Miracle-dz/UniFAR-FTUs huggingface dataset:
The androgen receptor messenger RNA: what do we know?

ABSTRACT The Androgen Receptor (AR), transcriptionally activated by its ligands, testosterone and dihydrotestosterone (DHT), is widely expressed in cells and tissues, influencing normal biology and disease states. The protein product of the AR gene is involved in the regulation of numerous biological functions, including the development and maintenance of the normal prostate gland and of the cardiovascular, musculoskeletal and immune systems. Androgen signalling, mediated by AR protein, plays a crucial role in the development of prostate cancer (PCa), and is presumed to be involved in other cancers including those of the breast, bladder, liver and kidney. Significant research and reviews have focused on AR protein function; however, inadequate research and literature exist to define the function of AR mRNA in normal and cancer cells. The AR mRNA transcript is nearly 11 Kb long and contains a long 3’ untranslated region (UTR), suggesting its biological role in post-transcriptional regulation, consequently affecting the overall functions of both normal and cancer cells. Research has demonstrated that many biological activities, including RNA stability, translation, cellular trafficking and localization, are associated with the 3’ UTRs of mRNAs. In this review, we describe the potential role of the AR 3’ UTR and summarize RNA-binding proteins (RBPs) that interact with the AR mRNA to regulate post-transcriptional metabolism. We highlight the importance of AR mRNA as a critical modulator of carcinogenesis and its important role in developing therapy-resistant prostate cancer.
Trend and epidemiology of suicide attempts by self-poisoning among Egyptians

Suicide attempts by self-poisoning have become a critical health problem. This study aimed to investigate the trend, incidence, and the associated risk factors of suicide attempts by self-poisoning. A total of 7398 Egyptian patients were analyzed. The trend of suicide attempts by self-poisoning was analyzed using 6745 patients over four registry years from January 1, 2016, to January 1, 2020. Then, the associated risk factors behind attempted suicide by self-poisoning from January 1, 2019, to January 1, 2020, were assessed using 2523 suicide attempters by self-poisoning, 201 fatalities by self-poisoning, and another 653 survivors of accidental poisoning. Results showed a rising trend of suicide attempts by self-poisoning over the studied years. The incidence of suicide attempts through deliberate self-poisoning represented 26.63/1,000 (CI95%: 25.63–27.86) to the admitted patients and 26.10/100,000 (CI95%: 25.10–27.14) to the regional population. The death rate due to suicide attempts by self-poisoning was 2.08/100,000 (1.90–2.49). The case fatality rate and the proportionate mortality rate for suicide by self-poisoning were 7.38% (CI95%: 6.45–8.42) and 14.11% (CI95%: 12.4–16.0) respectively. Multivariate analysis revealed that attempted suicide by self-poisoning was predicted among patients aged <25 or 25–40 years old (OR = 27.49, CI95%: 15.28–49.64 and OR = 59.42, CI95%: 32.76–107.77 respectively), those of low or moderate socioeconomic status (OR = 35.03, CI95%: 21.32–57.56 and OR = 14.11, CI95%: 10.86–18.43 respectively), students (OR = 2.91, CI95%: 1.57–5.43) and those living in rural residency (OR = 4.12, CI95%: 3.27–5.19). Suicide attempts by self-poisoning exhibited an incremental rise across time which raises a serious concern. Efforts should be directed to overcome the mentioned risk factors triggering suicide attempts by self-poisoning.
Papaverine, a promising therapeutic agent for the treatment of COVID‐19 patients with underlying cardiovascular diseases (CVDs)

The causative agent of coronavirus disease‐2019 (COVID‐19), severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), enters the host cells via an angiotensin‐converting enzyme 2 (ACE2)‐mediated endocytosis‐dependent manner. Because ACE2 is highly expressed in the heart, SARS‐CoV‐2 can severely infect heart tissue and arteries, causing acute and chronic damage to the cardiovascular system. Therefore, special attention should be paid to finding appropriate agents to protect this vital system during COVID‐19 treatment. Papaverine is a unique vasodilator alkaloid that is clinically used in the treatment of vasospasm. Interestingly, this compound has potent and direct effects on a wide range of viruses, and could also prevent viral exploitation mechanisms of the host cell facilities by inhibiting some cellular signaling pathways such as p38 MAPK. This pathway was recently introduced as a promising target for the treatment of COVID‐19. Papaverine also has anti‐inflammatory effects which is useful in combating the hyper‐inflammatory phase of the COVID‐19. Unlike some medications that have severe dosage‐restrictions in the treatment of COVID‐19 due to cardiac side effects, papaverine is recommended for use in many heart disorders. The ability of papaverine to treat COVID‐19 has become more promising when the results of some extensive screenings showed the strong ability of this compound to inhibit the cytopathic effects of SARS‐CoV‐2 with EC50 of 1.1 μM. Having several therapeutic effects along with desired safety profile raises this hypothesis that papaverine could be a promising compound for the suppression of SARS‐CoV‐2 and prevention of ischemia/vasoconstriction‐related complications in COVID‐19 disease, especially in patients with underlying cardiovascular diseases (CVDs).
Reasons people refrain from sex in later life

Abstract There has been an increase in research on sexual activity in later life, yet far less is known about the actual perceptions and experiences of older adults who refrain from sexual activity. In the current study, a thematic analysis was conducted to identify patterns in semi-structured interviews with 47 older adults, aged 60-91. The analysis yielded seven themes that describe why older adults refrain from sex: 1) avoiding confronting sexual dysfunctions, 2) avoiding confronting the aging body, 3) avoiding performance anxiety, 4) being uninterested in sexual activity, 5) taking time to grieve the loss of a partner, 6) avoiding judgment, and 7) seeing sexuality as evolving and changing. Themes were organized according to the bio-psycho-social perspective and based on the axis of personal (self-focused) and interpersonal (partner-focused) motives. It is perfectly acceptable for people to refrain from sexual activity for their own reasons. However, if older adults want to remain sexually active, they should receive complete information about the many possibilities of treating different sexual problems in later life and about the many ways, beyond sexual penetration, one can enjoy sexual activity even in old age.
Point-prevalence survey of antibiotic use at three public referral hospitals in Kenya

Antimicrobial stewardship encourages appropriate antibiotic use, the specific activities of which will vary by institutional context. We investigated regional variation in antibiotic use by surveying three regional public hospitals in Kenya. Hospital-level data for antimicrobial stewardship activities, infection prevention and control, and laboratory diagnostic capacities were collected from hospital administrators, heads of infection prevention and control units, and laboratory directors, respectively. Patient-level antibiotic use data were abstracted from medical records using a modified World Health Organization point-prevalence survey form. Altogether, 1,071 consenting patients were surveyed at Kenyatta National Hospital (KNH, n = 579), Coast Provincial General Hospital (CPGH, n = 229) and Moi Teaching and Referral Hospital (MTRH, n = 263). The majority (67%, 722/1071) were ≥18 years and 53% (563/1071) were female. Forty-six percent (46%, 489/1071) were receiving at least one antibiotic. Antibiotic use was higher among children <5 years (70%, 150/224) than among other age groups (40%, 339/847; P < 0.001). Critical care (82%, 14/17 patients) and pediatric wards (59%, 155/265) had the highest proportion of antibiotic users. Amoxicillin/clavulanate was the most frequently used antibiotic at KNH (17%, 64/383 antibiotic doses), and ceftriaxone was most used at CPGH (29%, 55/189) and MTRH (31%, 57/184). Forty-three percent (326/756) of all antibiotic prescriptions had at least one missed dose recorded. Forty-six percent (204/489) of patients on antibiotics had a specific infectious disease diagnosis, of which 18% (37/204) had soft-tissue infections, 17% (35/204) had clinical sepsis, 15% (31/204) had pneumonia, 13% (27/204) had central nervous system infections and 10% (20/204) had obstetric or gynecological infections. Of these, 27% (56/204) had bacterial culture tests ordered, with culture results available for 68% (38/56) of tests. Missed antibiotic doses, low use of specimen cultures to guide therapy, high rates of antibiotic use, particularly in the pediatric and surgical population, and preference for broad-spectrum antibiotics suggest antibiotic use in these tertiary care hospitals is not optimal. Antimicrobial stewardship programs, policies, and guidelines should be tailored to address these areas.
Determining Level of Service for Multilane Median Opening Zone

The road system is a capital-intensive investment, requiring thorough schematic framework and funding. Roads are built to provide an intrinsic quality of service which satisfies the road users. Roads that provide good services are expected to deliver operational performance that is consistent with their design specifications. Level of service and cumulative percentile speed distribution methods have been used in previous studies to estimate the quality of multilane highway service. Whilst the level of service approach relies on speed/flow curve, the cumulative percentile speed distribution is based solely speed. These estimation methods were used in studies carried out in Johor Malaysia. The aim of the studies is to ascertain the extent of speed reduction caused by midblock U-turn facilities as well as verify which estimation method is more reliable. At selected sites, road segments for both directional flows were divided into free-flow and midblock zones. Traffic volume, speed and vehicle type data for each zone were collected continuously for six weeks. Both estimation methods confirmed that speed reduction would be caused by midblock u-turn facilities. However level of service methods suggested that the quality of service would improve from level F to E or D at midblock zone in spite of speed reduction. Level of service was responding to traffic volume reduction at midblock u-turn facility not travel speed reduction. The studies concluded that since level of service was more responsive to traffic volume reduction than travel speed, it cannot be solely relied upon when assessing the quality of multilane highway service.
Sequential relationships of food intake in nursing home residents with dementia: Behavioural analyses of videotaped mealtime observations.

AIMS AND OBJECTIVES This study examined the sequential relationships of food intake and the moderating role of the characteristics of intake and resident conditions. BACKGROUND Nursing home residents commonly experience insufficient food intake. While multilevel factors influence intake, evidence on sequential relationships is lacking. DESIGN The study was an observational study using secondary, behavioural analyses following the STROBE Statement. METHODS Videotaped observations (N = 160) collected from a dementia communication trial during 2011-2014 were coded using the refined Cue Utilisation and Engagement in Dementia Mealtime Video-coding Scheme during 2018-2019. The 160 videos involved 27 residents living with dementia and 36 staff in 9 nursing homes. Independent variables were the state (solid intake, liquid intake, no intake) of an intake episode occurring during mealtime (current episode), eating technique (resident-initiated, staff-facilitated) used in the next episode occurring after the current episode (subsequent episode), interval between adjacent episodes, and resident comorbidities and dementia stage. The dependent variable was the state of subsequent episode. RESULTS Successful liquid and solid intake increased odds of subsequent liquid and solid intake. Comorbidities were associated with decreased odds of subsequent liquid and solid intake for staff-facilitated episodes. When liquid intake occurred, staff-facilitation decreased odds of subsequent liquid intake; longer intervals between adjacent episodes increased odds of subsequent solid intake. CONCLUSION Food intake was strongly and sequentially associated, and such temporal relationships were dependent on characteristics of the intake process and resident conditions. RELEVANCE TO CLINICAL PRACTICE The study findings supported that initiating successful intake facilitates continuity of successful intake during mealtime. Behavioural interventions tailored by comorbidities that modify characteristics of the food intake process may improve food intake.
Addressing long-term and repeat antibiotic prescriptions in primary care: considerations for a behavioural approach

© Author(s) (or their employer(s)) 2022. No commercial reuse. See rights and permissions. Published by BMJ. Overprescribing of antibiotics in primary care is one of the important drivers of antimicrobial resistance (AMR) internationally. Previous studies estimated that onefifth to onethird of UK antibiotic prescriptions in primary care are unnecessary or inappropriate. The study by van Staa and colleagues published in this issue of BMJ Quality & Safety delivers additional insights into prescribing practices by primary care physicians (general practitioners, GPs) in the UK. Analysing data from more than 6000 GPs in 466 general practices between 2012 and 2017, they found large variability in prescribing practices as measured, for example, by the overall antibiotic prescribing rate per consultation, the percentage of patients receiving repeat prescriptions and the use of broadspectrum antibiotics. The percentage of repeat prescriptions (ie, antibiotics that were prescribed within 30 days of another antibiotic prescription) ranged from 13.1% to 34.3%, with a mean of 23.2%. They also found that patients prescribed an antibiotic during the study period had a mean of 8.9 antibiotic prescriptions (SD=6.1) in the 3 years prior to the study, indicating that regular antibiotic use is common for a substantial group of patients. The authors highlight considerable variability in case mix, with some clinicians facing greater challenges due to the high baseline risk of microbial infection among their patients. Using Poisson generalised additive mixed effect models, it is proposed that the largest potential reduction in antibiotic prescribing could be achieved through riskbased prescribing, especially for patients receiving repeat prescriptions. It is also suggested that reducing repeat antibiotic courses to the prescribing habit of a median clinician would save 21 813 antibiotic prescriptions per 1000 clinicians per year. If this was further reduced to the lowest 25th percentile, this would result in 38 871 fewer antibiotic prescriptions per 1000 clinicians per year. van Staa and colleagues’ repeat prescription rates are higher than those from a 2002–2017 UK cohort study, which reported a median percentage of 10% of antibiotics being repeat prescriptions. However, the mean figure of 23.2% is still lower than the results from a study on UK care home prescribing, which suggested that 30% of antibiotic prescriptions met the definition of repeats. In the UK care home study, the antibiotics that were most frequently repeated for long durations were azithromycin, cephalexin, nitrofurantoin and trimethoprim. These medicines were usually recommended for use as prophylaxis for chronic obstructive pulmonary disease and urinary tract infections. A different UK study showed that most repeat antibiotic prescriptions occurred in the absence of a specific coded clinical condition, suggesting that repeat prescriptions were potentially used as treatment in cases of clinical uncertainty.
Phytoremediation of soil contaminated with weathered petroleum hydrocarbons by applying mineral fertilization, an anionic surfactant, or hydrocarbonoclastic bacteria

Abstract This study evaluated the effect of the application of mineral fertilization (F), the anionic surfactant Triton X-100 (TX100), or the inoculation with a hydrocarbooclastic bacterial consortium (BCons) on the growth of Clitoria ternatea during the phytoremediation of a Gleysol contaminated with weathered petroleum hydrocarbons (39,000 mg kg−1 WPH) collected from La Venta, Tabasco (Mexico). The experiment consisted of a completely randomized design with seven treatments and four replications each under greenhouse conditions. The application of F (biostimulation) increased plant growth and biomass production; in contrast, TX100 only favored root biomass (11%) but significantly favored WPH degradation. Bioaugmentation with BCons did not show significant effects on plant growth. Nevertheless, the combination of biostimulation with bioaugmentation (BCons + F, BCons + TX100, and BCons + F+TX100) enhanced plant growth, hydrocarbonoclastic bacteria population, and WPH degradation when compared to treatments with the single application of bioaugmentation (BCons) or biostimulation (F). NOVELTY STATEMENT Application of mineral fertilization and commercial surfactant favored root biomass and degradation of weathered petroleum hydrocarbons (WPH). The reintroduction of hydrocarbonoclastic and surfactant-producer bacteria did not enhance plant growth but significantly contributed on WPH degradation from a chronically contaminated soil.
Operative vaginal delivery: practice patterns and outcomes at a tertiary general hospital

Introduction: There has been a global decrease in operative vaginal deliveries, with a marked shift towards the vacuum extractor. However, little is known about the trends in operative vaginal delivery in Singapore. Methods: A retrospective study was conducted on all operative vaginal deliveries performed from 2012 to 2017 at Singapore General Hospital (SGH). Maternal outcomes in terms of postpartum haemorrhage and obstetric anal sphincter injuries were compared between forceps- and vacuum-assisted deliveries. Neonatal outcomes in terms of neonatal intensive care unit (NICU) admission and clinically significant neonatal events were compared. The instrument preference of obstetricians was analysed. Results: A total of 906 consecutive operative vaginal deliveries were included in the study, comprising 461 forceps- and 445 vacuum-assisted deliveries. The rate of operative vaginal delivery was maintained at approximately 10% from 2012 to 2017. Neonatal cephalohematomas were more common after vacuum-assisted deliveries. Other maternal and neonatal outcomes did not differ significantly between the two groups. Clinically significant neonatal events were mostly due to shoulder dystocia, whereas all cases of NICU admissions were not directly related to the mode of delivery. Obstetricians' choice of instrument appeared to reflect personal preference and was not affected by the year of graduation. Conclusion: The rates of neonatal and maternal morbidity were low at SGH. Overall instrument use of forceps and vacuum was balanced, and proficiency in both was demonstrated by all operators. Operative vaginal delivery remains an essential skill in facilitating safe vaginal delivery, which should be maintained to keep Caesarean section rates in check.
on muscle mass in suspended rats and exercise

Interactive effects of growth hormone and exercise on muscle mass in suspended rats. Physiol. 267 Comp. Physiol. 36): R316-R322, 1994. --Measures to attenu- ate muscle atrophy in rats in response to simulated micrograv- ity [hindlimb suspension (HS)] have been only partially success-ful. In the present study, hypophysectomized rats were in HS for 7 days, and the effects of recombinant human growth hormone (GH), exercise (Ex), or GH+Ex on the weights, protein concentrations, and fiber cross-sectional areas (CSAs) of hindlimb muscles were determined. The weights of four extensor muscles, i.e., the soleus (Sol), medial (MG) and lateral (LG) gastrocnemius, and plantaris (Plt), and one adductor, i.e., the adductor
Evolving Landscape of Initial Treatments for Patients with Malignant Pleural Mesotheliomas: Clinical Trials to Clinical Practice

Malignant pleural mesothelioma (MPM) is the most common form of mesothelioma and the type most often studied in prospective clinical trials.This review reports the trials that have shaped first-line treatment for patients with advanced/unresectable MPM and the real-world integration of first-line immune checkpoint inhibitors into clinical practice.
Premature transcription termination at the expanded GAA repeats and aberrant alternative polyadenylation contributes to the Frataxin transcriptional deficit in Friedreich’s ataxia

Abstract Frataxin deficiency in Friedreich’s ataxia results from transcriptional downregulation of the FXN gene caused by expansion of the intronic trinucleotide guanine-adenine-adenine (GAA) repeats. We used multiple transcriptomic approaches to determine the molecular mechanism of transcription inhibition caused by long GAAs. We uncovered that transcription of FXN in patient cells is prematurely terminated upstream of the expanded repeats leading to the formation of a novel, truncated and stable RNA. This FXN early terminated transcript (FXN-ett) undergoes alternative, non-productive splicing and does not contribute to the synthesis of functional frataxin. The level the FXN-ett RNA directly correlates with the length of the longer of the two expanded GAA tracts. Targeting GAAs with antisense oligonucleotides or excision of the repeats eliminates the transcription impediment, diminishes expression of the aberrant FXN-ett, while increasing levels of FXN mRNA and frataxin. Non-productive transcription may represent a common phenomenon and attractive therapeutic target in diseases caused by repeat-mediated transcription aberrations.
Lessons from Acquired Natural Immunity and Clinical Trials to Inform Next-Generation Human Cytomegalovirus Vaccine Development.

Human cytomegalovirus (HCMV) infection, the most common cause of congenital disease globally, affecting an estimated 1 million newborns annually, can result in lifelong sequelae in infants, such as sensorineural hearing loss and brain damage. HCMV infection also leads to a significant disease burden in immunocompromised individuals. Hence, an effective HCMV vaccine is urgently needed to prevent infection and HCMV-associated diseases. Unfortunately, despite more than five decades of vaccine development, no successful HCMV vaccine is available. This review summarizes what we have learned from acquired natural immunity, including innate and adaptive immunity; the successes and failures of HCMV vaccine human clinical trials; the progress in related animal models; and the analysis of protective immune responses during natural infection and vaccination settings. Finally, we propose novel vaccine strategies that will harness the knowledge of protective immunity and employ new technology and vaccine concepts to inform next-generation HCMV vaccine development. Expected final online publication date for the Annual Review of Virology, Volume 9 is September 2022. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.