Miracle-dz/UniFAR-FTUs huggingface dataset:
The RNA binding protein DND1 is elevated in a subpopulation of pro-spermatogonia and targets chromatin modifiers and translational machinery during late gestation

DND1 is essential to maintain germ cell identity. Loss of Dnd1 function results in germ cell differentiation to teratomas in some inbred strains of mice or to somatic fates in zebrafish. Using our knock-in mouse line in which a functional fusion protein between DND1 and GFP is expressed from the endogenous locus (Dnd1GFP), we distinguished two male germ cell (MGC) populations during late gestation cell cycle arrest (G0), consistent with recent reports of heterogeneity among MGCs. Most MGCs express lower levels of DND1-GFP (DND1-GFP-lo), but some MGCs express elevated levels of DND1-GFP (DND1-GFP-hi). A RNA-seq time course confirmed high Dnd1 transcript levels in DND1-GFP-hi cells along with 5-10-fold higher levels for multiple epigenetic regulators. Using antibodies against DND1-GFP for RNA immunoprecipitation (RIP)-sequencing, we identified multiple epigenetic and translational regulators that are binding targets of DND1 during G0 including DNA methyltransferases (Dnmts), histone deacetylases (Hdacs), Tudor domain proteins (Tdrds), actin dependent regulators (Smarcs), and a group of ribosomal and Golgi proteins. These data suggest that in DND1-GFP-hi cells, DND1 hosts coordinating mRNA regulons that consist of functionally related and localized groups of epigenetic enzymes and translational components.
High carbon emissions from thermokarst lakes and their determinants in the Tibet Plateau

Thermokarst lakes are potentially important sources of methane (CH4) and carbon dioxide (CO2). However, considerable uncertainty exists regarding carbon emissions from thermokarst lakes owing to a limited understanding of their patterns and motivators. In this study, we measured CH4 and CO2 diffusive fluxes in 163 thermokarst lakes in the Qinghai–Tibet Plateau (QTP) over 3 years from May to October. The median carbon emissions from the QTP thermokarst lakes were 1440 mg CO2 m−2 day−1 and 60 mg CH4 m−2 day−1, respectively. The diffusive rates of CO2 and CH4 are related to the catchment land cover type. Sediment microbial abundance and hydrochemistry explain 51.9% and 38.3% of the total variance in CH4 diffusive emissions, respectively, while CO2 emissions show no significant relationship with environmental factors. When upscaling carbon emissions from the QTP thermokarst lakes, the annual average CH4 release per lake area is equal to that of the pan‐Arctic region. Our findings highlight the importance of incorporating in situ observation data with different emission pathways for different land cover types in predicting carbon emissions from thermokarst lakes in the future.
Theory of hydromagnetic propagation in the ionospheric waveguide

In this paper, we consider the propagation of low-frequency (Pc 1) hydromagnetic waves in the ionospheric duct, which results from the minimum in the Alfven speed near the F2 ionization peak. We consider an inhomogeneous (in the vertical direction) waveguide in the presence of a uniform static magnetic field and treat the case of horizontal propagation in the plane of the magnetic meridian. Propagation in the waveguide is governed by two coupled equations for the horizontal components of the electric field. For nighttime conditions, where the ionized region of interest starts at sufficiently high altitude that the collision frequency of ions with neutrals is small compared with the ion cyclotron frequency, the two components become uncoupled, and only the isotropic, or fast wave, need be considered. For daytime conditions, however, coupling between the fast and slow waves must be taken into account; to simplify the analysis, the static field is assumed uniform in this case. To obtain analytic solution of the waveguide equations, it is necessary to have analytic approximations to the height dependence of the relevant ionospheric parameters; such approximations are constructed to fit some representative tabulated ionospheric profiles for a variety of conditions of time of day and sunspot activity. Solution of the waveguide equations subject to the appropriate boundary conditions results in a rather complicated dispersion relation between complex (horizontal) wave number and angular frequency. The solutions of the dispersion relation prescribe the allowed bands of propagation in the guide. It is shown that each band, including the lowest, has a low-frequency cutoff, and that the existence of a low-frequency cutoff is a consequence of the boundary conditions and not of attenuation, as assumed in some theories. Numerical solutions of the dispersion equation are obtained for the two lowest bands for each of the conditions considered. From the dependence of the real part of the wave number on frequency, the cutoff frequencies and the phase and group velocities are determined, while the imaginary part provides the attenuation length. For nighttime conditions, attenuation is not large, and propagation can take place over distances of thousands of km, whereas daytime propagation is restricted by attenuation to distances of the order of hundreds of km. For nighttime minimum conditions, the calculated waveguide cutoff is about 0.4 cps, and the group velocity for the lowest band is about 720 km/sec, both in reasonable agreement with experiment. Finally, it is pointed out that there is an effective high-frequency ‘cutoff’ (in any band) as far as ground-level signals are concerned due to an exponential decrease of transmission coefficient with frequency at high frequencies.
An umbrella review of the acceptability of fiscal and pricing policies to reduce diet-related noncommunicable disease

Abstract Context Poor diet has been implicated in a range of noncommunicable diseases. Fiscal and pricing policies (FPs) may offer a means by which consumption of food and non-alcoholic beverages with links to such diseases can be influenced to improve public health. Objective To examine the acceptability of FPs to reduce diet-related noncommunicable disease, based on systematic review evidence. Data Sources MEDLINE, EMBASE, PsychInfo, SCI, SSCI, Web of Science, Scopus, EconLit, the Cochrane Library, Epistemonikos, and the Campbell Collaboration Library were searched for relevant studies published between January 1, 1990 and June 2021. Data Extraction The studies included systematic reviews of diet-related FPs and: used real-world evidence; examined real or perceived barriers/facilitators; targeted the price of food or non-alcoholic beverages; and applied to entire populations within a jurisdiction. A total of 9996 unique relevant records were identified, which were augmented by a search of bibliographies and recommendations from an external expert advisory panel. Following screening, 4 systematic reviews remained. Data Analysis Quality appraisal was conducted using the AMSTAR 2 tool. A narrative synthesis was undertaken, with outcomes grouped according to the WHO-INTEGRATE criteria. The findings indicated a paucity of high-quality systematic review evidence and limited public support for the use of FPs to change dietary habits. This lack of support was related to a number of factors that included: their perceived potential to be regressive; a lack of transparency, ie, there was mistrust around the use of revenues raised; a paucity of evidence around health benefits; the deliberate choice of rates that were lower than those considered necessary to affect diet; and concerns about the potential of such FPs to harm economic outcomes such as employment. Conclusion The findings underscore the need for high-quality systematic review evidence on this topic, and the importance of responding to public concerns and putting in place mechanisms to address these when implementing FPs. This study was funded by Safefood [02A-2020]. Systematic Review Registration PROSPERO registration no. CRD42021274454.
‘Off the shelf’ immunotherapies: Generation and application of pluripotent stem cell‐derived immune cells

In recent years, great strides have been made toward the development of immune cell‐based therapies in the treatment of refractory malignancies. Primary T cells and NK cells armed with chimeric antigen receptors have achieved tremendous clinical success especially in patients with leukaemia and lymphoma. However, the autologous origin of these effector cells means that a single batch of laboriously engineered cells treats only a certain patient, leading to high cost, ununiform product quality, and risk of delay in treatment, and therefore results in restricted accessibility of these therapies to the overwhelming majority of the patients. Addressing these tricky obstacles calls for the development of universal immune cell products that can be provided ‘off the shelf’ in a large amount. Pluripotent stem cells (PSCs), owing to their unique capacity of self‐renewal and the potential of multi‐lineage differentiation, offer an unlimited cell source to generate uniform and scalable engineered immune cells. This review discusses the major advances in the development of PSC‐derived immune cell differentiation approaches and their therapeutic potential in treating both hematologic malignancies and solid tumours. We also consider the potency of PSC‐derived immune cells as an alternative therapeutic strategy for other diseases, such as autoimmune diseases, fibrosis, infections, et al.
Effects of traditional stretching versus self-myofascial release warm-up on physical performance in well-trained female athletes

Objective: The purpose of this study was to compare the acute effects of self-myofascial release (SMR) versus traditional stretching used as a part of warm-up on physical performance in well-trained female athletes. Methods: Twenty-three participants (age, 21.8±1.73 years; experience in sport, 114.8±30.5 months) were recruited. Isokinetic peak torque and muscle endurance ratio were measured during knee extension and flexion at 60°/s and 180°/s. Jump height, reactive strength index, and leg stiffness were measured using a jump mat during a counter-movement jump. Hamstring flexibility was measured using a sit-and-reach test. Three interventions were performed by all athletes randomly within 72 hours intervals. Results: The jump height and hamstring flexibility test scores improved significantly more after dynamic stretching (DS) as compared to SMR and static stretching (SS). The DS and SMR exercises were more effective than the SS exercises in terms of right and left knee muscle isokinetic strength both at 60°/s, and 180°/s. With regard to keeping muscular endurance ratio (%), SS exercises were found more effective than DS and SMR exercises for only the right knee at 180°/s, but not left knee muscle. Conclusion: Dynamic stretching and SMR showed better flexibility, strength, and jump performance than SS. Trainers and players may replace SS with DS and SMR to acutely improve muscle power, strength, and flexibility.
Epidemiology and characteristics of acral lentiginous melanoma compared to lentigo melanoma in France: a multicentric retrospective study from the French cohort RIC-Mel database

Skin phototype, latitude and sun exposure are classic risk factors for melanomas but are not relevant to acrolentiginous melanomas (ALM). ALM is not related to chronic sun exposure because the thick stratum corneum acts as a barrier to penetration of UV rays, whereas LMM occurs in skin with high photoaging due to chronic sun exposure. This study aimed to determine if any difference exists between “solar” melanomas and “non-solar” melanomas based on a comparison between LMM and ALM. We extracted all data for ALM and LMM patients, from March 2012 to September 2020, from the RIC-Mel national database to perform a descriptive cohort analysis of 1,056 Caucasian cases. The profiles of solar-related and non-solar melanoma seem to be different, and prognostic factors of ALM at diagnosis are less favourable compared to LMM, suggesting that non-solar melanoma is more aggressive than solar-related melanoma and that sentinel lymph node biopsy should be performed.
Application of a burn scar assessment tool for the evaluation of visual scarring following immunocryosurgery for facial basal cell carcinoma

The therapeutic interventions for basal cell carcinoma (BCC) impact facial cosmesis. Our aim was to assess the aesthetic burden of facial BCC treatment by evaluating the extent of the tumour site visually based on clinical images before and after immunocryosurgery; a minimally invasive combination treatment of topical imiquimod and cryosurgery. A three-item (texture, height, colour) burn scar scale was independently applied by four physicians (two dermatologists and two plastic surgeons) on archival semi-standardized clinical images of facial BCC before and one year after immunocryosurgery. The score assessments were compared using non-parametric statistical tests; internal consistency (reliability) and inter-rater agreement were assessed using Cronbach’s α and Gwet’s AC2, respectively. Images (before and one year after treatment) of 27 BCCs from 26 patients (15 males) were analysed. The reliability was good (α > 0.80) for all items before surgery and for colour after surgery. The inter-rater agreement was acceptable (AC2 > 0.70) for all items except for height pre-treatment (AC2 = 0.482). Based on averaging of all raters, cosmesis improved significantly after treatment at all tumour sites (p < 0.001, Wilcoxon signed ranks test). The main limitations of the study are the inclusion of cases from a single centre and its retrospective nature. The evaluated burn scar scale can be reliably used to compare the extent of the BCC site visually before therapy and after resultant scars have formed. In this way, the impact of therapeutic interventions on cosmesis (from tumour to scar) can be evaluated, particularly for less aggressive facial skin tumours, such as most BCC.
The coat protein of tobacco mosaic virus as an anti-tobacco mosaic virus: a molecular dynamics simulation

Abstract The Coat Protein (CP) of the Tobacco Mosaic Virus (TMV) executes an important duty in the protection of virus RNA. The interaction between the virus CP and host plant proteins induces infection in the host and creates dark and light green mosaics on crops, which disturb the growth and function of the plant. The interaction between the virus CP and the modified CP, expressed in transgenic plants, causes Coat Protein-Mediated Resistance (CP-MR), which reduces virus infection in transgenic plants. In this study, a model is suggested for resistance as “stop assembly of CP” in the virus. It is based on the fact that the CP, when mutated, acts as a dead-end in virus assembly. For evaluation of the model, we investigated the effect of four mutants including CBT28I, ABT42W, ABD77R, and ABT89W complexes on plant resistance against TMV infection by molecular dynamics simulation. Previous studies had shown the influence of such mutations on the CP-MR. The MD results of in the present study further confirmed the mentioned effect and demonstrated how the mutations could be the cause of CP-MR. The results are calculated by the RMSD, Rg, H-bond, and g-MMPBSA scripts. The change in binding energy between two chains is consistent with CP-MR such that with increase in binding energy, the affinity between two chains was reduced and the CP-MR increased. Based on this model, it is possible to design mutants with a high level of efficiency. Communicated by Ramaswamy H. Sarma
Myocardial Metabolomics of Human Heart Failure With Preserved Ejection Fraction

Background: The human heart primarily metabolizes fatty acids, and this decreases as alternative fuel use rises in heart failure with reduced ejection fraction (HFrEF). Patients with severe obesity and diabetes are thought to have increased myocardial fatty acid metabolism, but whether this is found in those who also have heart failure with preserved ejection fraction (HFpEF) is unknown. Methods: Plasma and endomyocardial biopsies were obtained from HFpEF (n=38), HFrEF (n=30), and nonfailing donor controls (n=20). Quantitative targeted metabolomics measured organic acids, amino acids, and acylcarnitines in myocardium (72 metabolites) and plasma (69 metabolites). The results were integrated with reported RNA sequencing data. Metabolomics were analyzed using agnostic clustering tools, Kruskal-Wallis test with Dunn test, and machine learning. Results: Agnostic clustering of myocardial but not plasma metabolites separated disease groups. Despite more obesity and diabetes in HFpEF versus HFrEF (body mass index, 39.8 kg/m2 versus 26.1 kg/m2; diabetes, 70% versus 30%; both P<0.0001), medium- and long-chain acylcarnitines (mostly metabolites of fatty acid oxidation) were markedly lower in myocardium from both heart failure groups versus control. In contrast, plasma levels were no different or higher than control. Gene expression linked to fatty acid metabolism was generally lower in HFpEF versus control. Myocardial pyruvate was higher in HFpEF whereas the tricarboxylic acid cycle intermediates succinate and fumarate were lower, as were several genes controlling glucose metabolism. Non–branched-chain and branched-chain amino acids (BCAA) were highest in HFpEF myocardium, yet downstream BCAA metabolites and genes controlling BCAA metabolism were lower. Ketone levels were higher in myocardium and plasma of patients with HFrEF but not HFpEF. HFpEF metabolomic-derived subgroups were differentiated by only a few differences in BCAA metabolites. Conclusions: Despite marked obesity and diabetes, HFpEF myocardium exhibited lower fatty acid metabolites compared with HFrEF. Ketones and metabolites of the tricarboxylic acid cycle and BCAA were also lower in HFpEF, suggesting insufficient use of alternative fuels. These differences were not detectable in plasma and challenge conventional views of myocardial fuel use in HFpEF with marked diabetes and obesity and suggest substantial fuel inflexibility in this syndrome.
Neoadjuvant-Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma.

BACKGROUND Whether pembrolizumab given both before surgery (neoadjuvant therapy) and after surgery (adjuvant therapy), as compared with pembrolizumab given as adjuvant therapy alone, would increase event-free survival among patients with resectable stage III or IV melanoma is unknown. METHODS In a phase 2 trial, we randomly assigned patients with clinically detectable, measurable stage IIIB to IVC melanoma that was amenable to surgical resection to three doses of neoadjuvant pembrolizumab, surgery, and 15 doses of adjuvant pembrolizumab (neoadjuvant-adjuvant group) or to surgery followed by pembrolizumab (200 mg intravenously every 3 weeks for a total of 18 doses) for approximately 1 year or until disease recurred or unacceptable toxic effects developed (adjuvant-only group). The primary end point was event-free survival in the intention-to-treat population. Events were defined as disease progression or toxic effects that precluded surgery; the inability to resect all gross disease; disease progression, surgical complications, or toxic effects of treatment that precluded the initiation of adjuvant therapy within 84 days after surgery; recurrence of melanoma after surgery; or death from any cause. Safety was also evaluated. RESULTS At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group (154 patients) had significantly longer event-free survival than the adjuvant-only group (159 patients) (P = 0.004 by the log-rank test). In a landmark analysis, event-free survival at 2 years was 72% (95% confidence interval [CI], 64 to 80) in the neoadjuvant-adjuvant group and 49% (95% CI, 41 to 59) in the adjuvant-only group. The percentage of patients with treatment-related adverse events of grades 3 or higher during therapy was 12% in the neoadjuvant-adjuvant group and 14% in the adjuvant-only group. CONCLUSIONS Among patients with resectable stage III or IV melanoma, event-free survival was significantly longer among those who received pembrolizumab both before and after surgery than among those who received adjuvant pembrolizumab alone. No new toxic effects were identified. (Funded by the National Cancer Institute and Merck Sharp and Dohme; S1801 ClinicalTrials.gov number, NCT03698019.).
Analyzing referencing patterns in grey literature produced by influential global management consulting firms and international organizations

Given the growing influence of non-academic organizations in the policy sphere, it is important to investigate the evidence both produced by and relied on by these organizations. Using citation analysis, a methodology primarily used in academic literature, we investigated the evidence base supporting the grey literature published by leading global management consulting firms (GMCFs) and international organizations (IOs). With the topic of the skills needed for the future of work as a case study, we collected 234 reports published by influential GMCFs and IOs over twenty years. By extracting references from the bibliographies of these reports we: 1) analyzed referencing patterns by measuring citation counts, institutional self-referencing and utilization of scholarly sources; 2) compared reference patterns across GMCFs and IOs; and 3) described the most influential sources. Overall, both GMCFs and IOs showed increasing reliance on grey literature, demonstrated high levels of self-referencing, and had considerable variation in the number of sources referred to. Across type of publishing organization, we found that IOs had better referencing practices than GMCFs. Our findings call into question the evidence-base behind the reports published by these policy actors. We emphasize the need to rely on strong academic literature to inform policy decisions around the future of work.
Predicting the stalking of celebrities from measures of persistent pursuit and threat directed toward celebrities, sensation seeking and celebrity worship

The stalking of celebrities is a serious issue for thousands of celebrities worldwide who are occasionally confronted by fans who merit the label “fanatic. ” We administered measures of obnoxious celebrity stalking, celebrity worship, persistent pursuit of celebrities, threat directed toward celebrities, boredom susceptibility, disinhibition, experience seeking, thrill and adventure seeking, relationship styles, and anger to 596 college students from the U.S.A. We developed a model consisting of all but the latter five measures that successfully predicted actual obnoxious stalking behaviors of celebrities. Our results partially replicate earlier research and presents some new findings. Individuals who have personal thoughts about their favorite celebrity frequently, feel compelled to learn more about them, pursue them consistently, threatened to harm them and were prone to boredom were more likely to engage in celebrity stalking. Controlling for these predictors, individuals who admire their favorite celebrity almost exclusively because of their ability to entertain were less likely to engage in celebrity stalking.