Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessment of Maturational Changes in White Matter Anisotropy and Volume in Children: A DTI Study

BACKGROUND AND PURPOSE: Anisotropy is a good indicator of white matter fascicle macrostructure and organization but the interpretation of its changes with age remains difficult. The increase of WM fascicle fractional anisotropy with time and its relationship with WM fascicle volume have never been examined during childhood. We studied the maturation of associative WM fascicles during childhood using MR imaging–based DTI. We explored whether the fractional anisotropy increase of the main WM fascicles persists beyond the period of brain growth and is related to WM fascicle volume increase. MATERIALS AND METHODS: In a series of 25 healthy children, the fractional anisotropy and volume of 15 associative WM fascicles were calculated. Several regression linear mixed models were used to study maturation parameters (fractional anisotropy, volume, and total telencephalon volume) considered as dependent variables, while age and sex were independent variables (the variable identifying the different WM fascicles was considered as a repeated measure). RESULTS: In children older than 8 years of age, WM fascicle fractional anisotropy increased with age (P value = .045) but not its volume (P value = .7) or the telencephalon volume (P value = .16). The time course of WM fascicle fractional anisotropy and volume suggested that each WM fascicle might follow a specific pattern of maturation. CONCLUSIONS: The fractional anisotropy increase of several WM fascicles after 8 years of age may not result from an increase in WM fascicle volume. It might be the consequence of other developmental processes such as myelination.
Calcium flares and compartmentalization in rod photoreceptors

Significance Rod photoreceptor outer segments (OSs) are specialized ciliary architectures. Our imaging experiments reveal three properties of rods. First, intracellular calcium and key proteins have a concentration varying from the OS base to the tip. At the OS base, [Ca2+]i is approximately 80 nM and increases up to ∼200 nM at the OS tip; second, there are spontaneous calcium flares in functional OSs, and these flares are highly localized and are more pronounced at the OS tip; third, a bright flash of light at 488 nm induces a drop in [Ca2+]i at the OS base but often a flare at the OS tip. This structural and functional gradient of the phototransduction machinery is a fundamental aspect of transduction in vertebrate photoreceptors. Rod photoreceptors are composed of a soma and an inner segment (IS) connected to an outer segment (OS) by a thin cilium. OSs are composed of a stack of ∼800 lipid discs surrounded by the plasma membrane where phototransduction takes place. Intracellular calcium plays a major role in phototransduction and is more concentrated in the discs, where it can be incorporated and released. To study calcium dynamics in rods, we used the fluorescent calcium dye CaSiR-1 AM working in the near-infrared (NIR) (excitation at 650 and emission at 664 nm), an advantage over previously used dyes. In this way, we investigated calcium dynamics with an unprecedented accuracy and most importantly in semidark-adapted conditions. We observed light-induced drops in [Ca2+]i with kinetics similar to that of photoresponses recorded electrophysiologically. We show three properties of the rods. First, intracellular calcium and key proteins have concentrations that vary from the OS base to tip. At the OS base, [Ca2+]i is ∼80 nM and increases up to ∼200 nM at the OS tip. Second, there are spontaneous calcium flares in healthy and functional rod OSs; these flares are highly localized and are more pronounced at the OS tip. Third, a bright flash of light at 488 nm induces a drop in [Ca2+]i at the OS base but often a flare at the OS tip. Therefore, rod OSs are not homogenous structures but have a structural and functional gradient, which is a fundamental aspect of transduction in vertebrate photoreceptors.
Self-assembled non-covalent protein-drug nanoparticles: an emerging delivery platform for anti-cancer drugs

ABSTRACT Introduction Protein nanocarriers offer advantageous delivery platforms for anti-cancer drugs, provided by their biocompatibility, high drug loading capacity, and their ability to encapsulate hydrophobic active therapeutics. However, the conventional fabrication techniques of protein nanoparticles (NPs) often suffer from incorporation of considerable amounts of toxic solvents and crosslinking agents which may result in significant toxicity or compromise the drug stability. Therefore, novel strategies were proposed to induce non-covalent self-assembly of proteins by exploiting hydrophobic interactions or manipulation of disulfide bonds to produce nontoxic crosslinker-free drug-loaded protein NPs. Thermal mediated unfolding, the use of reducing agents, modulation of pH and ionic strength, chemical-induced denaturation as well as photochemical methods can be efficiently utilized to induce the protein self-assembly process. Areas covered In this review, we highlight the novel approaches used in the development of non-covalent protein-drug nano-assemblies, formulation factors, their implications, limitations, and treatment outcomes as well as future challenges. Expert opinion Formulation of protein-drug nanocarriers via non-covalent self-assembly can be advantageous as a promising strategy for efficient and safe tumor-targeted delivery of anti-cancer drugs compared to the conventional nano-fabrication technologies.
A Division of Labor between YAP and TAZ in Non–Small Cell Lung Cancer

These findings show that oncogenic paralogs YAP and TAZ have distinct roles in NSCLC and are associated with differential response to anticancer drugs, knowledge that may assist lung cancer therapy decisions. Lung cancer is the leading cause of cancer-related deaths worldwide. The paralogous transcriptional cofactors Yes-associated protein (YAP) and transcriptional coactivator with PDZ-binding motif (TAZ, also called WWTR1), the main downstream effectors of the Hippo signal transduction pathway, are emerging as pivotal determinants of malignancy in lung cancer. Traditionally, studies have tended to consider YAP and TAZ as functionally redundant transcriptional cofactors with similar biological impact. However, there is growing evidence that each of them also possesses distinct attributes. Here we sought to systematically characterize the division of labor between YAP and TAZ in non–small cell lung cancer (NSCLC), the most common histological subtype of lung cancer. Representative NSCLC cell lines as well as patient-derived data showed that the two paralogs orchestrated nonoverlapping transcriptional programs in this cancer type. YAP preferentially regulated gene sets associated with cell division and cell-cycle progression, whereas TAZ preferentially regulated genes associated with extracellular matrix organization. Depletion of YAP resulted in growth arrest, whereas its overexpression promoted cell proliferation. Likewise, depletion of TAZ compromised cell migration, whereas its overexpression enhanced migration. The differential effects of YAP and TAZ on key cellular processes were also associated with differential response to anticancer therapies. Uncovering the different activities and downstream effects of YAP and TAZ may thus facilitate better stratification of patients with lung cancer for anticancer therapies. Significance: Thease findings show that oncogenic paralogs YAP and TAZ have distinct roles in NSCLC and are associated with differential response to anticancer drugs, knowledge that may assist lung cancer therapy decisions.
Massively parallel classical logic via coherent dynamics of an ensemble of quantum systems with dispersion in size

Significance There is a worldwide effort toward quantum technology. Information processing, sensing, communication, and related areas are getting much of the attention. The advantages offered by the quantum domain are well recognized and acclaimed. Proposed implementations rely on systems operating at rather low temperatures and on the need to isolate the system from outside sources of noise. We discuss a theoretical scheme that suggests operating with a classical collection of quantum systems. An experimental demonstration of the principle is available. The ensemble is an array of size-disordered quantum dots addressed and probed by laser pulses. The algebraic approach encodes information in the coherences between quantum levels of the dots and demonstrates resilience to size disorder. Quantum parallelism can be implemented on a classical ensemble of discrete level quantum systems. The nanosystems are not quite identical, and the ensemble represents their individual variability. An underlying Lie algebraic theory is developed using the closure of the algebra to demonstrate the parallel information processing at the level of the ensemble. The ensemble is addressed by a sequence of laser pulses. In the Heisenberg picture of quantum dynamics the coherence between the N levels of a given quantum system can be handled as an observable. Thereby there are N2 logic variables per N level system. This is how massive parallelism is achieved in that there are N2 potential outputs for a quantum system of N levels. The use of an ensemble allows simultaneous reading of such outputs. Due to size dispersion the expectation values of the observables can differ somewhat from system to system. We show that for a moderate variability of the systems one can average the N2 expectation values over the ensemble while retaining closure and parallelism. This allows directly propagating in time the ensemble averaged values of the observables. Results of simulations of electronic excitonic dynamics in an ensemble of quantum dot (QD) dimers are presented. The QD size and interdot distance in the dimer are used to parametrize the Hamiltonian. The dimer N levels include local and charge transfer excitons within each dimer. The well-studied physics of semiconducting QDs suggests that the dimer coherences can be probed at room temperature.
Training Load, Injury Burden, and Team Success in Professional Rugby Union: Risk Versus Reward.

CONTEXT Individual and team injury burden and performance are 2 key considerations facing practitioners in the daily prescription of an athlete's training load. Whereas a considerable number of researchers have examined univariate relationships between training load and performance, training load and injury, or injury and performance, few investigators have examined all 3 concurrently. OBJECTIVE To assess the association among training load, injury burden, and performance in professional rugby union. DESIGN Descriptive epidemiology study. SETTING The English Premiership competition. PATIENTS OR OTHER PARTICIPANTS Individual injury and training load data, as well as team performance data, were captured during the 2015-2016 (n = 433 players) and 2016-2017 (n = 569 players) seasons. MAIN OUTCOME MEASURE(S) Data were aggregated into team average scores for each week, including weekly (acute) load, smoothed chronic load, changes in load, injury burden, and weekly performance. Linear mixed modelling techniques were used to assess the association among measures. RESULTS Injury burden was negatively associated with performance, with a high weekly burden associated with a likely harmful (P = .01) decrease in performance. Training load measures displayed only trivial associations with performance. Only the acute:chronic workload ratio measure was clearly associated with injury burden, with a possibly harmful effect (P = .02). Both squad size and player availability were associated with only trivial changes in performance. CONCLUSIONS Whereas no association between average training load and performance existed, associations between training load and injury burden and between injury burden and performance were clear. Further investigation using more sensitive and individualized measures of load, performance, and injury may elicit a clearer relationship and should be considered for future work.
Population Pharmacokinetics of Caspofungin among Extracorporeal Membrane Oxygenation Patients during the Postoperative Period of Lung Transplantation

Little is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and to investigate covariates influencing caspofungin PK. We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning as self-controls, to analyzed changes in caspofungin PK. Eight serial blood samples were collected from each patient for PK analysis. ABSTRACT Little is known about the influence of extracorporeal membrane oxygenation (ECMO) on the pharmacokinetics (PK) of caspofungin. The aim of this study was to describe population PK of caspofungin in patients with and without ECMO during the postoperative period of lung transplantation (LTx) and to investigate covariates influencing caspofungin PK. We compared ECMO patients with non-ECMO patients, and patients before and after ECMO weaning as self-controls, to analyzed changes in caspofungin PK. Eight serial blood samples were collected from each patient for PK analysis. The population PK of caspofungin was described using nonlinear mixed-effects modeling. Twelve ECMO and 7 non-ECMO lung transplant recipients were enrolled in this study. None of the patients received renal replacement therapy during any part of the study period. The PK of caspofungin was best described by a two-compartment model. There were no significant differences in the PK parameters and concentrations of caspofungin among the ECMO, non-ECMO, and self-control group. In the final covariate model, we found that there was a significant association between the male gender and increased distribution volume, that a higher sequential organ failure assessment score was related to an increase in intercompartmental clearance, and that a longer operative time was related to an increase in clearance and the volume of distribution. ECMO did not have a significant impact on the PK of caspofungin in patients after LTx. Some factors were identified as statistically significant covariates related to the PK of caspofungin; however, their impact on clinical practice of caspofungin needs to be investigated further in more studies. (This study has been registered at ClinicalTrials.gov under identifier NCT03766282.)
Status of meat alternatives and their potential role in the future meat market — A review

Plant-based meat analogues, edible insects, and cultured meat are promising major meat alternatives that can be used as protein sources in the future. It is also believed that the importance of meat alternatives will continue to increase because of concerns on limited sustainability of the traditional meat production system. The meat alternatives are expected to have different roles based on their different benefits and limitations. Plant-based meat analogues and edible insects can replace traditional meat as a good protein source from the perspective of nutritional value. Furthermore, plant-based meat can be made available to a wide range of consumers (e.g., as vegetarian or halal food products). However, despite ongoing technical developments, their palatability, including appearance, flavor, and texture, is still different from the consumers’ standard established from livestock-based traditional meat. Meanwhile, cultured meat is the only method to produce actual animal muscle-based meat; therefore, the final product is more meat-like compared to other meat analogues. However, technical difficulties, especially in mass production and cost, remain before it can be commercialized. Nevertheless, these meat alternatives can be a part of our future protein sources while maintaining a complementary relationship with traditional meat.
Angiogenic and Immune-Related Biomarkers and Outcomes Following Axitinib/Pembrolizumab Treatment in Patients with Advanced Renal Cell Carcinoma

Purpose: Combined axitinib/pembrolizumab is approved for advanced renal cell carcinoma (aRCC). This exploratory analysis examined associations between angiogenic and immune-related biomarkers and outcomes following axitinib/pembrolizumab treatment. Patients and Methods: Prospectively defined retrospective correlative exploratory analyses tested biospecimens from 52 treatment-naïve patients receiving axitinib and pembrolizumab (starting doses 5 mg twice daily and 2 mg/kg respectively, every 3 weeks). Tumor tissue, serum, and whole blood samples were collected at baseline, at cycle 2 day 1 (C2D1), and end of treatment (EOT) for blood-based samples. Clinical outcomes were objective response rate (ORR) and progression-free survival (PFS). Results: Higher baseline tumor levels of CD8 showed a trend toward longer PFS (HR 0.4; P = 0.091). Higher baseline serum levels of CXCL10 (P = 0.0197) and CEACAM1 (P = 0.085) showed a trend toward better ORR and longer PFS, respectively. Patients for whom IL6 was not detected at baseline had longer PFS versus patients for whom it was detected (HR 0.4; P = 0.028). At C2D1 and/or EOT, mainly immune-related biomarkers showed any association with better outcomes. The genes CA9 (P = 0.084), HIF1A (P = 0.064), and IFNG (P = 0.073) showed trending associations with ORR, and AKT3 (P = 0.0145), DDX58 (P = 0.0726), GZMA (P = 0.0666), LCN2 (NGAL; P = 0.0267), and PTPN11 (P = 0.0287) with PFS. Conclusions: With combined axitinib/pembrolizumab treatment in patients with aRCC, mostly immune-related biomarkers are associated with better treatment outcomes. This exploratory analysis has identified some candidate biomarkers to consider in future prospective testing.
Virtual geriatric clinics and the COVID-19 catalyst: a rapid review

Abstract Background During the current COVID-19 health crisis virtual geriatric clinics have become increasingly utilised to complete outpatient consultations, although concerns exist about feasibility of such virtual consultations for older people. The aim of this rapid review is to describe the satisfaction, clinic productivity, clinical benefit, and costs associated with the virtual geriatric clinic model of care. Methods A rapid review of PubMed, MEDLINE and CINAHL databases was conducted up to April 2020. Two independent reviewers extracted the information. Four subdomains were focused on: satisfaction with the virtual geriatric clinic, clinic productivity, clinical benefit to patients, costs and any challenges associated with the virtual clinic process. Results Nine studies with 975 patients met our inclusion criteria. All were observational studies. Seven studies reported patients were satisfied with the virtual geriatric clinic model of care. Productivity outcomes included reports of cost-effectiveness, savings on transport, and improved waiting list metrics. Clinical benefits included successful polypharmacy reviews, and reductions in acute hospitalisation rates. Varying challenges were reported for both clinicians and patients in eight of the nine studies. Hearing impairments and difficulty with technology added to anxieties experienced by patients. Physicians missed the added value of a thorough physical examination and had concerns about confidentiality. Conclusion Virtual geriatric clinics demonstrate evidence of productivity, benefit to patients, cost effectiveness and patient satisfaction with the treatment provided. In the current suboptimal pandemic climate, virtual geriatric clinics may allow Geriatricians to continue to provide an outpatient service, despite the encountered inherent challenges.
Phf21b imprints the spatiotemporal epigenetic switch essential for neural stem cell differentiation

Here, Basu et al. investigated the spatiotemporal regulation of the transition of neural stem and progenitor cells (NSCs) from proliferative to differentiative divisions to generate neurons and the upstream epigenetic triggers during cerebral cortical development in mammals. They report that a cortex-specific PHD finger protein, Phf21b, is induced as NSCs begin to differentiate, and their findings establish how a precisely timed spatiotemporal expression of Phf21b creates an epigenetic program that triggers neural stem cell differentiation during cortical development.
Access to Healthcare in a time of COVID-19: Sex Workers in Crisis in Nairobi, Kenya

ABSTRACT This paper uses empirical data collected from 117 female sex workers living in informal settlements in Nairobi and 15 healthcare providers to highlight specific effects of COVID-19 and related restrictions on healthcare access for the sex workers. We highlight the existing gender and health inequalities that have now been reinforced by the initial outbreak of the COVID-19 pandemic. Specifically, we focus on the most concerning healthcare needs for the sex workers including HIV prevention, care and treatment and sexual and reproductive healthcare. Our study findings reveal that the various restrictions imposed by the government to help curb the spread of COVID-19 to a large extent made it difficult for the sex workers to access their healthcare needs. The paper discusses the challenges of healthcare service delivery reflecting on some innovative and pioneering responses from health care providers to address the emergency situation.
Modifying macronutrients is superior to microbiome transplantation in treating nonalcoholic fatty liver disease

ABSTRACT Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver injury and liver transplantation in Western countries. The pathogenesis of NAFLD includes overnutrition-associated metabolic syndrome or the improper consumption of dietary macro- and micro-nutrients that either support or prevent disease development. This altered nutrient landscape has been linked to shifts within the gut microbiota which can exacerbate liver pathology and the progression of NAFLD. Treatment goals for NAFLD target lifestyle and dietary modifications that restrict calories and adjust macronutrient content. It is not well understood how different macronutrients alter the microbiota and whether the diet-educated microbiota contribute to the resolution of disease. We fed mice a diet high in fat, cholesterol and fructose for 6 weeks and then in two different arms of the study, intervened with either a diet high in saturated and polyunsaturated fats and fiber or low in fats and fiber. In a second set of experiments, we performed microbiota transplants using cecal contents from mice fed one of the intervention diets to assess whether the diet-educated microbiota could impact clinical outcomes in mice fed a NAFLD-inducing diet. Pathology, steatosis, ALT/AST levels, and liver cytokine levels were measured as primary outcomes. We found that despite different microbiota compositions, both of the intervention diets reversed the progression of NAFLD and dampened inflammation. In contrast, transplantation of cecal contents from the intervention diet-fed mice to mice receiving a NAFLD-inducing diet was unable to prevent disease progression, and, in some cases, worsened disease. These data underscore the importance of dietary modifications to treat NAFLD and caution against the use of microbiota transplantation in the absence of dietary and lifestyle modifications.