Miracle-dz/UniFAR-FTUs huggingface dataset:
Longitudinal change in regional brain volumes with exposure to repetitive head impacts

Objective This study tests the hypothesis that certain MRI-based regional brain volumes will show reductions over time in a cohort exposed to repetitive head impacts (RHI). Methods Participants were drawn from the Professional Fighters Brain Health Study, a longitudinal observational study of professional fighters and controls. Participants underwent annual 3T brain MRI, computerized cognitive testing, and blood sampling for determination of neurofilament light (NfL) and tau levels. Yearly change in regional brain volume was calculated for several predetermined cortical and subcortical brain volumes and the relationship with NfL and tau levels determined. Results A total of 204 participants who had at least 2 assessments were included in the analyses. Compared to controls, the active boxers had an average yearly rate of decline in volumes of the left thalamus (102.3 mm3/y [p = 0.0004], mid anterior corpus callosum (10.2 mm3/y [p = 0.018]), and central corpus callosum (16.5 mm3/y [p = <0.0001]). Retired boxers showed the most significant volumetric declines compared to controls in left (32.1 mm3/y [p = 0.002]) and right (30.6 mm3/y [p = 0.008]) amygdala and right hippocampus (33.5 mm3/y [p = 0.01]). Higher baseline NfL levels were associated with greater volumetric decline in left hippocampus and mid anterior corpus callosum. Conclusion Volumetric loss in different brain regions may reflect different pathologic processes at different times among individuals exposed to RHI.
Low oxygen enhances trophoblast column growth by potentiating differentiation of the extravillous lineage and promoting LOX activity

ABSTRACT Early placental development and the establishment of the invasive trophoblast lineage take place within a low oxygen environment. However, conflicting and inconsistent findings have obscured the role of oxygen in regulating invasive trophoblast differentiation. In this study, the effect of hypoxic, normoxic and atmospheric oxygen on invasive extravillous pathway progression was examined using a human placental explant model. Here, we show that exposure to low oxygen enhances extravillous column outgrowth and promotes the expression of genes that align with extravillous trophoblast (EVT) lineage commitment. By contrast, supra-physiological atmospheric levels of oxygen promote trophoblast proliferation while simultaneously stalling EVT progression. Low oxygen-induced EVT differentiation coincided with elevated transcriptomic levels of lysyl oxidase (LOX) in trophoblast anchoring columns, in which functional experiments established a role for LOX activity in promoting EVT column outgrowth. The findings of this work support a role for low oxygen in potentiating the differentiation of trophoblasts along the extravillous pathway. In addition, these findings generate insight into new molecular processes controlled by oxygen during early placental development. Summary: Trophoblast exposure to low levels of oxygen promotes transcriptional programmes that are consistent with the extravillous lineage, a cell state important in placental development and function.
Effects of Li Confined Motion on NMR Quadrupolar Interactions: A Combined 7Li NMR and DFT‐MD Study of LiR2(PO4)3 (R=Ti or Zr) Phases

Abstract Ab initio molecular dynamics (MD) simulations and NMR GIPAW (gauge including projector augmented wave) calculations have been used to analyze the coordination and mobility of Li ions in LiTi2(PO4)3 (rhombohedral), LiZr2(PO4)3 (triclinic), and LiZr2(PO4)3 (rhombohedral) phases. Significant discrepancies are observed between static calculations of 7Li quadrupolar parameters and experimental values. The dynamical origin of this disagreement is demonstrated by incorporating in the calculations thermal vibrations and local motion of atoms with MD simulations. For LiTi2(PO4)3, the quadrupolar constant associated with Li ions grows with temperature because the local symmetry of the system decreases, whereas for the Zr phases, the quadrupolar constant decreases because thermal vibrations reduce the anisotropy of the interaction. Finally, for both Zr phases, MD yields Li distributions that compare well with disorder reported from diffraction studies.
Rapid gut microbiome changes in a world‐class ultramarathon runner

The human gut microbiome is a dynamic ecosystem with prolific health connotations. Physical activity is emerging as a potent regulator of human microbiome composition. This study examined changes in the gut microbiome of a world‐class ultramarathon runner before and after competing in the Western States Endurance Run (WSER), a 163 km mountain footrace. Anthropometrics and body composition were assessed and the ultramarathoner's submaximal and maximal performance profiles were evaluated. Gut microbiome analyses were performed at four time‐points: 21 weeks and 2 weeks before and 2 hours and 10 days after WSER. Aerobic power (VO2max) was 4.24 L/min (66.7 ml kg−1 min−1), and running economy (51.1 ml kg−1 min−1 at 268 m/min) and lactate threshold (~83% VO2max) values were comparable to that of highly trained distance runners. Two hours post‐race, considerable changes in the ultrarunners’ gut microbiome were observed. Alpha diversity (Shannon Diversity Index) increased from 2.73 to 2.80 and phylum‐level bacterial composition (Firmicutes/Bacteroidetes ratio) rose from 4.4 to 14.2. Underlying these macro‐level microbial alterations were demonstrable increases in select bacterial genera such as Veillonella (+14,229%) and Streptococcus (+438%) concomitant with reductions in Alloprevotella (−79%) and Subdolingranulum (−50%). To our knowledge, this case study shows the most rapid and pronounced shifts in human gut microbiome composition after acute exercise in the human literature. These findings provide yet another example of how exercise can be a powerful modulator of human health.
SwsB and SafA Are Required for CwlJ-Dependent Spore Germination in Bacillus subtilis

Spore formation in Bacillus subtilis has been studied for over half a century, and virtually every step in this developmental process has been characterized in molecular detail. In contrast, how spores exit dormancy remains less well understood. A key step in germination is the degradation of the specialized cell wall surrounding the spore called the cortex. Two enzymes (SleB and CwlJ) specifically target this protective layer, but how they are regulated and whether additional factors promote their activity are unknown. Here, we identified the coat protein SafA and a conserved but uncharacterized protein YlxY as additional factors required for CwlJ-dependent degradation of the cortex. Our analysis provides a more complete picture of this essential step in the exit from dormancy. ABSTRACT When Bacillus subtilis spores detect nutrients, they exit dormancy through the processes of germination and outgrowth. A key step in germination is the activation of two functionally redundant cell wall hydrolases (SleB and CwlJ) that degrade the specialized cortex peptidoglycan that surrounds the spore. How these enzymes are regulated remains poorly understood. To identify additional factors that affect their activity, we used transposon sequencing to screen for synthetic germination defects in spores lacking SleB or CwlJ. Other than the previously characterized protein YpeB, no additional factors were found to be specifically required for SleB activity. In contrast, our screen identified SafA and YlxY (renamed SwsB) in addition to the known factors GerQ and CotE as proteins required for CwlJ function. SafA is a member of the spore’s proteinaceous coat and we show that, like GerQ and CotE, it is required for accumulation and retention of CwlJ in the dormant spore. SwsB is broadly conserved among spore formers, and we show that it is required for CwlJ to efficiently degrade the cortex during germination. Intriguingly, SwsB resembles polysaccharide deacetylases, and its putative catalytic residues are required for its role in germination. However, we find no chemical signature of its activity on the spore cortex or in vitro. While the precise, mechanistic role of SwsB remains unknown, we explore and discuss potential activities. IMPORTANCE Spore formation in Bacillus subtilis has been studied for over half a century, and virtually every step in this developmental process has been characterized in molecular detail. In contrast, how spores exit dormancy remains less well understood. A key step in germination is the degradation of the specialized cell wall surrounding the spore called the cortex. Two enzymes (SleB and CwlJ) specifically target this protective layer, but how they are regulated and whether additional factors promote their activity are unknown. Here, we identified the coat protein SafA and a conserved but uncharacterized protein YlxY as additional factors required for CwlJ-dependent degradation of the cortex. Our analysis provides a more complete picture of this essential step in the exit from dormancy.
Low-density polyethylene films incorporated with silver nanoparticles to promote antimicrobial efficiency in food packaging

Technological innovations in packaging are intended to prevent microbiological contaminations for ensuring food safety and preservation. In this context, researchers have investigated the antimicrobial effect of low-density polyethylene films incorporated with the following concentrations of silver nanoparticles: 1.50, 3.75, 7.50, 15.00, 30.00, 60.00, and 75.00 µg/ml. The films were characterized using field emission gun scanning electron microscopy, Fourier transform infrared spectroscopy, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. From the results of these techniques, it could be concluded that the silver nanoparticles incorporated in the low-density polyethylene films did not influence their physical, chemical, and thermal properties. The direct contact assays, shake-flask assays, and bacterial images obtained using scanning electron microscopy were used to analyze the antimicrobial activity of the films. In the microbial analyses, it was verified that the nanostructured films exhibited antimicrobial properties against all the microorganisms studied, although more notably for fungi and Gram-negative bacteria than the Gram-positive bacteria. Moreover, it was discovered that the packages, in which silver nanoparticles were incorporated, inhibited the growth and reproduction of bacterial cells during the early stages. These results suggest that the extruded low-density polyethylene films incorporated with silver nanoparticles may be an essential tool for improving food quality and safety.
Antibacterial and Anticancer Activities of Fenugreek Seed Extract

This work is about the utilization of fenugreek seed as an antibacterial and anticancer agents. The antibacterial activity of fenugreek seed extract on six pathological bacteria strains were specified through conventional biochemical tests using the Vitek2 automated system and diffusion agar method. The anticancer activities of fenugreek seed extract, on MCF-7 breast cancer cells, liver cancer HCAM cells and the non-cancerous Vero cell lines, were investigated using colorimetric MTT assay. Results showed that the highest activity of the extract of the seed was found on Staphylococcus aureus and Pseudomonas aeruginosa (22 mm and 17 mm diameter of inhibition zones respectively). The seed extract showed proliferative inhibition on MCF-7 cell line at a concentration of 400 µg/ml and 72 h of the incubation period. This was accompanied by insignificant apoptosis or necrosis. The seed extract showed no anticancer effect on liver and Vero cell lines. This work emphasizes that fenugreek seed extract is a potential source of antibacterial and anticancer agents.
A brief primer on big data for surgeons

With the advent of the age of massively‐parallel assays like Next Generation Sequencing (NGS), our capacity to generate large‐scale data has out‐paced clinicians’ ability to interpret these data in a way that is computationally and statistically robust, let alone relevant to patient care. The addition of high‐dimensional assays to more traditional methodologies carries the promise of a depth of biologic insight that was previously unattainable, but it is important to recognize the divide between the way big data scientists think and the way we think as clinicians. Increasing the dimensionality of the dataspace we are querying requires an adjustment in how we interpret data. Failure to account for the peculiarities of large‐scale data, or innocent application of scientific methodologies not intended for this dataspace will, at best, lead to the great expenditure of effort and resources in chasing false leads and, at worst, could result in misguided patient management. For those of us who spend the lion’s share of our energy in the clinical realm, acquiring the skill set required to responsibly interpret results derived from high‐ dimensional assays may seem daunting. This primer is intended to highlight some key concepts in analyzing big data and provide a framework for the critical assessment of conclusions drawn from the same.
Deriving Electrophysiological Brain Network Connectivity via Tensor Component Analysis During Freely Listening to Music

Recent studies show that the dynamics of electrophysiological functional connectivity is attracting more and more interest since it is considered as a better representation of functional brain networks than static network analysis. It is believed that the dynamic electrophysiological brain networks with specific frequency modes, transiently form and dissolve to support ongoing cognitive function during continuous task performance. Here, we propose a novel method based on tensor component analysis (TCA), to characterize the spatial, temporal, and spectral signatures of dynamic electrophysiological brain networks in electroencephalography (EEG) data recorded during free music-listening. A three-way tensor containing time-frequency phase-coupling between pairs of parcellated brain regions is constructed. Nonnegative CANDECOMP/PARAFAC (CP) decomposition is then applied to extract three interconnected, low-dimensional descriptions of data including temporal, spectral, and spatial connection factors. Musical features are also extracted from stimuli using acoustic feature extraction. Correlation analysis is then conducted between temporal courses of musical features and TCA components to examine the modulation of brain patterns. We derive several brain networks with distinct spectral modes (described by TCA components) significantly modulated by musical features, including higher-order cognitive, sensorimotor, and auditory networks. The results demonstrate that brain networks during music listening in EEG are well characterized by TCA components, with spatial patterns of oscillatory phase-synchronization in specific spectral modes. The proposed method provides evidence for the time-frequency dynamics of brain networks during free music listening through TCA, which allows us to better understand the reorganization of electrophysiological networks.
Exploring the Viability of NARNIA with Cognitive–Communication Difficulties: A Pilot Study

Abstract Everyday discourse is a common context for the difficulties experienced by people with acquired neurogenic communication disorders. While evidence is present for effective manualized interventions that directly improve the discourse skills in aphasia, this remains limited for people with cognitive–communication disorders. This proof of concept study used an in-depth case series approach to trial the NARNIA discourse intervention used successfully in aphasia to explore transferability of the protocol and effectiveness in people with cognitive–communication impairments. Four female participants with mild to moderate cognitive–communication difficulties (mean age: 52.8 years)—two following traumatic brain injury and two following vascular episodes—were recruited. Modifications were made to the protocol to accommodate the participant group. Cognitive-linguistic abilities, self-perceptions of communicative behavior and psychosocial recovery, and repeated discourse measures were assessed pre-, immediately post, and at 4 weeks following intervention, to measure treatment effectiveness. Significant gains were observed in quantity of output, informativeness, and efficiency of information across both everyday and narrative discourse genres for all participants. However, in contrast to previous studies, minimal change was observed in discourse macrostructure elements. Significant improvements were also observed in memory or working memory for two participants. This study provides preliminary evidence for the effectiveness of using an adapted protocol with people with cognitive–communication disorders, highlighting how adaptations may address the cognitive needs of this diverse clinical group.
Systematic review of barriers and facilitators to clinical trial enrollment among adolescents and young adults with cancer: Identifying opportunities for intervention

Adolescents and young adults (AYAs) are underrepresented in cancer clinical trials (CCTs). Limited trial enrollment slows progress in improving survival rates and prevents the collection of valuable biospecimens. A systematic literature review was conducted to assess barriers and facilitators to AYA enrollment in CCTs and to identify opportunities to improve enrollment. The PubMed MEDLINE, Web of Science, Scopus, and PsycINFO databases were searched to identify studies relevant to AYA CCT enrollment. Eligibility criteria included the qualitative and/or quantitative evaluation of barriers and facilitators to AYA enrollment. One hundred fifty‐five unique publications were identified; 13 were included in the final analysis. Barriers to AYA enrollment in CCTs included a lack of existing trials applicable to the patient population, limited access to available CCTs, and a lack of physician awareness of relevant trials. Facilitators of enrollment included optimizing the research infrastructure, improving the awareness of available CCTs among providers, and enhancing communication about CCTs between providers and patients. In conclusion, the limited available research reports institution‐ and patient‐level barriers and facilitators to AYA CCT enrollment. Because of persistent disparities in AYA enrollment, there is an urgent need to further identify the barriers and facilitators to AYA CCT enrollment to determine actionable areas for intervention.
Shared social identification in mass gatherings lowers health risk perceptions via lowered disgust

Previous research concerning mass gathering‐associated health risks has focused on physical factors while largely neglecting the role of psychological factors. The present research examined the effect of experiencing shared social identification on perceptions of susceptibility to health risks in mass gatherings. Participants in Study 1 were asked to either recall a crowd in which they shared a social identity with other crowd members or a crowd in which they did not. Participants subsequently completed measures assessing shared social identity, disgust, and health risk perceptions. Study 2 involved administering the same measures as part of a survey to participants who had recently attended a music festival. The results from both studies indicated that sharing a social identity lowered health risk perceptions; this effect was indirect and mediated via disgust. This highlights the importance of considering social identity processes in the design of health communication aimed at reducing mass gathering‐associated health risks.
Bacteriophage Therapeutics: A Primer for Clinicians on Phage‐Antibiotic Combinations

Multidrug‐resistant organisms have caused a marked depletion of effective antimicrobials, and the narrow pipeline of antibiotics has demanded the need to find novel therapeutic alternatives including nonantibiotic agents. Bacteriophages (phages) are viruses that use the bacterial machinery to infect, replicate, and kill bacterial cells. Although a marked decline in their use was driven by the discovery of antibiotics, the era of antibiotic resistance has led to a resurgence of phage therapy into clinical practice. The term phage‐antibiotic synergy (PAS) was coined just over a decade ago and described that sublethal concentrations of antibiotics could stimulate phage production by bacterial cells. Recent literature has described PAS and other encouraging interactions with various phage and antibiotic combinations against a variety of bacterial strains. The primary objective of this review is to discuss the positive interactions between phage and antibiotic combinations, with an emphasis on PAS, reductions in bacterial growth or minimum inhibitory concentrations, enhanced biofilm eradication, and alterations in the emergence of bacterial resistance. A peer‐reviewed literature search was conducted (1890–2019) using the PubMed, Medline, and Google Scholar databases. Although more investigation is certainly needed, the combination of bacteriophages with antibiotics is a promising strategy to target organisms with limited or no therapeutic options. This approach may also foster the ability to lower the antibiotic dose and may reduce the potential for antibiotic resistance emergence during therapy.
The Impact of Stroma Admixture on Molecular Subtypes and Prognostic Gene Signatures in Serous Ovarian Cancer

Background: Recent efforts to improve outcomes for high-grade serous ovarian cancer, a leading cause of cancer death in women, have focused on identifying molecular subtypes and prognostic gene signatures, but existing subtypes have poor cross-study robustness. We tested the contribution of cell admixture in published ovarian cancer molecular subtypes and prognostic gene signatures. Methods: Gene signatures of tumor and stroma were developed using paired microdissected tissue from two independent studies. Stromal genes were investigated in two molecular subtype classifications and 61 published gene signatures. Prognostic performance of gene signatures of stromal admixture was evaluated in 2,527 ovarian tumors (16 studies). Computational simulations of increasing stromal cell proportion were performed by mixing gene-expression profiles of paired microdissected ovarian tumor and stroma. Results: Recently described ovarian cancer molecular subtypes are strongly associated with the cell admixture. Tumors were classified as different molecular subtypes in simulations where the percentage of stromal cells increased. Stromal gene expression in bulk tumors was associated with overall survival (hazard ratio, 1.17; 95% confidence interval, 1.11–1.23), and in one data set, increased stroma was associated with anatomic sampling location. Five published prognostic gene signatures were no longer prognostic in a multivariate model that adjusted for stromal content. Conclusions: Cell admixture affects the interpretation and reproduction of ovarian cancer molecular subtypes and gene signatures derived from bulk tissue. Elucidating the role of stroma in the tumor microenvironment and in prognosis is important. Impact: Single-cell analyses may be required to refine the molecular subtypes of high-grade serous ovarian cancer.