Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein kinase C signalling involved in prothoracicotropic hormone‐stimulated prothoracic glands in the silkworm, Bombyx mori

In the present study, the participation of protein kinase C (PKC) signalling in prothoracicotropic hormone (PTTH)‐stimulated ecdysteroidogenesis in Bombyx prothoracic glands (PGs) is demonstrated and characterized. PTTH stimulated phosphorylation of a 37‐kDa protein in Bombyx PGs both in vitro and in vivo, as recognized by a PKC substrate antibody. Treatment with either A23187 or thapsigargin also stimulated this 37‐kDa protein phosphorylation. PTTH‐stimulated phosphorylation of the 37‐kDa protein was markedly attenuated in the absence of Ca2+. The phospholipase C (PLC) inhibitor, U73122, greatly inhibited PTTH‐stimulated phosphorylation of this protein, indicating the involvement of Ca2+ and PLC. A mitogen‐activated protein kinase/extracellular signal‐regulated kinase (ERK) kinase (MEK) inhibitor (U0126), a phosphoinositide 3‐kinase (PI3K) inhibitor (LY294002) and a chemical activator of adenosine 5′‐monophosphate‐activated protein kinase (AMPK) (5‐aminoimidazole‐4‐carboxamide‐1‐β‐d‐ribofuranoside) did not affect PTTH‐stimulated phosphorylation of the 37‐kDa protein, implying that ERK and PI3K/AMPK are not the upstream signalling pathways for PKC‐dependent protein phosphorylation. The mitochondrial oxidative phosphorylation inhibitors (the uncoupler carbonyl cyanide p‐trifluoromethoxyphenylhydrazone and diphenylene iodonium) inhibited PTTH‐stimulated phosphorylation of the 37‐kDa protein, indicating its redox regulation. Treatment with PKC inhibitors (either calphostin C, chelerythrine C or rottlerin) reduced PTTH‐stimulated phosphorylation of the 37‐kDa protein. PTTH‐stimulated ecdysteroidogenesis was also inhibited by treatment with rottlerin, thus further confirming participation of PKC‐dependent phosphorylation in PTTH signalling. From these results, we demonstrated that redox‐regulated PTTH‐stimulated PKC signalling is involved in ecdysteroid secretion in Bombyx PGs.
Influence of the COVID‐19 pandemic on executive skills in Canadians experiencing social vulnerability: A descriptive study

Abstract The objective of this study was to describe executive skills in clients experiencing social vulnerability in the context of COVID‐19 from the perspective of social service agency staff. COVID‐19 has required transformational changes to livelihood and day‐to‐day living. Socially vulnerable individuals are likely to be disproportionally impacted because many have experienced serious early childhood adversity, which may compromise their executive skills in adulthood. Using a cross‐sectional survey, we collected data between 05 May 2020 and 03 July 2020, for this mixed methods study of 53 staff in two agencies in western Canada serving clients experiencing social vulnerability. The first case of COVID‐19 in this jurisdiction was identified 05 March 2020. Using investigator‐designed survey items, we captured executive skills in five areas: (a) planning tasks of daily living, (b) managing time, (c) keeping track of information and appointments, (d) managing emotions, and (e) managing self‐control. Staff reported their clients struggled with executive skills and these struggles increased during COVID‐19, particularly in the areas of managing daily tasks and emotional regulation. COVID‐19 restrictions overwhelmed clients with the decisions required to maintain health, employment, and childcare. With the loss of structure and routine, clients lost track of time and delayed completion of tasks, which further increased stress. Disrupted goals and uncertainty about the future contributed to hopelessness for clients who were trying to regain control over their lives, which made it difficult to manage emotions. Some clients acted more impulsively because of the added stressors, lack of routine and access to friends and extended family. A better understanding of the impact of COVID‐19 on socially vulnerable clients will inform social service agencies about areas to focus programming to support their socially vulnerable clients.
Healthcare Provider Communication Patterns during Consultations about Treating Localized Prostate Cancer.

Background Disparities in mortality in prostate cancer may reflect differences in healthcare providers' communication. Objective This study examined physicians' communication with African American and Caucasian men when making decisions about treatment for localized prostate cancer to determine whether information-giving and partnership-building behaviors varied by the age, education level, and race of the patient. Methods The study was a secondary analysis of data from a larger study examining decisionmaking among men with prostate cancer. Verbatim transcripts of physician communication with 13 African American and 32 Caucasian patients were coded using a well-established scheme. Results Physicians tended to use information-giving and partnership-building behaviors more often with patients who were Caucasian, but this practice was tempered by the patient's age or education level. Conclusion Information-giving and partnership-building behaviors should be studied relative to patient outcomes, such as treatment adherence and satisfaction. Communication is a two-way interaction, and patients' perceptions should be included in future studies. Practice implications Biases, assumptions, and differential behavior toward patients who are older, minorities, or less educated must be addressed during all healthcare providers' socialization and education. All will benefit from their education in communication and partnership-building with patients.
Long non-coding RNA (LncRNA) SNHG7/ Eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) involves in the malignant events of ovarian cancer cells with paclitaxel resistant

ABSTRACT LncRNA SNHG7 shows a strong relationship with malignant behavior of cancer cells and poor clinical outcome in cancer. The resistance of ovarian cancer for Paclitaxel seriously limits the clinical efficacy in chemotherapy for ovarian cancer patients. In this study, we investigated whether lncRNA SNHG7 was involved in Paclitaxel sensitivity of ovarian cancer as well as the underlying mechanism regulating the behavior of ovarian cancer cells with Paclitaxel resistance. The experiment results of wound healing and transwell showed that in paclitaxel-resistant ovarian cancer cells, transfection with siRNA-SNHG7 in ovarian cancer cells reduced cell migration and invasion. And cell cycle was observed by means of Flow cytometry. RNA immunoprecipitation assay was performed to analyze the interaction of lncRNA SNHG7 and EIF4G2. Overexpression of EIF4G2 by transfection with Ov- EIF4G2 plasmids efficiently blocked the changes of migration and invasion, as well as G0/1 arrest caused by lncRNA SNHG7 silencing. Taken together, these results demonstrated that lncRNA SNHG7 could affect the degradation of EIF4G2 to regulate the sensitivity of ovarian cancer to Paclitaxel, inhibit cell viability, migration, and invasion. The interaction of lncRNA SNHG7 and EIF4G2 plays an important role in the migrative and invasive activity and Paclitaxel resistance of ovarian cancer cells.
Idiopathic Interstitial Pneumonias: A Review of the Past and Emerging Therapies

Purpose This article is an in-depth review of the complex classification, diagnosis, and treatment of idiopathic interstitial pneumonias (IIP), as well as emergence of new treatment options. Summary: Idiopathic interstitial pneumonias consist of various subgroup classifications that require expert analysis of imaging and histology to accurately diagnose this broad group of patients. Timely and accurate assessment of these patients is key in developing an appropriate pharmacological plan. The pathophysiology of IIP is not well understood but has been linked to an immune response resulting in inflammation, fibrosis, or proliferation of lung tissue which reduces lung function. Lung transplantation is currently the only curative option for treatment, but many new antiproliferative and immunosuppressive agents are being used to effectively slow the progression of lung dysfunction. Conclusion: An often mixed radiological and histological pattern along with the invasive nature of biopsy for gold standard diagnosis create a challenge for the accurate identification of IIP. Further understanding of these idiopathic interstitial pneumonias will pave the way forward to the emergence of new treatment options and updates to standards of care.
Rho-dependent transcription termination: a revisionist view

ABSTRACT Rho is a hexameric bacterial RNA helicase, which became a paradigm of factor-dependent transcription termination. The broadly accepted (“textbook”) model posits a series of steps, wherein Rho first binds C-rich Rho utilization (rut) sites on nascent RNA, uses its ATP-dependent translocase activity to catch up with RNA polymerase (RNAP), and either pulls the transcript from the elongation complex or pushes RNAP forward, thus terminating transcription. However, this appealingly simple mechano-chemical model lacks a biological realism and is increasingly at odds with genetic and biochemical data. Here, we summarize recent structural and biochemical studies that have advanced our understanding of molecular details of RNA recognition, termination signaling, and RNAP inactivation in Rho-dependent transcription termination, rebalancing the view in favor of an alternative “allosteric” mechanism. In the revised model, Rho binds RNAP early in elongation assisted by the cofactors NusA and NusG, forming a pre-termination complex (PTC). The formation of PTC allows Rho to continuously sample nascent transcripts for a termination signal, which subsequently traps the elongation complex in an inactive state prior to its dissociation.
Folktales of Recovery – From Addiction to Becoming a Helper: Deep Structures of Life Stories Applying Propp’s Theory: A Narrative Analysis

ABSTRACT Addiction research suggests that recovery narratives share common structural elements. For further investigation of this topic, the current study invoked Propp’s folktale theory and method to identify narratemes within retrospectives to depict the stages of recovery. Semi-structured interviews were recorded about the experiences of six recovering helpers who had been sober for a minimum of five years and worked as a professional for at least one year. A deductive narrative analysis was carried out. From the 31 Proppian narratemes, 28 were identified and different recovery stories were threaded into a commonly shared narrative strand, where the hero’s relationship and struggle with the villain (drug) are depicted in process. Applying Propp’s narratemes to analyze recovery stories is a new development that seems applicable according to our results, as it is consistent with fairytale therapy within addiction treatment, which helps the lost wanderer to create structure in their life.
Current status and future possibilities of retinal imaging in diabetic retinopathy care applicable to low- and medium-income countries

Diabetic retinopathy (DR) is a leading cause of blindness among adults and the numbers are projected to rise. There have been dramatic advances in the field of retinal imaging since the first fundus image was captured by Jackman and Webster in 1886. The currently available imaging modalities in the management of DR include fundus photography, fluorescein angiography, autofluorescence imaging, optical coherence tomography, optical coherence tomography angiography, and near-infrared reflectance imaging. These images are obtained using traditional fundus cameras, widefield fundus cameras, handheld fundus cameras, or smartphone-based fundus cameras. Fluorescence lifetime ophthalmoscopy, adaptive optics, multispectral and hyperspectral imaging, and multicolor imaging are the evolving technologies which are being researched for their potential applications in DR. Telemedicine has gained popularity in recent years as remote screening of DR has been made possible. Retinal imaging technologies integrated with artificial intelligence/deep-learning algorithms will likely be the way forward in the screening and grading of DR. We provide an overview of the current and upcoming imaging modalities which are relevant to the management of DR.
When Helping is Risky: The Behavioral and Neurobiological Tradeoff of Social and Risk Preferences

Helping other people can entail risks for the helper. For example, when treating infectious patients, medical volunteers risk their own health. In such situations, decisions to help should depend on the individual’s valuation of others’ well-being (social preferences) and the degree of personal risk the individual finds acceptable (risk preferences). We investigated how these distinct preferences are psychologically and neurobiologically integrated when helping is risky. We used incentivized decision-making tasks (Study 1; N = 292 adults) and manipulated dopamine and norepinephrine levels in the brain by administering methylphenidate, atomoxetine, or a placebo (Study 2; N = 154 adults). We found that social and risk preferences are independent drivers of risky helping. Methylphenidate increased risky helping by selectively altering risk preferences rather than social preferences. Atomoxetine influenced neither risk preferences nor social preferences and did not affect risky helping. This suggests that methylphenidate-altered dopamine concentrations affect helping decisions that entail a risk to the helper.
Gastrointestinal , Hepatobiliary and Pancreatic Pathology Pigment Epithelium-Derived Factor Inhibits Lysosomal Degradation of Bcl-xL and Apoptosis in HepG 2 cells

From the Departments of Digestive Disease Information and Research,* Medicine, Pathophysiology and Therapeutics of Diabetic Vascular Complications, and Surgery, Kurume University School of Medicine, Kurume; the Research Center for Innovative Cancer Therapy, and the 21st Century Center of Excellence, Program for Medical Science, Kurume University, Kurume; and the Third Department of Internal Medicine, School of Medicine, University of Occupational and Environmental Health, Kurume, Japan
X-treme loss of sequence diversity linked to neo-X chromosomes in filarial nematodes

The sequence diversity of natural and laboratory populations of Brugia pahangi and Brugia malayi was assessed with Illumina resequencing followed by mapping in order to identify single nucleotide variants and insertions/deletions. In natural and laboratory Brugia populations, there is a lack of sequence diversity on chromosome X relative to the autosomes (πX/πA = 0.2), which is lower than the expected (πX/πA = 0.75). A reduction in diversity is also observed in other filarial nematodes with neo-X chromosome fusions in the genera Onchocerca and Wuchereria, but not those without neo-X chromosome fusions in the genera Loa and Dirofilaria. In the species with neo-X chromosome fusions, chromosome X is abnormally large, containing a third of the genetic material such that a sizable portion of the genome is lacking sequence diversity. Such profound differences in genetic diversity can be consequential, having been associated with drug resistance and adaptability, with the potential to affect filarial eradication.
Complete Genome Sequence of the Nonmotile Myxococcus xanthus Strain NM

Myxobacteria exhibit multicellular swarming behavior, which depends on the coordination of cell motility. Unlike other myxobacteria, Myxococcus xanthus NM is not capable of forming swarms due to a defective motility system. Here, we present the 9.35-Mbp genome sequence of this nonmotile myxobacterium. ABSTRACT Myxobacteria exhibit multicellular swarming behavior, which depends on the coordination of cell motility. Unlike other myxobacteria, Myxococcus xanthus NM is not capable of forming swarms due to a defective motility system. Here, we present the 9.35-Mbp genome sequence of this nonmotile myxobacterium.
Do strict decision criteria hamper productivity in the pharmaceutical industry?

ABSTRACT The discouragingly high rates of attrition in drug development, and in particular in Phase 2, warrant a closer look at the decision criteria applied for investment in the next phase (Phase 3). We have in this article evaluated Stop/Go criteria after Phase 2, based on a model encompassing both Phase 2 and 3, as well as the eventual outcome on the market. The results indicate that the value of a drug project is often maximized if rather liberal decision criteria are applied. The routine adherence to standard criteria, e.g. requiring significance at 5% level, may lead to an unduly high rate of false negative decisions. This might ultimately hamper the productivity of drug development and leading to potentially useful drugs not being taken forward to benefit the intended patients.
Alpha Globin Gene Copy Number Is Associated with Prevalent Chronic Kidney Disease and Incident End-Stage Kidney Disease among Black Americans

Significance Statement Resistance artery endothelial cells express α-globin, which limits nitric oxide signaling and enhances α-adrenergic–mediated vasoconstriction—two signaling pathways involved in renal blood flow regulation and kidney disease pathogenesis. A common HBA gene deletion might therefore confer protection against kidney disease by increasing endothelial nitric oxide signaling and decreasing vasoconstriction in response to α-1–adrenergic stimuli. Among Black Americans, HBA copy number varied from 2 to 6; an increase by one HBA gene copy was associated with 14% greater risk of CKD and 32% greater hazard of incident ESKD. This study identifies HBA deletions as protective against CKD and ESKD and highlights the importance of understanding the role of α-globin in renovascular pathophysiology. Visual Abstract Background α-Globin is expressed in endothelial cells of resistance arteries, where it limits endothelial nitric oxide signaling and enhances α-adrenergic–mediated vasoconstriction. α-Globin gene (HBA) copy number is variable in people of African descent and other populations worldwide. Given the protective effect of nitric oxide in the kidney, we hypothesized that HBA copy number would be associated with kidney disease risk. Methods Community-dwelling Black Americans aged ≥45 years old were enrolled in a national longitudinal cohort from 2003 through 2007. HBA copy number was measured using droplet digital PCR. The prevalence ratio (PR) of CKD and the relative risk (RR) of incident reduced eGFR were calculated using modified Poisson multivariable regression. The hazard ratio (HR) of incident ESKD was calculated using Cox proportional hazards multivariable regression. Results Among 9908 participants, HBA copy number varied from 2 to 6. In analyses adjusted for demographic, clinical, and genetic risk factors, a one-copy increase in HBA was associated with 14% greater prevalence of CKD (PR, 1.14; 95% CI, 1.07 to 1.21; P<0.0001). While HBA copy number was not associated with incident reduced eGFR (RR, 1.06; 95% CI, 0.94 to 1.19; P=0.38), the hazard of incident ESKD was 32% higher for each additional copy of HBA (HR, 1.32; 95% CI, 1.09 to 1.61; P=0.005). Conclusions Increasing HBA copy number was associated with a greater prevalence of CKD and incidence of ESKD in a national longitudinal cohort of Black Americans.
HIF-1–regulated expression of calreticulin promotes breast tumorigenesis and progression through Wnt/β-catenin pathway activation

Significance Breast cancer stem cells (BCSCs) have the property of infinite self-renewal. When these cells divide, they give rise to one BCSC and one transient amplifying cell that can rapidly proliferate but only for a limited number of cell divisions. Only BCSCs can give rise to secondary (recurrent and/or metastatic) tumors. It is believed that breast cancer recurrence is due to the survival of a small number of BCSCs. Because the BCSCs represent a very small minority of cells within the primary tumor, their unique characteristics may not be detected by bulk tumor analyses. BCSCs are often located within regions of intratumoral hypoxia, and hypoxia-inducible factors activate the transcription of genes that promote BCSC specification and/or maintenance. Calreticulin (CALR) is a multifunctional protein that participates in various cellular processes, which include calcium homeostasis, cell adhesion, protein folding, and cancer progression. However, the role of CALR in breast cancer (BC) is unclear. Here, we report that CALR is overexpressed in BC compared with normal tissue, and its expression is correlated with patient mortality and stemness indices. CALR expression was increased in mammosphere cultures, CD24−CD44+ cells, and aldehyde dehydrogenase–expressing cells, which are enriched for breast cancer stem cells (BCSCs). Additionally, CALR knockdown led to BCSC depletion, which impaired tumor initiation and metastasis and enhanced chemosensitivity in vivo. Chromatin immunoprecipitation and reporter assays revealed that hypoxia-inducible factor 1 (HIF-1) directly activated CALR transcription in hypoxic BC cells. CALR expression was correlated with Wnt/β-catenin pathway activation, and an activator of Wnt/β-catenin signaling abrogated the inhibitory effect of CALR knockdown on mammosphere formation. Taken together, our results demonstrate that CALR facilitates BC progression by promoting the BCSC phenotype through Wnt/β-catenin signaling in an HIF-1–dependent manner and suggest that CALR may represent a target for BC therapy.
Complete Genome Sequences of Two Shiga Toxin-Producing Escherichia coli O146:H10 Strains Recovered from a Foodborne Outbreak in China

Shiga toxin-producing Escherichia coli (STEC) is one of the primary pathogenic contaminants of foods, contributing to several foodborne outbreaks in recent years. Here, we report the complete genome sequences of two non-O157 STEC strains isolated from an outbreak of diarrhea in the city of Guilin, Guangxi Zhuang Autonomous Region, China. ABSTRACT Shiga toxin-producing Escherichia coli (STEC) is one of the primary pathogenic contaminants of foods, contributing to several foodborne outbreaks in recent years. Here, we report the complete genome sequences of two non-O157 STEC strains isolated from an outbreak of diarrhea in the city of Guilin, Guangxi Zhuang Autonomous Region, China.
The effect of walking and stationary work on the acute back pain, muscle activation, posture and postural control of older women

Abstract Back pain is associated with activity such as walking or assembly line work that involves upper-body movement. However, no single study has explored the effect of these tasks on back pain, spinal angles and balance in an older adult female population. This study investigated changes in back pain, postural sway, upper-, lower- and full-spine angle and EMG activation of trunk muscles following 30 minutes of walking and a modified quiet standing task. Fourteen older adult females (62 ± 11yrs) with low to moderate chronic back pain were recruited as participants. Findings demonstrated that following these activities, increased acute back pain and upper-spine flexion occur although acute back pain was not clinically significant; postural control and muscle activation remained unchanged. This suggests that walking and modified quiet standing can lead to subtle acute back pain in older females that could be due to an increased upper spinal flexion rather than muscle fatigue. Practitioner summary: Back pain and postural problems are common in older adults. Older adult female participants experienced increased back pain and greater upper-spine flexion following 30-minute walking and standing with trunk rotation, but the practical importance was less clear. However, balance was unaffected, suggesting no increase in fall risk. Abbreviations: CBP: chronic back pain; MQS: modified quiet standing; QS: quiet standing; RPE: rating of perceived exertion; TD: trapezius descendens; TT: trapezius transversalis; TA: trapezius ascendens; ESL: erector spinae longissimus; C7: seventh cervical vertebrae; T7: seventh thoracic vertebrae; T10: tenth thoracic vertebrae; T12: twelfth thoracic vertebrae; L2: second lumbar vertebrae; S2: second sacral vertebrae; AP: anterior-posterior; ML: medial-lateral; SWAYtot: total postural sway; M: mean