Miracle-dz/UniFAR-FTUs huggingface dataset:
Pollinator assemblage and pollen load differences on sympatric diploid and tetraploid cytotypes of the desert‐dominant Larrea tridentata

Premise Whole‐genome duplication (polyploidy) is an important force shaping flowering‐plant evolution. Ploidy‐specific plant–pollinator interactions represent important community‐level biotic interactions that can lead to nonrandom mating and the persistence of mixed‐ploidy populations. Methods At a naturally occurring diploid–tetraploid contact zone of the autopolyploid desert shrub Larrea tridentata, we combined flower phenology analyses, collections of bees on plants of known cytotype, and flow cytometry analyses of bee‐collected pollen loads to investigate whether (1) diploid and tetraploid plants have unique bee pollinator assemblages, (2) bee taxa exhibit ploidy‐specific visitation and pollen collection biases, and (3) specialist and generalist bee taxa have ploidy‐specific visitation and pollen collection biases. Results Although bee assemblages overlapped, we found significant differences in bee visitation to co‐occurring diploids and tetraploids, with the introduced honeybee (Apis mellifera) and one native species (Andrena species 12) more frequently visiting tetraploids. Consistent with bee assemblage differences, we found that diploid pollen was overrepresented among pollen loads on native bees, while pollen loads on A. mellifera did not deviate from the random expectation. However, mismatches between the ploidy of pollen loads and plants were common, consistent with ongoing intercytotype gene flow. Conclusions Our data are consistent with cytotype‐specific bee visitation and suggest that pollinator behavior contributes to reduced diploid–tetraploid mating. Differences in bee visitation and pollen movement potentially contribute to an easing of minority cytotype exclusion and the facilitation of cytotype co‐occurrence.
Metabolomic analysis of uremic pruritus in patients on hemodialysis

Pruritus is a common debilitating symptom experienced by hemodialysis patients. Treatment is difficult because the cause of uremic pruritus is not known. This study addressed the hypothesis that pruritus is caused by solutes that accumulate in the plasma when the kidneys fail. We sought to identify solutes responsible for uremic pruritus using metabolomic analysis to compare the plasma of hemodialysis patients with severe pruritus versus mild/no pruritus. Pruritus severity in hemodialysis patients was assessed using a 100-mm visual analogue scale (VAS), with severe pruritus defined as >70 mm and mild/no pruritus defined as <10 mm. Twelve patients with severe pruritus (Itch) and 24 patients with mild/no pruritus (No Itch) were included. Pre-treatment plasma and plasma ultrafiltrate were analyzed using an established metabolomic platform (Metabolon, Inc.). To identify solutes associated with pruritus, we compared the average peak area of each solute in the Itch patients to that of the No Itch patients using the false discovery rate (q value) and principal component analysis. Dialysis vintage, Kt/Vurea, and serum levels of calcium, phosphorus, PTH, albumin, ferritin, and hemoglobin were similar in the Itch and No Itch patients. Metabolomic analysis identified 1,548 solutes of which 609 were classified as uremic. No difference in the plasma or plasma ultrafiltrate levels of any solute or group of solutes was found between the Itch and No Itch patients. Metabolomic analysis of hemodialysis patients did not reveal any solutes associated with pruritus. A limitation of metabolomic analysis is that the solute of interest may not be included in the metabolomic platform’s chemical library. A role for uremic solutes in pruritus remains to be established.
Prevalence of Traumas and PTSD Among Individuals Adjudicated Not Guilty by Reason of Insanity

Trauma and posttraumatic stress disorder (PTSD) are common among psychiatric and criminal populations, yet there have been few studies among forensic psychiatric populations and no known studies have specifically examined insanity acquittees. This study aimed to identify the prevalence of trauma and to assess recognition of PTSD in forensic settings. Using a cross-sectional self-report survey methodology, we examined traumas, adverse childhood experiences (ACEs), and PTSD in insanity acquittees (n = 107). Most insanity acquittees experienced trauma (86%, averaging 11 events) and ACEs (76%, averaging 3 types). The most commonly experienced traumas were sudden death of a loved one, witnessed death or serious injury, adult physical assault, and motor vehicle accident. Women were significantly more likely to experience any ACE (especially witnessing domestic violence, household members with mental illness, emotional abuse, and emotional neglect) and adult sexual assault. PTSD prevalence was 25 percent, with 97 percent of cases being previously undiagnosed. Sexual traumas and younger age were significantly associated with PTSD. These results suggest that insanity acquittees have high levels of trauma, ACEs, and PTSD. While PTSD was about seven times more common than in previous findings in the general population, it frequently goes undiagnosed in forensic settings. Potential explanations and implications of our findings are discussed.
Outpatient metformin use is associated with reduced severity of COVID‐19 disease in adults with overweight or obesity

Observational studies suggest outpatient metformin use is associated with reduced mortality from coronavirus disease‐2019 (COVID‐19). Metformin is known to decrease interleukin‐6 and tumor‐necrosis factor‐α, which appear to contribute to morbidity in COVID‐19. We sought to understand whether outpatient metformin use was associated with reduced odds of severe COVID‐19 disease in a large US healthcare data set. Retrospective cohort analysis of electronic health record (EHR) data that was pooled across multiple EHR systems from 12 hospitals and 60 primary care clinics in the Midwest between March 4, 2020 and December 4, 2020. Inclusion criteria: data for body mass index (BMI) > 25 kg/m2 and a positive SARS‐CoV‐2 polymerase chain reaction test; age ≥ 30 and ≤85 years. Exclusion criteria: patient opt‐out of research. Metformin is the exposure of interest, and death, admission, and intensive care unit admission are the outcomes of interest. Metformin was associated with a decrease in mortality from COVID‐19, OR 0.32 (0.15, 0.66; p = .002), and in the propensity‐matched cohorts, OR 0.38 (0.16, 0.91; p = .030). Metformin was associated with a nonsignificant decrease in hospital admission for COVID‐19 in the overall cohort, OR 0.78 (0.58–1.04, p = .087). Among the subgroup with a hemoglobin HbA1c available (n = 1193), the adjusted odds of hospitalization (including adjustment for HbA1c) for metformin users was OR 0.75 (0.53–1.06, p = .105). Outpatient metformin use was associated with lower mortality and a trend towards decreased admission for COVID‐19. Given metformin's low cost, established safety, and the mounting evidence of reduced severity of COVID‐19 disease, metformin should be prospectively assessed for outpatient treatment of COVID‐19.
The integrity of the U12 snRNA 3′ stem–loop is necessary for its overall stability

Abstract Disruption of minor spliceosome functions underlies several genetic diseases with mutations in the minor spliceosome-specific small nuclear RNAs (snRNAs) and proteins. Here, we define the molecular outcome of the U12 snRNA mutation (84C>U) resulting in an early-onset form of cerebellar ataxia. To understand the molecular consequences of the U12 snRNA mutation, we created cell lines harboring the 84C>T mutation in the U12 snRNA gene (RNU12). We show that the 84C>U mutation leads to accelerated decay of the snRNA, resulting in significantly reduced steady-state U12 snRNA levels. Additionally, the mutation leads to accumulation of 3′-truncated forms of U12 snRNA, which have undergone the cytoplasmic steps of snRNP biogenesis. Our data suggests that the 84C>U-mutant snRNA is targeted for decay following reimport into the nucleus, and that the U12 snRNA fragments are decay intermediates that result from the stalling of a 3′-to-5′ exonuclease. Finally, we show that several other single-nucleotide variants in the 3′ stem-loop of U12 snRNA that are segregating in the human population are also highly destabilizing. This suggests that the 3′ stem-loop is important for the overall stability of the U12 snRNA and that additional disease-causing mutations are likely to exist in this region.
Clinical Syndromic Phenotypes and the Potential Role of Genetics in Pulmonary Vein Stenosis

Pulmonary vein stenosis (PVS) is a rare, frequently lethal disease with heterogeneous phenotypes and an unclear etiology. Limited studies have reported associations between PVS and congenital heart disease (CHD), chronic lung disease (CLD), and/or prematurity; however, to date, there have been no studies that report detailed clinical syndromic phenotypes and the potential role of genetics in PVS. An existing registry of multivessel PVS patients seen at Boston Children’s Hospital (BCH) was queried between August 2006 and January 2017 for all existing genetic testing data on these patients. PVS was defined as an intraluminal pulmonary venous obstruction in ≥2 vessels with mean pressure gradients > 4 mmHg. One-hundred-and-fifty-seven patients (46% female, with a median age at PVS diagnosis of 3 months) formed the cohort. Seventy-one (45%) patients had available genetic testing information. Of the 71 patients, a likely genetic diagnosis was found in 23 (32%) patients: 13 (57%) were diagnosed with Trisomy 21 (T21), five (22%) with Smith–Lemli–Opitz Syndrome, five (22%) had other pathologic genetic disease, and 24 (33%) had variants of unknown significance. The majority of 13 patients with T21 and PVS had common atrioventricular canal (CAVC) (10, 77%) and all had severe pulmonary hypertension (PHTN), which led to their PVS diagnosis. In our study, PVS was associated with T21, the majority of whom also had CAVC and PHTN. Therefore, complete assessment of the pulmonary veins should be considered for all T21 patients, especially those with CAVC presenting with PHTN. Furthermore, prospective standardized genetic testing with detailed clinical phenotyping may prove informative about potential genetic etiologies of PVS.
Long-term Outcomes and Complications of the New Carlevale Sutureless Scleral Fixation Posterior Chamber IOL.

PURPOSE To evaluate the visual outcomes and possible complications of a new foldable sutureless scleral fixation intraocular lens (SSF-IOL), the Carlevale IOL (Soleko). METHODS The SSF-IOL, which has two T-shaped self-blocking plugs on each haptic, was inserted into the posterior chamber. Both haptics was grabbed through two sclerotomies and the two short arms were blocked under the scleral flap, without any suture. A complete clinical evaluation was done preoperatively and at 3, 6, and 12 months postoperatively. RESULTS A total of 54 eyes of 50 consecutive patients were retrospectively analyzed. The mean corrected distance visual acuity was 0.93 ± 0.61 logMAR preoperatively and improved to 0.42 ± 0.34 logMAR at 3 months, 0.42 ± 0.37 logMAR at 6 months, and 0.38 ± 0.38 logMAR at 12 months postoperatively (all P < .0001). The mean corneal endothelial cell density decreased from 1,725.37 ± 528.06 to 1,612.81 ± 522.91 cells/mm2 at 12 months postoperatively (P < .0001). The mean IOL tilt value was 3.1 ± 1.1° at 12 months postoperatively. The authors observed 6 cases (11.1%) of intraoperative rupture of the IOL haptics, 4 cases (7.4%) of early hyphema, 4 cases (7.4%) of macular cystoid edema, 2 cases (3.7%) of haptic exposure under the conjunctiva, and 1 (1.8%) late retinal detachment. CONCLUSIONS This newly introduced surgical technique provided promising results regarding efficacy and safety. Complications occurred in a few cases and were successfully managed. The Carlevale IOL seems to be a surgical solution combining the advantages of an easy and minimally invasive implantation with a good functional recovery with minimal complications. [J Refract Surg. 2021;37(2):126-132. ].
Extracellular Vesicles Act as Nano-Transporters of Tyrosine Kinase Inhibitors to Revert Iodine Avidity in Thyroid Cancer

A new approach for using extracellular vesicles (EVs) to deliver tyrosine kinase inhibitors (TKIs) to enhance iodine avidity in radioactive iodine-refractory thyroid cancer is needed. We isolated and characterized primary human adipose-derived stem cells (ADSCs) and isolated their EVs. The EVs were characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. A new TKI was loaded into the EVs by incubation (37 °C; 10 min) or sonication (18 cycles; 4 s per cycle) with 2 s intervals and a 2 min ice bath every six cycles. TKI loading was confirmed and measured by mass spectrometry. EV uptake into radioactive iodine-refractory thyroid cancer cells (SW1736 cells) was confirmed by microscopy. We treated the SW1736 cells with vehicle, TKI, or TKI-loaded EVs (sonication TKI-loaded EVs [EVsTKI(S)]) and examined the expression of iodide-metabolizing proteins and radioiodine uptake in the SW1736 cells. ADSCs cells showed >99% of typical stem cell markers, such as CD90 and CD105. The EVs displayed a round morphology, had an average size of 211.4 ± 3.83 nm, and were positive for CD81 and Alix and negative for cytochrome c. The mass spectrometry results indicate that the sonication method loaded ~4 times more of the TKI than did the incubation method. The EVsTKI(S) were used for further experiments. Higher expression levels of iodide-metabolizing mRNA and proteins in the EVsTKI(S)-treated SW1736 cells than in TKI-treated SW1736 cells were confirmed. EVsTKI(S) treatment enhanced 125I uptake in the recipient SW1736 cells compared with free-TKI treatment. This is the first study that demonstrated successful delivery of a TKI to radioactive iodine-refractory thyroid cancer cells using EVs as the delivery vehicle. This approach can revert radioiodine-resistant thyroid cancer cells back to radioiodine-sensitive thyroid cancer cells.
Efficacy of an inpatient smoking cessation program at a single regional cancer center

Abstract Smoking is the leading cause of preventable death and a risk factor for cancer, but smoking cessation is difficult even in patients who need hospitalization. This study aimed to investigate the usefulness of an inpatient smoking cessation consultation program and to analyze the clinical factors associated with abstinence. In this observational study, patients received regular counseling for 6 months, and abstinence was objectively assessed via urine and exhaled carbon monoxide testing. Cessation rates were assessed at 4 weeks and 6 months, and clinical characteristics associated with cessation success were investigated. Of the 571 patients referred to participate in the program, 170 (29.8%) were enrolled, and only 2 (1.2%) used smoking cessation drugs in addition to counseling. The smoking cessation rate was 77.6% after 4 weeks and 59.1% after 6 months. The cessation rates were significantly higher in patients with cancer than in those without cancer at both timepoints (63.8% vs 21.9%, P < .001, 53.6% vs 12.5%, P < .001), and they were also higher in the first admission group than in the re-admission group (87.4% vs 74.7%, P = .033, 88.5% vs 76.1%, P = .037). In patients with lung cancer, progression-free survival and overall survival tended to be better in those enrolled in the program (P = .158, P = .183). In conclusion, the inpatient smoking cessation program was associated with a high abstinence rate. Most patients maintained cessation without medication, suggesting that initial admission, along with a cancer diagnosis, can provide enough motivation to abstain from smoking. In addition, the smoking cessation effort showed potential to improve survival during lung cancer treatment.
Biodegradation of di-n-octyl phthalate by Gordonia sp. Lff and its application in soil

ABSTRACT A previous isolated Gordonia sp. (Lff) was used to degrade di-n-octyl phthalate (DOP) contamination in both aqueous solution and soil. The influence of temperature, pH, inoculum size, salt content and initial concentration of DOP on DOP degradation by Lff were analysed. The response of soil bacterial community to DOP and Lff was also analysed by Illumina MiSeq sequence method. Results showed that the optimal temperature, pH, inoculum size and salt content were 35oC, 8.0, 5% and <5%, respectively. Under the optimal condition, more than 91.25% of DOP with different initial concentrations (100–2000 mg/L) could be degraded by Lff. Kinetics analysis indicated that biodegradation of DOP by Lff could be described by first-order kinetics (R 2 > 0.917) with the half-life (t 1/2) changing irregularly between 0.58 and 0.83 d. In addition, Lff enhanced the removal of DOP in soil and alleviated the toxicity of DOP on soil microorganisms. Furthermore, its influence on soil bacterial community is not obvious. These results suggested that Lff was effective in remediating DOP contamination in different environments. GRAPHICAL ABSTRACT
Gut Microbiota Profile and Changes in Body Weight in Elderly Subjects with Overweight/Obesity and Metabolic Syndrome

Gut microbiota is essential for the development of obesity and related comorbidities. However, studies describing the association between specific bacteria and obesity or weight loss reported discordant results. The present observational study, conducted within the frame of the PREDIMED-Plus clinical trial, aims to assess the association between fecal microbiota, body composition and weight loss, in response to a 12-month lifestyle intervention in a subsample of 372 individuals (age 55–75) with overweight/obesity and metabolic syndrome. Participants were stratified by tertiles of baseline body mass index (BMI) and changes in body weight after 12-month intervention. General assessments, anthropometry and biochemical measurements, and stool samples were collected. 16S amplicon sequencing was performed on bacterial DNA extracted from stool samples and microbiota analyzed. Differential abundance analysis showed an enrichment of Prevotella 9, Lachnospiraceae UCG-001 and Bacteroides, associated with a higher weight loss after 12-month of follow-up, whereas in the cross-sectional analysis, Prevotella 2 and Bacteroides were enriched in the lowest tertile of baseline BMI. Our findings suggest that fecal microbiota plays an important role in the control of body weight, supporting specific genera as potential target in personalized nutrition for obesity management. A more in-depth taxonomic identification method and the need of metabolic information encourages to further investigation.
Interventions to Improve the Cast Removal Experience for Children and Their Families: A Scoping Review

Background: Cast removal can be a distressing experience for a child. This scoping review aims to provide a comprehensive review of interventions designed to reduce anxiety and improve the child’s and family’s experience of pediatric cast removal. Methods: A scoping review was conducted (Medline, Embase, PsycINFO, CINAHL, Scopus, grey literature sources). Inclusion criteria: studies published January 1975–October 2019 with a primary focus on pediatric patients undergoing cast removal/cast room procedures. Screening, full text review, data extraction, and quality appraisal were conducted in duplicate. Results: 974 unique articles and 1 video were screened. Nine articles (eight unique studies) with a total of 763 participants were included. Interventions included the following, alone or in combination: noise reduction, electronic device use, preparatory information, music therapy, play therapy, and child life specialist-directed intervention. Heart rate was used as a primary (88%) or secondary (12%) outcome measure across studies. Each study reported some positive effect of the intervention, however effects varied by age, outcome measure, and measurement timing. Studies scored low on outcome measure validity and blinding as assessed by the Joanna Briggs Institute Critical Appraisal Checklist for Randomized Controlled Trials. Conclusion: Various methods have been tested to improve the pediatric cast removal experience. Results are promising, however the variation in observed effectiveness suggests a need for the use of consistent and valid outcome measures. In addition, future research and quality improvement projects should evaluate interventions that are tailored to a child’s age and child/family preference.
The effect of transcranial direct current stimulation combined with functional task training on motor recovery in stroke patients

Abstract Background: Motor deficits are common after stroke and are a major contributor to stroke-related disability and the potential for long-lasting neurobiological consequences of stroke remains unresolved. There are only a few treatments available for the improvement of motor function in stroke patients. However, the mechanisms underlying stroke recovery remain poorly understood, and effective neurorehabilitation interventions remain insufficiently proven for widespread implementation. Methods: Herein, we propose to enhance the effects of brain plasticity using a powerful noninvasive technique for brain modulation consisting of navigated transcranial magnetic stimulation (TMS) priming with transcranial direct current stimulation (tDCS) in combination with motor-training-like constraint-induced movement therapy (CIMT). Our hypothesis is that navigated low-frequency rTMS stimulus priming with precise location provided by neuronavigation on the healthy side of the brain and with anodal tDCS on the affected side combined with CIMT will induce a greater motor function improvement than that obtained with sham tDCS combined with CIMT alone. We predict that the application of this technique will result in a large reduction in cortical excitability and dis-inhibition in the affected hemisphere and lead to improvements in behavioral measures of hand function in stroke patients. Discussion: The proposed study, therefore, is important for several reasons. The results could potentially lead to improved stroke therapeutics, and the approach makes use of 2 potential pathways to modulate brain function. Trial registration: This study protocol was registered in Clinical Trials Registry (https://clinicaltrials.gov/ct2/show/NCT04646577). Ethics and dissemination: The study has been reviewed and approved by the Human Research Ethics Committee of the King Fahad Specialist Hospital Dammam. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, broadcast media, print media, the internet and various community/stakeholder engagement activities.