Miracle-dz/UniFAR-FTUs huggingface dataset:
Strain-specific metabarcoding reveals rapid evolution of copper tolerance in populations of the coastal diatom Skeletonema marinoi.

Phytoplankton have short generation times, flexible reproduction strategies, large population sizes and high standing genetic diversity, traits that should facilitate rapid evolution under directional selection. We quantified local adaptation of copper tolerance in a population of the diatom Skeletonema marinoi from a mining-exposed inlet in the Baltic Sea and in a non-exposed population 100 km away. We hypothesized that mining pollution has driven evolution of elevated copper tolerance in the impacted population of S. marinoi. Assays of 58 strains originating from sediment resting stages revealed no difference in the average tolerance to copper between the two populations. However, variation within populations was greater at the mining site, with three strains displaying hyper-tolerant phenotypes. In an artificial evolution experiment, we used a novel intraspecific metabarcoding locus to track selection and quantify fitness of all 58 strains during co-cultivation in one control and one toxic copper treatment. As expected, the hyper-tolerant strains enabled rapid evolution of copper tolerance in the mining-exposed population through selection on available strain diversity. Within 42 days, in each experimental replicate a single strain dominated (30%-99% abundance) but different strains dominated the different treatments. The reference population developed tolerance beyond expectations primarily due to slowly developing plastic response in one strain, suggesting that different modes of copper tolerance are present in the two populations. Our findings provide novel empirical evidence that standing genetic diversity of phytoplankton resting stage allows populations to evolve rapidly (20-50 generations) and flexibly on timescales relevant for seasonal bloom progressions.
Predictive overfitting in immunological applications: Pitfalls and solutions

ABSTRACT Overfitting describes the phenomenon where a highly predictive model on the training data generalizes poorly to future observations. It is a common concern when applying machine learning techniques to contemporary medical applications, such as predicting vaccination response and disease status in infectious disease or cancer studies. This review examines the causes of overfitting and offers strategies to counteract it, focusing on model complexity reduction, reliable model evaluation, and harnessing data diversity. Through discussion of the underlying mathematical models and illustrative examples using both synthetic data and published real datasets, our objective is to equip analysts and bioinformaticians with the knowledge and tools necessary to detect and mitigate overfitting in their research.
Small regulatory RNAs are mediators of the Streptococcus mutans SloR regulon

ABSTRACT Dental caries is among the most prevalent chronic diseases worldwide. Streptococcus mutans, the chief causative agent of caries, uses a 25-kDa manganese-dependent SloR protein to coordinate the uptake of essential manganese with the transcription of its virulence attributes. Small non-coding RNAs (sRNAs) can either enhance or repress gene expression, and reports in the literature ascribe an emerging role for sRNAs in the environmental stress response. Herein, we focused our attention on 18–50 nt sRNAs as mediators of the S. mutans SloR and manganese regulons. Specifically, the results of RNA sequencing revealed 19 sRNAs in S. mutans, which were differentially transcribed in the SloR-proficient UA159 and SloR-deficient GMS584 strains, and 10 sRNAs that were differentially expressed in UA159 cells grown in the presence of low vs high manganese. We describe SmsR1532 and SmsR1785 as SloR- and manganese-responsive sRNAs that are processed from large transcripts and that bind SloR directly in their promoter regions. The predicted targets of these sRNAs include regulators of metal ion transport, growth management via a toxin-antitoxin operon, and oxidative stress tolerance. These findings support a role for sRNAs in coordinating intracellular metal ion homeostasis with virulence gene control in an important oral cariogen. IMPORTANCE Small regulatory RNAs (sRNAs) are critical mediators of environmental signaling, particularly in bacterial cells under stress, but their role in Streptococcus mutans is poorly understood. S. mutans, the principal causative agent of dental caries, uses a 25-kDa manganese-dependent protein, called SloR, to coordinate the regulated uptake of essential metal ions with the transcription of its virulence genes. In the present study, we identified and characterized sRNAs that are both SloR and manganese responsive. Taken together, this research can elucidate the details of regulatory networks that engage sRNAs in an important oral pathogen and that can enable the development of an effective anti-caries therapeutic. Small regulatory RNAs (sRNAs) are critical mediators of environmental signaling, particularly in bacterial cells under stress, but their role in Streptococcus mutans is poorly understood. S. mutans, the principal causative agent of dental caries, uses a 25-kDa manganese-dependent protein, called SloR, to coordinate the regulated uptake of essential metal ions with the transcription of its virulence genes. In the present study, we identified and characterized sRNAs that are both SloR and manganese responsive. Taken together, this research can elucidate the details of regulatory networks that engage sRNAs in an important oral pathogen and that can enable the development of an effective anti-caries therapeutic.
Transcriptome and secretome profiling of sensory neurons reveals sex differences in pathways relevant to insulin sensing and insulin secretion

Sensory neurons in the dorsal root ganglia (DRG) convey somatosensory and metabolic cues to the central nervous system and release substances from stimulated terminal endings in peripheral organs. Sex‐biased variations driven by the sex chromosome complement (XX and XY) have been implicated in the sensory–islet crosstalk. However, the molecular underpinnings of these male–female differences are not known. Here, we aim to characterize the molecular repertoire and the secretome profile of the lower thoracic spinal sensory neurons and to identify molecules with sex‐biased insulin sensing‐ and/or insulin secretion‐modulating activity that are encoded independently of circulating gonadal sex hormones. We used transcriptomics and proteomics to uncover differentially expressed genes and secreted molecules in lower thoracic T5‐12 DRG sensory neurons derived from sexually immature 3‐week‐old male and female C57BL/6J mice. Comparative transcriptome and proteome analyses revealed differential gene expression and protein secretion in DRG neurons in males and females. The transcriptome analysis identified, among others, higher insulin signaling/sensing capabilities in female DRG neurons; secretome screening uncovered several sex‐specific candidate molecules with potential regulatory functions in pancreatic β cells. Together, these data suggest a putative role of sensory interoception of insulin in the DRG–islet crosstalk with implications in sensory feedback loops in the regulation of β‐cell activity in a sex‐biased manner. Finally, we provide a valuable resource of molecular and secretory targets that can be leveraged for understanding insulin interoception and insulin secretion and inform the development of novel studies/approaches to fathom the role of the sensory–islet axis in the regulation of energy balance in males and females.
Transgenic expression of the HERV-W envelope protein leads to polarized glial cell populations and a neurodegenerative environment

Significance Although neurodegeneration is a hallmark of multiple sclerosis (MS), its progression is still not fully understood. However, it is the major factor leading to clinical disability that still cannot be addressed therapeutically. With the here presented study, we provide direct evidence that HERV-W (human endogenous retrovirus type W) ENV (envelope) expression results in multiple glial cell deteriorations and accompanied neuropathology in vivo. These data therefore suggest that activation of this endogenous retroviral element is indeed causally contributing to MS. Our findings will therefore help understand the molecular and cellular processes being modulated by the currently clinically tested anti-HERV-W neutralization strategy and will support the development of this approach into clinical therapy.
Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions

Abstract Background Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in ≥60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease (“conditions of interest”). Methods Medically stable ≥60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups. Results In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had ≥1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with ≥1 condition of interest (94.6%), ≥1 cardiorespiratory (92.1%), ≥1 endocrine/metabolic (100%), and ≥2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with ≥1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with ≥2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with ≥1 condition of interest as in those without. Conclusions RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease. Clinical Trials Registration ClinicalTrials.gov: NCT04886596.
Activation of GPR81 aggravated intestinal ischemia/reperfusion injury-induced acute lung injury via HMGB1-mediated neutrophil extracellular traps formation

Introduction Intestinal ischemia/reperfusion (II/R) injury is a life-threatening situation accompanied by severe organ injury, especially acute lung injury (ALI). A great body of evidence indicates that II/R injury is usually associated with hyperlactatemia. G-protein-coupled receptor 81 (GPR81), a receptor of lactate, has been recognized as a regulatory factor in inflammation, but whether it was involved in II/R injury-induced ALI is still unknown. Methods To establish the II/R injury model, the superior mesenteric artery of the mice was occluded gently by a microvascular clamp for 45 min to elicit intestinal ischemia and then a 90-min reperfusion was performed. Broncho-alveolar lavage fluid (BALF) and lung tissues were obtained to evaluate the lung injury after II/R. The pulmonary histopathological alteration was evaluated by H&E staining. The concentration of proteins, the number of infiltrated cells, and the level of IL-6 were measured in BALF. The formation of neutrophil extracellular traps (NETs) was evaluated by the level of double-stranded DNA (dsDNA) and myeloperoxidase- double-stranded DNA (MPO-dsDNA) complex in BALF, and the content of citrullinated histone H3 (Cit-H3) in lung tissue. The level of HMGB1 in the BALF and plasma was measured by enzyme linked immunosorbent assay (ELISA). Results Administration of the GPR81 agonist 3,5-dihydroxybenzoic acid (DHBA) aggravated II/R injury-induced lung histological abnormalities, upregulated the concentration of proteins, the number of infiltrated cells, and the level of IL-6 in BALF. In addition, DHBA treatment increased the level of dsDNA and MPO-dsDNA complex in BALF, and promoted the elevation of Cit-H3 in lung tissue and the release of HMGB1 in BALF and plasma. Conclusion After induction of ALI by II/R, the administration of DHBA aggravated ALI through NETs formation in the lung.
Linear Discriminant Analysis Based on Kernel-Based Possibilistic C-Means for Hyperspectral Images

In this mymargin letter, we propose a novel supervised dimensionality reduction (DR) method termed linear discriminant analysis based on kernel-based possibilistic c-means (LDA-KPCM) for hyperspectral images (HSIs). The basic idea of this method is to use KPCM algorithm to generate different weights for different samples so that the newly-proposed method can learn the optimal transformation directions according to the relative importance of samples. The weights generated by KPCM are relatively higher for important samples but relatively lower for outliers. The experimental results on two HSI benchmark data sets demonstrate that LDA-KPCM can achieve better performance than the other state-of-the-art DR methods.
Targeted glycan degradation potentiates cellular immunotherapy for solid tumors

Significance The upregulation of sialoglycans is a phenomenon that contributes to the long circulation of red cells and convenient migration of stem and cancer cells. Inspired by this, we designed tumor-targeting molecule–sialidase conjugates that selectively stripped different sialoglycans from a variety of cancer cells. Desialylation of cancer cells triggered CAR-iMac cell activation, increased donor cell polyfunctionality, and enhanced antitumor efficacy against solid tumors, which depends on the blockade of the Siglec-5 and Siglec-10 checkpoints on CAR-iMac cells. Siglec-5 and Siglec-10 gene knockouts allowed for the construction of a CAR-iMac with stronger anticancer activity due to glycoimmune checkpoint blocking. The cancer cell desialylation strategy that reverts the immune escape state is significant for enhancing the effect of solid tumor cellular immunotherapy.
Quality of life, fatigue, sleep quality, and mental health in systemic lupus erythematosus patients with a high cardiovascular risk profile

Systemic lupus erythematosus (SLE) patients report worse health-related quality of life (HRQL), fatigue, anxiety, depression, and sleep quality, when compared to the general population and other chronic diseases. Furthermore, cardiometabolic diseases are highly prevalent in SLE and are also associated with these parameters. Thus, it is plausible to suggest that SLE patients with a high cardiovascular risk may report worse results for these parameters. The aim of the study is to describe HRQL, fatigue, anxiety and depression symptoms, and sleep quality in a sample of SLE patients with a high cardiovascular risk profile (i.e., BMI between 25 and 40 kg/m2 and/or dyslipidemia, hypertension, or diabetes). This was a cross-sectional study where patients were assessed for (i) demographic, anthropometric, and disease-related parameters, (ii) HRQL, (iii) fatigue, (iv) anxiety and depression symptoms, and (v) sleep quality. One-hundred patients completed the study; however, only 87 patients were assessed for sleep quality data. Patients averaged 41.7 ± 9 years, and most patients were classified as overweight/obese (87%). SF-36 scores for physical and mental components summary were 51.3 ± 9.6 and 54.2 ± 15.6, respectively, with “bodily pain” and “role emotional” presenting the lower scores. The total SLEQOL score was 105.1 ± 42.0, with lower scores reported for “self-image” and “mood. ” Fatigue score was 30.8 ± 8.9, and 78% and 93% reported severe symptoms of anxiety and depression, respectively. The average sleep effectiveness was 82.9 ± 6.6%. Sleep latency, total time in bed (TTiB), and total sleep time (TST) were 8.4 ± 8.9, 495.8 ± 79.7, and 409.7 ± 69.9 min, respectively. Patients reported an average of 17.8 ± 6.2 WE, with 4.5 ± 1.5 min duration and a WASO of 77.7 ± 36.6 min. Despite similar HRQL, fatigue, and sleep quality parameters to those reported by other SLE populations, SLE patients with a high cardiovascular risk had a higher prevalence of depression and anxiety. Understanding SLE patients’ quality of life and psychological symptoms is of utmost importance to improve disease management. The findings of this study highlight the need for more intensive and global care regarding mental health when considering a high cardiovascular risk in SLE.
Perceptions of Urban Father Support in Early Parenthood: A Critical Incident Analysis

ABSTRACT Becoming a father is a common transitional event, however men are often not adequately prepared for their fathering role. The United States (U.S.) health care system does little to support fathers’ parenting needs during the postnatal and infancy period. Moreover, father’s support needs are often perceived as secondary to the mother’s needs in the maternal-child system. It is important that fathers’ social support needs be investigated in the first year of his newborn’s life, especially in diverse populations. Therefore, the purpose of this study was to determine the social support needs of urban, African American fathers during early parenthood. Using the Critical Incident Technique (CIT), a descriptive, qualitative design was used to interview 35 fathers about their social support at 2–12 months after the birth of their baby. Using a semi-structured interview guide, fathers were asked to describe helpful and unhelpful events they experienced since the birth of their baby. Fathers reported 36 helpful events and 32 unhelpful events for an overall total of 68 events. Data was analyzed using House’s Social Support Theory and the four social support categories: instrumental, informational, emotional, and appraisal. Using the CIT, main categories and subcategories were developed. The helpful categories included: 1) Helping father with infant care, 2) Providing information on infant care, 3) Receiving HCP assistance, 4) Managing relationships, and 5) Becoming a father. The unhelpful categories included: 1) Receiving unhelpful assistance, 2) Receiving unreliable or unwanted assistance, 3) Offering bad advice, 4) Conflicting relationships, 5) Conflicts with friends, 6) Unsatisfying HCP experience, and 7) Receiving no support from family/organizations. The results of the study validated House’s Social Support Theory and served as an excellent framework for exploring social support needs in fathers. More research needs to be conducted on the social support needs of fathers during the first year of their infants’ lives, especially with experienced African American fathers and nonresidential fathers, and how health care professionals (HCPs), specifically postnatal and child health nurses, can better support fathers during the infancy period.
Retuning Mitochondrial Apoptosis/Mitophagy Balance via SIRT3‐Energized and Microenvironment‐Modulated Hydrogel Microspheres to Impede Osteoarthritis

Full‐range therapeutic regimens for osteoarthritis (OA) should consider organs (joints)‐tissues (cartilage)‐cells (chondrocytes)‐organelles cascade, of which the subcellular mitochondria dominate eukaryotic cells' fate, and thus causally influence OA progression. However, the dynamic regulation of mitochondrial rise and demise in impaired chondrocytes and the exact role of mitochondrial metronome sirtuins 3 (SIRT3) is not clarified. Herein, chondrocytes are treated with SIRT3 natural agonist dihydromyricetin (DMY) or chemical antagonist 3‐TYP, respectively, to demonstrate the positive action of SIRT3 on preserving cartilage extracellular matrix (ECM). Molecular mechanical investigations disclose that SIRT3‐induced chondroprotection depended on the repression of mitochondrial apoptosis (mtApoptosis) and the activation of mitophagy. Inspired by the high‐level matrix proteinases and reactive oxygen species (ROS) in the OA environment, by anchoring gelatin methacrylate (GelMA) and benzenediboronic acid (PBA) to hyaluronic acid methacrylate (HAMA) with microfluidic technology, a dual‐responsive hydrogel microsphere laden with DMY is tactfully fabricated and named as DMY@HAMA‐GelMA‐PBA (DMY@HGP). In vivo injection of DMY@HGP ameliorated cartilage abrasion and subchondral bone sclerosis, as well as promoted motor function recovery in post‐traumatic OA (PTOA) model via recouping endogenous mtApoptosis and mitophagy balance. Overall, this study unveils a novel mitochondrial dynamic‐oriented strategy, holding great promise for the precision treatment of OA.
Therapeutic efficacy of platelet‐rich fibrin on surgical site wound healing in patients undergoing oral carcinoma resection: A meta‐analysis

Abstract Oral carcinoma, a prevalent malignancy of the oral cavity, often results in surgical site wounds post‐resection. The therapeutic efficacy of platelet‐rich fibrin (PRF) in wound healing and scar formation has garnered significant attention. This meta‐analysis aimed to evaluate the role of PRF in promoting surgical site wound healing and reducing scar formation following oral carcinoma resection. A systematic search, adhering to PRISMA guidelines, was conducted across multiple databases. The primary outcomes assessed were the Landry, Turnbull and Howley (LTH) wound healing index and the Manchester scar scale (MSS). Statistical evaluations were performed using RevMan 5.4 software. Six studies were incorporated, involving 93 patients treated with PRF and 97 in the control group. For the LTH index, significant improvements in wound healing were observed in the PRF group with I 2 = 74%, (Random: SMD: 3.70, 95% CIs: 2.66 to 4.75, p < 0.01). The Manchester scar scale assessment, which included 60 PRF‐treated patients and 60 controls, indicated a significant reduction in scar formation in the PRF group I 2 = 79%, (Random: SMD: 9.13, 95% CIs: 6.06 to 12.20, p < 0.01). PRF demonstrates promising therapeutic potential in enhancing surgical site wound healing and reducing scar formation post oral carcinoma resection. The application of PRF has been associated with improved wound healing metrics and diminished scar severity. However, further high‐quality studies are warranted to confirm these findings.
Negative emotion amplifies retrieval practice effect for both task-relevant and task-irrelevant information

ABSTRACT Selective retrieval of task-relevant information often facilitates memory retention of that information. However, it is still unclear if selective retrieval of task-relevant information can alter memory for task-irrelevant information, and the role of emotional arousal in it. In two experiments, we used emotional and neutral faces as stimuli, and participants were asked to memorise the name (who is this person? ) and location (where does he/she come from? ) associated with each face in initial study. Then, half of the studied faces were presented as cues, and participants were asked to retrieve the corresponding names (Experiment 1) or locations (Experiment 2). Finally, all the faces were presented and participants were asked to retrieve both the corresponding names and locations. The results of the final test showed that retrieval practice not only enhanced memory of task-relevant information but also enhanced memory of task-irrelevant information. More importantly, negative emotion amplified the retrieval practice effect overall, with a larger retrieval-induced benefit for the negative than neutral condition. These findings demonstrated an emotional arousal amplification effect on retrieval-induced enhancement effects, suggesting that the advantage of the retrieved memory representations can be amplified by emotional arousal even without explicit goals in a task setting.