Miracle-dz/UniFAR-FTUs huggingface dataset:
Advancing human in vitro pulmonary disease models in preclinical research: opportunities for lung-on-chips

The past years havewitnessed concerted efforts across the respiratory community to establishmore relevant in vitro preclinical tools for pulmonary research [1–3]. A strong incentive for such endeavors stems from the need to deliver novel therapies for respiratory diseases, a point sharply underlined at the 2014 European Respiratory Society Presidential Summit [4]. Very few new classes of safe and effective drugs have been introduced over the past half century. In contrast to other disease areas (e.g. cardiovascular, neurological), pulmonary medicine has witnessed substantially fewer drugs approved, a situation coinciding with comparatively less drug candidates and a higher failure rate. Such facts are concurrent with the observation that pulmonary diseases represent a vast and growing health-care financial burden worldwide, associated with high morbidity and mortality [5]. Yet, there has been little impact in therapies treating, for example, chronic obstructive pulmonary disease (COPD), the fourth leading cause of death globally [4]. In parallel, asthma continues to be among the most prevalent worldwide diseases, underscoring the need for effective treatments in pediatric [6] and severe asthmatic populations [7]. Meanwhile, infectious diseases such as tuberculosis (TB) represent an increasing risk due to lack of effective therapies resulting from low efficacy and high toxicity in the face of multidrug-resistant TB [8,9]. The same is true for pulmonary infections by biofilm-forming bacteria (as a consequence of cystic fibrosis) when the increasing occurrence of antimicrobial resistance will require novel anti-infective therapies, complementary to established antibiotics [10]. With a dire need to advance available pulmonary therapies, this short editorial underlines bioengineering opportunities for leveraging microfluidic-based lung-on-chips in devising novel human-relevant in vitro models of respiratory disorders and ultimately help accelerate pulmonary preclinical research.
Soil fungi enable the control of gastrointestinal nematodes in wild bovidae captive in a zoological park: a 4-year trial

Abstract The control of gastrointestinal nematodes among ruminants maintained in zoological parks remains difficult due to infective stages develop in the soil. For the purpose to improve the possibilities of the control of gastrointestinal nematodes (genera Trichostrongylus, Nematodirus, Chabertia and Haemonchus) affecting wild captive bovidae ruminants belonging to the subfamilies Antilopinae, Caprinae, Bovinae and Reduncinae, commercial pelleted feed enriched with a blend of 104–105 spores of both filamentous fungi Mucor circinelloides + Duddingtonia flagrans per kg meal was provided for a period of 3.5 years. All animals were dewormed at the beginning of the trial and also when exceeding a cut-off point of 300 eggs per gram of feces (EPG). The anthelmintic efficacy ranged between 96 and 100%. The need for repeating the administration of parasiticide treatment disappeared at the 24th month of study in the Antilopinae individuals, and at the 8th month in the Caprinae, Bovinae and Reduncinae. No side-effects were observed on the skin or in the digestive, respiratory or reproductive system. It was concluded that this strategy provides a sustainable tool for preventing the contamination of paddocks where captive ruminants are maintained, decreasing the risk of infection by gastrointestinal nematodes and consequently the need of frequent deworming.
Too hot to handle: Unprecedented seagrass death driven by marine heatwave in a World Heritage Area

The increased occurrence of extreme climate events, such as marine heatwaves (MHWs), has resulted in substantial ecological impacts worldwide. To date, metrics of thermal stress within marine systems have focussed on coral communities, and less is known about measuring stress relevant to other primary producers, such as seagrasses. An extreme MHW occurred across the Western Australian coastline in the austral summer of 2010–2011, exposing marine communities to summer seawater temperatures 2–5°C warmer than average. Using a combination of satellite imagery and in situ assessments, we provide detailed maps of seagrass coverage across the entire Shark Bay World Heritage Area (ca. 13,000 km2) before (2002 and 2010) and after the MHW (2014 and 2016). Our temporal analysis of these maps documents the single largest loss in dense seagrass extent globally (1,310 km2) following an acute disturbance. Total change in seagrass extent was spatially heterogeneous, with the most extensive declines occurring in the Western Gulf, Wooramel Bank and Faure Sill. Spatial variation in seagrass loss was best explained by a model that included an interaction between two heat stress metrics, the most substantial loss occurring when degree heating weeks (DHWm) was ≥10 and the number of days exposed to extreme sea surface temperature during the MHW (DaysOver) was ≥94. Ground truthing at 622 points indicated that change in seagrass cover was predominantly due to loss of Amphibolis antarctica rather than Posidonia australis, the other prominent seagrass at Shark Bay. As seawater temperatures continue to rise and the incidence of MHWs increase globally, this work will provide a basis for identifying areas of meadow degradation, or stability and recovery, and potential areas of resilience.
Reverse-engineering forces responsible for dynamic clustering and spreading of multiple nuclei in developing muscle cells

How cells position their organelles is a fundamental biological question. During Drosophila embryonic muscle development, multiple nuclei transition from being clustered together to splitting into two smaller clusters to spreading along the myotube’s length. Perturbations of microtubules and motor proteins disrupt this sequence of events. These perturbations do not allow intuiting which molecular forces govern the nuclear positioning; we therefore used computational screening to reverse-engineer and identify these forces. The screen reveals three models. Two suggest that the initial clustering is due to nuclear repulsion from the cell poles, while the third, most robust, model poses that this clustering is due to a short-ranged internuclear attraction. All three models suggest that the nuclear spreading is due to long-ranged internuclear repulsion. We test the robust model quantitatively by comparing it with data from perturbed muscle cells. We also test the model using agent-based simulations with elastic dynamic microtubules and molecular motors. The model predicts that, in longer mammalian myotubes with a large number of nuclei, the spreading stage would be preceded by segregation of the nuclei into a large number of clusters, proportional to the myotube length, with a small average number of nuclei per cluster.
Good things come to those who wait—Decreasing impatience for health gains and losses

Historically, time preferences are modelled by assuming constant discounting, which implies a constant level of impatience. The prevailing empirical finding, however, is decreasing impatience (DI), meaning that levels of impatience decrease over time. Theoretically, such changes in impatience are crucial to understand behavior and self-control problems. Very few methods exist to measure DI without being restricted to or confounded by certain assumptions about the discounting function or utility curve. One such measure is the recently introduced DI-index, which has been applied to both monetary and health outcomes. The DI-index quantifies the deviation from constant impatience and is flexible enough to capture both increasing and decreasing impatience. In this study, we apply the DI-index to measure impatience for health outcomes in a reference-dependent framework. That is, we measure impatience for both health gains and health losses compared to a reference-point, in individual and societal settings, using a within-subjects design (n = 98). We allowed for both positive and negative discounting, since negative discounting has been observed for losses (i.e. preferring to incur losses earlier rather than later) in earlier work. To capture changes in time inconsistency when subjects show negative discounting (i.e. patience), we modify the DI-index to a decreasing (im)patience (DIP)-index, which can be applied without loss of generality. As in earlier work, we observe large heterogeneity in time consistency; i.e., a mix of decreasing, increasing and constant (im)patience. Across all DIP-indices elicited, increasing impatience was the modal preference for those satisfying impatience, and decreasing patience for those satisfying patience. No systematic differences were observed between health gains and losses or between societal and individual outcomes. This suggests that for health outcomes both patient and impatient individuals assign more importance to time differences delayed further in the future.
Zinc Supplementation: Immune Balance of Pregnancy During the Chronic Phase of the Chagas Disease

Chagas disease or American trypanosomiasis is caused by the protozoan Trypanosoma cruzi and is endemic of the Americas. The control of the disease is restricted to toxic and potentially teratogenic drugs, which limit the use during pregnancy. The use of food supplementation offers a safe and low-cost form to alleviate Chagas disease symptoms, mostly in areas with alimentary risk. For example, zinc demonstrates positive effects in immune response, including in Chagas disease during pregnancy. This study describes the innate response in pregnant rats chronically infected with T. cruzi and supplemented with zinc. Pregnant female Wistar rats, infected with T. cruzi, were treated with 20 mg/kg/day zinc sulfate and euthanized on the 18th day. Samples (plasma, splenocytes, and peritoneal exudate) were collected and several immune parameters (nitric oxide, RT1B, CD80/CD86, MCP-1, CD11b/c, NK/NKT, IL-2, IL-10, INF-cc, and apoptosis) evaluated. Under Zinc supplementation and/or T. cruzi infection, the gestation developed normally. Several innate immune parameters such as RT1B, CD80/CD86, MCP-1 expressing lymphocytes, IL-2, and IL-17 were positively altered, whereas nitric oxide, CD11b/c, NK/NKT, apoptosis, INF-γ, and corticosterone demonstrated a pro-pregnancy pattern. Our results indicated that zinc has diverse effects on immune response during pregnancy. An anti-T. cruzi immunity, as well as a pro-gestation response, were observed after zinc supplementation. The complete comprehension of zinc supplementation in pregnancy will base an adequate strategy to alleviate Chagas disease symptoms and propagation, especially for populations from endemic areas.
Colorectal Cancer in Northern Tanzania: Increasing Trends and Late Presentation Present Major Challenges

PURPOSE A trend of increasing incidence of colorectal cancer (CRC) has been observed in northern Tanzania. Studies have shown a six-fold increase in CRC in the past decade, with 90% of patients presenting in late stages, with resultant high morbidity and mortality rates. In this study, we aimed to document the burden of CRC in the northern zone of Tanzania from 1998 to 2018, focusing on patient presentation, clinical features, and treatment at a tertiary hospital. METHODS Pathological and clinical records for all patients from 1998 to 2018 were identified and reviewed. Records of patients whose CRC was diagnosed histologically were retrospectively reviewed. RESULTS Approximately 313 CRC cases were documented. The majority age group (29.1%) was between 50 and 64 years (mean [standard deviation], 54.28 [16.75] years). However, together, the age groups of patients younger than 50 years was 41.5% (n = 130). Of 174 patients with complete records, most (29.3%) were between 35 and 49 years of age. The median age was 52 (interquartile range, 40-67) years. Men accounted for 62.1% of patients and were mostly from the Kilimanjaro region. More than half (54.7%) presented > 3 months after symptom debut; 62.6% first sought care at lower-level health facilities. Most (64.9%) presented as emergencies, necessitating colostomy for fecal diversion as the initial surgical procedure in 60.3% of patients. Colonoscopy was performed for 38.6% of the study participants. Most tumors (72.7%) originated from the sigmoid and rectum. Adenocarcinoma was the most prevalent histologic type. CONCLUSION High proportions of young individuals with CRC pose great concern and a need for further appraisal. Furthermore, late emergency presentation and low colonoscopy rates highlights underlying system challenges and need for education campaigns.
The Interaction of Camptothecin with Model Cellular Membranes.

Accurate and efficient prediction of drug partitioning in model membranes is of significant interest to the pharmaceutical industry. Herein we utilize advanced sampling methods, specifically, the Adaptive Biasing Force methodology to calculate the potential of mean force for a model hydrophobic anti-cancer drug, camptothecin (CPT), across three model interfaces. We consider a octanol bilayer, a thick octanol/water interface, and a model 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC)/water interface. We characterize the enthalpic and entropic contributions of the drug to the potential of mean force. We show that the rotational entropy of the drug is inversely related to the probability of hydrogen bond formation of the drug with the POPC membrane. In addition, in long-time microsecond simulations of a high concentration of CPT above the POPC membrane, we show that strong drug-drug aromatic interactions shift the spatial orientation of the drug with the membrane. Stacks of hydrophobic drugs form, allowing penetration of the drug just under the POPC head groups. These results imply that inhomogeneous membrane models need to take into account the effect of drug aggregation on the membrane environment.
Validating a non-invasive technique for monitoring physiological stress in the samango monkey

The non-invasive monitoring of physiological stress can provide conservation and wildlife managers with an invaluable tool for assessing animal welfare and psychological health of captive and free-ranging populations. A significant decrease in free-ranging primate populations globally and an increase in captive-housed primates have led to a need to monitor the stress and general welfare of these animals. We examined the suitability of three enzyme immunoassays (EIAs) for monitoring stress-related physiological responses in the samango monkey, Cercopithecus albogularis erythrarchus. We conducted an adrenocorticotropic hormone (ACTH) challenge on a male and female at the National Zoological Garden, Pretoria, South Africa. Individual faecal samples were collected 8 days pre- and post-ACTH administration and subsequently analysed for faecal glucocorticoid metabolite (fGCM) concentrations. During the study, biological stressors occurred for both the male and female. Two of the three EIAs tested (11-oxoetiocholanolone I and II) were able to reliably monitor fGCM alterations throughout the study period in both sexes. The 11-oxoetiocholanolone I EIA, however, had the lowest mean deviation from the calculated baseline value and was thus chosen as the preferred assay. Both the physiological activation of the stress response and the biological response to a stressor could be monitored with the chosen assay. The successful establishment of a reliable, non-invasive method for monitoring adrenocortical activity in C. albogularis erythrarchus will now allow conservationists, scientific researchers and wildlife managers to evaluate the level of stress experienced, and general welfare, by animals in captivity as well as free-ranging populations.
Appraising Otolaryngology–Head and Neck Surgery Clinical Practice Guidelines for Effective Dissemination and Implementation Design

Objectives Dissemination and implementation (D&I) science analyzes interventional strategies that aid in spreading scientific knowledge, adopting evidence into practice, and identifying barriers to maximize successful integration of science into practice. This study set out to critically appraise the published D&I strategies of the American Academy of Otolaryngology–Head and Neck Surgery Foundation (AAO-HNSF) Clinical Practice Guidelines (CPGs) and to introduce the theories of D&I science. Methods The 15 AAO-HNSF CPGs underwent appraisal by 2 independent reviewers using the Appraisal of Guidelines for Research & Evaluation II (AGREE II) instrument. CPGs were rated over 23 key items in 6 domains. Each item was rated on a 7-point scale from 1 (strongly disagree) to 7 (strongly agree). CPGs were rated and quality assessments were performed. Intrarater reliability was assessed. Results The overall mean score of the CPGs was 85.2% (95% confidence interval, 83.4%-86.9%). Individual CPG mean scores ranged from 80.4% to 90.9%. Mean interrater reliability was strong. All domains of the AGREE II instrument, except the Applicability domain, scored a mean of 90.7% or better. D&I strategies within the CPGs, as calculated by the Applicability domain score, ranged from 22.9% to 77.1%. Discussion There is a paucity of published D&I strategies within the AAO-HNSF CPGs. Nesting a D&I framework, such as the Quality Improvement Framework, within CPGs would allow for identification of barriers to CPG adoption and evaluation of CPG-directed interventions. Implications for Practice A D&I framework within the AAO-HNSF CPGs would allow for objective measurement of the overall impact of CPGs on otolaryngology practices.
Hypoxia-induced small extracellular vesicle proteins regulate proinflammatory cytokines and systemic blood pressure in pregnant rats.

Small extracellular vesicles (sEVs) released from the extravillous trophoblast (EVT) are known to regulate uterine spiral artery remodeling during early pregnancy. The bioactivity and release of these sEVs differ under differing oxygen tensions and in aberrant pregnancy conditions. Whether the placental cell-derived sEVs released from the hypoxic placenta contribute to the pathophysiology of preeclampsia is not known. We hypothesize that, in response to low oxygen tension, the EVT packages a specific set of proteins in sEVs and that these released sEVs interact with endothelial cells to induce inflammation and increase maternal systemic blood pressure. Using a quantitative MS/MS approach, we identified 507 differentially abundant proteins within sEVs isolated from HTR-8/SVneo cells (a commonly used EVT model) cultured at 1% (hypoxia) compared with 8% (normoxia) oxygen. Among these differentially abundant proteins, 206 were upregulated and 301 were downregulated (p < 0.05), and they were mainly implicated in inflammation-related pathways. In vitroincubation of hypoxic sEVs with endothelial cells, significantly increased (p<0.05) the release of GM-CSF, IL-6, IL-8, and VEGF, when compared to control (i.e., cells without sEVs) and normoxic sEVs. In vivo injection of hypoxic sEVs into pregnant rats significantly increased (p < 0.05) mean arterial pressure with increases in systolic and diastolic blood pressures. We propose that oxygen tension regulates the release and bioactivity of sEVs from EVT and that these sEVs regulate inflammation and maternal systemic blood pressure. This novel oxygen-responsive, sEVs signaling pathway, therefore, may contribute to the physiopathology of preeclampsia.
Effect of the muslims' ablution practice on nasal colonization of staphylococcus aureus

Background: The human nose contains many different types of bacteria including Staphylococcus aureus (S. aureus). It is possible to get rid of this pathogen using many topical antiseptics or antibiotics. However, good washing using clean water may be valuable to decrease colonization by this organism. Objectives: This study determined the effect of daily repeated nasal washing in the ablution process performed by Muslims before every prayer on the presence and density of S. aureus nasal colonization. Material and methods: Two groups of volunteers were selected from the students and staff who were selected from Taif University, Saudi Arabia and Menoufia University, Egypt. The first group included 200 subjects who are practicing ablution and prayer and the second group included 100 subjects who do not do ritual ablutions. Personal data were collected and swabs were obtained from inside of the nostrils from all volunteers. Swabs were obtained from worshipers before, directly after, and 2-hours after ablution. Cultures were performed on suitable media and identification of S. aureus was performed according to the standard bacteriological methods. Results: The rate of colonization by S. aureus was 62% among non-worshipers and 38% among worshipers before ablution with a non- significant difference. Among worshipers, the rate of isolation of S. aureus just before ablution was 38% and significantly reduced to 20% directly after ablution (p< 0.01). It rises to 32% 2-hours after ablution. The microbial density of S. aureus was significantly (p< 0.001) lower among worshipers than nonworshipers. Conclusion: Nasal washing in ablution can reduce S. aureus nasal colonization. It can be a simple, easy and effective way to reduce colonization by this organism and thereby decrease the occurrence of serious staphylococcal diseases.
Evolución de la epidemia de diabetes mellitus tipo 2 en población derechohabiente del IMSS

El aumento mundial de diabetes mellitus tipo 2 (DMT2) tiene creciente demanda en las instituciones de salud; es una emergencia mundial debido a los excesivos gastos que atentan la seguridad social, por complicaciones renales y dano cardiovascular, que afectan a millones enfermos.1 El objetivo de este trabajo es caracterizar la epidemia de DMT2, con sindrome metabolico y defi nir la respuesta institucional de contencion-control con intervenciones educativas universales de estilos de vida saludables para evitar muerte prematura y discapacidades por cardiopatia isquemica (CI), enfermedad vascular cerebral (EVC), insuficiencia renal terminal, (IRT), ceguera y amputaciones. Metodos: revision de los anos 1990 a 2013: Boletin Epidemiologico; consultas de los servicios: Medicina Familiar, Especialidades, Urgencias, Hospitalizaciones, y estudios de prevencion con estimacion del gasto y ahorro institucional. Resultados: la incidencia se incremento 48 %, la prevalencia paso de 7 a 10.6 %, y la mortalidad de 35.6 a 77.2 por cada 100 000 derechohabientes. La hipertension arterial, y las defunciones por CI y EVC, se incrementaron 58, 197, 142.5 % respectivamente. Las consultas en 2013 fueron 9 113 082. La estimacion del gasto por deteccion de prediabetes y atencion medica para evitar complicaciones, generaria un ahorro del 60 % del gasto actual. Conclusiones: el control de la epidemia mediante la capacitacion de pacientes, familias y personal de salud en el estilo de vida saludable es el tratamiento para revertir a normalidad el IMC, glucemia, trigliceridos, colesterol HDL, LDL, presion arterial y adicciones a tabaco/alcohol, para desacelerar complicaciones del sindrome metabolico