Miracle-dz/UniFAR-FTUs huggingface dataset:
Use of Model-Based Compartmental Analysis and a Super-Child Design to Study Whole-Body Retinol Kinetics and Vitamin A Total Body Stores in Children from 3 Lower-Income Countries

ABSTRACT Background Model-based compartmental analysis has been used to describe and quantify whole-body vitamin A metabolism and estimate total body stores (TBS) in animals and humans. Objectives We applied compartmental modeling and a super-child design to estimate retinol kinetic parameters and TBS for young children in Bangladesh, Guatemala, and the Philippines. Methods Children ingested [13C10]retinyl acetate and 1 or 2 blood samples were collected from each child from 6 h to 28 d after dosing. Temporal data for fraction of dose in plasma [13C10]retinol were modeled using WinSAAM software and a 6-component model with vitamin A intake included as weighted data. Results Model-predicted TBS was 198, 533, and 1062 μmol for the Bangladeshi (age, 9–17 mo), Filipino (12–18 mo), and Guatemalan children (35–65 mo). Retinol kinetics were similar for Filipino and Guatemalan groups and generally faster for Bangladeshi children, although fractional transfer of plasma retinol to a larger exchangeable storage pool was the same for the 3 groups. Recycling to plasma from that pool was ∼2.5 times faster in the Bangladeshi children compared with the other groups and the recycling number was 2–3 times greater. Differences in kinetics between groups are likely related to differences in vitamin A stores and intakes (geometric means: 352, 727, and 764 μg retinol activity equivalents/d for the Bangladeshi, Filipino, and Guatemalan children, respectively). Conclusions By collecting 1 or 2 blood samples from each child to generate a composite plasma tracer data set with a minimum of 5 children/time, group TBS and retinol kinetics can be estimated in children by compartmental analysis; inclusion of vitamin A intake data increases confidence in model predictions. The super-child modeling approach is an effective technique for comparing vitamin A status among children from different populations. These trials were registered at www.clinicaltrials. gov as NCT03000543 (Bangladesh), NCT03345147 (Guatemala), and NCT03030339 (Philippines).
Critical Peri-implant Buccal Bone Wall Thickness Revisited: An Experimental Study in the Beagle Dog.

PURPOSE There is a lack of knowledge concerning the critical buccal bone thickness required for securing favorable functional and esthetic outcomes, conditioned to the dimensional changes after implant placement. A preclinical study was therefore carried out to identify the critical buccal bone wall thickness for minimizing bone resorption during physiologic and pathologic bone remodeling. MATERIALS AND METHODS A randomized, two-arm in vivo study in healthy beagle dogs was carried out. The first group of dogs was sacrificed 8 weeks after implant placement for histomorphometric examination of postsurgical resorption of the buccal bone wall. The second group of dogs was monitored during three ligature-induced peri-implantitis episodes and a spontaneous progression episode. Morphometric and clinical variables were defined for the study of physiologic and pathologic buccal and lingual bone loss. RESULTS Seventy-two implants were placed in healed mandibular ridges of 12 beagle dogs. Two groups were defined: 36 implants were placed in sites with a thin buccal bone wall (< 1.5 mm), and 36 were placed in sites with a thick buccal bone wall (≥ 1.5 mm). No implants failed during the study period. For the great majority of the histomorphometric parameters, a critical buccal bone wall thickness of at least 1.5 mm seemed to be essential for maintaining the buccal bone wall during physiologic and pathologic bone resorption. Suppuration (+) and mucosal recession (-) were more often associated with implants placed in sites with a thin buccal bone wall. CONCLUSION A critical buccal bone wall thickness of 1.5 mm at implant placement is advised, since a thicker peri-implant buccal bone wall (> 1.5 mm) is exposed to significantly less physiologic and pathologic bone loss compared with a thinner buccal bone wall (< 1.5 mm).
Mobility Mining in Disaster Scenarios to Improve Geographic Routing in Delay Tolerant Networks

This paper explores mobility mining to extract relevant node and network characteristics in Delay Tolerant Networks during disaster scenarios. Through mobility analysis, this paper aims to discover location hotspots and look at mobility entropy of different node groups with different roles during a disaster. In general, this paper presents a routing scheme for DTN that aims to improve the effective delivery of messages on specific geographic locations and entities. The routing scheme incorporates Area of Interest (AoI) of nodes and calculation of encounter probability in the routing decision and proposes better message management to optimize node’s memory. Simulation results show significant advantages of the proposed scheme compared to Epidemic for geographic routing and Epidemic scheme with Angle of Deviation (AoD) in terms of delivery rate, delivery latency, and message overhead.
Prevalence, Virulence, and Antimicrobial Resistance of Campylobacter spp. in Raw Milk, Beef, and Pork Meat in Northern Poland

The purpose of this study was to determine whether raw milk, unpasteurized dairy products, pork, and beef available for sale in the Kujawsko-Pomorskie and Wielkopolska regions in Poland are contaminated with Campylobacter spp. bacteria and may be a potential source of infection. For isolated strains, antibiotic susceptibility and the presence of genes responsible for virulence were examined. Material for research included 1058 food samples collected between 2014 and 2018 with 454 samples of raw milk and unpasteurized dairy products (milk from vending machines, milk from owners of dairy cows, cheese, milk cream) and 604 samples of raw meat (pork, beef). The results indicated that 9.3% of the samples were positive for Campylobacter spp. , and Campylobacter jejuni was predominant in this study. Campylobacter bacteria was not found in milk collected from vending machines, as well as cheese and milk cream samples. Campylobacter was noted in 12.7% of beef samples, 11.8% of raw milk purchased from individual suppliers, and 10.9% of pork samples. Resistance to erythromycin (2.0%), azithromycin (3.1%), gentamicin (4.1%), tetracycline (65.3%), and ciprofloxacin (71.4%) was determined using the disc diffusion method. Furthermore, the prevalence of racR, sodB, csrA, virB11, cdtB, iam, and wlaN genes were examined using the PCR method. The sodB, csrA, and cdtB genes exhibited the highest detection rate, but none of the genes were identified in 100% of the isolates. Statistically significant differences between the presence of virulence marker genes, including for iam, racR, and csrA markers, were noted among different sources of the isolates. Differences in the distribution of iam, wlaN, and virB11 were also shown between C. jejuni and C. coli strains. As a result of the analysis, it has been concluded that unpasteurized milk, beef, and pork could be a sources of Campylobacter pathogens. Moreover, this study revealed virulent properties of Campylobacter isolated from such food products and high resistance rates to fluoroquinolones, which may represent difficulties in campylobacteriosis treatment.
Assessment of elite junior tennis serve and return practice: A cross-sectional observation

ABSTRACT Practice tasks that more closely represent the demands of competition are thought to augment skill learning and transfer. This study observed the serve and return performances of junior grand slam tennis and used this benchmark to evaluate the representativeness of serve and return practice among elite junior tennis players. The serve and return behaviour of 26 junior tennis players competing in junior Australian Open grand slam matches were observed and compared with the serve and return practice behaviours of 12 elite junior tennis players over an 8-week period. The variables measured included the number of serves/returns landing in, serve/return type, serve direction and the variability of practised skills. Serve and return practice contributed to <13% of total practice time, with each skill predominately practised in isolation. Compared to the matchplay benchmark, players typically had less success (i.e., fewer serves/returns landing in the court), were less variable in shot selection and hit fewer serves to the extremities of the service box. As task representativeness increased fewer differences between practice and matchplay were observed. Tennis serve and return practice could be improved by better simulating specific competition affordances, providing greater opportunities to practice serve/return tactics and/or increasing the variability of practised skills.
Melatonin attenuates ER stress and mitochondrial damage in septic cardiomyopathy: A new mechanism involving BAP31 upregulation and MAPK‐ERK pathway

Septic cardiomyopathy is associated with mitochondrial damage and endoplasmic reticulum (ER) dysfunction. However, the upstream mediator of mitochondrial injury and ER stress has not been identified and thus little drug is available to treat septic cardiomyopathy. Here, we explored the role of B‐cell receptor‐associated protein 31 (BAP31) in septic cardiomyopathy and figure out whether melatonin could attenuate sepsis‐mediated myocardial depression via modulating BAP31. Lipopolysaccharide (LPS) was used to establish the septic cardiomyopathy model. Pathway analysis was performed via western blot, quantitative polymerase chain reaction and immunofluorescence. Mitochondrial function and ER stress were detected via enzyme‐linked immunosorbent assay, western blot, and immunofluorescence. After exposure to LPS, cardiac function was reduced due to excessive inflammation response and extensive cardiomyocyte death. Mechanistically, melatonin treatment could dose‐dependently improve cardiomyocyte viability via preserving mitochondrial function and reducing ER stress. Further, we found that BAP31 transcription was repressed by LPS whereas melatonin could restore BAP31 expression; this effect was dependent on the MAPK‐ERK pathway. Inhibition of the ERK pathway and/or knockdown of BAP31 could attenuate the beneficial effects of melatonin on mitochondrial function and ER homeostasis under LPS stress. Altogether, our results indicate that ERK‐BAP31 pathway could be used as a critical mediator for mitochondrial function and ER homeostasis in sepsis‐related myocardial injury. Melatonin could stabilize BAP31 via the ERK pathway and thus contribute to the preservation of cardiac function in septic cardiomyopathy.
Politics as an Explanation to the Health Divide in Different Settings: A Comparative Study of England and Ghana

Informed by the theoretical perspective of the political economy of health and in the context of the recommendations of World Health Organization’s Commission on Social Determinants of Health, this article examines the political explanations of geographical health inequities in 2 extremely different settings: Ghana and England. Based on the “north-south health divide” in the 2 countries, the article finds that, while the drivers of health inequities in both countries are policy driven, historically situated contextual factors (colonialism in the case of Ghana and deindustrialization in the case of England) offer explanations for health inequities in both countries. We conclude by discussing the importance of paying attention to structural factors such as colonialism for understanding contemporary health inequities in formerly colonized countries such as Ghana.
A new experimental mouse model of water intoxication with sustained increased intracranial pressure and mild hyponatremia without side effects of antidiuretics

The most used experimental mouse model of hyponatremia and elevated intracranial pressure (ICP) is intraperitoneal injection of water in combination with antidiuretics. This model of water intoxication (WI) results in extreme pathological changes and death within 1 h. To improve preclinical studies of the pathophysiology of elevated ICP, we characterized diuresis, cardiovascular parameters, blood ionogram and effects of antidiuretics in this model. We subsequently developed a new mouse model with mild hyponatremia and sustained increased ICP. To investigate the classical protocol (severe WI), C57BL/6mice were anesthetized and received an intraperitoneal injection of 20% body weight of MilliQ water with or without 0.4 µg·kg−1 desmopressin acetate (dDAVP). Corresponding Sham groups were also studied. In the new WI protocol (mild WI), 10% body weight of a solution containing 6.5 mM NaHCO3, 1.125 mM KCl and 29.75 mM NaCl was intraperitoneally injected. By severe WI, ICP and mean arterial pressure increased until brain stem herniation occurred (23 ± 3 min after injection). The cardiovascular effects were accelerated by dDAVP. Severe WI induced a halt to urine production irrespective of the use of dDAVP. Following the new mild WI protocol, ICP also increased but was sustained at a pathologically high level without inducing herniation. Mean arterial pressure and urine production were not affected during mild WI. In conclusion, the new mild WI protocol is a superior experimental model to study the pathophysiological effects of elevated ICP induced by water intoxication.
Genome wide genetic dissection of wheat quality and yield related traits and their relationship with grain shape and size traits in an elite × non-adapted bread wheat cross

The genetic gain in yield and quality are two major targets of wheat breeding programs around the world. In this study, a high density genetic map consisting of 10,172 SNP markers identified a total of 43 genomic regions associated with three quality traits, three yield traits and two agronomic traits in hard red spring wheat (HRSW). When compared with six grain shape and size traits, the quality traits showed mostly independent genetic control (~18% common loci), while the yield traits showed moderate association (~53% common loci). Association of genomic regions for grain area (GA) and thousand-grain weight (TGW), with yield suggests that targeting an increase in GA may help enhancing wheat yield through an increase in TGW. Flour extraction (FE), although has a weak positive phenotypic association with grain shape and size, they do not share any common genetic loci. A major contributor to plant height was the Rht8 locus and the reduced height allele was associated with significant increase in grains per spike (GPS) and FE, and decrease in number of spikes per square meter and test weight. Stable loci were identified for almost all the traits. However, we could not find any QTL in the region of major known genes like GPC-B1, Ha, Rht-1, and Ppd-1. Epistasis also played an important role in the genetics of majority of the traits. In addition to enhancing our knowledge about the association of wheat quality and yield with grain shape and size, this study provides novel loci, genetic information and pre-breeding material (combining positive alleles from both parents) to enhance the cultivated gene pool in wheat germplasm. These resources are valuable in facilitating molecular breeding for wheat quality and yield improvement.
Stability of extracts from pollens of allergenic importance in Korea

Background/Aims Accurate diagnosis and the effects of allergen-specific immunotherapy for pollinosis are greatly dependent on the potency and stability of the extract. This study aimed to examine factors, such as temperature and storage buffer composition, that affect the stability of allergen extracts from pollens of allergenic importance in Korea. Methods We prepared four pollen allergen extracts from ragweed, mugwort, Japanese hop, and sawtooth oak, which are the most important causes of seasonal rhinitis in Korea. Changes of protein and major allergen concentration were measured over 1 year by Bradford assay, two-site enzyme-linked immunosorbent assay, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis after reconstitution of the lyophilized allergen extract in various buffers and stored at room temperature (RT, 18°C to 26°C) or refrigerated (4°C). Results More than 90% of the original protein concentration in all four extracts examined was detected over 1 year when 50% glycerol was added and refrigerated, whereas 57.9% to 94.5% remained in the extracts at RT. The addition of 50% glycerol to the storage buffer was found to prevent protein degradation at RT. Amb a 1, a major allergen of ragweed, was almost completely degraded in 9 weeks at RT when reconstituted in a buffer without 50% glycerol. However, 55.6% to 92.8% of Amb a 1 content was detected after 1 year of incubation at 4°C in all buffer conditions except 0.3% phenol. Conclusions Addition of 50% glycerol as well as refrigeration was found to be important in increasing the shelf-life of allergen extracts from pollens of allergenic importance.
BRAF Mutations Classes I, II, and III in NSCLC Patients Included in the SLLIP Trial: The Need for a New Pre-Clinical Treatment Rationale

BRAF V600 mutations have been found in 1–2% of non-small-cell lung cancer (NSCLC) patients, with Food and Drug Administration (FDA) approved treatment of dabrafenib plus trametinib and progression free survival (PFS) of 10.9 months. However, 50–80% of BRAF mutations in lung cancer are non-V600, and can be class II, with intermediate to high kinase activity and RAS independence, or class III, with impaired kinase activity, upstream signaling dependence, and consequently, sensitivity to receptor tyrosine kinase (RTK) inhibitors. Plasma cell-free DNA (cfDNA) of 185 newly diagnosed advanced lung adenocarcinoma patients (Spanish Lung Liquid versus Invasive Biopsy Program, SLLIP, NCT03248089) was examined for BRAF and other alterations with a targeted cfDNA next-generation sequencing (NGS) assay (Guardant360®, Guardant Health Inc., CA, USA), and results were correlated with patient outcome. Cell viability with single or combined RAF, MEK, and SHP2 inhibitors was assessed in cell lines with BRAF class I, II, and III mutations. Out of 185 patients, 22 had BRAF alterations (12%) of which seven patients harbored amplifications (32%) and 17 had BRAF mutations (77%). Of the BRAF mutations, four out of 22 (18%) were V600E and 18/22 (82%) were non-V600. In vitro results confirmed sensitivity of class III and resistance of class I and II BRAF mutations, and BRAF wild type cells to SHP2 inhibition. Concomitant MEK or RAF and SHP2 inhibition showed synergistic effects, especially in the class III BRAF-mutant cell line. Our study indicates that the class of the BRAF mutation may have clinical implications and therefore should be defined in the clinical practice and used to guide therapeutic decisions.
Genetically Encoded Photosensitizers as Light-Triggered Antimicrobial Agents

Diseases caused by multi-drug resistant pathogens have become a global concern. Therefore, new approaches suitable for treating these bacteria are urgently needed. In this study, we analyzed genetically encoded photosensitizers (PS) related to the green fluorescent protein (GFP) or light-oxygen-voltage (LOV) photoreceptors for their exogenous applicability as light-triggered antimicrobial agents. Depending on their specific photophysical properties and photochemistry, these PSs can produce different toxic ROS (reactive oxygen species) such as O2•− and H2O2 via type-I, as well as 1O2 via type-II reaction in response to light. By using cell viability assays and microfluidics, we could demonstrate differences in the intracellular and extracellular phototoxicity of the applied PS. While intracellular expression and exogenous supply of GFP-related PSs resulted in a slow inactivation of E. coli and pathogenic Gram-negative and Gram-positive bacteria, illumination of LOV-based PSs such as the singlet oxygen photosensitizing protein SOPP3 resulted in a fast and homogeneous killing of these microbes. Furthermore, our data indicate that the ROS type and yield as well as the localization of the applied PS protein can strongly influence the antibacterial spectrum and efficacy. These findings open up new opportunities for photodynamic inactivation of pathogenic bacteria.
Depression prevention via digital cognitive behavioral therapy for insomnia: a randomized controlled trial.

STUDY OBJECTIVES Insomnia is a common precursor to depression; yet, the potential for insomnia treatment to prevent depression has not been demonstrated. Cognitive behavioral therapy for insomnia (CBT-I) effectively reduces concurrent symptoms of insomnia and depression and can be delivered digitally (dCBT-I); however, it remains unclear whether treating insomnia leads to sustained reduction and prevention of depression. This randomized controlled trial examined the efficacy of dCBT-I in reducing and preventing depression over a 1-year follow-up period. METHODS Patients with Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) insomnia disorder were randomly assigned to receive dCBT-I or an attentional control. The follow-up sample included 358 patients in the dCBT-I condition and 300 patients in the online sleep education condition. The primary outcome measure was relative rate ratios for depression at 1-year follow-up. Insomnia responses to treatment were also tested as predictors of incident depression at the 1-year follow-up. RESULTS At 1-year follow-up, depression severity continued to be significantly lower in the dCBT-I condition relative to control. In addition, the number of individuals who reported no depression at 1-year follow-up was 51% higher in the dCBT-I condition relative to control. In those with minimal to no depression at baseline, the incident rate of moderate-to-severe depression at 1-year follow-up was reduced by half in the dCBT-I condition relative to the control condition. CONCLUSION dCBT-I showed robust effects as an intervention that prevents depression. Future research should examine dose-response requirements and further characterize mechanisms of action of dCBT-I for depression prevention. CLINICAL TRIAL Sleep to Prevent Evolving Affective Disorders; NCT02988375.
Softening Damage Analysis of Gypsum Rock With Water Immersion Time Based on Laboratory Experiment

In view of the effect of water on the physical and mechanical parameters of natural gypsum rock, in this study, gypsum rock in the goaf of a gypsum mine was selected as the research object, and gypsum rock samples were prepared with different immersion times. In addition, uniaxially tests were performed separately on the gypsum rock samples. Compression and scanning electron microscopy experiments were carried out to analyze the effects of immersion time on the uniaxial compressive strength, elastic modulus, Poisson’s ratio, and microstructure of gypsum. The results show that the uniaxial compressive strength and elastic modulus of gypsum are inversely proportional to the water content. However, the Poisson’s ratio is direly proportional to the water content, and the failure mode is destroyed by the brittle fracture of a single crack and is transformed into the shear ductile failure of the Y-shaped crack. Microscopically, with increasing immersion time, the bonds in the crystal of the microporous cracks and microcrack tips are weakened by hydrolysis, and the macroscopic structure is complicated by the internal structure of gypsum, and the end of the crack is expanded by the compressive action of water. Based on the damage mechanics, the evolution equation of gypsum soaking softening damage based on time factor was derived. The relationship between the brittleness coefficient and softening damage variable is revealed, providing a theoretical basis for the determination of the softening degree of gypsum in the goaf.