inflammatory cells, which start and sustain pulmonary and systemic damage, thus causing complications that lead to multi organ failure and death. Therefore, we suggest that blocking key inflammation receptors could help to reduce migration and activation of T cells, monocytes/macrophages and neutrophils, thus mitigating the cytokine dysregulation and averting severe complications and death. Importantly, the optimum treatment for COVID-19 severe patients should combine a modulator of the immune response plus a direct antiviral drug against SARS-CoV-2, in order to address both the hyperinflammatory effects of the immune dysregulation and the viral load. Methods: Maraviroc (MVC), a CCR5 antagonist, and Favipiravir (FPV), an antiviral, will be evaluated single and combined, added to the treatment currently used at the Hospital General de México Dr. Eduardo Liceaga for severe COVID-19 patients. One hundred patients will be allocated in four arms [Current treatment only (CT), CT+MVC, CT+FPV, CT+MVC+FPV]. Percentage of patients free of mechanical ventilation or death at day 28, immunophenotyping and viral load will be compared between groups. Discussion: New immune focused therapies are targeting strong inflammation mediators such as IL-6 and IL1-β; nevertheless, to our best knowledge, only one study explores chemotaxis control. The use of a drug therapy that addresses both the regulation of the immune response and the inhibition of viral replication could at the same time, help to alleviate the hyperinflammatory condition and reduce the time of the viral clearance process, therefore improving treatment outcomes

Fat Distribution and Differential Effects on Metabolic Liver Fat Infiltration in Young Mexicans in Reynosa, Mexico: A Collaborative Study across the U.S.-Mexico Border

Introduction: Metabolic-associated fatty liver disease (MAFLD) is a descriptive term for NAFLD (Non-alcoholic) physiopathology associated with obesity. The age of onset linked to body fat distribution is poorly studied. Therefore, we aimed to assess the body fat effect on liver fat infiltration and stiffness (LSt) mediated by insulin resistance (IR). Methods: After obtaining informed consent, five hundred freshmen from two universities in Reynosa, Mexico (UMAN & UAT) were enrolled in the study. They completed a questionnaire focused on familial cardiometabolic risk and provided anthropometric measurements. In a subset of N=200, we obtained blood samples for biochemical measurements, body fat percentage (BF%) by bioimpedance, LSt (kPa), and fat infiltration (Continued Attenuation Parameter, CAP) by elastography. We used mediation analysis with structural equation models (Stata v16.1) to determine the relationship between BMI, BF%, and abdominal obesity with IR and liver stiffness and fat infiltration. The term “-\u3e” means ‘explain’ or ‘cause’. Results: We found that AO-\u3eIR (standardized values b=0.53, p=0.005), AO-\u3eCAP (b=0.69, pIR (b=0.23, p=0.007). BMI did not have an effect on CAP or IR. Also, BMI-\u3eLS (b=0.47, p=0.05) but AO-\u3eLS was absent. Finally, there was a bidirectional relationship between LS and IR [LS-\u3eIR (b=0.18, p=0.001), and IR-\u3eLS (b=0.27, p=0.001)]. Conclusion: Our findings suggest the adipose tissue measured as AO or BMI showed different phenotypic effects on liver fat infiltration or stiffness. Visceral fat had a direct effect on IR, meanwhile, subcutaneous adipose tissue was associated with liver stiffness. Our findings suggest that early age interventions should be focused on reducing visceral fat deposition

Evaluating the Applicability of Data-Driven Dietary Patterns to Independent Samples with a Focus on Measurement Tools for Pattern Similarity

BACKGROUND: Diet is a key modifiable risk for many chronic diseases, but it remains unclear whether dietary patterns from one study sample are generalizable to other independent populations. OBJECTIVE: The primary objective of this study was to assess whether data-driven dietary patterns from one study sample are applicable to other populations. The secondary objective was to assess the validity of two criteria of pattern similarity. METHODS: Six dietary patterns-Western (n=3), Mediterranean, Prudent, and Healthy- from three published studies on breast cancer were reconstructed in a case-control study of 973 breast cancer patients and 973 controls. Three more internal patterns (Western, Prudent, and Mediterranean) were derived from this case-control study's own data. STATISTICAL ANALYSIS: Applicability was assessed by comparing the six reconstructed patterns with the three internal dietary patterns, using the congruence coefficient (CC) between pattern loadings. In cases where any pair met either of two commonly used criteria for declaring patterns similar (CC ≥0.85 or a statistically significant [P0.9) to their corresponding dietary pattern derived from the case-control study's data. Similar associations with risk for breast cancer were found in all pairs of dietary patterns that had high CC but not in all pairs of dietary patterns with statistically significant correlations. CONCLUSIONS: Similar dietary patterns can be found in independent samples. The P value of a correlation coefficient is less reliable than the CC as a criterion for declaring two dietary patterns similar. This study shows that diet scores based on a particular study are generalizable to other populations.This study was funded by Fundación Científica Asociación Española Contra el Cáncer (Scientific Foundation of the Spanish Association Against Cancer), the Spanish Ministry of Economy and Competitiveness (IJCI-2014-20900); Fundación Cerveza y Salud 2005 (Beer and Health Foundation 2005), Sociedad Española de Oncología Médica (Spanish Society of Medical Oncology), Federación de Mujeres con Cáncer de Mama (Association of Women with Breast Cancer) (EPY 1169-10 grant) and Association of Women with Breast Cancer from Elche (EPY 1394/15 grant)

Mycobacterium manresensis induces trained immunity in vitro

The COVID-19 pandemic posed a global health crisis, with new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants weakening vaccine-driven protection. Trained immunity could help tackle COVID-19 disease. Our objective was to analyze whether heat-killed Mycobacterium manresensis (hkMm), an environmental mycobacterium, induces trained immunity and confers protection against SARS-CoV-2 infection. To this end, THP-1 cells and primary monocytes were trained with hkMm. The increased secretion of tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-1β, and IL-10, metabolic activity, and changes in epigenetic marks suggested hkMm-induced trained immunity in vitro. Healthcare workers at risk of SARS-CoV-2 infection were enrolled into the MANRECOVID19 clinical trial (NCT04452773) and were administered Nyaditum resae (NR, containing hkMm) or placebo. No significant differences in monocyte inflammatory responses or the incidence of SARS-CoV-2 infection were found between the groups, although NR modified the profile of circulating immune cell populations. Our results show that M. manresensis induces trained immunity in vitro but not in vivo when orally administered as NR daily for 14 days.The MANRECOVID19 clinical trial has been sponsored by the Reig Jofre Group. This research was funded by the Consorcio Centro de Investigación Biomédica en Red (CIBERES and CIBEREHD) and the European Union’s Horizon 2020 research and innovation programme under grant agreement No 847762. MDH is supported by a Margarita Salas grant from NextGenerationEU. LS-M is supported by Juan de la Cierva fellowship (FJC2019-041213-I). NI-U is supported by the Spanish Ministry of Science and Innovation (grant PID2020-117145RB-I00), EU HORIZON-HLTH-2021-CORONA-01 (grant 101046118), and institutional funding from Grifols, Pharma Mar, HIPRA, Amassence, and Palobiofarma. The Innate Immunity lab and the UTE are accredited by the Catalan Agency for Management of University and Research Grants (2017-SGR-490/2021-SGR-01186, 2021-SGR-00931, and 2017-SGR-500/2021 SGR 00920). IGTP is a member of the CERCA network of institutes supported by the Health Department of the Government of Catalonia.info:eu-repo/semantics/publishedVersio

Understanding 34 Years of Forest Cover Dynamics across the Paraguayan Chaco: Characterizing Annual Changes and Forest Fragmentation Levels between 1987 and 2020

Over the past 40 years, Paraguay has lost the majority of its natural forest cover, thus becoming one of the countries with the highest deforestation rates in the world. The rapid expansion of the agricultural frontier, cattle ranching, and illegal logging between 1987 and 2012 resulted in the loss of 27% of original forest cover, equivalent to almost 44,000 km2. Within this context, the present research provides the first yearly analysis of forest cover change in the Paraguayan Chaco between the years 1987 and 2020. Remote sensing data obtained from Landsat images were applied to derive annual forest cover masks and deforestation rates over 34 years. Part of this study is a comprehensive assessment of the effectiveness of protected areas, as well as an analysis of the degree of fragmentation of the forest. All classification results obtained accuracies above 80% and revealed a total forest cover loss of approximately 64,700 km2. Forest clearing within protected areas was not frequent; however, some natural reserves presented losses of up to 25% of their forest cover. Through the consideration of several landscape metrics, this study reveals an onward fragmentation of forest cover, which endangers the natural habitat of numerous species

High p16 expression and heterozygous RB1 loss are biomarkers for CDK4/6 inhibitor resistance in ER+ breast cancer

Breast cancer; Cancer models; Predictive markersCáncer de mama; Modelos de cáncer; Marcadores predictivosCàncer de pulmó; Models de càncer; Marcadors predictiusCDK4/6 inhibitors combined with endocrine therapy have demonstrated higher antitumor activity than endocrine therapy alone for the treatment of advanced estrogen receptor-positive breast cancer. Some of these tumors are de novo resistant to CDK4/6 inhibitors and others develop acquired resistance. Here, we show that p16 overexpression is associated with reduced antitumor activity of CDK4/6 inhibitors in patient-derived xenografts (n = 37) and estrogen receptor-positive breast cancer cell lines, as well as reduced response of early and advanced breast cancer patients to CDK4/6 inhibitors (n = 89). We also identified heterozygous RB1 loss as biomarker of acquired resistance and poor clinical outcome. Combination of the CDK4/6 inhibitor ribociclib with the PI3K inhibitor alpelisib showed antitumor activity in estrogen receptor-positive non-basal-like breast cancer patient-derived xenografts, independently of PIK3CA, ESR1 or RB1 mutation, also in drug de-escalation experiments or omitting endocrine therapy. Our results offer insights into predicting primary/acquired resistance to CDK4/6 inhibitors and post-progression therapeutic strategies

Randomized Clinical Trials of obesity treatments in Mexican population. Systematic Review and Meta-Analysis

Background: Mexicans and Mexican Americans share similar culture, genetic background, and predisposition for obesity and diabetes. Randomized clinical trials (RCT) assessing obesity treatments (ObT) are reliable to assess efficacy. To date, there is no systematic review to investigate ObT tested by RCT in Mexican adults. Methods: We conducted systematic searches in Pubmed, Scopus, and Web of Science to retrieve ObT RCT from 1990 to 2019. The ObT included alternative medicine, pharmacological, nutritional, behavioral, and surgical interventions. The analyzed RCT were at least three months of duration, and reported: BMI, weight, waist circumference, triglycerides, glucose and blood pressure. Results: We found 634 entries; after removal of duplicates and exclusions based on eligibility criteria, we analyzed 43 and 2 multinational-collaborative studies. Most of the national studies had small sample sizes, and did not have replications from other studies. The nutrition/behavioral interventions were difficult to blind, and most studies had medium to high risk of bias. Random effects meta-analysis of nutritional/behavioral interventions and medications showed effects on BMI, waist circumference, and blood pressure. Simple measures like plain water instead of sweet beverages decreased triglycerides and systolic blood pressure. Participants with obesity and hypertension had beneficial effects with antioxidants, and the treatment with insulin increased weight in those with T2D. Conclusions: The RCT’s in Mexico reported effects on metabolic components despite small sample sizes and lack of replication. In the future we should analyze ObT in population living on the U.S.-Mexico border; therefore, bi-national collaboration is desirable to disentangle cultural effects on ObT response