Miracle-dz/UniFAR-FTUs huggingface dataset:
Bacterial TLR2/6 Ligands Block Ciliogenesis, Derepress Hedgehog Signaling, and Expand the Neocortex

Fetal brain development in early gestation can be impacted by transplacental infection, altered metabolites from the maternal microbiome, or maternal immune activation. It is less well understood how maternal microbial subcomponents that cross the placenta, such as bacterial cell wall (BCW), directly interact with fetal neural progenitors and neurons and affect development. ABSTRACT Microbial components have a range of direct effects on the fetal brain. However, little is known about the cellular targets and molecular mechanisms that mediate these effects. Neural progenitor cells (NPCs) control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. We identify ventricular radial glia (vRG), the primary NPC, as the target of bacterial cell wall (BCW) generated during the antibiotic treatment of maternal pneumonia. BCW enhanced proliferative potential of vRGs by shortening the cell cycle and increasing self-renewal. Expanded vRGs propagated to increase neuronal output in all cortical layers. Remarkably, Toll-like receptor 2 (TLR2), which recognizes BCW, localized at the base of primary cilia in vRGs and the BCW-TLR2 interaction suppressed ciliogenesis leading to derepression of Hedgehog (HH) signaling and expansion of vRGs. We also show that TLR6 is an essential partner of TLR2 in this process. Surprisingly, TLR6 alone was required to set the number of cortical neurons under healthy conditions. These findings suggest that an endogenous signal from TLRs suppresses cortical expansion during normal development of the neocortex and that BCW antagonizes that signal through the TLR2/cilia/HH signaling axis changing brain structure and function. IMPORTANCE Fetal brain development in early gestation can be impacted by transplacental infection, altered metabolites from the maternal microbiome, or maternal immune activation. It is less well understood how maternal microbial subcomponents that cross the placenta, such as bacterial cell wall (BCW), directly interact with fetal neural progenitors and neurons and affect development. This scenario plays out in the clinic when BCW debris released during antibiotic therapy of maternal infection traffics to the fetal brain. This study identifies the direct interaction of BCW with TLR2/6 present on the primary cilium, the signaling hub on fetal neural progenitor cells (NPCs). NPCs control the size and architecture of the brain and understanding the mechanisms regulating NPCs is crucial to understanding brain developmental disorders. Within a window of vulnerability before the appearance of fetal immune cells, the BCW-TLR2/6 interaction results in the inhibition of ciliogenesis, derepression of Sonic Hedgehog signaling, excess proliferation of neural progenitors, and abnormal cortical architecture. In the first example of TLR signaling linked to Sonic Hedgehog, BCW/TLR2/6 appears to act during fetal brain morphogenesis to play a role in setting the total cell number in the neocortex.
Validated assessment tools for screen media use: A systematic review

Objective Accurate measurement of adult and child screen media use are needed to robustly assess its impact on health outcomes. Our objective was to systematically review screen media use measurement tools that have been validated against an objective “gold standard” tool. Methods The search strategy was initially conducted in Medline Ovid and translated to Embase, Web of Science, PsychInfo and Cochrane. A modified natural language search was conducted in Google Scholar and IEEE. The initial search was conducted in March 2021, and an updated search was conducted in June 2022. Additional studies were included from the references. Studies had to describe the validation of a tool to measure screen media use on participants of any age against a ‘gold standard’ or comparable objective measure. The COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) was used to assess the criterion validity. Four authors reviewed the titles in two rounds and extracted data. Results Twenty-nine articles were included in the review. Studies measured TV, computer, mobile device and social media site screen media use through: self or parent report, direct or video observation, computer and mobile device use tracking programs, and through other novel devices such as wearable devices and cameras. Correlations of self or parent report of screen media with the gold standard were lower than correlations of technology-based measures, and video observation with the gold standard. The COSMIN criterion validity ratings ranged from poor to excellent; most of the studies received a global score of fair or poor. Conclusions Technology based validated tools that more directly measure screen use are emerging that have been validated against a gold standard for measuring screen use. However, practical, objective measures of diverse types of screen media use that have been tested on diverse populations are needed to better understand the impact of screen media use on the development and physical and mental health of children and adults.
Automated Prediction of Infant Cognitive Development Risk by Video: A Pilot Study

Objective: Cognition is an essential human function, and its development in infancy is crucial. Traditionally, pediatricians used clinical observation or medical imaging to assess infants’ current cognitive development (CD) status. The object of pediatricians’ greater concern is however their future outcomes, because high-risk infants can be identified early in life for intervention. However, this opportunity has not yet been realized. Fortunately, some recent studies have shown that the general movement (GM) performance of infants around 3–4 months after birth might reflect their future CD status, which gives us an opportunity to achieve this goal by cameras and artificial intelligence. Methods: First, infants’ GM videos were recorded by cameras, from which a series of features reflecting their bilateral movement symmetry (BMS) were extracted. Then, after at least eight months of natural growth, the infants’ CD status was evaluated by the Bayley Infant Development Scale, and they were divided into high-risk and low-risk groups. Finally, the BMS features extracted from the early recorded GM videos were fed into the classifiers, using late infant CD risk assessment as the prediction target. Results: The area under the curve, recall and precision values reached 0.830, 0.832, and 0.823 for two-group classification, respectively. Conclusion: This pilot study demonstrates that it is possible to automatically predict the CD of infants around the age of one year based on their GMs recorded early in life. Significance: This study not only helps clinicians better understand infant CD mechanisms, but also provides an economical, portable and non-invasive way to screen infants at high-risk early to facilitate their recovery.
Sodium oxybate in treatment-resistant rapid-eye-movement sleep behavior disorder

Abstract Study Objectives Symptomatic therapies for rapid-eye-movement (REM) sleep behavior disorder (RBD) are limited. Sodium oxybate (SXB), a gamma-aminobutyric acid (GABA)-B agonist, could be effective but has not been evaluated against placebo. Methods This double-blind, parallel-group, randomized, placebo-controlled trial in 24 participants was conducted at the Stanford Sleep Center. Patients were adults with definite iRBD or Parkinson’s disease and probable RBD (PD-RBD), and persistence of ≥ 2 weekly episodes despite standard therapy. Patients were randomized 1:1 to receive SXB during a 4-week titration followed by a 4-week stable dosing period. Primary outcome was number of monthly RBD episodes according to a diary filled by patients and partners. Secondary outcomes were severity, number of severe RBD episodes, and objective RBD activity on video polysomnography. Results Twelve iRBD and 12 PD-RBD participated (mean 65.8 years), and 22 (n = 10 SXB, 12 placebo) completed the study. Although no significant between-group difference was found, SXB showed reduction of monthly RBD episodes by 23.1 (95% CI −36.0, −10.2; p = 0.001) versus 10.5 with placebo (95% CI, −22.6, 1.6; p = 0.087). Improvement from baseline was similarly observed for RBD overall severity burden (each episode weighted for severity), number of severe episodes, and objective RBD activity per video-polysomnography. Two participants receiving SXB withdrew due to anxiety and dizziness. The majority of adverse events are otherwise resolved with dose adjustment. Conclusion SXB could reduce RBD symptoms; however, response was inconsistent and a large placebo effect was observed across patient-reported outcomes. Larger studies using objective endpoints are needed. Clinical Trial Treatment of REM Sleep Behavior Disorder (RBD) With Sodium Oxybate https://clinicaltrials.gov/ct2/show/NCT04006925 ClinicalTrials.gov identifier: NCT04006925
The SARS-CoV-2 Alpha variant was associated with increased clinical severity of COVID-19 in Scotland: A genomics-based retrospective cohort analysis

Objectives The SARS-CoV-2 Alpha variant was associated with increased transmission relative to other variants present at the time of its emergence and several studies have shown an association between Alpha variant infection and increased hospitalisation and 28-day mortality. However, none have addressed the impact on maximum severity of illness in the general population classified by the level of respiratory support required, or death. We aimed to do this. Methods In this retrospective multi-centre clinical cohort sub-study of the COG-UK consortium, 1475 samples from Scottish hospitalised and community cases collected between 1st November 2020 and 30th January 2021 were sequenced. We matched sequence data to clinical outcomes as the Alpha variant became dominant in Scotland and modelled the association between Alpha variant infection and severe disease using a 4-point scale of maximum severity by 28 days: 1. no respiratory support, 2. supplemental oxygen, 3. ventilation and 4. death. Results Our cumulative generalised linear mixed model analyses found evidence (cumulative odds ratio: 1.40, 95% CI: 1.02, 1.93) of a positive association between increased clinical severity and lineage (Alpha variant versus pre-Alpha variants). Conclusions The Alpha variant was associated with more severe clinical disease in the Scottish population than co-circulating lineages.
Dual career experiences of elite coaches enrolled at university level

The lifelong education of coaches is one of the priorities of the European Union. Therefore, the purpose of this study was to investigate Italian elite coaches’ motivation to engage in a sport-related academic education, and its demands, barriers, support, and relocation issues in relation to their dual career (DC) path. Sixteen Italian elite coaches (e.g., certified fourth-level national team coaches, senior team coaches) enrolled in a specifically tailored Bachelor’s degree in sports sciences at the University of Rome Foro Italico (Italy) volunteered for this study. A qualitative approach integrating inductive and deductive reasoning, and thematic analysis was applied to participants’ responses to an open-ended item survey. Independently from relocation, student-coaches’ DC perceptions resulted in 15 lower-order themes further organized in 5 high-er-order themes (e.g., Benefit, Challenge, Expectation, Organization, and Support), each related to the contexts (e.g., Personal, Academic, Sport), the DC dimension (e.g., micro, meso, macro, and policy), and the DC push (e.g., facilitating) /pull (e.g., hindering) factors. The elite coaches’ insights emphasize the complexity of the coach lifelong education at university level, and provide valuable information for promoting European and National (e.g., Italian) DC recommendations for elite sportspersons through a cooperation between sport bodies and higher educational institutions.
Diagnosis and prognosis of serum Fut8 for epilepsy and refractory epilepsy in children

With adequate serum concentration of antiepileptic drugs, the epilepsy symptoms in many patients still cannot be controlled well. The alteration of glycosyltransferase has obvious influence on the pathogenesis of epilepsy. In this study, we focus on the diagnostic and prognostic value of fucosyltransferase 8 (Fut8) on epilepsy and refractory epilepsy. Serum samples of 199 patients with epilepsy, 59 patients with refractory epilepsy and 22 healthy controls who were diagnosed in Shenzhen Children’s hospital from August 2018 to August 2019 were collected. The level of lectins was further analyzed by lectin chip and enzyme linked immunosorbent assay (ELISA). The diagnostic value of serum Fut8 for epilepsy and refractory epilepsy was evaluated by receiver operating characteristic curve. Finally, the difference in the recurrence rate of convulsion in patients with epilepsy or refractory epilepsy within 2 years were observed in different Fut8 expression patients. The concentration of valproic acid (VPA) were significant different between epilepsy and refractory epilepsy group. The expression of α1, 6-fucosylation and Fut8 was significantly increased in the refractory epilepsy group compared with healthy controls. The area under the curve of Fut8 as a biomarker for predicting epilepsy or refractory epilepsy was 0.620 and 0.856, respectively. There was a significant difference in the recurrence rate of convulsion within 2 years in the children with refractory epilepsy (p = 0.0493) not epilepsy (p = 0.1865) between the high and low Fut8 expression groups. Fut8 was one of the effective indicators for the diagnosis and prognosis of refractory epilepsy.
Prognostic assessment of patients who receive radiotherapy for bone metastases from breast cancer

For prognostic assessment in women who receive radiotherapy (RT) for bone metastases (BMs) from breast cancer (BC), prognostic factors specific for BMs from BC were investigated in the present study. The prognostic assessment was performed by retrospectively reviewing 143 women who received first-time RT for BMs from BC between January 2007 and June 2018. The median follow-up time and median overall survival (OS) time from the first-time RT for BMs were 22 and 18 months, respectively. In the multivariate analysis, nuclear grade 3 (NG 3) [hazard ratio, 2.18; 95% confidence interval (CI), 1.34-3.53], brain metastases (hazard ratio, 1.96; 95% CI, 1.01-3.81), liver metastases (hazard ratio, 1.75; 95% CI, 1.17-2.63), performance status (PS) (hazard ratio, 1.63; 95% CI, 1.10-2.41) and previous systemic therapy (hazard ratio, 1.58; 95% CI, 1.03-2.42) were significant factors for OS, whereas age, hormone-receptor/human epidermal growth factor receptor 2 status, number of BMs and synchronous lung metastases were not significant factors. When points according to risk levels [unfavorable points (UFPs)] were assigned to each risk factor (1.5 points for NG 3 and brain metastases; and 1 point for PS ≥2, previous systemic therapy and liver metastases), the median OS times of patients with a total number of UFPs ≤1 (n=45), 1.5–3 (n=55) and ≥3.5 (n=43) were 36, 17 and 6 months, respectively. Overall, in patients who received first-time RT for BMs from BC, NG 3, brain/liver metastases, poor PS and previous systemic therapy were unfavorable prognostic factors. Comprehensive prognostic assessment using these factors seemed to be useful for the prediction of prognoses in patients with BMs from BC.
Influence of contrast agent on artificial intelligence-based CT low attenuation volume percentage measurement

Background Low attenuation volume percentage (LAV%) has been identified as a quantitative imaging biomarker for emphysema with good correlation with spirometry. The influence of intravenous contrast agent on LAV% and its correlation with spirometry is not well known. Purpose To evaluate the influence of intravenous contrast agent on artificial intelligence (AI)-based LAV% in correlation with spirometric Tiffeneau-Pinelli Index (TI). Material and Methods In a retrospective study, two groups of 47 patients (mean age 68.04 ± 12.64 and 67.89 ± 11.54 years) with either non-enhanced chest computed tomography (CT) or contrast-enhanced CT were compared. Using an AI-based software, LAV% was quantified using a threshold <−950 HU. TI was calculated from spirometry and pathologic airway obstruction was considered with a TI <70. The effect of contrast agent on LAV% and the relationship between TI and LAV% was analyzed. Correlation coefficients between TI and LAV% were compared for both groups. Results Patients with non-enhanced CT had a mean LAV% of 9.07 ± 7.53. Of them, 22 patients had a TI <70% and 25 patients a TI ≥70%. Patients with contrast-enhanced CT had a mean LAV% of 6.54 ± 4.62. Of them, 20 patients had a TI <70% and 27 patients had a TI ≥70%. Contrast agent did not show a major effect on LAV% (P = 0.099) and the relationship between TI and LAV% (P = 0.88). In both groups, a significant correlation between TI and LAV% was found (ρ = −0.317 for non-enhanced CT; ρ = −0.514 for contrast-enhanced CT). Difference between correlation coefficients was insignificant. Conclusion Our findings suggest that contrast agent does not influence LAV% nor its correlation with TI.
The effects of hormone replacement therapy on the microbiomes of postmenopausal women

Abstract The sex steroid hormone estrogen plays a number of regulatory roles in female development. During menopause, estrogen synthesis in the ovaries decreases, which results in adverse physiological remodeling and increased risk of disease. Reduced bone density, changes in the community composition profiles of the gut and vaginal microbiome, mood swings and changes in the vaginal environment are to be expected during this time. To alleviate these changes, postmenopausal women can be prescribed hormone replacement therapy (HRT) through the use of exogenous estradiol, often in conjunction with progestin treatment, which re-induces estrogenic action throughout the body. The microbiome and estrogen have a bidirectional, regulatory relationship in the gut, while in the vaginal environment estrogen works indirectly on the microbiome through restoring the vaginal tissue environment that leads to microbial homeostasis. This review discusses what is known about how the gut and vaginal microbiomes of postmenopausal women are responding to HRT, and the potential future of microbe-based therapeutics for symptoms of menopause.
Right ventricular-arterial uncoupling as an independent prognostic factor in acute heart failure with preserved ejection fraction accompanied with coronary artery disease

Abstract Background: Right ventricular (RV)-arterial uncoupling is a powerful independent predictor of prognosis in heart failure with preserved ejection fraction (HFpEF). Coronary artery disease (CAD) can contribute to the pathophysiological characteristics of HFpEF. This study aimed to evaluate the prognostic value of RV-arterial uncoupling in acute HFpEF patients with CAD. Methods: This prospective study included 250 consecutive acute HFpEF patients with CAD. Patients were divided into RV-arterial uncoupling and coupling groups by the optimal cutoff value, based on a receiver operating characteristic curve of tricuspid annular plane systolic excursion to pulmonary artery systolic pressure (TAPSE/PASP). The primary endpoint was a composite of all-cause death, recurrent ischemic events, and HF hospitalizations. Results: TAPSE/PASP ≤0.43 provided good accuracy in identifying patients with RV-arterial uncoupling (area under the curve, 0.731; sensitivity, 61.4%; and specificity, 76.6%). Of the 250 patients, 150 and 100 patients could be grouped into the RV-arterial coupling (TAPSE/PASP >0.43) and uncoupling (TAPSE/PASP ≤0.43) groups, respectively. Revascularization strategies were slightly different between groups; the RV-arterial uncoupling group had a lower rate of complete revascularization (37.0% [37/100] vs. 52.7% [79/150], P <0.001) and a higher rate of no revascularization (18.0% [18/100] vs. 4.7% [7/150], P <0.001) compared to the RV-arterial coupling group. The cohort with TAPSE/PASP ≤0.43 had a significantly worse prognosis than the cohort with TAPSE/PASP >0.43. Multivariate Cox analysis showed TAPSE/PASP ≤0.43 as an independent associated factor for the primary endpoint, all-cause death, and recurrent HF hospitalization (hazard ratios [HR]: 2.21, 95% confidence interval [CI]: 1.44–3.39, P <0.001; HR: 3.32, 95% CI: 1.30–8.47, P = 0.012; and HR: 1.93, 95% CI: 1.10–3.37, P = 0.021, respectively), but not for recurrent ischemic events (HR: 1.48, 95% CI: 0.75–2.90, P = 0.257). Conclusion: RV-arterial uncoupling, based on TAPSE/PASP, is independently associated with adverse outcomes in acute HFpEF patients with CAD.
Natural variation of maize root hydraulic architecture underlies highly diverse water uptake capacities

Abstract Plant water uptake is determined by the root system architecture and its hydraulic capacity, which together define the root hydraulic architecture. The current research aims at understanding the water uptake capacities of maize (Zea mays), a model organism and major crop. We explored the genetic variations within a collection of 224 maize inbred Dent lines and successively defined core genotype subsets to access multiple architectural, anatomical, and hydraulic parameters in the primary root (PR) and seminal roots (SR) of hydroponically grown seedlings. We found 9-, 3.5-, and 12.4-fold genotypic differences for root hydraulics (Lpr), PR size, and lateral root size, respectively, that shaped wide and independent variations of root structure and function. Within genotypes, PR and SR showed similarities in hydraulics and, to a lesser extent, in anatomy. They had comparable aquaporin activity profiles that, however, could not be explained by aquaporin expression levels. Genotypic variations in the size and number of late meta xylem vessels were positively correlated with Lpr. Inverse modeling further revealed dramatic genotypic differences in the xylem conductance profile. Thus, tremendous natural variation of maize root hydraulic architecture underlies a high diversity of water uptake strategies and paves the way to quantitative genetic dissection of its elementary traits.
Chronotherapy in dentistry: A scoping review

ABSTRACT The circadian clock modulates almost all vital aspects of our physiology and metabolism, including processes relevant to dentistry, such as healing, inflammation and nociception. Chronotherapy is an emerging field aiming to improve therapeutic efficacy and decrease adverse effects on health outcomes. This scoping review aimed to systematically map the evidence underpinning chronotherapy in dentistry and to identify gaps in knowledge. We conducted a systematic scoping search using four databases (Medline, Scopus, CINAHL and Embase). We identified 3908 target articles screened by two blinded reviewers, and only original animal and human studies investigating the chronotherapeutic use of drugs or interventions in dentistry were included. Of the 24 studies included, 19 were human studies and five were animal studies. Chrono-radiotherapy and chrono-chemotherapy reduced treatment side effects and improved therapeutic response, leading to higher survival rates in cancer patients. Animal studies reported that tooth movement and periodontal tissue response to orthodontic forces follow a diurnal rhythm that might influence bone metabolism. Profound and prolonged local anesthesia could be achieved when injected in the evening. Although the overall quality of the included studies was low, chronotherapy applications in dentistry seem to have favourable outcomes, especially in head and neck cancer treatments.