Miracle-dz/UniFAR-FTUs huggingface dataset:
Coevolution-based prediction of protein-protein interactions in polyketide biosynthetic assembly lines

Polyketide synthases are multimodular enzymes that generate diverse molecules of great pharmaceutical importance, including a range of clinically used antimicrobials and antitumor agents. Many polyketides are synthesized by type I polyketide synthases (PKSs), which are organized in assembly lines, in which multiple enzymes line up in a specific order. This order is defined by specific protein-protein interactions. The unique modular structure and catalyzing mechanism of these assembly lines makes their products predictable and also spurred combinatorial biosynthesis studies to produce novel polyketides using synthetic biology. However, predicting the interactions of PKSs, and thereby inferring the order of their assembly line, is still challenging, especially for cases in which this order is not reflected by the ordering of the PKS-encoding genes in the genome. Here, we introduce PKSpop, which uses a coevolution-based protein-protein interaction prediction algorithm to infer protein order in PKS assembly lines. Our method accurately predicts protein orders (80% accuracy). Additionally, we identify new residue pairs that are key in determining interaction specificity, and show that coevolution of N- and C-terminal docking domains of PKSs is significantly more predictive for protein-protein interactions than coevolution between ketosynthase and acyl carrier protein domains.
Potential Impacts of Coyotes and Snowmobiles on Lynx Conservation in the Intermountain West

Abstract Researchers and managers have hypothesized that coyote (Canis latrans) incursions into deep snow areas, facilitated by packed trails created by snowmobiles, may negatively impact lynx (Lynx canadensis) populations through interference or exploitation competition. In response to this hypothesis, federal agencies have limited snowmobile use within potential lynx habitat. We used aerial track counts and ground tracking to compare coyote activity in deep snow areas with and without snowmobile trails on the Uinta Mountain Range of northeastern Utah, USA, and 3 comparable sites in the Intermountain West to test this hypothesis. Our analysis suggests that snowmobile trail presence is a good predictor of coyote activity in deep snow areas. Over 90% of coyote tracks observed in our study areas associated with a snowmobile trail were within 350 m of the trail. Snow depth and prey density estimates influenced whether a coyote returned to a snowmobile trail. Our results suggest that restrictions placed on snowmobiles in lynx conservation areas by land management agencies because of the potential impacts of coyotes may be appropriate.
Sex-Based Performance Responses to an Acute Sprint Interval Cycling Training Session in Collegiate Athletes

ABSTRACT There are limited data pertaining to the effects of sex on sprint interval cycling (SIC) training session performance. Purpose: We investigated sex-based differences on sprint interval cycling (SIC) performance in collegiate soccer players. Methods: Twelve men and twelve women completed two identical lab trials, 7–14 days apart. The first lab session served as familiarization, “dry run,” trial. Reported data were collected and analyzed during the second, “testing” SIC training trial. Each SIC training session was comprised of a warm-up, at 50 revolutions per min (RPM) with no resistance, and six repeated 30-s Wingate Anaerobic Tests (WAnT) separated by a 4-min recovery period between each sprint. Results: Significant (P ≤ .05) sex differences were observed in peak power (PP), peak power relative to body mass (RPP), mean power (MP), mean power relative to body mass (RMP) but not in peak power relative to fat free mass (FFMPP). When WAnT bouts 2–6 were expressed as %Δ of WAnT1, there were no significant (P > .05) differences between the sexes across all performance variables. Further, Cohen’s d statistics demonstrated only trivial and small effect size between the groups. Average HR and RPE were not significantly (P > .05) different between the sexes. Correlational analysis revealed a significant (P ≤ .05) relationship between FFM, and PP and MP. Conclusion: Although overall performance may be affected by a number of physiological mechanisms, the results of the current study indicate that differences between men and women soccer players performing SIC training, are likely attributed to differences in body composition.
Preclinical drug studies in MEN1-related neuroendocrine neoplasms (MEN1-NENs).

Neuroendocrine neoplasms (NENs) occur usually as sporadic tumours; however, rarely, they may arise in the context of a hereditary syndrome, such as multiple endocrine neoplasia type 1 (MEN1), an autosomal dominant disorder characterised by the combined development of pancreatic NENs (pNENs) together with parathyroid and anterior pituitary tumours. The therapeutic decision for sporadic pNENs patients is multi-disciplinary and complex: based on the grade and stage of the tumor, various options (and their combinations) are considered, such as surgical excision (either curative or for debulking aims), biological drugs (somatostatin analogues), targeted therapies (mTOR inhibitors or tyrosine kinases (TK)/receptors inhibitors), peptide receptor radioligand therapy (PRRT), chemotherapy, and liver-directed therapies. However, treatment of MEN1-related NENs' patients is even more challenging, as these tumours are usually multifocal with co-existing foci of heterogeneous biology and malignant potential, rendering them more resistant to the conventional therapies used in their sporadic counterparts, and therefore associated with a poorer prognosis. Moreover, clinical data using standard therapeutic options in MEN1-related NENs are scarce. Recent preclinical studies have identified potentially new targeted therapeutic options for treating MEN1-associated NENs, such as epigenetic modulators, Wnt pathway-targeting β-catenin antagonists, Ras signalling modulators, Akt/mTOR signalling modulators, novel somatostatin receptors analogues, anti-angiogenic-drugs, and MEN1 gene replacement therapy. The present review aims to summarize these novel therapeutic opportunities for NENs developing in the context of MEN1 syndrome, with an emphasis on pancreatic NENs, as they are the most frequent ones studied to date; moreover, relevant data on MEN1-pituitary NENs are briefly described.
When a Specialty Becomes "Women's Work": Trends in and Implications of Specialty Gender Segregation in Medicine.

Even after 20 years of near gender parity among medical students, the gender composition of physician specialties varies dramatically with some becoming increasingly female-predominant while others remain overwhelmingly male. In their analysis of physician workforce data, the authors demonstrate that despite large increases in the number of female physicians over 4 decades, the degree of gender segregation between specialties has not declined. The authors describe lessons from the highly gender-segregated U.S. workforce as a whole to understand these demographic patterns in the physician workforce. Echoing U.S. workforce findings, women physicians are becoming overrepresented in certain specialties and this appears be associated with a relative decline in earnings for physicians in these specialties over time. The authors found a strong negative relationship between the proportion of female physicians in a specialty and its mean salary, with gender composition explaining 64% of the variation in salaries among the medical specialties.Female physicians face biases in the workplace and fall behind male peers in leadership attainment, academic advancement, and earnings. Tenacious gender stereotypes and the conflation of gender and status contribute to these biases and reinforce occupational gender segregation. The clustering of women in certain specialties means these specialties will be disproportionately affected by gender bias. Recognizing the consequences of gender demographics within physician specialties is important to maintain the strong and diverse physician workforce needed to support the health care needs of the populations who depend on these specialties for care.
Accuracy of Telephone-Based Cognitive Screening Tests: Systematic Re-view and Meta-Analysis.

BACKGROUND Telephone-based cognitive assessments may be preferable to in-person testing in terms of test burden, economic and opportunity cost. OBJECTIVE We sought to determine the accuracy of telephone-based screening for the identification of dementia or mild cognitive impairment (MCI). METHODS Five multidisciplinary databases were searched. Two researchers independently screened articles and extracted data. Eligible studies compared any multi-domain telephone-based assessment of cognition to the face-to-face diagnostic evaluation. Where data allowed, we pooled test accuracy metrics using the bivariate approach. RESULTS From 11,732 titles, 34 papers were included, describing 15 different tests. There was variation in test scoring and quality of included studies. Pooled analyses of accuracy for dementia: Telephone Interview for Cognitive Status (TICS) (<31/41) sensitivity:0.92, specificity:0.66 (6 studies); TICS-modified (<28/50) sensitivity:0.91, specificity:0.91 (3 studies). For MCI: TICS-modified (<33/50) sensitivity:0.82, specificity:0.87 (3 studies); Telephone-Montreal Cognitive Assessment (<18/22) sensitivity:0.98, specificity:0.69 (2 studies). CONCLUSION There is limited diagnostic accuracy evidence for the many telephonic cognitive screens that exist. The TICS and TICS-m have the greatest supporting evidence; their test accuracy profiles make them suitable as initial cognitive screens where face to face assessment is not possible.
Omics technologies for kidney disease research

Omics‐based technologies in the areas of genomics, transcriptomics, and proteomics are revolutionizing research into many types of human and experimental disease. This review focuses on the potential of omics technologies to identify pathogenic mechanisms and biomarkers of disease in order to improve the diagnosis, prognosis, monitoring, and treatment of kidney disease.
Factors Associated with Time Intervals for Diagnosis of Colorectal Cancer: A Hospital Based Study in Khon Kaen, Thailand

Background: Colorectal cancer (CRC) is among the five-leading cancers in Thailand. Delayed diagnosis is crucial for undermining the prognosis of the patients. This study aims to evaluate the factors associated with the time interval for diagnosis (TID). Methods: A cross-sectional analytical study of 191 CRC patients with histological confirmation who were undergoing treatment in the tertiary hospital in Khon Kaen Province was conducted. The data were obtained by interview and retrieving from medical records. The time interval in each diagnostic process is reported in geometric mean. The geometric mean ratio (GMR) used to interpret the results from multiple linear regressions that analyze the relationship between factors and log-transformed TID. Results: Most patients were males (61.78%) with mean age of 61.28±10.2 years old. The geometric mean of TID was 263.48 days. Two factors were significantly associated with longer TID: first visit at a tertiary hospital (GMR=7.77 relative to secondary hospital; 95%CI=1.95 to 30.57) and distance to tertiary healthcare. Two factors were significantly associated with shorter TID: officer/ state enterprise (GMR=0.53 relative to agriculture; 95%CI=0.28 to 0.98) and cost of traveling to secondary healthcare. Conclusions: The results showed the occupation, first health care visit, distance and cost were factors associated with TID. Improving the facilities at the secondary healthcare units for diagnosing CRC would be likely to help to reduce the wasted time in the healthcare system.
Sarcopenia as a Prognostic Factor for 90-Day and Overall Mortality in Patients Undergoing Spine Surgery for Metastatic Tumors: A Multicenter Retrospective Cohort Study.

BACKGROUND Novel methods in predicting survival in patients with spinal metastases may help guide clinical decision-making and stratify treatments regarding surgery vs palliative care. OBJECTIVE To evaluate whether the frailty/sarcopenia paradigm is predictive of survival and morbidity in patients undergoing surgery for spinal metastasis. METHODS A total of 271 patients from 4 tertiary care centers who had undergone surgery for spinal metastasis were identified. Frailty/sarcopenia was defined by psoas muscle size. Survival hazard ratios were calculated using multivariate analysis, with variables from demographic, functional, oncological, and surgical factors. Secondary outcomes included improvement of neurological function and postoperative morbidity. RESULTS Patients in the smallest psoas tertile had shorter overall survival compared to the middle and largest tertile. Psoas size (PS) predicted overall mortality more strongly than Tokuhashi score, Tomita score, and Karnofsky Performance Status (KPS). PS predicted 90-d mortality more strongly than Tokuhashi score, Tomita score, and KPS. Patients with a larger PS were more likely to have an improvement in deficit compared to the middle tertile. PS was not predictive of 30-d morbidity. CONCLUSION In patients undergoing surgery for spine metastases, PS as a surrogate for frailty/sarcopenia predicts 90-d and overall mortality, independent of demographic, functional, oncological, and surgical characteristics. The frailty/sarcopenia paradigm is a stronger predictor of survival at these time points than other standards. PS can be used in clinical decision-making to select which patients with metastatic spine tumors are appropriate surgical candidates.
Rediscovery of Juliomys pictipes (Rodentia: Cricetidae) in Argentina: emended diagnosis, geographic distribution, and insights on genetic structure

Juliomys pictipes, the type species of this sylvan cricetid genus, remains poorly known. In Argentina, country where the type locality is placed, it is only known from the holotype. Here we report the first new Argentinean individuals, after a gap of 80 years; the new specimens -three in total- include one topotype and allow adding two new recording localities for the species. In addition, we refined the geographical location of their type locality and described in detail several morphological traits of this peculiar mouse, producing an emended diagnosis of both the type species and the genus. Molecular data provided in this paper reinforce the identity of J. pictipes and the reference of the southern Brazilian populations of this genus to the type species.
Problem drinking before and during the COVID-19 crisis in US and UK adults: Evidence from two population-based longitudinal studies

Background The impact of the COVID-19 crisis on potentially harmful alcohol consumption is unclear. Aims To test whether the prevalence of problem drinking has changed from before to during the COVID-19 crisis in the US and UK. Design/Setting We examined nationally representative longitudinal data on how problem drinking has changed from pre-pandemic levels among adults in the US (N=7,327; Understanding America Study) and UK (N=12,594; UK Household Longitudinal Study). Methods In the US, we examined rates of consuming alcohol [≥] 4 times in the past week at baseline (March, 2020) and across four waves of follow-up (April-May, 2020). In the UK we assessed the prevalence of consuming alcohol [≥] 4 times per week and weekly heavy episodic drinking using the AUDIT-C at baseline (2017-2019) and during the COVID-19 lockdown (April, 2020). We also tested whether there were specific groups at greater risk of increased problem drinking during the pandemic. Results Among US adults, there was a statistically significant increase in the percentage of participants reporting drinking alcohol [≥] 4 times a week which rose significantly from 11.7% to 17.9% (53% increase, p < .001) as the COVID-19 crisis developed in the US. Among UK adults, the percentage of participants reporting drinking [≥] 4 times a week increased significantly from 14.2% to 23% (62% increase, p < .001) and heavy episodic drinking at least weekly increased significantly from 9.7% to 16.6% (71% increase, p < .001) when compared to pre-COVID-19 lockdown levels. Trends were similar across population demographics, although those aged under 50 years and higher income groups displayed the largest increases. Conclusions The COVID-19 crisis has been associated with substantial increases in problematic drinking in both US and UK adults.
Some Considerations on External Audits of SDG Implementation

Supreme audit institutions (SAIs) have started to audit the implementation of the Sustainable Development Goals (SDGs). While there is no one single audit model or approach to audit SDG implementation, audits should incorporate a few core methodological features related to the principles of the 2030 Agenda. Four methodological and practical challenges associated with conducting performance audits of SDG implementation, as they differ from traditional audits, are discussed in this paper: 1) problem definition, including the level of investigation in the SDG hierarchy of goals and targets and the audit scope; 2) conceptual challenges inherent in going from the level of individual entities or programs to that of whole-of-government performance; 3) practical considerations that should inform an analysis of the coherence of government actions in a given policy area; and 4) the ways in which audit guidance at the international level can help individual SAIs going forward. Ultimately, this paper aims to inform the broader discussion on evaluation of the SDGs. JEL Classification: H83; O19; O20
Produtividade de pastagens de Coastcross-1 em consórcio com diferentes leguminosas de ciclo hibernal

Objetivou-se com esta pesquisa avaliar tres sistemas forrageiros constituidos por Coastcross-1 (CC) + 100kg de N ha-1 ano-1 + ervilhaca comum; CC + 100kg de N ha-1 ano-1 + trevo vesiculoso; e CC + 200kg de N ha-1 ano-1. Durante o periodo experimental (345 dias), foram realizados treze pastejos. Para avaliacao, foram utilizadas vacas em lactacao da raca Holandesa. Foram avaliadas a massa de forragem, composicao botânica, relacao folha/colmo; taxa de acumulo diario, producao e consumo de forragem; eficiencia de pastejo e taxa de lotacao. Os valores medios de producao de forragem e lotacao foram de 21,0; 20,3 e 24,3t ha-1; 7,0; 6,5 e 7,7 unidades animais ha-1 dia-1, para os respectivos sistemas forrageiros. Melhores resultados foram obtidos no consorcio de CC com ervilhaca e no cultivo singular de CC
Age Associated Coronavirus Disease 2019 Incubation Period: Impact on Quarantine Policy

A unified 14-day quarantine may not effectively contain the spread of COVID-19. With the current recommendation of a uniform 14-day quarantine, up to 9.2% of patients 42 or younger and 18.6% of patients older than 42 years could develop symptoms after the end of the period.
The foliose Bangiales (Rhodophyta) in the northern part of the North Atlantic and the relationship with the North Pacific foliose Bangiales -- Diversity, distribution, phylogeny and phylogeography

Foliose Bangiales species have a long history of study in the North Atlantic, but regions, especially in the northern parts, need more attention. Based on both new collections and herbarium material from Iceland, the Faroe Islands, West Greenland, UK, Norway, Sweden, Denmark and the Northwest Atlantic coast (from Newfoundland to Florida) the aim was to document diversity and distribution of foliose Bangiales species in the North Atlantic and to make floristic comparisons between the geographical areas. Species Identification was based on DNA sequences using the mitochondrial cox1, chloroplast rbcL and 3' rbcL + 5' rbcL-S markers. The North Atlantic species were analysed in a larger phylogenetic context based on rbcL sequences, with special emphasis on the relationship between the North Atlantic and North Pacific foliose Bangiales. Using the mitochondrial cox2-3 and nuclear ITS1 spacers a preliminary phylogeographic study was carried out for Wildemania amplissima that is represented in both the North Atlantic and North Pacific. Four foliose Bangiales genera and 26 species were documented from the North Atlantic, and including both recent collections and herbarium material, the work documented both present and historic foliose Bangiales species diversity and geographic distribution, and demonstrated the value of well-preserved historic collections. Eleven foliose Bangiales species were reported from Iceland and the Faroe Islands, and seven species were reported from West Greenland. The Northwestand Northeast Atlantic foliose Bangiales floras were equally diverse but with some differences in species composition. Pyropia njordii sp. nov. was described from the Faroe Islands, with distribution records from Iceland, West Greenland, Northeast Canada and Northeast America, and Wildemania abyssicola comb. nov. was documented from from Iceland and northern Norway. Pyropia thulaea was reported for the first time from the Northwest Atlantic coast, and Py. peggicovensis and "Py. novae-angliae" were reported for the first time in the Northeast Atlantic. A close phylogenetic relationship was observed between the North Atlantic and North Pacific foliose Bangiales, especially between the West Greenland flora and the North Pacific flora. The ITS1 spacer was used in resolving phylogeogaphic patterns in W. amplisima, with 16 haplotypes recovered, and a much higher haplotype diversity recovered in the North Atlantic than in the North Pacific.
ANTIOXIDANT ACTIVITY OF ETHANOLIC ROOT EXTRACT OF ANACYCLUS PYRETHRUM

The ethanolic extract of Anacyclus pyrethrum root was screened for invitro and exvivo antioxidant ac tivities by using different experimental models . Safer antioxidants suitable for long term use are needed to prevent or stop the progression of free radical mediated disorders such as arthritis , hemorrhagic shock, atherosclerosis, diabetes, hepatic injur y, aging neurodegenerative diseases and carcinogenesis . Antioxidant activity of ethanolic extract of Anacyclus pyrethrum root were assessed using DPPH, hydroxyl, hydrogen peroxide ,determination of reducing power ,nitric oxide in vitro scavenging models a nd ex vivo models such as assay on lipid peroxidation using rat brain homogenate . The extract were also studied for total phenolic, flavonoids ,and ascorbic acid compounds content . The ethanolic extract of Anacyclus pyrethrum root exhibited significant sca venging activity in DPPH, hydroxyl, hydrogen peroxide, nitric oxide in vitro scavenging models.The reducing power of the extract increased in dose dependant manner and the extract also showed marked protection in lipid peroxidation The ethanolic extract of Anacyclus pyrethrum root shows significant antioxidant activity in different in vitro and ex vivo models. The antioxidant potential of the Anacyclus pyrethrum root extract may due to their photochemical constituents such as phenols, flavonoids, alkaloids, tannins . Thus augmenting the wide use of plant in the indigenous system of medicine for free radical mediated disease.