Miracle-dz/UniFAR-FTUs huggingface dataset:
NSUN2-mediated m5C modification of HBV RNA positively regulates HBV replication

Chronic hepatitis B virus (HBV) infection is a major cause of liver cirrhosis and liver cancer, despite strong prevention and treatment efforts. The study of the epigenetic modification of HBV has become a research hotspot, including the N6-methyladenosine (m6A) modification of HBV RNA, which plays complex roles in the HBV life cycle. In addition to m6A modification, 5-methylcytosine (m5C) is another major modification of eukaryotic mRNA. In this study, we explored the roles of m5C methyltransferase and demethyltransferase in the HBV life cycle. The results showed that m5C methyltransferase NSUN2 deficiency could negatively regulate the expression of HBV while m5C demethyltransferase TET2 deficiency positively regulates the expression of HBV. Subsequently, we combined both in vitro bisulfite sequencing and high-throughput bisulfite sequencing methods to determine the distribution and stoichiometry of m5C modification in HBV RNA. Two sites: C2017 and C131 with the highest-ranking methylation rates were identified, and mutations at these two sites could lead to the decreased expression and replication of HBV, while the mutation of the “fake” m5C site had no effect. Mechanistically, NSUN2-mediated m5C modification promotes the stability of HBV RNA. In addition, compared with wild-type HepG2-NTCP cells and primary human hepatocytes, the replication level of HBV after NSUN2 knockdown decreased, and the ability of the mutant virus to infect and replicate in wild-type HepG2-NTCP cells and PHHs was substantially impaired. Similar results were found in the experiments using C57BL/6JGpt-Nsun2+/- mice. Interestingly, we also found that HBV expression and core protein promoted the endogenous expression of NSUN2, which implied a positive feedback loop. In summary, our study provides an accurate and high-resolution m5C profile of HBV RNA and reveals that NSUN2-mediated m5C modification of HBV RNA positively regulates HBV replication by maintaining RNA stability.
Daratumumab for patients with myeloma with early or late relapse after initial therapy: subgroup analysis of CASTOR and POLLUX

Key Points • Post hoc analyses of CASTOR/POLLUX showed PFS and depth of response benefit with daratumumab, regardless of relapse timing (early or late). • These results support daratumumab use for patients with MM who relapse early after initial therapy and have functional high-risk disease.
Mitochondrial Quality Control: Its Role in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease, is characterized by hepatic steatosis and metabolic dysfunction and is often associated with obesity and insulin resistance. Recent research indicates a rapid escalation in MASLD cases, with projections suggesting a doubling in the United States by 2030. This review focuses on the central role of mitochondria in the pathogenesis of MASLD and explores potential therapeutic interventions. Mitochondria are dynamic organelles that orchestrate hepatic energy production and metabolism and are critically involved in MASLD. Dysfunctional mitochondria contribute to lipid accumulation, inflammation, and liver fibrosis. Genetic associations further underscore the relationship between mitochondrial dynamics and MASLD susceptibility. Although U.S. Food and Drug Administration-approved treatments for MASLD remain elusive, ongoing clinical trials have highlighted promising strategies that target mitochondrial dysfunction, including vitamin E, metformin, and glucagon-like peptide-1 receptor agonists. In preclinical studies, novel therapeutics, including nicotinamide adenine dinucleotide+ precursors, urolithin A, spermidine, and mitoquinone, have shown beneficial effects, such as improving mitochondrial quality control, reducing oxidative stress, and ameliorating hepatic steatosis and inflammation. In conclusion, mitochondrial dysfunction is central to MASLD pathogenesis. The innovative mitochondria-targeted approaches discussed in this review offer a promising avenue for reducing the burden of MASLD and improving global quality of life.
Teneurin-3 regulates the generation of non-image-forming visual circuitry and responsiveness to light in the suprachiasmatic nucleus

Visual system function depends upon the elaboration of precise connections between retinal ganglion cell (RGC) axons and their central targets in the brain. Though some progress has been made in defining the molecules that regulate RGC connectivity required for the assembly and function of image-forming circuitry, surprisingly little is known about factors required for intrinsically photosensitive RGCs (ipRGCs) to target a principal component of the non-image-forming circuitry: the suprachiasmatic nucleus (SCN). Furthermore, the molecules required for forming circuits critical for circadian behaviors within the SCN are not known. We observe here that the adhesion molecule teneurin-3 (Tenm3) is highly expressed in vasoactive intestinal peptide (VIP) neurons located in the core region of the SCN. Since Tenm3 is required for other aspects of mammalian visual system development, we investigate roles for Tenm3 in regulating ipRGC-SCN connectivity and function. Our results show that Tenm3 negatively regulates association between VIP and arginine vasopressin (AVP) neurons within the SCN and is essential for M1 ipRGC axon innervation to the SCN. Specifically, in Tenm3-/- mice, we find a reduction in ventro-medial innervation to the SCN. Despite this reduction, Tenm3-/- mice have higher sensitivity to light and faster re-entrainment to phase advances, probably due to the increased association between VIP and AVP neurons. These data show that Tenm3 plays key roles in elaborating non-image-forming visual system circuitry and that it influences murine responses to phase-advancing light stimuli.
A postmeiotically bifurcated roadmap of honeybee spermatogenesis marked by phylogenetically restricted genes

Haploid males of hymenopteran species produce gametes through an abortive meiosis I followed by meiosis II that can either be symmetric or asymmetric in different species. Thus, one spermatocyte could give rise to two spermatids with either equal or unequal amounts of cytoplasm. It is currently unknown what molecular features accompany these postmeiotic sperm cells especially in species with asymmetric meiosis II such as bees. Here we present testis single-cell RNA sequencing datasets from the honeybee (Apis mellifera) drones of 3 and 14 days after emergence (3d and 14d). We show that, while 3d testes exhibit active, ongoing spermatogenesis, 14d testes only have late-stage spermatids. We identify a postmeiotic bifurcation in the transcriptional roadmap during spermatogenesis, with cells progressing toward the annotated spermatids (SPT) and small spermatids (sSPT), respectively. Despite an overall similarity in their transcriptomic profiles, sSPTs express the fewest genes and the least RNA content among all the sperm cell types. Intriguingly, sSPTs exhibit a relatively high expression level for Hymenoptera-restricted genes and a high mutation load, suggesting that the special meiosis II during spermatogenesis in the honeybee is accompanied by phylogenetically young gene activities.
The Value of Trichoscopy in the Follow-up of Treatment Response in Patients with Androgenetic Alopecia.

INTRODUCTION Although trichoscopy has been used successfully in the diagnosis of androgenetic alopecia (AGA), its utility in monitoring the therapeutic outcome is not clear. OBJECTIVE To investigate the value of trichoscopy in the follow-up of treatment response in patients with AGA. METHODS Ninety-five patients with AGA were included. Trichoscopic images were obtained on a 1 cm2 circular area in the left frontoparietal scalp pre- and post-treatment in all and in 61 patients, respectively. Two doctors evaluated those images who are less experienced (doctor A) and experienced (doctor B) in hair diseases and trichoscopy. Terminal, vellus and total hair count (THC, VHC, ToHC) and terminal to vellus hair (T/V) ratio were determined. These numerical data were also calculated by TrichoScan analysis of the same area. The agreement between trichoscopy and TrichoScan data was assessed. RESULTS The agreement between doctor A and TrichoScan was moderate for THC and ToHC pre-treatment and good post-treatment; poor for VHC and T/V ratio pre- and post-treatment. The agreement between doctor B and TrichoScan was excellent for THC, VHC and ToHC; good for T/V ratio pre- and post-treatment. CONCLUSIONS Trichoscopy, when performed by a doctor experienced in hair diseases and trichoscopy, can be used as a sensitive method in monitoring the treatment response in patients with AGA which is based on the determination of THC, VHC, ToHC and T/V ratio. If it is to be performed by a less experienced doctor, it can be preferred as a sensitive follow-up method using THC and ToHC.
Long-Term Impact of Medicaid Expansion on Prostate Cancer Screening

Abstract Introduction: Prostate cancer is the most common noncutaneous malignancy in men. The updated PSA testing 2018 United States Preventive Services Task Force guidelines recommend shared decision-making for men ages 55 to 69. In 2010, the Affordable Care Act expanded Medicaid coverage to childless adults earning < 138% of the federal poverty level. Thereafter, individual states have chosen to adopt or defer Medicaid expansion at different times. This allows for the opportunity to study the effects of expansion on a population that did not previously qualify for Medicaid. We examine the long-term association of Medicaid expansion on prostate cancer screening. Methods: Data from the Behavioral Risk Factor Surveillance System were extracted for childless men earning less than 138% of the federal poverty level in states with different Medicaid expansion statuses from 2012 to 2020. States were classified into 4 expansion categories: very early expansion states, early expansion states, late expansion states, and nonexpansion states. Prevalence of PSA screening was determined for each category of expansion. Difference-in-difference analyses were used to understand variations in very early expansion states, early expansion states, and late expansion states trends with reference to nonexpansion states. Results: PSA screening prevalence decreased in very early expansion states (27.76% vs 18.50%), early expansion states (33.79% vs 18.09%), late expansion states (36.08% vs 19.14%), and nonexpansion states (38.82% vs 24.40%) from 2012 to 2020. However, the difference-in-difference analyses did not show statistically significant results among any of the years and expansion category groups in our study period. Conclusions: PSA screening prevalence decreased in all states, regardless of expansion category. No long-term effect of Medicaid expansion on PSA screening prevalence was observed among states with different expansion statuses.
Relationship among Osteoporosis, Sarcopenia, Locomotive Syndrome, and Spinal Kyphosis in Older Individuals Living in a Local Mountain Area

Study Design Cross-sectional cohort study. Purpose This study investigated the relationship among osteoporosis, sarcopenia, locomotive syndrome, and spinal kyphosis in older individuals living in a mountain area. Overview of Literature Kyphosis greatly reduces the quality of life of older individuals. Osteoporosis and sarcopenia are kyphosis-causing factors. Methods This cross-sectional study included 361 individuals aged ≥65 years (mean age, 75.0 years) living in a local mountain area and underwent medical check-ups from 2014 to 2018. The survey items included kyphosis index, body mass index, back pain prevalence, back pain Visual Analog Scale score, Oswestry Disability Index, walking speed, grip strength, skeletal mass index, osteoporosis (% young adult mean [YAM]), LOCOMO 5 score, and presence of sarcopenia (Asian Working Group for Sarcopenia). The participants were divided into the N (kyphosis index: <12; n=229, 63.4%), M (kyphosis index: 12–15; n=99, 27.4%), and K (kyphosis index: ≥15; n=33, 9.2%) groups. p-values of <0.05 were considered statistically significant. An association factor of kyphosis (kyphosis index: ≥15) was investigated with logistic regression analysis. Results Age and LOCOMO 5 scores were significantly higher (p<0.05) and %YAM and walking speed were significantly lower (p<0.05) in the K group than in the M and N groups. Other survey items showed significant differences. Only %YAM (odds ratio, 0.20; 95% confidence interval, 0.04–0.96) was an independent factor associated with a kyphosis index of ≥15. Conclusions Decreased muscle mass and muscle strength would be related to kyphosis; however, no such relations were noted. Bone loss was significantly related to kyphosis. Osteoporosis-induced decrease in vertebral body height is present in the background. Sarcopenia and locomotive syndrome were not related to kyphosis, whereas decreased bone density was independently associated with kyphosis in older individuals living in a mountain area.
Plane Waves Versus Correlation-Consistent Basis Sets: A Comparison of MP2 Non-Covalent Interaction Energies in the Complete Basis Set Limit

Second-order Møller–Plesset perturbation theory (MP2) is the most expedient wave function-based method for considering electron correlation in quantum chemical calculations and, as such, provides a cost-effective framework to assess the effects of basis sets on correlation energies, for which the complete basis set (CBS) limit can commonly only be obtained via extrapolation techniques. Software packages providing MP2 energies are commonly based on atom-centered bases with innate issues related to possible basis set superposition errors (BSSE), especially in the case of weakly bonded systems. Here, we present noncovalent interaction energies in the CBS limit, free of BSSE, for 20 dimer systems of the S22 data set obtained via a highly parallelized MP2 implementation in the plane-wave pseudopotential molecular dynamics package CPMD. The specificities related to plane waves for accurate and efficient calculations of gas-phase energies are discussed, and results are compared to the localized (aug-)cc-pV[D,T,Q,5]Z correlation-consistent bases as well as their extrapolated CBS estimates. We find that the BSSE-corrected aug-cc-pV5Z basis can provide MP2 energies highly consistent with the CBS plane wave values with a minimum mean absolute deviation of ∼0.05 kcal/mol without the application of any extrapolation scheme. In addition, we tested the performance of 13 different extrapolation schemes and found that the X–3 expression applied to the (aug-)cc-pVXZ bases provides the smallest deviations against CBS plane wave values if the extrapolation sequence is composed of points D and T, while performs slightly better for TQ and Q5 extrapolations. Also, we propose as a reliable alternative to extrapolate total energies from the DTQ, TQ5, or DTQ5 data points. In spite of the general good agreement between the values obtained from the two types of basis sets, it is noticed that differences between plane waves and (aug-)cc-pVXZ basis sets, extrapolated or not, tend to increase with the number of electrons, thus raising the question of whether these discrepancies could indeed limit the attainable accuracy for localized bases in the limit of large systems.
Sociodemographic profiles and organ damage accural in the Black Women’s Experience Living with Lupus study

Objective Black/African American women with systemic lupus erythematosus (SLE) experience greater organ damage and at younger ages than white women. The objective of this study was to advance research on SLE inequities by identifying sociodemographic risk profiles associated with organ damage accrual specifically among Black/African American women. Methods Latent profile analysis was conducted among 438 Black/African American women with SLE living in Atlanta, GA and enrolled in the Black Women’s Experiences Living with Lupus (BeWELL) Study (May 2015 to April 2017). Proportional hazard and Poisson regression models examined prospective associations between sociodemographic profiles and the timing and degree of organ damage accrual over 2 years. Results Four profiles emerged: (1) “Younger/Lower SES with Uncontrolled SLE” (44.8%), (2) “Older/Lower SES with Uncontrolled SLE” (23.3%), (3) “Mid-SES with Controlled SLE” (19.6%), and (4) “Higher SES with Controlled SLE” (11.2%). Approximately 42% of participants experienced new organ damage during the follow-up period. Proportional hazard models indicated that “Older/Lower SES with Uncontrolled SLE” participants were at greatest risk of new organ damage (HR = 2.41; 95% CI = 1.39, 4.19), followed by “Younger/Lower SES with Uncontrolled SLE” participants (HR = 1.56; 95% CI = 0.92, 2.67), compared to those in the “Higher SES with Controlled SLE” profile. Poisson regression models revealed that these two groups also exhibited greater organ damage accrual (b = 0.98, SE = 0.24, 95% CI = 0.52, 1.44 and b = 0.72, SE = 0.23, 95% CI = 0.27, 1.17, respectively). Conclusions Black/African American women with fewer socioeconomic resources and uncontrolled SLE are at greatest risk for increasing disease severity over time. Social inequities likely contribute to racial inequities in SLE progression.
Global transcriptional responses of Candida albicans to histone acetyltranferases deletion

[EN] Fungi are ubiquitous organisms found in almost all fungal species habitats. Many species are able to adapt to different environments, developed in a short period of time a specific physiological and transcriptional response to changing environmental conditions. The fact that fungi are eukaryotic organisms with rapid development and easier to manipulate than multicellular organisms, has stimulated the use of some species of yeasts as model organisms in genetics or molecular biology. ; [ES] Los hongos son organismos ubicuos encontrandose especies fungicas en casi todos los habitats. Muchas de estas especies son capaces de adaptarse a diferentes ambientes, desarrollando en un corto periodo de tiempo una respuesta transcripcional y fisiologica especifica ante un cambio de las condiciones del medio. El hecho de que los hongos sean organismos eucariotas con un desarrollo rapido y que resulten mas faciles de manipular que los organismos pluricelulares, ha estimulado la utilizacion de algunas especies de levaduras como organismos modelo en estudios geneticos y de biologia molecular.
Efficacy of two approaches for disinfecting surfaces and water infested with quagga mussel veligers

Disinfection tools and protocols are needed to reduce the probability of transferring invasive mollusk species as hitchhikers. Applications are needed to provide rapid disinfection of recreational equipment, boats, and tankers and other materials used in fire suppression. Moreover, tools are needed that are safe for hatchery and aquaculture operations. In two separate laboratory trials, we tested the lethality of elevated pH or a commonly used aquaculture disinfectant on quagga mussel (Dreissena rostriformis bugensis) veligers. We found that all reagents were effective in killing veligers. Aqueous solutions of pH 12 were created with NaOH or Ca(OH)2 and tested at 16°C and 20°C, and three aqueous concentrations of Virkon® Aquatic were tested at 20°C. We observed 100% mortality within a 10 min exposure in solutions of pH 12 prepared with Ca(OH)2 and within a 30 min exposure in solutions prepared with NaOH. We found that solutions of 5 g/L of Virkon Aquatic killed all veligers within a 10 min exposure. We concluded that all chemicals show promise as disinfectants, and use of Ca(OH)2 or NaOH to elevate the pH of disinfecting solutions may provide a more economical and environmentally acceptable way to disinfect large surfaces or tanks.
Enzymic recognition of amino acids drove the evolution of primordial genetic codes

Abstract How genetic information gained its exquisite control over chemical processes needed to build living cells remains an enigma. Today, the aminoacyl-tRNA synthetases (AARS) execute the genetic codes in all living systems. But how did the AARS that emerged over three billion years ago as low-specificity, protozymic forms then spawn the full range of highly-specific enzymes that distinguish between 22 diverse amino acids? A phylogenetic reconstruction of extant AARS genes, enhanced by analysing modular acquisitions, reveals six AARS with distinct bacterial, archaeal, eukaryotic, or organellar clades, resulting in a total of 36 families of AARS catalytic domains. Small structural modules that differentiate one AARS family from another played pivotal roles in discriminating between amino acid side chains, thereby expanding the genetic code and refining its precision. The resulting model shows a tendency for less elaborate enzymes, with simpler catalytic domains, to activate amino acids that were not synthesised until later in the evolution of the code. The most probable evolutionary route for an emergent amino acid type to establish a place in the code was by recruiting older, less specific AARS, rather than adapting contemporary lineages. This process, retrofunctionalisation, differs from previously described mechanisms through which amino acids would enter the code.
Development of the Protective Strategies for Psychedelics Scale: A novel inventory to assess safety strategies in the context of psychedelics

Background: Individuals who use psychedelics take efforts to mitigate unintended consequences. Despite the demonstrated utility of analogous protective behavioral strategies (PBS) assessments for other substances, no standardized scale exists to capture these protective strategies for psychedelic use. Objective: The present study addresses a notable gap concerning the assessment of psychedelic use, specifically by developing a scale measuring the protective strategies employed around use, called the Protective Strategies for Psychedelics Scale (PSPS). Methods: A sample (Mage = 36.85 years old, standard deviation = 10.3; male = 61.9%; White = 85.2%) of 434 adults with lifetime use of psychedelics reported on initial qualitatively developed items for the PSPS, PBS scales for cannabis and alcohol, and use of alcohol, cannabis, and psychedelics. Results: Iterative principal components analyses began with 37 items and yielded a 32-item two-factor solution demonstrating excellent internal reliability (Cronbach’s α = .95) and accounted for 51.3% of the variance. Nineteen items loaded on PSPS factor 1, which focused on long-term preparation, emphasizing strategies focused on mood/intentions, preparing the substance, environment, and scheduling episode of use; 13 items loaded on factor 2, which focused on short-term preparation, highlighting strategies surrounding social context, health, and other substances. The PSPS demonstrated convergent validity with validated PBS scales for cannabis and alcohol (r = 0.71–0.79, p < 0.001), and was moderately associated with lifetime psychedelic use (r = 0.28, p < 0.001). Conclusion: The PSPS demonstrates promising psychometric properties, and future work validating the scale for diverse samples across research and clinical settings is warranted.