Miracle-dz/UniFAR-FTUs huggingface dataset:
Allometric scaling of interspecific RNA transcript abundance to extend the use of metatranscriptomics in characterizing complex communities

Metatranscriptomics allows profiling of community mRNA and rRNA transcript abundance under certain environmental conditions. However, variations in the proportion of RNA transcripts across different community size structures remain less explained, thus limiting the possible applications of metatranscriptomics in community studies. Here, we extended the assumptions of the growth‐rate hypothesis (GRH) and the metabolic theory of ecology (MTE) to validate the allometric scaling of interspecific RNA transcript (mRNA and rRNA) abundance through metatranscriptomic analysis of mock communities consisting of model organisms. The results suggest that body size imposes significant constraints on RNA transcript abundance. Interestingly, the relationship between the total mitochondrial transcript abundance (mRNA and rRNA slopes were −0.30 and −0.28, respectively) and body size aligned with the MTE assumptions with slopes close to −¼, while the nuclear transcripts displayed much steeper slopes (mRNA and rRNA slopes were −0.33 and −0.40, respectively). The assumed temperature dependence was not observed in this study. At the gene level, the allometric slopes range from 0 to −1. Overall, the above results showed that larger individuals have lesser RNA transcript abundance per tissue mass than smaller ones regardless of temperature. Analyses of field‐collected microcrustacean zooplankton samples demonstrated that the correction of size effect, using the allometric exponents derived from the model organism mock community, explains better the patterns of interspecific RNA transcripts abundance within the metatranscriptome. Integrating allometry with metatranscriptomics can extend the use of RNA transcript reads in estimating ecological processes within complex communities.
Young bone marrow transplantation prevents aging‐related muscle atrophy in a senescence‐accelerated mouse prone 10 model

Young bone marrow transplantation (YBMT) has been shown to stimulate vascular regeneration in pathological conditions, including ageing. Here, we investigated the benefits and mechanisms of the preventive effects of YBMT on loss of muscle mass and function in a senescence‐associated mouse prone 10 (SAMP10) model, with a special focus on the role of growth differentiation factor 11 (GDF‐11).
The Relationship Between Dissociation and Complex Post-Traumatic Stress Disorder: A Scoping Review

Complex post-traumatic stress disorder (CPTSD) has recently been recognized as an official psychiatric diagnosis in ICD-11, after years of research and advocacy in the field. It has been suggested that dissociative symptoms are a major feature of CPTSD. This scoping review aimed to summarize the existing knowledge base on the relationship between dissociation and CPTSD, and to identify relevant research gaps. We searched the two largest and most widely used academic databases (i.e., the Web of Science and Scopus databases) and the ProQuest database and identified original studies published in English relevant to our research questions, namely: (1) Would CPTSD be associated with dissociative symptoms? 2) How common are dissociative symptoms among people with CPTSD? (3) What are the correlates of dissociative symptoms among people with CPTSD? In all, 26 studies were included. We found 10 studies which reported that people with CPTSD scored significantly higher on a dissociation measure than those without CPTSD, and 11 studies reported a positive correlation between CPTSD symptoms and psychoform/somatoform dissociation scores. While very few studies reported the prevalence and correlates of dissociative symptoms among people with CPTSD, there may be a considerable subgroup of people with CPTSD who have clinically significant levels of dissociative symptoms (e.g., 28.6–76.9%). Dissociation may also be associated with other comorbidities (e.g., DSM-IV Axis II features, shame, somatic symptoms) in people with CPTSD. We recommend that more studies are needed to investigate the prevalence of dissociative symptoms among people with CPTSD and examine how these symptoms are associated with other comorbid conditions and clinical needs in this vulnerable group.
Global Controllability and Stabilization of Nonlinear Systems

Part 1 Two-Dimensional Affine Nonlinear Systems: Controllability of a Cart Nonlinear Affine System on a Plane as a Carts Garland Semiglobal Stabilization of a Carts Garland Two-Dimensional Systems with Singularities. Part II Multi-Dimensional Nonlinear Systems: Global Controllability Analysis Local Stabilization Semiglobal Stabilization.
Estimating the Impact of Emergency Assistance on Educational Progress for Low-Income Adults: Experimental and Nonexperimental Evidence

Methods for estimating causal impact aim to either remove or reduce bias. This study estimates the degree of bias reduction obtained from regression adjustment and propensity score methods when only a weak set of predictors are available. The study uses an experimental test of providing emergency financial assistance to participants in a job training program to estimate an experimental benchmark and compares it to nonexperimental estimates of the impact of receiving assistance. When estimating the impact of receiving assistance, those who received it constitute the treatment group. The study explores two different comparison groups: those who could have (because they were assigned to the experimental treatment group) but did not receive emergency assistance; and those who could not receive emergency assistance because they were randomly assigned to the experimental control group. It uses these groups to estimate impacts by applying three estimation strategies: unadjusted mean comparison, regression adjustment, and inverse propensity weighting. It then compares these estimates to the experimental benchmark using statistical tests recommended by the within-study comparison literature. The nonexperimental approaches to addressing selection bias suggest large positive impacts. These are statistically different from the experimental benchmark, which shows that receipt of emergency assistance does not improve educational progress. Further, over 90% of the bias from a simple comparison of means remains. Unless a stronger set of predictors are available, future evaluations of such interventions should be wary of relying on these methods for either unbiased estimation of impacts or bias reduction.
5′‐nucleotidase, cytosolic II genotype, and clinical outcome in patients with acute myeloid leukemia with intermediate‐risk cytogenetics

Acute myeloid leukemia (AML) is a complex disease, and its treatment needs to be adjusted to the risk, which is conferred by cytogenetics and molecular markers. Cytarabine is the main drug to treat AML, and it has been suggested that the genotype of cytarabine metabolizing enzymes may have a prognostic relevance in AML. Here we report the association between the 5′‐nucleotidase, cytosolic II (NT5C2) rs10883841, cytidine deaminase (CDA) rs2072671 and rs532545 genotypes and the clinical outcome of 477 intermediate‐risk cytogenetic AML patients receiving cytarabine‐based chemotherapy. Patients younger than 50 years old with the NT5C2 rs10883841 AA genotype had lower overall survival (OS) (p: .003; HR 2.16, 95% CI 1.29–3.61) and lower disease‐free survival (DFS) (p: .002; HR 2.45, 95% CI 1.41–4.27), associated to a higher relapse incidence (p: .010; HR 2.23, 95% CI 1.21–4.12). Interestingly, subgroup analysis showed that the negative effect of the NT5C2 rs10883841 AA genotype was detected in all subgroups except in patients with nucleophosmin mutation without high ratio FLT‐3 internal tandem duplication. CDA polymorphisms were associated with the complete remission rate after induction chemotherapy, without influencing OS. Further studies are warranted to determine whether this pharmacogenomic approach may be helpful to individualize AML treatment.
Variation in caregivers' references to their toddlers: Child-directed speech in Vanuatu and Canada.

The authors examined similarities and differences in Canadian and ni-Vanuatu caregivers' child-directed speech to their toddlers (N = 35, Mage : 21 months, 20 girls). Speech samples were collected (2013-2016) during free play and analyzed with a focus on describing parents' references to their toddlers. Canadian caregivers referred significantly more to toddlers' tangible characteristics (relative risk, RR = 2.12) and internal states (RR = 2.31), whereas ni-Vanuatu caregivers referred more to actions (RR = 2.04). When referring to internal states, Canadian mothers referred significantly more to mind-minded states, whereas ni-Vanuatu caregivers referred more to body-minded states (RR = 7.98). These findings are interpreted as capturing meaningful differences in toddlers' opportunities to attend to themselves. Implications for self-concept development are discussed.
Comparative Outcomes of Candida auris Bloodstream Infections: A Multicenter Retrospective Case-control Study.

OBJECTIVE To compare clinical characteristics and outcomes of bloodstream infections (BSI) caused by Candida auris and other Candida spp. METHODS Multicenter, retrospective, case-control study at three hospitals in Brooklyn, New York between 2016 and 2020. Patients ≥18 years of age with a positive blood culture for any Candida spp. treated empirically with an echinocandin were included in the analysis. The primary outcome was 30-day mortality. Secondary outcomes were 14-day clinical failure, 90-day mortality, 60-day microbiologic recurrence, and in-hospital mortality. RESULTS 196 patients were included in the final analysis including 83 cases of candidemia caused by C. auris. After inverse propensity adjustment, C. auris BSI was not associated with increased odds of 30-day mortality (aOR 1.014 (0.563-1.828), p = 0.963) or 90-day mortality (aOR 0.863 (0.478-1.558), p = 0.625). A higher risk for microbiologic recurrence within 60 days of completion of antifungal therapy was observed in C. auris patients (aOR 4.461 (1.033-19.263), p = 0.045). CONCLUSIONS Candida auris BSI is not associated with an increased risk of mortality compared to BSI caused by other Candida spp. A higher risk for microbiologic recurrence occurred in the C. auris group.
Endogenous Viral Elements in Shrew Genomes Provide Insights into Pestivirus Ancient History

Abstract As viral genomic imprints in host genomes, endogenous viral elements (EVEs) shed light on the deep evolutionary history of viruses, ancestral host ranges, and ancient viral–host interactions. In addition, they may provide crucial information for calibrating viral evolutionary timescales. In this study, we conducted a comprehensive in silico screening of a large data set of available mammalian genomes for EVEs deriving from members of the viral family Flaviviridae, an important group of viruses including well-known human pathogens, such as Zika, dengue, or hepatitis C viruses. We identified two novel pestivirus-like EVEs in the reference genome of the Indochinese shrew (Crocidura indochinensis). Homologs of these novel EVEs were subsequently detected in vivo by molecular detection and sequencing in 27 shrew species, including 26 species representing a wide distribution within the Crocidurinae subfamily and one in the Soricinae subfamily on different continents. Based on this wide distribution, we estimate that the integration event occurred before the last common ancestor of the subfamily, about 10.8 million years ago, attesting to an ancient origin of pestiviruses and Flaviviridae in general. Moreover, we provide the first description of Flaviviridae-derived EVEs in mammals even though the family encompasses numerous mammal-infecting members. This also suggests that shrews were past and perhaps also current natural reservoirs of pestiviruses. Taken together, our results expand the current known Pestivirus host range and provide novel insight into the ancient evolutionary history of pestiviruses and the Flaviviridae family in general.
“Race, ethnicity, and health disparities in US children with COVID-19: a review of the evidence and recommendations for the future”

Abstract Coronavirus disease 2019 (COVID-19) is an important cause of morbidity in children in the United States (U.S.). Moreover, the U.S. has witnessed significant disparities affecting American Indian/Alaska Native, Black, and Hispanic/Latino children, stemming from systemic racism and social-structural inequalities and not differences in innate biological susceptibility. We review what is known on COVID-19 and health disparities in disease burden, access to care, pharmaceutical interventions, and clinical research in children, with a focus on the U.S. context. In addition, we propose strategies to communicate scientific data in ways that do not promote racism and biological susceptibility themes, and to address pediatric disparities in clinical infectious diseases research.
Investigating hypozincemia and validity of plasma zinc measurements in infected patients

Abstract Hypozincemia is a well-known phenomenon in patients with infection caused by the activation of the acute phase response (APR). Zn status is still based upon plasma Zn levels in venous blood samples. Recent trials have questioned the validity of this measurement in infected patients. The aim of this study was to assess plasma levels of Zn, albumin and Zinc-binding capacity in patients during and following infection. Furthermore, to assess if an assay for albumin-corrected Zn could potentially replace or add knowledge to existing tools for assessment of Zinc-status. A prospective clinical observational trial was conducted. Associations between P-Zn, -Albumin, -Albumin-corrected Zn and Zn binding capacity were analyzed. Analyzes were based upon two venous blood samples drawn during and following infection, respectively. Twenty-three patients admitted to a medical ward showing paraclinical signs of infection were included in the study. Significantly lower levels of Zn and albumin were found during infection compared with the levels post-infection. These findings corresponded to the changes found in Zn binding capacity. About 52% of patients were deemed Zn deficient by plasma Zn levels during infection but after applying the correction for P-Albumin, all patients were found to be within normal ranges of Zn levels. Furthermore, we found no statistically significant difference between albumin-corrected Zn during infection and P-Zn post-infection. The new assay was found to accurately estimate the ‘true’ Zn levels in infected patients. Based on our findings, we propose albumin-corrected P-Zn as a promising new tool, which may result in more precise diagnostics and treatment.
The Progress of the Specific and Rapid Genetic Detection Methods for Ovarian Cancer Diagnosis and Treatment

Cancer is a public health problem that threatens human health. Due to the lack of specific and rapid diagnosis and treatment methods, the 5-year survival rate of patients has not been effectively improved in the past 10 years. Abnormal gene expression is closely related to the occurrence and development of cancer. Cancer diagnosis and treatment methods based on genetic testing have received extensive attention in recent years. It is essential to explore specific and rapid cancer genetic testing methods. Taking ovarian cancer as an example, we reviewed the progress of specific and rapid nucleic acid detection methods related to cancer risk assessment, low-abundance mutation detection, and methylation detection, to provide new strategies and ideas for related research.
Vasopressin Response and Clinical Trajectory in Septic Shock Patients

Background In septic shock, vasopressors aim to improve tissue perfusion and prevent persistent organ dysfunction, a characteristic of chronic critical illness (CCI). Adjunctive vasopressin is often used to decrease catecholamine dosage, but the association of vasopressin response with subsequent patient outcomes is unclear. We hypothesized vasopressin response is associated with favorable clinical trajectory. Methods We included patients with septic shock receiving vasopressin as a catecholamine adjunct in this retrospective cohort study. We defined vasopressin response as a lowering of the catecholamine dose required to maintain mean arterial pressure ≥65 mm Hg, 6 h after vasopressin initiation. Clinical trajectories were adjudicated as early death (ED; death before day 14), CCI (ICU stay ≥14 days with persistent organ dysfunction), or rapid recovery (RR; not meeting ED or CCI criteria). Trajectories were placed on an ordinal scale with ED the worst outcome, CCI next, and RR the best outcome. The association of vasopressin response with clinical trajectory was assessed with multivariable ordinal logistic regression. Results In total 938 patients were included; 426 (45.4%) were vasopressin responders. The most frequent trajectory was ED (49.8%), 29.7% developed CCI, and 20.5% had rapid recovery. In survivors to ICU day 14 (those without ED), 59.2% had CCI and 40.8% experienced RR. Compared with vasopressin non-responders, vasopressin responders less frequently experienced ED (42.5% vs. 55.9%) and more frequently experienced RR (24.6% vs. 17.0%; P < 0.01). After controlling for confounders, vasopressin response was independently associated with higher odds of developing a better clinical trajectory (OR 1.63; 95% CI 1.26−2.10). Medical patients most frequently developed ED and survivors more commonly developed CCI than RR; surgical patients developed the three trajectories with similar frequency (P < 0.01). Conclusions Vasopressin responsive status was associated with improved clinical trajectory in septic shock patients. Early vasopressin response is a potential novel prognostic marker for short-term clinical trajectory.
A Novel Cryogenic Adhesive Retaining Fluidity at Dry-Ice Temperature for Low-Temperature Scanning Electron Microscopy

Abstract Scanning electron microscopy operated at cryogenic temperature (cryo-SEM) is a powerful tool for investigating surface and cross-sectional nanostructures of water-containing samples. Typically, cryo-SEM samples are frozen just before observation in specific metal carriers. However, pre-frozen samples are also of interest, such as frozen food and freeze-stored animal samples. In such cases, sample mounting with a defined orientation is required, but there has been a lack of ideal conductive adhesives that can be used without increasing the sample temperature. Here, we developed a mixture of graphite oxide and 1,3-butanediol as an adhesive, capable of gluing samples at dry-ice temperature and is frozen below that temperature. Dispersion of graphite oxide increased the conductivity and reduced the charge-up contrast. Acquisition of energy-dispersive X-ray spectrum, cross-sectional ion milling, and high-resolution imaging were successfully achieved using the adhesive. We tested and confirmed the usefulness of this new adhesive by applying it to cryo-SEM surface imaging of diatomite, freeze-fractured cross-sectional imaging of chicken liver, and ion milling cross-sectional imaging of a deep-sea snail. The new adhesive is not only useful for food science and field-preserved biological samples but also potentially applicable to wider fields such as archaeological and biological samples preserved under permafrost.
Efficacy and drug retention of tofacitinib in rheumatoid arthritis: from the nationwide Korean College of Rheumatology Biologics registry.

OBJECTIVES Janus kinase inhibitors are expected to change the management patterns and prognosis of chronic rheumatic diseases. This study aimed to evaluate the efficacy, drug retention, and adverse events of tofacitinib, a Janus kinase inhibitor, for rheumatoid arthritis (RA) using a Korean nationwide database. METHODS Data of patients with RA receiving tofacitinib were extracted from the Korean College of Rheumatology Biologics and Targeted Therapy registry, including clinical characteristics and disease activity markers for RA. Outcomes of clinical efficacy, drug survival rate, and safety profiles were compared between biologic disease-modifying anti-rheumatic drug (bDMARD)-naive and -failure patients. Mann-Whitney U-test, logistic regression analysis, Kaplan-Meier analysis, and log-rank test were used in data analysis. RESULTS Three hundred patients with RA received tofacitinib therapy (16.3% male; mean age 55.4±11.9 years); 91 patients were bDMARD-naive. Baseline disease activity markers and proportions of patients who were taking conventional synthetic DMARDs were not different between bDMARD-naive and bDMARD-failure patients. American College of Rheumatology responses and disease activity score-28 did not differ between bDMARD-failure and -naive patients at the 1-year follow-up. The drug retention rate of tofacitinib did not differ between bDMARD-failure (155 per 2.4 years) and -naive patients (89 per 1.9 years) (log-rank test, p=0.202). In logistic regression, the positivity of RF and ACPA were associated with reduced drug retention (p=0.01 and 0.02, respectively). Totally 83 (27.7%) of patients had adverse, and 14 (4.7%) patients had herpes zoster infection. CONCLUSIONS Nationwide real-world data showed that tofacitinib therapy is effective in patients with RA independent of previous use of a bDMARD. The drug retention of tofacitinib did not differ between bDMARD-failure and -naive patients, and RF or ACPA positivity may be associated with reduced discontinuation of tofacitinib.
Induction of robust humoral immunity against SARS‐CoV‐2 after vaccine administration in previously infected haematological cancer patients

The coronavirus disease 2019 (COVID- 19) is an ongoing, global pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS- CoV- 2). Impaired seroconversion has been repeatedly reported in patients with haematological malignancies (HM) and an important question remains as to whether the current anti- SARS- CoV- 2 vaccine- induced immune response offers adequate protection from severe COVID- 19 in ‘frail’ individuals, such as HM patients. 1– 5 Using a disease- overarching cohort of HM patients ( n = 120) already tested for their humoral response at post- infection, 6 assess reactions after at baseline
Gray and white matter astrocytes differ in basal metabolism but respond similarly to neuronal activity

Astrocytes are a heterogeneous population of glial cells in the brain, which adapt their properties to the requirements of the local environment. Two major groups of astrocytes are protoplasmic astrocytes residing in gray matter as well as fibrous astrocytes of white matter. Here, we compared the energy metabolism of astrocytes in the cortex and corpus callosum as representative gray matter and white matter regions, in acute brain slices taking advantage of genetically encoded fluorescent nanosensors for the NADH/NAD+ redox ratio and for ATP. Astrocytes of the corpus callosum presented a more reduced basal NADH/NAD+ redox ratio, and a lower cytosolic concentration of ATP compared to cortical astrocytes. In cortical astrocytes, the neurotransmitter glutamate and increased extracellular concentrations of K+, typical correlates of neuronal activity, induced a more reduced NADH/NAD+ redox ratio. While application of glutamate decreased [ATP], K+ as well as the combination of glutamate and K+ resulted in an increase of ATP levels. Strikingly, a very similar regulation of metabolism by K+ and glutamate was observed in astrocytes in the corpus callosum. Finally, strong intrinsic neuronal activity provoked by application of bicuculline and withdrawal of Mg2+ caused a shift of the NADH/NAD+ redox ratio to a more reduced state as well as a slight reduction of [ATP] in gray and white matter astrocytes. In summary, the metabolism of astrocytes in cortex and corpus callosum shows distinct basal properties, but qualitatively similar responses to neuronal activity, probably reflecting the different environment and requirements of these brain regions.