Miracle-dz/UniFAR-FTUs huggingface dataset:
Integral gene drives for population replacement

ABSTRACT A first generation of CRISPR-based gene drives has now been tested in the laboratory in a number of organisms, including malaria vector mosquitoes. Challenges for their use in the area-wide genetic control of vector-borne disease have been identified, including the development of target site resistance, their long-term efficacy in the field, their molecular complexity, and practical and legal limitations for field testing of both gene drive and coupled anti-pathogen traits. We have evaluated theoretically the concept of integral gene drive (IGD) as an alternative paradigm for population replacement. IGDs incorporate a minimal set of molecular components, including drive and anti-pathogen effector elements directly embedded within endogenous genes – an arrangement that in theory allows targeting functionally conserved coding sequences without disrupting their function. Autonomous and non-autonomous IGD strains could be generated, optimized, regulated and imported independently. We performed quantitative modeling comparing IGDs with classical replacement drives and show that selection for the function of the hijacked host gene can significantly reduce the establishment of resistant alleles in the population, while drive occurring at multiple genomic loci prolongs the duration of transmission blockage in the face of pre-existing target site variation. IGD thus has potential as a more durable and flexible population replacement strategy. Summary: Here, we describe and model a novel gene drive strategy – integral gene drive – for population replacement based on the hijacking of endogenous genes.
Two-year safety and clinical outcomes in chronic ischemic stroke patients after implantation of modified bone marrow-derived mesenchymal stem cells (SB623): a phase 1/2a study.

OBJECTIVEThe aim of this study was to evaluate the safety and clinical outcomes associated with stereotactic surgical implantation of modified bone marrow-derived mesenchymal stem cells (SB623) in patients with stable chronic ischemic stroke.METHODSThis was a 2-year, open-label, single-arm, phase 1/2a study; the selected patients had chronic motor deficits between 6 and 60 months after nonhemorrhagic stroke. SB623 cells were administered to the target sites surrounding the subcortical stroke region using MRI stereotactic image guidance.RESULTSA total of 18 patients were treated with SB623 cells. All experienced at least 1 treatment-emergent adverse event (TEAE). No patients withdrew due to adverse events, and there were no dose-limiting toxicities or deaths. The most frequent TEAE was headache related to the surgical procedure (88.9%). Seven patients experienced 9 serious adverse events, which resolved without sequelae. In 16 patients who completed 24 months of treatment, statistically significant improvements from baseline (mean) at 24 months were reported for the European Stroke Scale (ESS) score, 5.7 (95% CI 1.4-10.1, p < 0.05); National Institutes of Health Stroke Scale (NIHSS) score, -2.1 (95% CI -3.3 to -1.0, p < 0.01), Fugl-Meyer (F-M) total score, 19.4 (95% CI 9.9-29.0, p < 0.01); and F-M motor scale score, 10.4 (95% CI 4.0-16.7, p < 0.01). Measures of efficacy reached plateau by 12 months with no decline thereafter. There were no statistically significant changes in the modified Rankin Scale score. The size of transient lesions detected by T2-weighted FLAIR imaging in the ipsilateral cortex at weeks 1-2 postimplantation significantly correlated with improvement in ESS (0.619, p < 0.05) and NIHSS (-0.735, p < 0.01) scores at 24 months.CONCLUSIONSIn this completed 2-year phase 1/2a study, implantation of SB623 cells in patients with stable chronic stroke was safe and was accompanied by improvements in clinical outcomes.Clinical trial registration no.: NCT01287936 (clinicaltrials.gov).
Assessment of hepatitis C risk factors in center of Iran: A case–control study

Background: Hepatitis C virus (HCV) infections remain as one of the major public health problems worldwide. The current study aimed at investigating the potential risk factors of HCV+ in a sample of Iranian patients. Materials and Methods: In a case–control study, 436 HCV-infected patients and 531 age-matched HCV antibody negative controls were recruited in a central region of Iran. Sociodemographic characteristics, blood and therapeutic factors, underlying diseases, and behavioral risk factors were evaluated through a standard checklist and compared between two study groups. Results: Although among studied potential risk factors, many of them were significantly associated with infected with HCV; however, in multivariable logistic regression model in the presence of other variables being male gender (odds ratio [OR]: 4.1; 95% confidence interval [CI]: 2.2–7.8), illiterate or less educated (OR: 62.64; 95% CI: 5.94–660.35), having history of intravenous (IV) drug addiction (OR: 33.0; 95% CI: 5.43–250.0), and tattooing (OR: 14.29; 95% CI: 1.82–90.91) increased risk of infection with HCV. Conclusion: In total, the current case–control study documented that socioecomical factors including economical state, marital status, education, and ethnicity and also other expected factors such as hospitalization, imprisonment, dialysis, tattooing, needle sharing, IV drug abuse, and extramarital sexual relationship represent an important source of HCV infection among adults in a central region of Iran. Thus, we suggest further considerations for prevention of HCV infection as most of related factors are preventable by close considerations.
A Novel R2R3-MYB Transcription Factor Contributes to Petal Blotch Formation by Regulating Organ-Specific Expression of PsCHS in Tree Peony (Paeonia suffruticosa)

Flower color patterns play critical roles in plant-pollinator interactions and represent one of the most common adaptations during angiosperm evolution. However, the molecular mechanisms underlying flower color pattern formation are less understood in non-model organisms. The aim of this study was to identify genes involved in the formation of petal blotches in tree peony (Paeonia suffruticosa) through transcriptome profiling and functional experiments. We identified an R2R3-MYB gene, PsMYB12, representing a distinct R2R3-MYB subgroup, with a spatiotemporal expression pattern tightly associated with petal blotch development. We further demonstrated that PsMYB12 interacts with a basic helix-loop-helix (bHLH) and a WD40 protein in a regulatory complex that directly activates PsCHS expression, which is also specific to the petal blotches. Together, these findings advance our understanding of the molecular mechanisms of pigment pattern formation beyond model plants. They also benefit molecular breeding of tree peony cultivars with novel color patterns and promote germplasm innovation.
A Prospective Study of Circulating Tumor DNA to Guide Matched Targeted Therapy in Lung Cancers.

Background Liquid biopsy for plasma circulating tumor DNA (ctDNA) next-generation sequencing (NGS) is commercially available and increasingly adopted in clinical practice despite a paucity of prospective data to support its use. Methods Patients with advanced lung cancers who had no known oncogenic driver or developed resistance to current targeted therapy (n = 210) underwent plasma NGS, targeting 21 genes. A subset of patients had concurrent tissue NGS testing using a 468-gene panel (n = 106). Oncogenic driver detection, test turnaround time (TAT), concordance, and treatment response guided by plasma NGS were measured. All statistical tests were two-sided. Results Somatic mutations were detected in 64.3% (135/210) of patients. ctDNA detection was lower in patients who were on systemic therapy at the time of plasma collection compared with those who were not (30/70, 42.9% vs 105/140, 75.0%; OR = 0.26, 95% CI = 0.1 to 0.5, P < .001). The median TAT of plasma NGS was shorter than tissue NGS (9 vs 20 days; P < .001). Overall concordance, defined as the proportion of patients for whom at least one identical genomic alteration was identified in both tissue and plasma, was 56.6% (60/106, 95% CI = 46.6% to 66.2%). Among patients who tested plasma NGS positive, 89.6% (60/67; 95% CI = 79.7% to 95.7%) were also concordant on tissue NGS and 60.6% (60/99; 95% CI = 50.3% to 70.3%) vice versa. Patients who tested plasma NGS positive for oncogenic drivers had tissue NGS concordance of 96.1% (49/51, 95% CI = 86.5% to 99.5%), and directly led to matched targeted therapy in 21.9% (46/210) with clinical response. Conclusions Plasma ctDNA NGS detected a variety of oncogenic drivers with a shorter TAT compared with tissue NGS and matched patients to targeted therapy with clinical response. Positive findings on plasma NGS were highly concordant with tissue NGS and can guide immediate therapy; however, a negative finding in plasma requires further testing. Our findings support the potential incorporation of plasma NGS into practice guidelines.
Distribution of brain iron accrual in adolescence: Evidence from cross‐sectional and longitudinal analysis

To track iron accumulation and location in the brain across adolescence, we repurposed diffusion tensor imaging (DTI) and functional magnetic resonance imaging (fMRI) data acquired in 513 adolescents and validated iron estimates with quantitative susceptibility mapping (QSM) in 104 of these subjects. DTI and fMRI data were acquired longitudinally over 1 year in 245 male and 268 female, no‐to‐low alcohol‐consuming adolescents (12–21 years at baseline) from the National Consortium on Alcohol and NeuroDevelopment in Adolescence (NCANDA) study. Brain region average signal values were calculated for susceptibility to nonheme iron deposition: pallidum, putamen, dentate nucleus, red nucleus, and substantia nigra. To estimate nonheme iron, the corpus callosum signal (robust to iron effects) was divided by regional signals to generate estimated R2 (edwR2 for DTI) and R2* (eR2* for fMRI). Longitudinal iron deposition was measured using the normalized signal change across time for each subject. Validation using baseline QSM, derived from susceptibility‐weighted imaging, was performed on 46 male and 58 female participants. Normalized iron deposition estimates from DTI and fMRI correlated with age in most regions; both estimates indicated less iron in boys than girls. QSM results correlated highly with DTI and fMRI results (adjusted R2 = 0.643 for DTI, 0.578 for fMRI). Cross‐sectional and longitudinal analyses indicated an initial rapid increase in iron, notably in the putamen and red nucleus, that slowed with age. DTI and fMRI data can be repurposed for identifying regional brain iron deposition in developing adolescents as validated with high correspondence with QSM.
The epidemiology of nonviral microbial keratitis in a tertiary care center in Muscat, Oman

OBJECTIVE: The objective of this study is to describe the epidemiology, risk factors, etiology, and outcome of microbial keratitis in a tertiary care center in Muscat, Oman. METHODS: The electronic records of all patients diagnosed with keratitis or corneal ulcer between January 2013 and January 2016 in Al-Nahdha Hospital were retrospectively reviewed. Patients who presented with a corneal ulcer requiring admission and who underwent culture and sensitivity studies were included in the study. Patients with viral keratitis or sterile corneal ulcers were excluded from the study. RESULTS: A total of 606 electronic medical records of all presumed microbial keratitis were reviewed. Out of these, 304 met the eligibility criteria. The mean age of patients was 52.2 years (standard deviation [SD]: ±23.2 years; range: 0.1–89 years). A total of 198 (65%) microbial cultures yielded positive results. Of these, 182 (92%) were bacterial, 13 (7%) were fungal, and 3 (1%) cases were due to a combined (bacterial and fungal) etiology. Gram-positive bacteria accounted for 102 (55.1%), of which the majority was due to Streptococcus pneumoniae. Gram-negative bacteria accounted for 77 (41.6%) cases; half were caused by Pseudomonas aeruginosa. Keratitis in patients aged 18 years and younger was more likely to be associated with trauma (48.3%, P < 0.001) in young adults with contact lens wear (64%, P < 0.001) and in adults over 40 years with blepharitis (55.6%), sequelae of previous trachoma infection (26.3%), and eyelid abnormalities (18.4%). Following recovery, corneal scarring was seen in 63.2% of patients. CONCLUSION: Microbial keratitis affects patients of all age groups but is more common in older adults. The vast majority of culture-proven cases are due to bacterial infections. Children and teenagers are more likely to develop keratitis following eye trauma whereas young adults mostly develop the condition in association with contact lens wear. Ocular surface disease is the most important risk factor in older adults. The majority of patients end up with corneal scarring.
Knowledge, Attitudes and Behavior Regarding Topical Corticosteroids in a Sample of Pharmacy Students: A Cross Sectional Survey

Introduction and Background: The abuse and misuse of topical corticosteroids, especially over the face, is an increasing problem encountered by dermatologists in India. Lack of patient awareness and the ease of obtaining topical corticosteroids without a prescription are important underlying factors. As the first point of contact, the pharmacist has an important role in controlling topical corticosteroid abuse. Aims: This study aimed to evaluate the knowledge, attitudes, and behavior regarding topical corticosteroids in a sample of pharmacy students. Methods: A cross-sectional survey was carried out among pharmacy students using convenience sampling method. A total of 110 questionnaires were distributed, and 103 valid responses were obtained. Results: Majority of the students were conversant of the fact that different classes of topical corticosteroids effectuate different effects. Majority of the students concurred on points such as topical corticosteroids can have significant cutaneous adverse effects, the important role pharmacist plays in preventing topical steroid abuse, and the need to hold fast dispensing of topical corticosteroids on a prescription-only basis. However, a significant gap in knowledge related to specific side effects and awareness of different classes of topical corticosteroids was noted. Moreover, there was no statistical significant difference in terms of knowledge and awareness regarding topical corticosteroid use between postgraduate and undergraduate students. Conclusion: In our study, although several students were aware of the potential adverse effects of topical corticosteroids, there were gaps in the awareness about specific classes and adverse effects. Knowledge regarding the ethical and rational use of topical corticosteroids should be disseminated among pharmacy students, and the dermatologists should play a key role in this.
Long noncoding RNA OIP5-AS1 targets Wnt-7b to affect glioma progression via modulation of miR-410

The present study was undertaken to investigate the underlying mechanisms of long noncoding RNA OIP5-AS1 via regulating miR-410 to modulate Wnt-7b in the progression of glioma. To address this problem, we measured the expression of OIP5-AS1 and miR-410 in glioma tissues by qRT-PCR. Glioma U87 cells were transfected with OIP5-AS1 siRNA or miR-410 inhibitors. The targeting relationships among miR-410, OIP5-AS1 and Wnt-7b were verified by luciferase reporter assays. Western blotting was employed to determine the expression of Wnt-7b/β-catenin pathway-related proteins, while MTT, flow cytometry, Transwell assays and wound-healing assays were used to measure the biological characteristics of glioma cells. The results showed that OIP5-AS1 expression was higher and miR-410 was lower in glioma tissues. Luciferase reporter assays confirmed a targeting relationship between OIP5-AS1 and miR-410, as well as between miR-410 and Wnt-7b. Silencing OIP5-AS1 reduced cell proliferation, invasion and migration of glioma U87 cells and led to depressed expression levels of miR-410, Wnt-7b, p-β-catenin, GSK-3β-pS9, c-Myc and cyclin D1. Furthermore, down-regulation of OIP5-AS1 induced G0/G1 phase cell cycle arrest and apoptosis of glioma cells. Inhibitors of miR-410 abolished the biological effects of OIP5-AS1 siRNA in glioma cells. In vivo, OIP5-AS1 knockdown also inhibited tumor growth. Taken together, this research suggested that silencing OIP5-AS1 may specifically block the Wnt-7b/β-catenin pathway via targeted up-regulating miR-410, thereby inhibiting growth, invasion and migration while promoting apoptosis in glioma cells.
Real-life data patterns of C-reactive protein and albumin level trajectories around bacteremia.

AIM To assess trajectory patterns of C-reactive protein (CRP) and plasma albumin (PA) levels around bacteremia. PATIENTS & METHODS Population-based study, 2418 community-acquired bacteremia patients, CRP and PA specimens from 30 days before through 30 days after bacteremia (day 0). A pattern was based on specimen occurring or not in days -30/-1, 0, 1/7 or 8/30. Mean daily CRP and PA levels on day -30/30 were computed for pattern subgroups. RESULTS & CONCLUSION Mean CRP rose on day -5 and reached its peak on day 1. Mean steady PA on day -30/0 declined abruptly on day 1, increasing slowly thereafter. Trajectories did not differ between subgroups. We conclude that longitudinal analysis results can be extrapolated to all community-acquired bacteremia patients.
Trematode Parasite Infection Affects Temperature Selection in Aquatic Host Snails

Animals infected by parasites or pathogens can exhibit altered behaviors that may reduce the costs of infection to the host or represent manipulations that benefit the parasite. Given that temperature affects many critical physiological processes, changes in thermoregulatory behaviors are an important consideration for infected hosts, especially ectotherms. Here we examined the temperature choices of freshwater snails (Helisoma trivolvis) that were or were not infected by a trematode (flatworm) parasite (Echinostoma trivolvis). Active snails that explored the experimental temperature gradient differed in their thermal preference based on their infection status, as parasitized snails chose to position themselves at a significantly higher temperature (mean: 25.4°C) compared to those that were uninfected (mean: 23.3°C). Given that snails rarely eliminate established trematode infections, we suggest that this altered thermal preference shown by infected hosts likely benefits the parasite by increasing the odds of successful transmission, either through enhanced production and emergence of infectious stages or by increasing spatial overlap with the next hosts of the complex life cycle. Further studies that employ experimental infections to examine temperature selection at different time points will be needed to understand the extent of altered host thermal preferences, as well as the possible benefits to both host and parasite.
Dual-band unidirectional reflectionlessness at exceptional points in a plasmonic waveguide system based on near-field coupling between two resonators

Dual-band unidirectional reflectionlessness at exceptional points is investigated theoretically in a non-Hermitian plasmonic waveguide system, based on near-field coupling by using only two resonators. The system consists of a metal-insulator-metal waveguide end-coupled to two nanohole resonators. The reflectivity for the forward (backward) direction is ∼0 (∼0) at frequency 205.20 THz (194.56 THz), while for the backward (forward) direction it is ∼0.76 (∼0.78). Moreover, the quality factors of the dual-band unidirectional reflectionlessness for forward and backward directions can reach ∼132 and ∼137, respectively.
Using interprofessional dementia learning opportunities to prepare the future healthcare workforce: findings from a pilot study

ABSTRACT Nearly 50 million people worldwide are living with dementia. Communication difficulties linked to this illness demand that all healthcare professionals are prepared to meet the needs of this group of service users. In response to this, the United Kingdom government is calling for professionals to acquire a basic (Tier 1) Dementia Awareness (DA) qualification. As healthcare students need to engage in interprofessional learning (IPL), this report describes the development, implementation and evaluation of an initiative to link the DA qualification to an existing IPL module delivered to first-year healthcare students (IPL1). A DA learning package was developed by a group of educators from a range of professions to ensure an interprofessional focus. It comprised of a set of practical exercises that students completed during and after IPL1. Sixty students evaluated the DA learning package by completing a post-intervention survey. 57 students rated it helpful or very helpful, in enhancing their knowledge of how to care for a person with dementia, while 3 students rated it as average. Two themes emerged from open-ended questions, which highlighted the importance of: i) learning to work together; and ii) blended learning. Students also suggested some changes for the full roll out, such as moving the Dementia Friends component into IPL1. This is an innovative approach that can be used to meet the challenges linked with the large-scale preparation of our future workforce and to ensure purposeful IPL.
Complementary and Alternative Medicine Use in Children With Inflammatory Bowel Disease

ABSTRACT Complementary and alternative medicine (CAM) consists of products and practices that are not considered to be a part of conventional medicine. This article reviews pediatric studies on CAM in inflammatory bowel disease (IBD) along with relevant adult studies. Prevalence of CAM use ranges from 22% to 84% in children with IBD all over the world. CAM use in IBD includes diet changes, supplements, herbals, botanicals, and mind-body therapies. Common reasons for using CAM include severe disease and concern for adverse effects of conventional medicines. Despite widespread use, there are limited studies on efficacy and safety of CAM in children. Small studies suggest a favorable evidence for use of probiotics, fish oil, marijuana, and mind-body therapy in IBD. Adverse effects of CAM are reported but are rare. The article provides current state of knowledge on the topic and provides guidance to physicians to address CAM use in pediatric patients with IBD.