An international, multi-center study evaluated rituximab therapy in childhood steroid-resistant nephrotic syndrome.

The efficacy and safety of rituximab in childhood steroid-resistant nephrotic syndrome (SRNS) remains unclear. Therefore, we conducted a retrospective cohort study at 28 pediatric nephrology centers from 19 countries in Asia, Europe, North America and Oceania to evaluate this. Children with SRNS treated with rituximab were analyzed according to the duration of calcineurin inhibitors (CNIs) treatment before rituximab [6 months or more (CNI-resistant) and under 6 months]. Primary outcome was complete/partial remission (CR/PR) as defined by IPNA/KDIGO guidelines. Secondary outcomes included kidney failure and adverse events. Two-hundred-forty-six children (mean age, 6.9 years; 136 boys; 57% focal segmental glomerulosclerosis, FSGS) were followed a median of 32.4 months after rituximab. All patients were in non-remission before rituximab. (146 and 100 children received CNIs for 6 month or more or under 6 months before rituximab, respectively). In patients with CNI-resistant SRNS, the remission rates (CR/PR) at 3-, 6-, 12- and 24-months were 26% (95% confidence interval 19.3-34.1), 35.6% (28.0-44.0), 35.1% (27.2-43.8) and 39.1% (29.2-49.9), respectively. Twenty-five patients were in PR at 12-months, of which 22 had over 50% reduction in proteinuria from baseline. The remission rates among children treated with CNIs under 6 months before rituximab were 42% (32.3-52.3), 52% (41.8-62.0), 54% (44.3-64.5) and 60% (47.6-71.3) at 3-, 6-, 12-, and 24-months. Upon Kaplan-Meier analysis, non-remission and PR at 12-months after rituximab, compared to CR, were associated with significantly worse kidney survival. Adverse events occurred in 30.5% and most were mild. Thus, rituximab enhances remission in a subset of children with SRNS, is generally safe and CR following rituximab is associated with favorable kidney outcome.

Autism in patients with eosinophilic gastrointestinal disease: A systematic review with meta-analysis.

PURPOSE: Neurodevelopmental disorders, such as autism spectrum disorder (ASD), have been increasingly associated with eosinophilic gastrointestinal disorders (EGID). However, the relationship between these diseases remains unclear. We performed a systematic review with meta-analysis to address this issue. METHODS: The search was performed according to the PRISMA guidelines using descriptors for ASD and EGIDs from the MEDLINE, Embase, PsycInfo, LILACS, and Web of Science databases. Observational studies with the prevalence of ASD in any EGID were included. The study protocol was registered on the PROSPERO platform under the number CRD42023455177. RESULTS: The total dataset comprised 766,082 participants. The result of the single-arm meta-analysis showed an overall prevalence of ASD in the population with EGID of 21.59% (95% CI: 10.73-38.67). There was an association between EGID and ASD (OR: 3.44; 95% CI: 1.25-2.21), also significant when restricted only to EoE (OR: 3.70; 95% CI: 2.71-5.70). DISCUSSION: Recent studies have implicated the influence of an inadequate epithelial barrier integrity in the pathogenesis of several diseases. The role of this mechanism can be extended to situations beyond allergic reactions, including other conditions with underlying immunological mechanisms. Several diseases are potentially related to the systemic effect of bacterial translocation in tissues with defective epithelial barriers. CONCLUSION: Our meta-analysis provides evidence that supports the consideration of EGID in patients with ASD and ASD in patients with EGID. Despite its limitations, the results should also be validated by future studies, preferably using multicenter prospective designs in populations with low referral bias.

It was not possible to detect BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma: A diagnostic accuracy study.

BACKGROUND: The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma. METHODS: This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated. RESULTS: Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%. CONCLUSION: Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.

The protective effect of breastfeeding on febrile seizures: a systematic review with meta-analysis.

Several potential risk factors have been identified in the etiopathogenesis of febrile seizures (FS), including the type and extent of breastfeeding (BF). Given the lack of conclusive data, this study aims to systematically evaluate the evidence on the association between BF and FS. We conducted a systematic review and meta-analysis according to PRISMA guidelines. The search was conducted using descriptors for FS, BF, and formula feeding in MEDLINE, Embase, and Web of Science databases. We included observational studies that compared the incidence of FS between those who had ever breastfed and those who were formula fed. The study protocol was registered on the PROSPERO platform under the number CRD42023474906. A total of 1,893,079 participants from 8 datasets were included. Our main analysis showed no significant association of any type of BF on the incidence of FS compared with formula-fed children (OR: 0.84; CI: 0.67-1.04; I2 = 78%; Cochran's Q = 0.0001), although meta-regression showed that BF was associated with a lower incidence of FS in preterm infants. Our secondary outcome showed a significantly reduced incidence of FS in children who received BF exclusively (OR: 0.80; CI: 0.65-0.99; I2 = 70%; Cochran's Q = 0.02).    Conclusion: There was no significant reduction in the incidence of FS in those who were breastfed compared to formula feeding. However, our meta-regression analysis indicated an association between BF and a lower incidence of FS in preterm infants. Additionally, children who exclusively received BF had a significantly reduced incidence of FS. These findings should be further investigated in prospective cohorts. What is Known: • Breastfeeding can modify risk factors for febrile seizures, such as susceptibility to viral and bacterial infections, micronutrient deficiencies, and low birth weight. • However, studies have shown conflicting results regarding the impact of breastfeeding on febrile seizures. What is New: • When comparing any breastfeeding pattern with no breastfeeding, there is no significant difference in the incidence of febrile seizures. • When comparing exclusive breastfeeding with no breastfeeding, there may be a decrease in the occurrence of febrile seizures.

Artificial intelligence methods in diagnosis of retinoblastoma based on fundus imaging: a systematic review and meta-analysis.

BACKGROUND: Artificial intelligence (AI) algorithms for the detection of retinoblastoma (RB) by fundus image analysis have been proposed as a potentially effective technique to facilitate diagnosis and screening programs. However, doubts remain about the accuracy of the technique, the best type of AI for this situation, and its feasibility for everyday use. Therefore, we performed a systematic review and meta-analysis to evaluate this issue. METHODS: Following PRISMA 2020 guidelines, a comprehensive search of MEDLINE, Embase, ClinicalTrials.gov and IEEEX databases identified 494 studies whose titles and abstracts were screened for eligibility. We included diagnostic studies that evaluated the accuracy of AI in identifying retinoblastoma based on fundus imaging. Univariate and bivariate analysis was performed using the random effects model. The study protocol was registered in PROSPERO under CRD42024499221. RESULTS: Six studies with 9902 fundus images were included, of which 5944 (60%) had confirmed RB. Only one dataset used a semi-supervised machine learning (ML) based method, all other studies used supervised ML, three using architectures requiring high computational power and two using more economical models. The pooled analysis of all models showed a sensitivity of 98.2% (95% CI: 0.947-0.994), a specificity of 98.5% (95% CI: 0.916-0.998) and an AUC of 0.986 (95% CI: 0.970-0.989). Subgroup analyses comparing models with high and low computational power showed no significant difference (p=0.824). CONCLUSIONS: AI methods showed a high precision in the diagnosis of RB based on fundus images with no significant difference when comparing high and low computational power models, suggesting a viability of their use. Validation and cost-effectiveness studies are needed in different income countries. Subpopulations should also be analyzed, as AI may be useful as an initial screening tool in populations at high risk for RB, serving as a bridge to the pediatric ophthalmologist or ocular oncologist, who are scarce globally. KEY MESSAGES: What is known Retinoblastoma is the most common intraocular cancer in childhood and diagnostic delay is the main factor leading to a poor prognosis. The application of machine learning techniques proposes reliable methods for screening and diagnosis of retinal diseases. What is new The meta-analysis of the diagnostic accuracy of artificial intelligence methods for diagnosing retinoblastoma based on fundus images showed a sensitivity of 98.2% (95% CI: 0.947-0.994) and a specificity of 98.5% (95% CI: 0.916-0.998). There was no statistically significant difference in the diagnostic accuracy of high and low computational power models. The overall performance of supervised machine learning was best than unsupervised, although few studies were available on the second type.

Identification of genetic markers associated with hyperketonemia patterns in early lactation Holstein cows.

Ketosis, evidenced by hyperketonemia with elevated blood ß-hydroxybutyrate (BHB) levels, is a significant metabolic disorder of dairy cattle, typically diagnosed within the first 6 weeks post-calving when high energy levels are essential to milk production. Our study aimed to identify genetic markers linked to hyperketonemia (HYK) patterns in Holstein cows during early lactation and compare these to HYK-negative cows. We screened 964 cows for HYK using a threshold of BHB ≥1.2 mmol/L during the first 2 weeks postpartum (screening period, SP). Cows that tested negative initially were retested the following week. Cows were deemed HYK-negative (CON group) if BHB levels were below 1.2 mmol/L in both tests, while those with BHB levels exceeding this threshold at any test were treated and classified as HYK-positive (HYK+). Post-treatment, HYK+ cows were monitored for two-week follow-up period (FP) and classified based on their recovery: cured (CUR; consistently low BHB), recurrent (REC; fluctuating BHB levels), severe (SEV; high initial BHB that decreased), or chronic (CHR; persistently high BHB). Using 489 cows that were genotyped, a GWAS was conducted using GCTA software, revealing significant associations of several SNPs across different HYK patterns when compared to the CON group. These SNPs were primarily linked to genes affecting milk traits and were enriched in biological pathways relevant to protein glycosylation, inflammatory response, glucose homeostasis, and fatty acid synthesis. Our findings highlight genomic regions, potential candidate genes, and biological pathways related to ketosis, underscoring potential targets for improving health management in dairy cattle. These insights could lead to better strategies for managing ketosis through genetic selection, ultimately enhancing dairy cattle welfare and productivity. Further research with a larger number of cows is recommended to validate these findings and help confirm the implicated SNPs and genes.

Nitrogen-Induced Hysteresis in Grassland Biodiversity: A Theoretical Test of Litter-Mediated Mechanisms.

AbstractThe global rise in anthropogenic reactive nitrogen and the negative impacts of N deposition on terrestrial plant diversity are well documented. The R* theory of resource competition predicts reversible decreases in plant diversity in response to N loading. However, empirical evidence for the reversibility of N-induced biodiversity loss is mixed. In a long-term N-enrichment experiment in Minnesota, a low-diversity state that emerged during N addition has persisted for decades after additions ceased. Hypothesized mechanisms preventing recovery of biodiversity include nutrient recycling, insufficient external seed supply, and litter inhibition of plant growth. Here, we present an ordinary differential equation model that unifies these mechanisms, produces bistability at intermediate N inputs, and qualitatively matches the observed hysteresis at Cedar Creek. Key features of the model, including native species' growth advantage in low-N conditions and limitation by litter accumulation, generalize from Cedar Creek to North American grasslands. Our results suggest that effective biodiversity restoration in these systems may require management beyond reducing N inputs, such as burning, grazing, haying, and seed additions. By coupling resource competition with an additional interspecific inhibitory process, the model also illustrates a general mechanism for bistability and hysteresis that may occur in multiple ecosystem types.

A Deep Potential model for liquid-vapor equilibrium and cavitation rates of water.

Computational studies of liquid water and its phase transition into vapor have traditionally been performed using classical water models. Here, we utilize the Deep Potential methodology-a machine learning approach-to study this ubiquitous phase transition, starting from the phase diagram in the liquid-vapor coexistence regime. The machine learning model is trained on ab initio energies and forces based on the SCAN density functional, which has been previously shown to reproduce solid phases and other properties of water. Here, we compute the surface tension, saturation pressure, and enthalpy of vaporization for a range of temperatures spanning from 300 to 600 K and evaluate the Deep Potential model performance against experimental results and the semiempirical TIP4P/2005 classical model. Moreover, by employing the seeding technique, we evaluate the free energy barrier and nucleation rate at negative pressures for the isotherm of 296.4 K. We find that the nucleation rates obtained from the Deep Potential model deviate from those computed for the TIP4P/2005 water model due to an underestimation in the surface tension from the Deep Potential model. From analysis of the seeding simulations, we also evaluate the Tolman length for the Deep Potential water model, which is (0.091 ± 0.008) nm at 296.4 K. Finally, we identify that water molecules display a preferential orientation in the liquid-vapor interface, in which H atoms tend to point toward the vapor phase to maximize the enthalpic gain of interfacial molecules. We find that this behavior is more pronounced for planar interfaces than for the curved interfaces in bubbles. This work represents the first application of Deep Potential models to the study of liquid-vapor coexistence and water cavitation.

Congenital herpes simplex with ophthalmic and multisystem features: a case report.

BACKGROUND: Neonatal herpes simplex virus (HSV) infection is rare and has significant morbimortality rates. Approximately 85% of newborns are infected intrapartum, and risk factors for mother-to-child transmission include vaginal delivery, primary maternal infection, and prolonged rupture of membranes. Neonatal HSV can manifest with isolated mucocutaneous lesions, neurological involvement, or disseminated disease. In general, herpetic infection can cause blepharoconjunctivitis or keratitis. We report a rare case of congenital herpes with ophthalmologic manifestations and multisystemic involvement. CASE PRESENTATION: A preterm infant, born at 32 weeks and 2 days, with presumed neonatal infection developed intestinal and respiratory complications, as well as hyperemic lesions on the left nostril and oral mucosa. An ophthalmological assessment was requested and brought up the suspicion of HSV infection, indicating empirical treatment with endovenous acyclovir. Later, a new ocular examination was suggestive of panuveitis. Afterward, serum IgM antibodies to HSV-1 and HSV-2 were positive. Proper antiviral therapy led to an improvement in the condition. DISCUSSION: Neonatal herpes is associated with a high risk of persistent skin lesions, long-term neurological disability and other lasting sequelae. It is essential to consider HSV infection in cases of neonatal conjunctivitis, especially in patients with an epithelial defect and no improvement after initial treatment with topical or systemic antibiotics. CONCLUSIONS: In the management of neonatal HSV, early diagnosis is essential for the timely initiation of antiviral therapy. Our report highlights that ocular assessment can be crucial in the correct diagnostic investigation of this condition.

Healthcare workers exposed to COVID-19 patients present an inflammatory status and Th2/Th17/Th22 immune profile: findings from before vaccine application in Brazil.

Healthcare workers present an increased risk of contagion for the SARS-CoV-2 virus due to their labor exposure. Here, we describe the clinical, laboratory, and immunological characteristics of healthcare workers, before vaccine application, exposed to SARS-CoV-2-infected patients. We collected sociodemographic, clinical, and laboratory information from 50 professionals who worked during the COVID-19 pandemic at the Clinical Hospital of the Northwest in Brazil. The results showed that most workers are women, over 50 years old, and worked as nursing technicians. Approximately 56% of workers were positive for a previous infection by RT-PCR and/or anti-SARS-CoV-2-immunoglobulin tests. Increased levels of hematocrit, neutrophils, NK lymphocytes, and fibrinogen, were found in positive healthcare workers, suggesting a light inflammatory status. The immunological findings showed an increase in IL-17 production and a Th2/Th17/Th22 profile followed by high serology for anti-SARS-CoV-2 IgM and IgG. Those data reveal the importance of studies with healthcare workers to investigate if the continuous exposition to the virus may result in chronic activation of the immune system and/or pulmonary inflammation in this target group.

Small genetic variation affecting mRNA isoforms associated with marbling and meat color in beef cattle.

The aim of this study was to identify mRNA isoforms and small genetic variants that may be affecting marbling and beef color in Nellore cattle. Longissimus thoracis muscle samples from 20 bulls with different phenotypes (out of 80 bulls set) for marbling (moderate (n = 10) and low (n = 10) groups) and beef color (desirable (n = 10) and undesirable (n = 9) group) traits were used to perform transcriptomic analysis using RNA sequencing. Fourteen and 15 mRNA isoforms were detected as differentially expressed (DE) (P-value ≤ 0.001) between divergent groups for marbling and meat color traits, respectively. Some of those DE mRNA isoforms have shown sites of splicing modified by small structural variants as single nucleotide variant (SNV), insertion, and/or deletion. Enrichment analysis identified metabolic pathways, such as O2/CO2 exchange in erythrocytes, tyrosine biosynthesis, and phenylalanine degradation. The results obtained suggest potential key regulatory genes associated with these economically important traits for the beef industry and for the consumer.

How do I: Evaluate the safety and legitimacy of unproven cellular therapies?

BACKGROUND: Unproven cellular therapies are being offered to patients for a variety of conditions and diseases for which other treatments have failed. The use of untested cellular therapies is a worldwide problem. Practitioners (e.g., physicians, scientists, QA/QI facility managers, and policy advocates) are perhaps unaware of the risks involved with such therapies. Therefore, a critical need exists to bring attention to the potential limitations and adverse effects of these therapies to inform and limit misinformation. STUDY DESIGN AND METHODS: We describe the extent of the unproven cellular therapy problem through a search of scientific literature and social media coverage. We also describe the regulatory framework that can be used by the practitioner to review and evaluate both proven and unproven cellular therapies. RESULTS: We report on the current state of unproven cellular therapies across the globe. A workflow to facilitate an understanding of the regulatory processes involved in the approval of cellular therapies is provided as well as a list of warnings required by regulatory agencies on various products. It is hoped that this article will serve as a tool kit to educate the practitioner on navigating the field of unproven cellular therapy products. DISCUSSION: Increasing awareness of the issues associated with unproven therapies through education is important to help in reducing misinformation and risks to patients.

Is oral microbiota associated with overweight and obesity in children and adolescents? A systematic review.

This article aims to verify the relationship between the composition and diversity of oral microbiota with overweight and obese children and adolescents. This systematic review was registered in PROSPERO, followed PRISMA 2020, and included an electronic search until March 2022, in PubMed/MEDLINE, Web of Science, Scopus, and The Cochrane Library databases. Studies were eligible if they compared the oral microbiota according to nutrition status among children and adolescents. Independent peers using JBI Critical Appraisal Checklists assessed the quality of studies. Eleven studies were eligible to be included in this review, with a total of 1,695 children and adolescents, 224 were obese, 190 were overweight, 1,154 were eutrophics and 127 were underweight. The most frequent phyla in overweight and obese children and adolescents, in comparison to their counterparts were Firmicutes, Bacteroidetes, Proteobacteria, Actinobacteria and Fusobacteria. It was identified that nine of the eleven articles selected showed an association between oral microbiota and overweight and obesity in children and adolescents. We observed that there is an important association between oral bacterial composition diversity and overweight and obesity. This finding indicates the relevance of the evaluation and surveillance in oral health to control cases of overweight and obesity in children and adolescents.

A deep potential model with long-range electrostatic interactions.

Machine learning models for the potential energy of multi-atomic systems, such as the deep potential (DP) model, make molecular simulations with the accuracy of quantum mechanical density functional theory possible at a cost only moderately higher than that of empirical force fields. However, the majority of these models lack explicit long-range interactions and fail to describe properties that derive from the Coulombic tail of the forces. To overcome this limitation, we extend the DP model by approximating the long-range electrostatic interaction between ions (nuclei + core electrons) and valence electrons with that of distributions of spherical Gaussian charges located at ionic and electronic sites. The latter are rigorously defined in terms of the centers of the maximally localized Wannier distributions, whose dependence on the local atomic environment is modeled accurately by a deep neural network. In the DP long-range (DPLR) model, the electrostatic energy of the Gaussian charge system is added to short-range interactions that are represented as in the standard DP model. The resulting potential energy surface is smooth and possesses analytical forces and virial. Missing effects in the standard DP scheme are recovered, improving on accuracy and predictive power. By including long-range electrostatics, DPLR correctly extrapolates to large systems the potential energy surface learned from quantum mechanical calculations on smaller systems. We illustrate the approach with three examples: the potential energy profile of the water dimer, the free energy of interaction of a water molecule with a liquid water slab, and the phonon dispersion curves of the NaCl crystal.

Low applicability of the ''Six-and-twelve score" in hepatocellular carcinoma treated with Drug-Eluting Beads Transarterial Chemoembolization.

OBJECTIVE: The effectiveness of transarterial chemoembolization (TACE) in hepatocellular carcinoma (HCC) depends on the selection of suitable patients. The ''Six-and-twelve score" distinguishes three groups of ideal patients with different overall survival, based on the sum of the number and size of tumors. This may impact on clinical practice and trial design. The aim of this study was to assess the reproducibility and prognostic value of the model in western patients treated with Drug-Eluting Beads (DEB)-TACE. METHODS: Observational, retrospective, unicentric study with consecutive compensated patients treated with DEB-TACE from October 2008 to October 2017. Exclusion criteria were Child-Pugh ≥ 8 and DEB-TACE used as a bridge to liver transplantation. RESULTS: 225 HCC consecutive patients were included; BCLC-0/A n=131 (single nodules > 5, n=29) and BCLC-B n=94. The median overall survival (OS) was 27 months (95% CI 23.8-30.2). OS was different between BCLC-0/A vs BCLC-B: 30 vs 24 months (p= 0.03), Child-Pugh A5 vs A6-B7: 30 vs 27 months (p= 0.003). ''Six-and-twelve score" groups discriminated OS: group 1, n=123, 32 months (95% CI 27.5-63.5), group 2, n=101, 24 months (95% CI 19.6-28.4) and group 3, n=1, 27 months (p=0.024). When comparing the three scores, the ''Six-and-twelve score" showed the best discrimination power: C-index 0.603, Akaike's information criterion (AIC) 1.642, likelihood ratio test (LRT) 16.21. CONCLUSION: The ''Six-and-twelve score" is a prognostic tool for patients with HCC treated with DEB-TACE. However, few patients were included in the third group (score >12) and no differences were observed with BCLC, therefore its applicability is limited. .

[The impact of novel drugs on the survival of patients with multiple myeloma in two chilean centers]. / Mieloma múltiple en Chile. Uso de drogas noveles en dos centros nacionales.

BACKGROUND: The incorporation of novel drugs, such as proteasome inhibitors and immunomodulators, improved considerably the survival of patients with multiple myeloma. AIM: To evaluate the effect on survival of proteasome inhibitors and immunomodulators in patients with multiple myeloma in two national hospitals. MATERIAL AND METHODS: Review of clinical records from two hospitals of Santiago. Epidemiological, clinical, laboratory and therapeutic data was obtained from 144 patients with multiple myeloma diagnosed between 2002 and 2016. RESULTS: Information was retrieved from 78 patients at one center and from 66 at the other center. The mean age at diagnosis was 58 and 62 years, the proportion of males was 53% and 52%, and presentation at stage III was 34% and 46%, respectively. The use of novel drugs, mainly bortezomib, was 90% in one of the centers and 3% in the other one. The use of autologous stem-cell transplantation was 47% and 3% respectively. The median overall survival of patients from the centers with and without access to novel drugs was 117 and 71 months respectively (p < 0.05). The five-year overall survival was 93 and 43% respectively (p < 0.05). CONCLUSIONS: The use of novel drugs, especially bortezomib, and autologous stem-cell transplantation significantly improved the survival of multiple myeloma patients treated in national hospitals. It is necessary to include them as a first line treatment.

When do short-range atomistic machine-learning models fall short?

We explore the role of long-range interactions in atomistic machine-learning models by analyzing the effects on fitting accuracy, isolated cluster properties, and bulk thermodynamic properties. Such models have become increasingly popular in molecular simulations given their ability to learn highly complex and multi-dimensional interactions within a local environment; however, many of them fundamentally lack a description of explicit long-range interactions. In order to provide a well-defined benchmark system with precisely known pairwise interactions, we chose as the reference model a flexible version of the Extended Simple Point Charge (SPC/E) water model. Our analysis shows that while local representations are sufficient for predictions of the condensed liquid phase, the short-range nature of machine-learning models falls short in representing cluster and vapor phase properties. These findings provide an improved understanding of the role of long-range interactions in machine learning models and the regimes where they are necessary.

Vapor-liquid equilibrium of water with the MB-pol many-body potential.

Among the many existing molecular models of water, the MB-pol many-body potential has emerged as a remarkably accurate model, capable of reproducing thermodynamic, structural, and dynamic properties across water's solid, liquid, and vapor phases. In this work, we assessed the performance of MB-pol with respect to an important set of properties related to vapor-liquid coexistence and interfacial behavior. Through direct coexistence classical molecular dynamics simulations at temperatures of 400 K < T < 600 K, we calculated properties such as equilibrium coexistence densities, vapor-liquid interfacial tension, vapor pressure, and enthalpy of vaporization and compared the MB-pol results to experimental data. We also compared rigid vs fully flexible variants of the MB-pol model and evaluated system size effects for the properties studied. We found that the MB-pol model predictions are in good agreement with experimental data, even for temperatures approaching the vapor-liquid critical point; this agreement was largely insensitive to system sizes or the rigid vs flexible treatment of the intramolecular degrees of freedom. These results attest to the chemical accuracy of MB-pol and its high degree of transferability, thus enabling MB-pol's application across a large swath of water's phase diagram.

Transcriptome profiling of muscle in Nelore cattle phenotypically divergent for the ribeye muscle area.

This study aimed to use RNA-Seq to identify differentially expressed genes (DEGs) in muscle of uncastrated Nelore males phenotypically divergent for ribeye muscle area (REA). A total of 80 animals were phenotyped for REA, and 15 animals each with the highest REA and the lowest REA were selected for analyses. DEGs found (N = 288) belonging to families related to muscle cell growth, development, motility and proteolysis, such as actin, myosin, collagen, integrin, solute carrier, ubiquitin and kelch-like. Functional analysis showed that many of the significantly enriched gene ontology terms were closely associated with muscle development, growth, and degradation. Through co-expression network analysis, we predicted three hub genes (PPP3R1, FAM129B and UBE2G1), these genes are involved in muscle growth, proteolysis and immune system. The genes expression levels and its biological process found this study may result in differences in muscle deposition, and therefore, Nelore animals with different REA proportions.

Use of gene expression profile to identify potentially relevant transcripts to myofibrillar fragmentation index trait.

The myofibrillar fragmentation index (MFI) is an indicative trait for meat tenderness. Longissimus thoracis muscle samples from the 20 most extreme bulls (out of 80 bulls set) for MFI (high (n = 10) and low (n = 10) groups) trait were used to perform transcriptomic analysis, using RNA Sequencing (RNA-Seq). An average of 24.616 genes was expressed in the Nellore muscle transcriptome analysis. A total of 96 genes were differentially expressed (p value ≤ 0.001) between the two groups of divergent bulls for MFI. The HEBP2 and BDH1 genes were overexpressed in animals with high MFI. The MYBPH and MYL6, myosin encoders, were identified. The differentially expressed genes were related to increase mitochondria efficiency, especially in cells under oxidative stress conditions, and these also were related to zinc and calcium binding, membrane transport, and muscle constituent proteins, such as actin and myosin. Most of those genes were involved in metabolic pathways of oxidation-reduction, transport of lactate in the plasma membrane, and muscle contraction. This is the first study applying MFI phenotypes in transcriptomic studies to identify and understand differentially expressed genes for beef tenderness. These results suggest that differences detected in gene expression between high and low MFI animals are related to reactive mechanisms and structural components of oxidative fibers under the condition of cellular stress. Some genes may be selected as positional candidate genes to beef tenderness, MYL6, MYBPH, TRIM63, TRIM55, TRIOBP, and CHRNG genes. The use of MFI phenotypes could enhance results of meat tenderness studies.