Miracle-dz/UniFAR-FTUs huggingface dataset:
CRISPRedict: a CRISPR-Cas9 web tool for interpretable efficiency predictions

Abstract The development of the CRISPR-Cas9 technology has provided a simple yet powerful system for genome editing. Current gRNA design tools serve as an important platform for the efficient application of the CRISPR systems. However, most of the existing tools are black-box models that suffer from limitations, such as variable performance and unclear mechanism of decision making. Here, we introduce CRISPRedict, an interpretable gRNA efficiency prediction model for CRISPR-Cas9 gene editing. Its strength lies in the fact that it can accurately predict efficient guide RNAs—with equivalent performance to state-of-the-art tools—while being a simple linear model. Implemented as a user-friendly web server, CRISPRedict offers (i) quick and accurate predictions across various experimental conditions (e.g. U6/T7 transcription); (ii) regression and classification models for scoring gRNAs and (iii) multiple visualizations to explain the obtained results. Given its performance, interpretability, and versatility, we expect that it will assist researchers in the gRNA design process and facilitate genome editing research. CRISPRedict is available for use at http://www.crispredict. org/.
The sedentary office : a growing case for change towards better health and productivity Expert statement commissioned by Public Health England and Active Working C.I.C.

An international group of experts was invited by Public Health England and a UK community interest company (Active Working CIC) to provide guidelines for employers to promote the avoidance of prolonged periods of sedentary work. The set of recommendations was developed from the totality of the current evidence, including long-term epidemiological studies and interventional studies of getting workers to stand and/or move more frequently. The evidence was ranked in quality using the four levels of the American College of Sports Medicine. The derived guidance is as follows: for those occupations which are predominantly desk based, workers should aim to initially progress towards accumulating 2 h/day of standing and light activity (light walking) during working hours, eventually progressing to a total accumulation of 4 h/day (prorated to part-time hours). To achieve this, seated-based work should be regularly broken up with standing-based work, the use of sit–stand desks, or the taking of short active standing breaks. Along with other health promotion goals (improved nutrition, reducing alcohol, smoking and stress), companies should also promote among their staff that prolonged sitting, aggregated from work and in leisure time, may significantly and independently increase the risk of cardiometabolic diseases and premature mortality. It is appreciated that these recommendations should be interpreted in relation to the evidence from which they were derived, largely observational and retrospective studies, or short-term interventional studies showing acute cardiometabolic changes. While longer term intervention studies are required, the level of consistent evidence accumulated to date, and the public health context of rising chronic diseases, suggest initial guidelines are justified. We hope these guidelines stimulate future research, and that greater precision will be possible within future iterations.
Variations in the carapace shape of whip spiders (Arachnida: Amblypygi)

Morphological studies often need to reference body size to correctly characterise the shape of organisms. In arthropods, the most commonly used reference for this is the length or width of the carapace, thorax, or the prosoma in the case of chelicerates. However, in the case of animals with unlimited growth, such as whip spiders, this measure could be irrelevant if growth is allometric. In this study, we analyse the ontogenetic modifications in prosoma outline shape in whip spiders during growth and compare the differences in shape between species. Differences are important for the relative prosoma width between species and, in the case of Damon medius, during growth in the juvenile stages, whereas the shape remains stable in mature stages. We conclude that a one‐dimensional measure (i.e., length or width) suffices for mature specimens of a single species or family, but for larger studies, or when including immature specimens, at least the prosoma area (within the outline shape) should be used as a size estimator.
Vogel Treatment Options for High-Risk T 1 Bladder Cancer Status Quo and Future Perspectives of Radiochemotherapy

Purpose: To review the standards and new developments in diagnosis and management of high-risk T1 bladder cancer with emphasis on the role of radiotherapy (RT) and radiochemotherapy (RCT). Material and Methods: A systematic review of the literature on developments in diagnosis and management of high-risk T1 bladder cancer was performed. Results: First transurethral resection (TUR), as radical as safely possible, supported by fluorescence cystoscopy, shows higher detection and decreased recurrence rates. An immediate single postoperative instillation with a chemotherapeutic drug reduces the relative risk of recurrence by 40%. A second TUR is recommended to assess residual tumor. For adjuvant intravesical therapy, bacille Calmette-Guérin (BCG) demonstrated the highest efficacy. Early cystectomy should be reserved for selected patients. A recent phase III trial comparing RT versus conservative treatment in T1 G3 tumors could not show any advantage for RT. Data from Erlangen, Germany, using combined RCT in 80% of the patients, compare favorably with most of the contemporary BCG series. Conclusion: Results of intravesical therapy are still unsatisfying and early cystectomy is associated with morbidity and mortality. RT alone proved not superior to other conservative treatment strategies. However, data on RCT are promising and demonstrate an alternative to intravesical therapy and radical cystectomy.
Professional values and ethical sensitivities of student nurses during the COVID‐19 pandemic

Abstract Background Professional values in nursing are the foundation of ethical practice affecting patient care quality. Aim The purpose of the present study was to evaluate the development of professional values and ethical sensitivities among new nurses during the COVID‐19 pandemic. Methods A prospective observational study with a pre‐test and post‐test design was used. The sample constituted students (n = 302). The Nurses Professional Values Scale‐Revised and Modified Moral Sensitivity Questionnaire for Student Nurses were used for collecting data. Results Professional values post‐test mean scores of participants were significantly higher than the pre‐test scores (p < 0.001). No significant difference was determined between the pre‐test and post‐test mean scores of ethical sensitivity (p > 0.05). Conclusion The current study concluded that the professional values of newly graduated nurses developed during the COVID‐19 pandemic, but there was no change in ethical sensitivities. Implications for nursing and health policy This study provides one of the first pieces of evidence for nursing educators and managers to assess the professional values and ethical sensitivities of newly qualified nurses who may have been affected both during and after the outbreak. Newly qualified nurses should are valued members of the health care institutions, and orientation programmes should be implemented to improve their perceptions of the profession.
NRD.E1, an innovative non‐opioid therapy for painful diabetic peripheral neuropathy—A randomized proof of concept study

Painful diabetic peripheral neuropathy (PDPN) affects up to 26% of patients with diabetes mellitus, with major impacts on their general health and well‐being. Most available drugs fail to deliver acceptable pain reduction in the majority of patients and are often poorly tolerated. NRD.E1 is a novel product that has shown anti‐nociceptive preclinical effects and good tolerability in healthy volunteer studies.
Contemporary Concise Review 2021: COVID‐19 and other respiratory infections

Bats are likely the primary source of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Minks are highly susceptible to infection by SARS‐CoV‐2. Transmission from asymptomatic individuals was estimated to account for over 50% of all transmissions of coronavirus disease 2019 (COVID‐19) cases. SARS‐CoV‐2 is evolving towards more efficient aerosol transmission. Remdesivir, baricitinib, tocilizumab and dexamethasone are frequently used for the treatment of patients with respiratory failure due to COVID‐19. There is a rising incidence of non‐tuberculous Mycobacterium pulmonary disease globally, with a higher prevalence in Asian countries than in the Western world. Protracted bacterial bronchitis is a common cause of chronic productive cough in childhood. Re‐emergence of respiratory syncytial virus may occur after the relaxation of infection control measures and the reopening of borders during COVID‐19 pandemic.
Multimorbidity and depression among older adults in India: Mediating role of functional and behavioural health

Researchers have long been concerned about the association between depression and the prevalence of multiple chronic diseases or multimorbidity in older persons. However, the underlying pathway or mechanism in the multimorbidity-depression relationship is still unknown. Data were extracted from a baseline survey of the Longitudinal Ageing Survey of India (LASI) conducted during 2017–18 (N = 31,464; aged ≥ 60 years). Depression was assessed using the 10-item Centre for Epidemiological Studies Depression Scale (CES-D-10). Multivariable logistic regression was used to examine the association. The Karlson–Holm–Breen (KHB) method was adopted for mediation analysis. The prevalence of depression among older adults was nearly 29% (men: 26% and women 31%). Unadjusted and adjusted estimates in binary logistic regression models suggested an association between multimorbidity and depression (UOR = 1.28; 95% CIs 1.27–1.44 and AOR = 1.12; 95% CIs 1.12–1.45). The association was particularly slightly strong in the older men. In addition, the association was mediated by functional health such as Self Rated Health (SRH) (proportion mediated: 40%), poor sleep (35.15%), IADL disability (22.65%), ADL disability (21.49%), pain (7.92%) and by behavioral health such as physical inactivity (2.28%). However, the mediating proportion was higher among older women as compared to older men. Physical inactivity was not found to be significant mediator for older women. The findings of this population-based study revealed that older people with multimorbidity are more likely to suffer depressive symptoms in older ages, suggesting the need for more chronic disease management and research. Multimorbidity and depression may be mediated by certain functional health factors, especially in older women. Further longitudinal research is needed to better understand the underlying mechanisms of this association so that future preventive initiatives may be properly guided.
The value of monitoring amended reports in cytopathology quality programs: A biennial review

Quality and safety are the foundation of the practice of cytopathology. Review of key performance indicator (KPI) data can shine a light on laboratory vulnerabilities and potential areas for targeted improvement. The rate and content of amendment reports is a frequently monitored KPI in anatomic pathology, but few have studied its value in cytopathology. The goal of this study was to examine the frequency, classification, and outcome of amendments for a large cytopathology laboratory.
Pain‐autonomic interaction is a reliable measure of pain habituation in healthy subjects

Habituation is a response decrement resulting from repeated stimuli. Reduced habituation to noxious stimuli is considered to be a proxy for central sensitization in subjects with chronic pain. Despite numerous investigations of pain habituation in relation to central sensitization, there is no consensus on the most sensitive and reliable readout, as well as analysis approach. Therefore, this study compared the usability and reliability of different readouts and habituation analysis approaches to measure pain habituation in response to repetitive heat simulation.
Pharmacist gender and physician acceptance of antibiotic stewardship recommendations: An analysis of the reducing overuse of antibiotics at discharge home intervention

Abstract Objective: To assess association of pharmacist gender with acceptance of antibiotic stewardship recommendations. Design: A retrospective evaluation of the Reducing Overuse of Antibiotics at Discharge (ROAD) Home intervention. Setting: The study was conducted from May to October 2019 in a single academic medical center. Participants: The study included patients receiving antibiotics on a hospitalist service who were nearing discharge. Methods: During the intervention, clinical pharmacists (none who had specialist postgraduate infectious disease residency training) reviewed patients on antibiotics and led an antibiotic timeout (ie, structured conversation) prior to discharge to improve discharge antibiotic prescribing. We assessed the association of pharmacist gender with acceptance of timeout recommendations by hospitalists using logistic regression controlling for patient characteristics. Results: Over 6 months, pharmacists conducted 295 timeouts: 158 timeouts (53.6%) were conducted by 12 women, 137 (46.4%) were conducted by 8 men. Pharmacists recommended an antibiotic change in 82 timeouts (27.8%), of which 51 (62.2%) were accepted. Compared to male pharmacists, female pharmacists were less likely to recommend a discharge antibiotic change: 30 (19.0%) of 158 versus 52 (38.0%) of 137 (P < .001). Female pharmacists were also less likely to have a recommendation accepted: 10 (33.3%) of 30 versus 41 (8.8%) of 52 (P < .001). Thus, timeouts conducted by female versus male pharmacists were less likely to result in an antibiotic change: 10 (6.3%) of 158 versus 41 (29.9%) of 137 (P < .001). After adjustments, pharmacist gender remained significantly associated with whether recommended changes were accepted (adjusted odds ratio [aOR], 0.10; 95%confidence interval [CI], 0.03–0.36 for female versus male pharmacists). Conclusions: Antibiotic stewardship recommendations made by female clinical pharmacists were less likely to be accepted by hospitalists. Gender bias may play a role in the acceptance of clinical pharmacist recommendations, which could affect patient care and outcomes.
Application of Controlled Hypotension During Surgery for Spinal Metastasis

With advances in tumor treatment, metastasis to bone is increasing, and surgery has become the only choice for most terminal patients. However, spinal surgery has a high risk and is prone to heavy bleeding. Controlled hypotension during surgery has outstanding advantages in reducing intraoperative bleeding and ensuring a clear field of vision, thus avoiding damage to important nerves and vessels. Antihypertensive drugs should be carefully selected after considering the patient's age, different diseases, etc, and a single or combined regimen can be used. Hypotension also inevitably leads to a decrease in perfusion of important organs, so the threshold of hypotension and the maintenance time of hypotension should be strictly limited, and the monitoring of important organs during the operation is particularly important. Information such as blood perfusion, blood oxygen saturation, cardiac output, and neurophysiological conduction potential changes should be obtained in a timely fashion, which will help to reduce the risk of hypotension. In short, when applying controlled hypotension, it is necessary to choose an appropriate threshold and duration, and appropriate monitoring should be conducted during the operation to ensure the safety of the patient.
Management of acute chest syndrome in patients with sickle cell disease: a systematic review of randomized clinical trials

ABSTRACT Introduction Acute chest syndrome (ACS) accounts for the highest mortality in Sickle cell disease patients. Early diagnosis and timely management of ACS results in better outcomes. However, the effectiveness of most treatment modalities for ACS management has not been established. Areas Covered To review the treatment modalities management protocols and highlight the effectiveness of each option a literature search was done. Randomized controlled trials that assessed the efficacy of different treatment modalities in ACS management in SCD patients were chosen and reviewed. Expert opinion 11 randomized controlled trials were found that evaluated the efficacy of incentive spirometry, positive expiratory pressure device, intravenous dexamethasone, oral vs. intravenous morphine, inhaled nitric oxide, unfractionated heparin, and blood transfusion in the prevention or treatment of ACS. Although there are guidelines for ACS treatment, the available evidence is very limited to delineating the effectiveness of various interventions in ACS management. More high-quality studies and trials with a larger patient population can benefit this area to support the recommendations with stronger evidence.
Effect of aqueous garlic (Allium sativum) extract against di‐(2‐ethylhexyl) phthalate induced reproductive toxicity in male mice

This study was designed to investigate testicular and male reproductive tract histopathologies and lipid profile against di‐ethylhexyl phthalate (DEHP) exposure in mice and curative potentials of aqueous garlic (Allium sativum) extract. Four groups (n = 10) were named and treated as follow (a) control (C): (normal feed and drinking water + 0.2 ml corn oil); (b) aqueous garlic extract group (AGE): (500 mg/kg body weight of aqueous garlic extract); (c) DEHP group: (500 mg/kg body weight of DEHP, dissolved in corn oil; (d) AGE + DEHP group (500 mg/kg body weight garlic aqueous extract, and DEHP 500 mg/kg body weight dissolved in corn oil). The doses were given once daily through gavages for 28 days and on the 29th day, all the animals were euthanized through cervical dislocation and reproductive organs and blood samples were collected. The results showed that exposure to DEHP caused a significant effect on body weight, testicular weight, serum cholesterol, triglycerides, lipid profile, average cross‐sectional area (ACSA) of the seminiferous tubule, ACSA of the lumen of seminiferous tubule, spermatogenic cells, Leydig's cells number, vas deferens diameter, lumen, muscular thickness, and epithelial cell height of vas deferens. This study revealed that exposure to DEHP can be injurious to male reproductive health and aqueous garlic extract can decrease the toxic effects of DEHP in male mice.
Conserved QTL and chromosomal inversion affect resistance to columnaris disease in 2 rainbow trout (Oncorhyncus mykiss) populations

Abstract We present a comparative genetic analysis of the quantitative trait loci underlying resistance to warm water columnaris disease in 2 farmed rainbow trout (Oncorhynchus mykiss) populations. We provide evidence for the conservation of a major quantitative trait loci on Omy03, and the putative role played by a chromosomal rearrangement on Omy05. A total of 3,962 individuals from the 2 populations experienced a natural Flavobacterium columnare outbreak. Data for 25,823 genome-wide SNPs were generated for both cases (fatalities) and controls (survivors). FST and pairwise additive genetic relationships suggest that, despite being currently kept as separate broodstocks, the 2 populations are closely related. Association analyses identified a major quantitative trait loci on chromosome Omy03 and a second smaller quantitative trait loci on Omy05. Quantitative trait loci on Omy03 consistently explained 3–11% of genetic variation in both populations, whereas quantitative trait loci on Omy05 showed different degree of association across populations and sexes. The quantitative trait loci on Omy05 was found within a naturally occurring, 54.84 cM long inversion which is easy to tag due to a strong linkage disequilibrium between the 375 tagging SNPs. The ancestral haplotype on Omy05 was associated with decreased mortality. Genetic correlation between mortality in the 2 populations was estimated at 0.64, implying that the genetic basis of resistance is partly similar in the 2 populations. Our quantitative trait loci validation identifies markers that can be potentially used to complement breeding value evaluations to increase resistance against columnaris disease, and help to mitigate effects of climate change on aquaculture.
EVALUATION OF TRACE ELEMENT CONCENTRATIONS IN THE SERUM AND VIBRISSAE OF PERUVIAN PINNIPEDS (ARCTOCEPHALUS AUSTRALIS AND OTARIA BYRONIA)

Abstract: Concentrations of 15 trace elements (aluminum, arsenic, cadmium, chromium, cobalt, copper, iron, lead, manganese, mercury, nickel, selenium, tin, vanadium, and zinc) were determined in vibrissae (whiskers) and serum of two sympatric pinniped species, the Peruvian fur seal population (PFS; Arctocephalus australis Peruvian subpopulation) and South American sea lion (SASL; Otaria byronia) at Punta San Juan, Peru during 2011–19 sampling events. Element concentrations were 2–20 times higher in vibrissae than in serum. Vibrissae and serum concentrations of several elements, including aluminum, arsenic, and lead, suggest that environmental contaminants may affect the health of pinnipeds at Punta San Juan. Although toxicity thresholds are unknown in pinnipeds, high concentrations of some elements (especially aluminum, arsenic, and lead) may have adverse impacts on their health such as immunosuppression and impaired reproduction. Arsenic was the only element that increased in mean vibrissae concentration throughout the study period. Female SASL vibrissae contained a mean arsenic concentration three times higher than the male SASL vibrissae mean arsenic concentration, and twice as high as the arsenic mean for all PFS vibrissae. The mean male SASL vibrissae cadmium concentration was five times higher than the vibrissae cadmium mean for both PFS males and females and nearly three times higher than the vibrissae cadmium mean for SASL females. Serum concentrations of aluminum, arsenic, copper, and manganese were significantly higher during moderate to extreme El Niño years compared to La Niña years. With stronger and more frequent El Niño-Southern Oscillation events predicted in the future, it is vital to understand how these trace elements may affect pinniped population health.
The Genomics of Auditory Function and Disease

Current estimates suggest that nearly half a billion people worldwide are affected by hearing loss. Because of the major psychological, social, economic, and health ramifications, considerable efforts have been invested in identifying the genes and molecular pathways involved in hearing loss, whether genetic or environmental, to promote prevention, improve rehabilitation, and develop therapeutics. Genomic sequencing technologies have led to the discovery of genes associated with hearing loss. Studies of the transcriptome and epigenome of the inner ear have characterized key regulators and pathways involved in the development of the inner ear and have paved the way for their use in regenerative medicine. In parallel, the immense preclinical success of using viral vectors for gene delivery in animal models of hearing loss has motivated the industry to work on translating such approaches into the clinic. Here, we review the recent advances in the genomics of auditory function and dysfunction, from patient diagnostics to epigenetics and gene therapy.
Functional traits shape ontogenetic growth trajectories of rain forest tree species

1. Functional traits are posited to explain interspecific differences in performance, but these relationships are difficult to describe for long‐lived organisms such as trees, which exhibit strong ontogenetic changes in demographic rates. Here, we use a size‐dependent model of tree growth to test the extent to which of 17 functional traits related to leaf and stem economics, adult stature and seed size predict the ontogenetic trajectory of tree growth.