Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid selection response to ethanol in Saccharomyces eubayanus emulates the domestication process under brewing conditions

Although the typical genomic and phenotypic changes that characterize the evolution of organisms under the human domestication syndrome represent textbook examples of rapid evolution, the molecular processes that underpin such changes are still poorly understood. Domesticated yeasts for brewing, where short generation times and large phenotypic and genomic plasticity were attained in a few generations under selection, are prime examples. To experimentally emulate the lager yeast domestication process, we created a genetically complex (panmictic) artificial population of multiple Saccharomyces eubayanus genotypes, one of the parents of lager yeast. Then, we imposed a constant selection regime under a high ethanol concentration in 10 replicated populations during 260 generations (6 months) and compared them with propagated controls exposed solely to glucose. Propagated populations exhibited a selection differential of 60% in growth rate in ethanol, mostly explained by the proliferation of a single lineage (CL248.1) that competitively displaced all other clones. Interestingly, the outcome does not require the entire time‐course of adaptation, as four lineages monopolized the culture at generation 120. Sequencing demonstrated that de novo genetic variants were produced in all propagated lines, including SNPs, aneuploidies, INDELs and translocations. In addition, the different propagated populations showed correlated responses resembling the domestication syndrome: genomic rearrangements, faster fermentation rates, lower production of phenolic off‐flavours and lower volatile compound complexity. Expression profiling in beer wort revealed altered expression levels of genes related to methionine metabolism, flocculation, stress tolerance and diauxic shift, likely contributing to higher ethanol and fermentation stress tolerance in the evolved populations. Our study shows that experimental evolution can rebuild the brewing domestication process in ‘fast motion’ in wild yeast, and also provides a powerful tool for studying the genetics of the adaptation process in complex populations.
SLUDGE ASH AS LIGHTWEIGHT CONCRETE MATERIAL

Sludge is an inevitable by‐product of wastewater treatment. Its abundance poses disposal problems that can be drastically reduced if sludge can be converted for economical uses in construction as substitute materials. Digested and dewatered sludge, after incineration at a high temperature, yields a hard, cellular, porous mass with low unit weight. This hardened mass of sludge ash can be crushed to smaller‐sized aggregates, which, when graded in suitable proportions, manifest the basic attributes required of lightweight aggregates. When used as aggregates in the production of lightweight concrete, experimental results show that the resulting concrete satisfies the physical requirements of a lightweight concrete in terms of unit weight, strength, heat‐insulating properties, and fire resistance, thus indicating that sludge ash could be a potential source of suitable lightweight aggregates.
Prediction of mortality by age and multi-morbidities among confirmed COVID-19 patients: Secondary analysis of surveillance data in Pune, Maharashtra, India

Maharashtra has reported the maximum number of COVID-19 cases in India. This study was conducted to describe the predictors of death among the confirmed cases of COVID-19 by carrying out a secondary analysis of surveillance data of 11,278 lab-confirmed COVID-19 cases and admitted in dedicated COVID hospitals and dedicated COVID health-care centers between April 4, 2020, and July 17, 2020, in Pune district of Maharashtra. A total of 1270 (11.2%, 95% confidence interval [CI]: 10.7–11.9) deaths out of 11,278 patients were reported. Out of the 1270 deaths, 825 (65%) were male and 788 (62%) had one or more comorbidities. Logistic regression was done for predictors of death, and males (adjusted odds ratio: 1.6, 95% CI: 1.4–1.8), those with symptoms at the time of admission (adjusted odds ratio: 2.9, 95% CI: 2.5–3.4), and those with the presence of two or more comorbidities (adjusted odds ratio: 2.7, 95% CI: 2.2–3.4) were having a higher risk of death.
The Modulatory Effect of Motor Cortex Astrocytes on Diabetic Neuropathic Pain

Diabetic neuropathic pain (DNP) is a common complication of diabetes characterized by persistent pain. Emerging evidence links astrocytes to mechanical nociceptive processing, and the motor cortex (MCx) is a cerebral cortex region that is known to play a key role in pain regulation. However, the association between MCx astrocytes and DNP pathogenesis remains largely unexplored. Here, we studied this association using designer receptors exclusively activated by designer drugs to specifically manipulate MCx astrocytes. We proved that the selective inhibition of MCx astrocytes reduced DNP in streptozocin (STZ)-induced DNP models and discovered a potential mechanism by which astrocytes release cytokines, including TNF-α and IL-1β, to increase neuronal activation in the MCx, thereby regulating pain. Together, these results demonstrate a pivotal role for MCx astrocytes in DNP pathogenesis and provide new insight into DNP treatment strategies.
The etiology of Down syndrome: Maternal MCM9 polymorphisms increase risk of reduced recombination and nondisjunction of chromosome 21 during meiosis I within oocyte

Altered patterns of recombination on 21q have long been associated with the nondisjunction chromosome 21 within oocytes and the increased risk of having a child with Down syndrome. Unfortunately the genetic etiology of these altered patterns of recombination have yet to be elucidated. We for the first time genotyped the gene MCM9, a candidate gene for recombination regulation and DNA repair in mothers with or without children with Down syndrome. In our approach, we identified the location of recombination on the maternal chromosome 21 using short tandem repeat markers, then stratified our population by the origin of meiotic error and age at conception. We observed that twenty-five out of forty-one single nucleotide polymorphic sites within MCM9 exhibited an association with meiosis I error (N = 700), but not with meiosis II error (N = 125). This association was maternal age-independent. Several variants exhibited aprotective association with MI error, some were neutral. Maternal age stratified characterization of cases revealed that MCM9 risk variants were associated with an increased chance of reduced recombination on 21q within oocytes. The spatial distribution of single observed recombination events revealed no significant change in the location of recombination among women harbouring MCM9 risk, protective, or neutral variant. Additionally, we identified a total of six novel polymorphic variants and two novel alleles that were either risk imparting or protective against meiosis I nondisjunction. In silico analyses using five different programs suggest the risk variants either cause a change in protein function or may alter the splicing pattern of transcripts and disrupt the proportion of different isoforms of MCM9 products within oocytes. These observations bring us a significant step closer to understanding the molecular basis of recombination errors in chromosome 21 nondisjunction within oocytes that leads to birth of child with Down syndrome.
Sensory and physical characteristics of foods that impact food intake without affecting acceptability: Systematic review and meta‐analyses

This systematic review with meta‐analyses aimed to identify the sensory and physical characteristics of foods/beverages which increase satiation and/or decrease/delay subsequent consumption without affecting acceptability. Systematic searches were first undertaken to identify review articles investigating the effects of any sensory and physical food characteristic on food intake. These articles provided some evidence that various textural parameters (aeration, hardness, homogeneity, viscosity, physical form, added water) can impact food intake. Individual studies investigating these effects while also investigating acceptability were then assessed. Thirty‐seven individual studies investigated a textural manipulation and provided results on food intake and acceptability, 13 studies (27 comparisons, 898 participants) investigated effects on satiation, and 29 studies (54 comparisons, 916 participants) investigated effects on subsequent intake. Meta‐analyses of within‐subjects comparisons (random‐effects models) demonstrated greater satiation (less weight consumed) from food products that were harder, chunkier, more viscous, voluminous, and/or solid, while demonstrating no effects on acceptability. Textural parameters had limited effects on subsequent consumption. Between‐subjects studies and sensitivity analyses confirmed these results. These findings provide some evidence that textural parameters can increase satiation without affecting acceptability. The development of harder, chunkier, more viscous, voluminous, and/or solid food/beverage products may be of value in reducing overconsumption.
SCRATCH Trial: An Initiative to Reduce Excess Use of High-Flow Nasal Cannula.

OBJECTIVES We aimed to reduce unnecessary use of high-flow nasal cannula (HFNC) at lower flow rates through the implementation of a standard daily trial off HFNC at a medium-sized academic center. METHODS We used an interprofessional quality improvement collaboration to develop and implement interventions to reduce HFNC waste in children aged 1 month to 24 months with bronchiolitis who were admitted to the inpatient ward or ICU. Key interventions included development and implementation of the Simple Cannula/Room Air Trial for Children (SCRATCH Trial), a standard trial off HFNC for eligible infants. Process measures were selected as metrics of use of the newly developed trial. The primary outcome measure was hours of treatment with ≤8 L per minute (LPM) of HFNC. Additional outcome measures included total hours of treatment with HFNC and length of stay. RESULTS A total of 271 patients were included in this study, 131 in the preimplementation group and 140 in the postimplementation group. The mean hours of treatment below our a priori determined waste line (≤8 LPM of HFNC) decreased from 36.3 to 16.8 hours after SCRATCH Trial implementation, and mean length of stay decreased from 4.1 to 3.0 days. CONCLUSIONS The SCRATCH Trial was successfully implemented across hospital units, with a significant reduction in hours on ≤8 LPM of flow. Rapid discontinuation of HFNC appears feasible and may be associated with a shorter length of stay.
Variants in ACE2 and TMPRSS2 Genes Are Not Major Determinants of COVID-19 Severity in UK Biobank Subjects

It is plausible that variants in the ACE2 and TMPRSS2 genes might contribute to variation in COVID-19 severity and that these could explain why some people become very unwell whereas most do not. Exome sequence data was obtained for 49,953 UK Biobank subjects, of whom 82 had tested positive for SARS-CoV-2 and could be presumed to have severe disease. A weighted burden analysis was carried out using SCOREASSOC to determine whether there were differences between these cases and the other sequenced subjects in the overall burden of rare, damaging variants in ACE2 or TMPRSS2. There were no statistically significant differences in weighted burden scores between cases and controls for either gene. There were no individual DNA sequence variants with a markedly different frequency between cases and controls. Whether there are small effects on severity, or whether there might be rare variants with major effect sizes, would require studies in much larger samples. Genetic variants affecting the structure and function of the ACE2 and TMPRSS2 proteins are not the main explanation for why some people develop severe symptoms in response to infection with SARS-CoV-2. This research was conducted using the UK Biobank Resource.
Unclear association between COVID-19 and Guillain-Barré syndrome

1 French Reference Center for Paraneoplastic Neurological Syndromes and Autoimmune Encephalitis, Hospices Civils de Lyon, Hôpital Neurologique, Bron, France 2 Institute NeuroMyoGène, INSERM U1217/CNRS UMR 5310, Lyon, France 3 University Claude Bernard Lyon 1, Université de Lyon, Lyon, France 4 Clinical Neurology Unit, Azienda Sanitaria Universitaria Friuli Centrale, Presidio Ospedaliero Santa Maria della Misericordia, Udine, Italy 5 University Jean Monnet, Saint-Étienne, France 6 Department of Neurology, University Hospital, Saint-Etienne, France 7 Reference Center for Rare Neuromuscular diseases, Saint-Etienne, France 8 Department of Biochemistry, University Hospital, Saint-Etienne, France 9 University of Udine Medical School, Udine, Italy 10 Department of Mathematics, Informatics and Physics (DMIF), University of Udine, Udine, Italy
Recovery of Symmetrical Peripheral Gangrene of Limbs in a Patient After Performing Hemoadsorption in Septic Shock

We report a 42‐year‐old patient who had Hodgkin lymphoma and developed bilateral symmetrical peripheral gangrene (SPG) in the feet and hands, which occurred during septic shock after autologous hematopoietic stem‐cell transplantation. SPG is a rare but severe complication of disseminated intravascular coagulation (DIC) and is frequently associated with sepsis. The pathophysiology of SPG includes DIC‐mediated intravascular thrombosis and thrombotic occlusion of microcirculation, resulting in low blood flow. Sepsis‐induced hypotension has been suspected as one of the other causes of SPG, and it is thought to be aggravated by vasopressor treatments given for hypotension. Our patient first experienced coldness, paleness, and cyanosis in his body's acral parts, and then SPG later developed in both his feet and hands. Septic shock management was performed with cytokine hemoadsorption, broad‐spectrum antibiotics, and massive fluid replacement rapidly. The patient fully recovered without the need for amputation. Hemoadsorption is an extracorporeal cytokine‐adsorption method for removing excess cytokines. Prompt management of septic shock and early monitoring of peripheral ischemia are essential to avoid SPG.
Teaching critical thinking about health using digital technology in lower secondary schools in Rwanda: A qualitative context analysis

Introduction Adolescents encounter misleading claims about health interventions that can affect their health. Young people need to develop critical thinking skills to enable them to verify health claims and make informed choices. Schools could teach these important life skills, but educators need access to suitable learning resources that are aligned with their curriculum. The overall objective of this context analysis was to explore conditions for teaching critical thinking about health interventions using digital technology to lower secondary school students in Rwanda. Methods We undertook a qualitative descriptive study using four methods: document review, key informant interviews, focus group discussions, and observations. We reviewed 29 documents related to the national curriculum and ICT conditions in secondary schools. We conducted 8 interviews and 5 focus group discussions with students, teachers, and policy makers. We observed ICT conditions and use in five schools. We analysed the data using a framework analysis approach. Results Two major themes found. The first was demand for teaching critical thinking about health. The current curriculum explicitly aims to develop critical thinking competences in students. Critical thinking and health topics are taught across subjects. But understanding and teaching of critical thinking varies among teachers, and critical thinking about health is not being taught. The second theme was the current and expected ICT conditions. Most public schools have computers, projectors, and internet connectivity. However, use of ICT in teaching is limited, due in part to low computer to student ratios. Conclusions There is a need for learning resources to develop critical thinking skills generally and critical thinking about health specifically. Such skills could be taught within the existing curriculum using available ICT technologies. Digital resources for teaching critical thinking about health should be designed so that they can be used flexibly across subjects and easily by teachers and students.
Population-Wide Peer Comparison Audit and Feedback to Reduce Antibiotic Initiation and Duration in Long-Term Care Facilities with Embedded Randomized Controlled Trial.

BACKGROUND Antibiotic over-prescribing in long-term care settings is driven by prescriber preferences and is associated with preventable harms for residents. We aimed to determine whether peer comparison audit and feedback reporting for physicians reduces antibiotic over-prescribing among residents. METHODS We employed a province wide, difference-in-differences study of antibiotic prescribing audit and feedback, with an embedded pragmatic randomized controlled trial (RCT) across all long-term care facilities in Ontario, Canada in 2019. The study year included 1,238 physicians caring for 96,185 residents. 895 (72%) physicians received no feedback; 343 (28%) were enrolled to receive audit and feedback and randomized 1:1 to static or dynamic reports. The primary outcomes were proportion of residents initiated on an antibiotic and proportion of antibiotics prolonged beyond 7 days per quarter. RESULTS Among all residents, between the first quarter of 2018 and last quarter of 2019, there were temporal declines in antibiotic initiation (28.4% to 21.3%) and prolonged duration (34.4% to 29.0%). Difference-in-differences analysis confirmed that feedback was associated with a greater decline in prolonged antibiotics (adjusted difference -2.65%, 95%CI -4.93 to -0.28%, p=0.026), but there was no significant difference in antibiotic initiation. The reduction in antibiotic durations was associated with 335,912 fewer days of treatment. The embedded RCT detected no differences in outcomes between the dynamic and static reports. CONCLUSIONS Peer comparison audit and feedback is a pragmatic intervention that can generate small relative reductions in the use of antibiotics for prolonged durations that translate to large reductions in antibiotic days of treatment across populations.
Spectral-domain optical coherence tomography in paracentral acute middle maculopathy associated with vasopressor exposure

Visual field deficits are a common presentation in optometric practice. Patients often report a unilateral or bilateral scotoma and decreased visual acuity. These symptoms are frequently accompanied by fundoscopic changes usually indicating an underlying macular pathology or optic nerve disorders. However, some patients present with a sudden onset of paracentral scotomas that affect one or both eyes. Paracentral scotomas are typically the only symptoms experienced by patients, as visual acuity is unaffected and fundus examination shows no abnormalities. Such a subtle presentation can indicate a diagnosis of paracentral acute middle maculopathy (PAMM) among other maculopathies, but the key to the diagnosis are retinal changes visible on spectral-domain optical coherence tomography images (SD-OCT). On SD-OCT scans, PAMM lesions present as a hyperreflective parafoveal band at the level of the inner nuclear layer and outer plexiform layer, which evolve into permanent inner nuclear layer thinning. Paracentral acute middle maculopathy is believed to be a manifestation of focal ischaemia of the deep retinal circulation. The underlying conditions associated with PAMM lesions vary widely and include various retinal, vascular, or systemic diseases including diabetic retinopathy, hypertensive retinopathy, sickle cell retinopathy, Purtscher retinopathy, central retinal vein occlusion, or retinal artery occlusion, as well as environmental risk factors such as vasopressor exposure (e.g. caffeine intake), dehydration, or oral contraceptive. In this report, we describe the clinical course and imaging findings of a single case of paracentral acute middle maculopathy secondary to hypertensive retinopathy, migraine, and vasopressor exposure.
Combined effects of 3-nitrooxypropanol and canola oil supplementation on methane emissions, rumen fermentation and biohydrogenation, and total-tract digestibility in beef cattle.

The individual and combined effects of 3-nitrooxypropanol (3-NOP) and canola oil (OIL) supplementation on enteric methane (CH4) and hydrogen (H2) emissions, rumen fermentation and biohydrogenation, and total-tract nutrient digestibility were investigated in beef cattle. Eight beef heifers (mean body weight ± SD, 732 ± 43 kg) with ruminal fistulas were used in a replicated 4 × 4 Latin square with a 2 (with and without 3-NOP) × 2 (with and without OIL) arrangement of treatments and 28-d periods (13 d adaption, 15 d measurements). The four treatments were: control (no 3-NOP, no OIL), 3-NOP (200 mg/kg dry matter [DM]), OIL (50 g/kg DM), and 3-NOP (200 mg/kg DM) plus OIL (50 g/kg DM). Animals were fed restrictively (7.6 kg DM/d) a basal diet of 900 g/kg DM barley silage and 100 g/kg DM supplement. 3-NOP and OIL decreased (P < 0.01) CH4 yield (g/kg DM intake) by 31.6% and 27.4%, respectively, with no 3-NOP × OIL interaction (P = 0.85). Feeding 3-NOP plus OIL decreased CH4 yield by 51% compared with control. There was a 3-NOP × OIL interaction (P = 0.02) for H2 yield (g/kg DM intake); the increase in H2 yield (P < 0.01) due to 3-NOP was less when it was combined with OIL. There were 3-NOP × OIL interactions for molar percentages of acetate and propionate (P < 0.01); individually 3-NOP and OIL decreased acetate and increased propionate percentages, with no further effect when supplemented together. 3-NOP slightly increased crude protein (P = 0.02) and starch (P = 0.01) digestibilities, while OIL decreased digestibilities of DM (P < 0.01) and neutral detergent fiber (P < 0.01), with no interactions (P = 0.15 and 0.10, respectively). 3-NOP and OIL increased (P = 0.04 and P < 0.01, respectively) saturated fatty acid concentration in rumen fluid, with no interaction effect. Interactions for ruminal trans-monounsaturated fatty acids (t-MUFA) concentration and percentage were observed (P = 0.02 and P < 0.01); 3-NOP had no effect on t-MUFA concentration and percentage, while OIL increased the concentration (P < 0.01) and percentage (P < 0.01) of t-MUFA, but to a lesser extent when combined with 3-NOP. In conclusion, the CH4-mitigating effects of 3-NOP and OIL were independent and incremental. Supplementing ruminant diets with a combination of 3-NOP and OIL may help mitigate CH4 emissions, but the decrease in total-tract digestibility due to OIL may decrease animal performance and needs further investigation.
Benefits and Risks of Non-Slip Socks in Hospitals: A Rapid Review.

BACKGROUND Non-slip socks are sometimes used in an attempt to prevent falls in hospitals despite limited evidence of benefit. We critique the current literature on their risks, benefits and effects. METHODS A rapid review was conducted following the Cochrane Rapid Review Methods Group Guidelines. To be included, studies needed to have data on single or multifactorial interventions that used non-slip socks in hospitals or their safety, risks or effects in a laboratory setting. Six electronic databases were searched: Medline, Embase, Cinahl, Cochrane, AMED and Proquest Central. RESULTS Fourteen articles met the inclusion criteria. Nine used non-slip socks as an intervention in hospitals. Three assessed their effects in laboratory settings. Two reported risks in relation to bacterial transfer. Most studies that used non-slip socks to prevent hospital falls had negative or equivocal results and were of comparatively low method quality, with a high risk of bias. Two of the laboratory tests reported traction socks to be no safer than walking barefoot and to have similar slip resistance. The laboratory studies had a low risk of bias and showed that bacteria can sometimes be acquired from socks. CONCLUSION Non-slip socks carry an infection control risk that requires careful management. There was no strong or conclusive evidence that they prevent hospital falls.