Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of the circadian system of the cockroach Rhyparobia (Leucophaea) maderae

The circadian pacemaker controlling locomotor activity rhythms in the Madeira cockroach is located to the accessory medulla (AMe). The ipsiand contralateral compound eyes provide light input to the AMe, possibly via the γ-aminobutyric acid (GABA)immunoreactive (-ir) distal tract which connects the glomeruli of the AMe to the ipsilateral medulla and lamina. To identify possible light-entrainment pathways, double-label immunocytochemistry was performed employing antibodies against GABA, myoinhibitory peptide (MIP), allatotropin (AT), and orcokinin (ORC). While all antisera tested except the anti-ORC prominently stained the glomeruli of the AMe, colocalization with anti-GABA was detected neither in the glomeruli nor in the distal tract. However, one median neuron which colocalized GABA-, ATand MIP-immunoreactivity appeared to connect all glomeruli of the AMe to medulla and lamina. Furthermore, one distal-frontoventral local neuron with arborizations in all glomeruli of the AMe colocalized anti-ATand anti-MIP immunoreactivity. As candidates for contralateral light entrainment pathways, one ventromedian and one ventral neuron colocalized MIPand ORC immunoreactivity projecting via posterior and anterior commissures. Both branched in the interglomerular region of the AMe, where arborizations co-labelled with anti-ORCand anti-MIP antisera. A possible role for MIP in light entrainment is supported also by injections of Rhyparobia maderaespecific MIP-2 which generated an all-advance phase-response curve at the late night. Future experiments will challenge our hypothesis that GABA-, MIP-, and AT-ir neurons provide ipsilateral light entrainment to all glomeruli, while MIPand ORC-ir neurons carry contralateral light entrainment to the AMe’s interglomerular region either delaying or advancing AMe neurons light-dependently.
Bootstrap simulations to estimate relationships between Type I error, power, effect size, and appropriate sample numbers for bioassessments of aquatic ecosystems

Abstract The Extended Bootstrap (EB) assessment approach was developed for the examination of relationships of Type I error, power, sample size (n), and effect size (ES) for statistical tests of ecological data. The EB approach was applied to univariate and multivariate statistical analyses of a large data set collected from an ongoing, multiple stressor bioassessment study of watersheds in the Central Valley, San Francisco, and Central Coast areas of California. Benthic metrics were created that either increased or decreased monotonically with stress (toxicants or metrics indicative of habitat quality). Type I errors were stable for all statistical tests that were evaluated. The relationships between n and ES displayed patterns of “diminishing returns” for all statistical tests: i.e. an increasingly larger n was required to detect decreasingly smaller ES. Nonetheless, the n’s collected across the watersheds and within a selected watershed were sufficient to detect even small correlations between representative benthic metrics and potential stressors with high power. The power and robustness of a novel method using EB and previously described statistical techniques designed to address multicollinearity were shown to approach those of simpler univariate regressions. Potential applications of the EB approach for experimental design, data assessment and interpretation, and hypothesis testing are discussed.
Do informal caregivers experience more burnout? A meta-analytic study

ABSTRACT Informal caregivers often report exhaustion when providing care, which can be related to forms of burnout. Yet, there is no systematic inventory of studies comparing caregivers and non-caregivers in terms of burnout. For the present meta-analysis, studies comparing burnout in informal caregivers and non-caregivers were screened and included. Two categories of studies were found: those on family care burnout (spousal or parental burnout) and those on professional burnout (mostly in healthcare). For family care burnout studies, informal caregivers reported more emotional exhaustion, and, to a lesser extent, depersonalization and reduced personal accomplishment than non-caregivers. For studies on professional burnout, workers providing informal care also reported more emotional exhaustion than workers not providing such a care. Overall, the results indicate that providing informal care represents a risk for role burnout. In family care burnout studies, these results confirm the assumption that providing informal care adds extra weight on the individuals’ shoulders. In professional burnout, these results support the role accumulation theory, pointing that an additional weight in one’s role, i.e., providing informal care, has an impact on another role, work. This work emphasizes the consideration of the multifaceted impact that the caregiving role can have on the individual.
Additional Og-Typing PCR Techniques Targeting Escherichia coli-Novel and Shigella-Unique O-Antigen Biosynthesis Gene Clusters

The O-serogrouping of pathogenic Escherichia coli is a standard method for subtyping strains for epidemiological studies and controls. O-serogroup diversification shows a strong association with the genetic diversity in some O-antigen biosynthesis gene clusters. Through genomic studies, in addition to the types of O-antigen biosynthesis gene clusters (Og-types) from conventional O-serogroup strains, a number of novel Og-types have been found in E. coli isolates. ABSTRACT The O-serogrouping of pathogenic Escherichia coli is a standard method for subtyping strains for epidemiological studies and controls. O-serogroup diversification shows a strong association with the genetic diversity in some O-antigen biosynthesis gene clusters. Through genomic studies, in addition to the types of O-antigen biosynthesis gene clusters (Og-types) from conventional O-serogroup strains, a number of novel Og-types have been found in E. coli isolates. To assist outbreak investigations and surveillance of pathogenic E. coli at inspection institutes, in previous studies, we developed PCR methods that could determine almost all conventional O-serogroups and some novel Og-types. However, there are still many Og-types that may not be determined by simple genetic methods such as PCR. Thus, in the present study, we aimed to develop an additional Og-typing PCR system. Based on the novel Og-types, including OgN32, OgN33, and OgN34, presented in this study, we designed an additional 24 PCR primer pairs targeting 14 novel and 2 diversified E. coli Og-types and 8 Shigella-unique Og-types. Subsequently, we developed 5 new multiplex PCR sets consisting of 33 primers, including the aforementioned 24 primers and 9 primers reported in previous studies. The accuracy and specificity of the PCR system was validated using approximately 260 E. coli and Shigella O-serogroup and Og-type reference strains. The Og-typing PCR system reported here can determine a wide range of Og-types of E. coli and may help epidemiological studies, in addition to the surveillance of pathogenic E. coli.
Effectiveness of honey for symptomatic relief in upper respiratory tract infections: a systematic review and meta-analysis

Background Antibiotic over prescription for upper respiratory tract infections (URTIs) in primary care exacerbates antimicrobial resistance. There is a need for effective alternatives to antibiotic prescribing. Honey is a lay remedy for URTIs, and has an emerging evidence base for its use. Honey has antimicrobial properties, and guidelines recommended honey for acute cough in children. Objectives To evaluate the effectiveness of honey for symptomatic relief in URTIs. Methods A systematic review and meta-analysis. We searched Pubmed, Embase, Web of Science, AMED, Cab abstracts, Cochrane Library, LILACS, and CINAHL with a combination of keywords and MeSH terms. Results We identified 1345 unique records, and 14 studies were included. Overall risk of bias was moderate. Compared with usual care, honey improved combined symptom score (three studies, mean difference −3.96, 95% CI −5.42 to −2.51, I2=0%), cough frequency (eight studies, standardised mean difference (SMD) −0.36, 95% CI −0.50 to −0.21, I2=0%) and cough severity (five studies, SMD −0.44, 95% CI −0.64 to −0.25, I2=20%). We combined two studies comparing honey with placebo for relieving combined symptoms (SMD −0.63, 95% CI −1.44 to 0.18, I2=91%). Conclusions Honey was superior to usual care for the improvement of symptoms of upper respiratory tract infections. It provides a widely available and cheap alternative to antibiotics. Honey could help efforts to slow the spread of antimicrobial resistance, but further high quality, placebo controlled trials are needed. PROSPERO registration No Study ID, CRD42017067582 on PROSPERO: International prospective register of systematic reviews (https://www.crd.york.ac.uk/prospero/).
Antifungal Susceptibility Profiles and Drug Resistance Mechanisms of Clinical Lomentospora prolificans Isolates

Lomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the in vitro susceptibility of 8 drugs against 42 clinical L. prolificans isolates. All isolates showed high MICs to voriconazole (MIC90>16 μg/ml), itraconazole (MIC90>16 μg/ml), posaconazole (MIC90>16 μg/ml), isavuconazole (MIC90>16 μg/ml), amphotericin B (MIC90>16 μg/ml), and terbinafine (MIC90>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC90>8 μg/ml), with the exception of miltefosine showing an MIC90 value of 4 μg/ml. ABSTRACT Lomentospora prolificans is an opportunistic fungal pathogen with low susceptibility to current antifungal drugs. Here, we tested the in vitro susceptibility of 8 drugs against 42 clinical L. prolificans isolates. All isolates showed high MICs to voriconazole (MIC90>16 μg/ml), itraconazole (MIC90>16 μg/ml), posaconazole (MIC90>16 μg/ml), isavuconazole (MIC90>16 μg/ml), amphotericin B (MIC90>16 μg/ml), and terbinafine (MIC90>64 μg/ml) and high minimum effective concentrations (MECs) to micafungin (MEC90>8 μg/ml), with the exception of miltefosine showing an MIC90 value of 4 μg/ml. We examined six different in vitro drug combinations and found that the combination of voriconazole and terbinafine achieved the most synergistic effort against L. prolificans. We then annotated the L. prolificans whole genome and located its Cyp51 and Fks1 genes. We completely sequenced the two genes to determine if any mutation would be related to azole and echinocandin resistance in L. prolificans. We found no amino acid changes in Cyp51 protein and no tandem repeats in the 5′ upstream region of the Cyp51 gene. However, we identified three intrinsic amino acid residues (G138S, M220I, and T289A) in the Cyp51 protein that were linked to azole resistance. Likewise, two intrinsic amino acid residues (F639Y, W695F) that have reported to confer echinocandin resistance were found in Fks1 hot spot regions. In addition, three new amino acid alterations (D440A, S634R, and H1245R) were found outside Fks1 hot spot regions, and their contributions to echinocandin resistance need future investigation. Overall, our findings support the notion that L. prolificans is intrinsically resistant to azoles and echinocandins.
Novel, abundant Drosha isoforms are deficient in miRNA processing in cancer cells

ABSTRACT MicroRNAs (miRNAs) are a class of small noncoding RNAs about 22-nucleotide (nt) in length that collectively regulate more than 60% of coding genes. Aberrant miRNA expression is associated with numerous diseases, including cancer. miRNA biogenesis is licenced by the ribonuclease (RNase) III enzyme Drosha, the regulation of which is critical in determining miRNA levels. We and others have previously revealed that alternative splicing regulates the subcellular localization of Drosha. To further investigate the alternative splicing landscape of Drosha transcripts, we performed PacBio sequencing in different human cell lines. We identified two novel isoforms resulting from partial intron-retention in the region encoding the Drosha catalytic domain. One isoform (AS27a) generates a truncated protein that is unstable in cells. The other (AS32a) produces a full-length Drosha with a 14 amino acid insertion in the RIIID domain. By taking advantage of Drosha knockout cells in combination with a previously established reporter assay, we demonstrated that Drosha-AS32a lacks cleavage activity. Furthermore, neither Drosha-27a nor Drosha-32a were able to rescue miRNA expression in the Drosha knockout cells. Interestingly, both isoforms were abundantly detected in a wide range of cancer cell lines (up to 15% of all Drosha isoforms). Analysis of the RNA-seq data from over 1000 breast cancer patient samples revealed that the AS32a is relatively more abundant in tumours than in normal tissue, suggesting that AS32a may play a role in cancer development.
Bio-purification of sugar industry wastewater and production of high-value industrial products with a zero-waste concept

Abstract In recent years, biorefinery approach with a zero-waste concept has gained a lot research impetus to boost the environment and bioeconomy in a sustainable manner. The wastewater from sugar industries contains miscellaneous compounds and need to be treated chemically or biologically before being discharged into water bodies. Efficient utilization of wastewater produced by sugar industries is a key point to improve its economy. Thus, interest in the sugar industry wastes has grown in both fundamental and applied research fields, over the years. Although, traditional methods being used to process such wastewaters are effective yet are tedious, laborious and time intensive. Considering the diverse nature of wastewaters from various sugar-manufacturing processes, the development of robust, cost-competitive, sustainable and clean technologies has become a challenging task. Under the recent scenario of cleaner production and consumption, the biorefinery and/or close-loop concept, though using different technologies and multi-step processes, namely, bio-reduction, bio-accumulation or biosorption using a variety of microbial strains, has stepped-up as the method of choice for a sustainable exploitation of a wide range of organic waste matter along with the production of high-value products of industrial interests. This review comprehensively describes the use of various microbial strains employed for eliminating the environmental pollutants from sugar industry wastewater. Moreover, the main research gaps are also critically discussed along with the prospects for the efficient purification of sugar industry wastewaters with the concomitant production of high-value products using a biorefinery approach. In this review, we emphasized that the biotransformation/biopurification of sugar industry waste into an array of value-added compounds such as succinic acid, L-arabinose, solvents, and xylitol is a need of hour and is futuristic approach toward achieving cleaner production and consumption.
Influence of evolving HIV treatment guidance on CD4 counts and viral load monitoring: A mixed-methods study in three African countries

ABSTRACT Little is known about how CD4 and viral load testing have evolved following implementation of universal test and treat (UTT) in African settings. We reviewed World Health Organization (WHO) guidance from 2013 to 2018, and compared it against national HIV policies in Malawi, Tanzania and South Africa. Three surveys rounds were conducted in 2013, 2016 and 2017–2018 in 33 health facilities across the three settings to assess implementation of national policies on the use of biological markers. Qualitative interviews were conducted with 26 HIV policymakers or programme managers, 21 providers and 66 people living with HIV to explore understandings and experiences of these tests. Various factors influenced adoption and implementation of WHO guidance, including historical policies on CD4 counts, governance issues, supply chain challenges and funding mechanisms. Facility-level practices relating to the use of these tests often diverged from national policies. Patients and providers valued both tests, but did not always understand their roles. In addition to continued support for scaling-up viral load testing, renewed focus should be placed on the ongoing value of point-of-care CD4 tests in the UTT era, including its role in assessing disease progression and informing clinical management of cases to reduce HIV-related mortality.
Leisure Activity Engagement Among the Oldest Old in China, 1998-2018.

Objectives. To examine the trends of leisure activity engagement among the oldest old in China for the past 2 decades.Methods. Our panel data came from the Chinese Longitudinal Healthy Longevity Survey, which systematically asked respondents about their current participation in leisure activities over a 20-year period. The final sample contained 66 789 interviews from 1998 to 2018. We applied generalized estimating equations regression models in our analysis.Results. Compared with 1998, odds ratios of television watching among Chinese oldest old individuals increased by about 2 to 3 times in 2018. Meanwhile, the odds ratio of exercise declined by 24%, mostly in men; playing cards and mah-jongg declined by about 30% for men. Results also showed that reading became less popular in the oldest old, and Chinese women tended to do more housework than before.Conclusions. Our findings indicated that Chinese oldest old persons have become more sedentary and solitary in the past 2 decades. The negative trend in leisure activity engagement among the elderly Chinese population warrants policy attention, and the urgent development of public health interventions is required to reverse such trends. (Am J Public Health. Published online ahead of print August 20, 2020: e1-e3. doi:10.2105/AJPH.2020.305798).
Cohort profile: COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO)

Purpose Migraine has consistently been connected with rosacea. Commonalities in epidemiology, trigger factors and associated neuropeptides support shared aetiology and pathophysiological pathways, though underlying mechanisms remain unclear. We established two cohorts of patients diagnosed with either migraine and/or rosacea. All patients were phenotyped in regard to migraine and rosacea. In this article, we describe the baseline parameters of the cohorts. In the future, we expect that these cohorts will help uncover potential disease overlaps and allow for prolonged follow-up through national Danish health registers. Participants COpenhagen ROsacea COhort (COROCO) and COpenhagen MIgraine COhort (COMICO) are prospective cohorts based in the Capital region of Denmark. Participants for COROCO were recruited primarily through two tertiary dermatology clinics in Copenhagen, Denmark and patients for COMICO were recruited through a tertiary neurology clinic in Copenhagen, Denmark. Findings to date COROCO: 67.7% women (median age 51 years (interquartile range (IQR) 43.0–61.0)). Family history of migraine: 44.3%. Family history of rosacea: 45%. There were 13% who currently smoked, and 36.6% were former smokers. Regular intake of alcohol was present in 79.3% (median 4 items/week (IQR 1.0–9.0)). Median body mass index (BMI): 25.7 (IQR 23.1–29.0). Median Dermatology Life Quality Index (DLQI): 2 (IQR 1–5). COMICO: 88.5% women (median age 41 years (IQR 29.5–51.0)). Family history of migraine: 73.4%. Family history of rosacea: 18.4%. There were 17.1% who currently smoked, and 26.0% former smokers. Regular intake of alcohol was present in 62.2% (median intake: 2 item/week (IQR 1.0–3.0)). Median BMI was 24.6 (IQR 21.5–28.2). Median DLQI was 1 (IQR 0–2). Future plans COROCO and COMICO serve as strong data sources that will be used for future studies on rosacea and migraine with focus on risk factors, occurrence, treatment, natural history, complications, comorbidities and prognosis. Trial registration number ClinicalTrials.gov Registry (NCT03872050).
CircTHBS1 targeting miR-211/CCND2 pathway to promote cell proliferation and migration potential in primary cystitis glandularis cells

Abstract The pathogenesis of cystitis glandular (CG) is unclear, but it is generally considered to be a neoplastic lesion of urothelial hyperplasia formed by long-term chronic stimulation. There is growing evidence that circRNAs play important roles in a variety of cellular processes. However, there are few reports on the role and molecular mechanism of circRNA in CG. In the present study, we first isolated primary cells from CG tissues and adjacent normal tissues. Further experiments showed that CircTHBS1 was up-regulated in primary CG cells (pCGs). The results of CCK-8 showed that the overexpression of CircTHBS1 promoted the viability of pCGs, while the deletion of CircTHBS1 reduced the cell viability. Knocking out CircTHBS1 also inhibited the migration of pCGs. In addition, we demonstrated that CircTHBS1 played a role in the adsorption of miR-211 by “sponge” in pCG. In turn, miR-211 can directly target CYCLIN D2 (CCND2) 3′UTR to perform its function. Finally, we confirmed the role and mechanism of CircTHBS1/miR-211/CCND2 regulation axis in pCGs. In summary, our study is the first to reveal the role and underlying mechanism of CircTHBS1 in CG, providing a potential biomarker and therapeutic target for human CG.
Circadian regulation of c-MYC in mice

Significance A molecular clock controls circadian rhythmicity in mammals. The interplay of the clock with cellular growth and development is of interest regarding possible connections between cancer and clock disruption. The c-MYC oncoprotein is a transcriptional activator that has been reported to control and be controlled by the clock. We have used knockout mice mutated in genes controlling either the negative or positive arm of the molecular clock to clarify the role of the clock in c-MYC regulation. Results with both types of mutant mice consistently show that the clock controls c-MYC protein levels by controlling expression of the c-Myc oncogene. These findings will aid in understanding the interplay of the clock and clock disruption on cell growth control and cancer. The circadian clock is a global regulatory mechanism that controls the expression of 50 to 80% of transcripts in mammals. Some of the genes controlled by the circadian clock are oncogenes or tumor suppressors. Among these Myc has been the focus of several studies which have investigated the effect of clock genes and proteins on Myc transcription and MYC protein stability. Other studies have focused on effects of Myc mutation or overproduction on the circadian clock in comparison to their effects on cell cycle progression and tumorigenesis. Here we have used mice with mutations in the essential clock genes Bmal1, Cry1, and Cry2 to gain further insight into the effect of the circadian clock on this important oncogene/oncoprotein and tumorigenesis. We find that mutation of both Cry1 and Cry2, which abolishes the negative arm of the clock transcription–translation feedback loop (TTFL), causes down-regulation of c-MYC, and mutation of Bmal1, which abolishes the positive arm of TTFL, causes up-regulation of the c-MYC protein level in mouse spleen. These findings must be taken into account in models of the clock disruption–cancer connection.