Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploiting NK Cell Surveillance Pathways for Cancer Therapy

Natural killer (NK) cells can evoke potent anti-tumour activity. This function is largely mediated through a battery of specialised cell-surface receptors which probe the tissue microenvironment for changes in surface and secretory phenotypes that may alert to the presence of infection or malignancy. These receptors have the potential to arouse the robust cytotoxic and cytokine-secreting functions of NK cells and so must be tightly regulated to prevent autoimmunity. However, such functions also hold great promise for clinical intervention. In this review, we highlight some of the latest breakthroughs in fundamental NK cell receptor biology that have illuminated our understanding of the molecular strategies NK cells employ to perceive malignant cells from normal healthy cells. Moreover, we highlight how these sophisticated tumour recognition strategies are being harnessed for cancer immunotherapies in the clinic.
Metabolic Profiling of Nine Mentha Species and Prediction of Their Antioxidant Properties Using Chemometrics

Mentha species are well recognized for their medicinal and aromatic properties. The comprehensive metabolite profiles of nine Mentha species have been determined. The extracts of these Mentha species were also screened for antioxidant and free radical scavenging activities. Forty-seven hydrophilic and seventeen lipophilic compounds were identified and quantified from the selected Mentha species. Also, eleven phenolic compounds, riboflavin and eight carotenoids were present, and their composition and content varied among the various Mentha species. The different Mentha species exhibited a range of antioxidant potencies. Horse mint especially exhibited the strongest antioxidant capacities (1,1-diphenyl-2-picryl-hydrazyl (DPPH), hydrogen peroxide, and reducing power assay) among the nine Mentha species. A difference between different samples from the same species was not observed by multivariate analysis. A high correlation between metabolites involved in closely linked biosynthetic pathways has been indicated. The projection to latent structure method, using the partial least squares (PLS) method, was applied to predict antioxidant capacities based on the metabolite profiles of Mentha leaves. According to the PLS analysis, several carotenoid contents, such as E-β-carotene, 9Z-β-carotene, 13Z-β-carotene and lutein, as well as phenolic compounds, showed a positive relationship in reducing the power of Mentha extracts. Horse mint is a good candidate because of its high antioxidant efficacy among the nine Mentha species included in the study.
Cryptogenic Organizing Pneumonia Presenting as a Solitary Mass: Clinical, Imaging, and Pathologic Features

Background Cryptogenic organizing pneumonia (COP), with a variety of radiologic findings, is a clinical pathological entity characterized by the presence of granulation tissue composed of fibroblasts/myofibroblasts and loose connective tissue in the alveoli and/or the distal bronchioles. Nevertheless, the presence of a solitary mass in COP is relatively rare. This study investigated the clinical, imaging, and pathologic features of COP with solitary mass form. Material/Methods This retrospective analysis included 12 patients (9 men and 3 women; age range 36–78 years; mean age 60±9 years) with surgery- or biopsy-proven COP with a solitary lung mass, diagnosed between June 2012 and December 2017 at the Department of Radiology in our hospital. Results All patients experienced cough with expectoration and 8 patients had hemoptysis. All lesions were adjacent to the pleura. Mean size of the lesions was 4.2±0.9 cm (range, 3.2–6.1 cm). The upper left lobe was the site of the lesion in 4 patients. Six masses had heterogeneous density; among these, 4 had cavities and distal obstructive inflammation. The mass caused pleural indentation in 4 patients. Lymphadenopathy was seen in 7 patients. All specimens showed buds of granulation tissue within the lumen of the distal pulmonary airspaces, with significant increase in interstitial lymphocytes in 4 specimens. Conclusions Patients with COP with solitary mass form are more susceptible to hemoptysis and the mass is prone to necrosis. Vascular bundles, exudation around the mass, interstitial lymphocyte infiltration, and mediastinal lymph node enlargement are common features.
The Good , the Bad , and the Ugly – role of the pancreas , endothelium , and adipose tissue axis in the management of pancreatic β-cell failure in obesity-related type 2 diabetes

D long-standing obesity and insulin resistance, pancreatic β-cells adapt in order to meet the growing demand of the periphery for insulin. The development of type 2 diabetes requires parallel pathological processes, during which β-cells are continuously exposed to an overabundant supply of specific lipid derivatives. The metabolic events that lead to inevitable β-cell damage are not completely uncovered, and for the time being, our understanding of the dynamic endothelium-adipose tissue-β-cell interactions is limited. Here, we explore various links between continuous obesity, adipose tissue spillover, a dysfunctional endothelium, and defects in islet angioarchitecture to elucidate the crosstalk between signaling systems, cellular mediators, and cell types that contribute to β-cell failure through diverse actions of fatty acids. These molecular and biochemical mechanisms initiate critical rearrangements of the pancreatic vasculature, intraorgan lipid storage capacity, and inflammatory status that subsequently have severe repercussions on β-cell function and promote diabetes.
Familial resemblance in gross motor coordination. The Peruvian Sibling Study on Growth and Health

Abstract Background: The development of gross motor coordination (GMC) is governed by biological and environmental factors whose effect sizes are still unclear. Aim: To investigate sibling resemblance in GMC, as well as biological and environmental correlates of GMC among Peruvian children. Materials and methods: The sample comprised 1256 biological siblings (6–15 years old), from three geographical areas of Peru. GMC was assessed using the Korperkoordinationtest für Kinder (KTK) test battery. Anthropometry, biological maturation and physical fitness (PF) were also measured. Multilevel modelling was performed using Stata 14 software. Results: In general, sister–sister pairs (SS) showed the highest resemblance in GMC (ρ = 0.24) compared to brother–sister (BS) (ρ = 0.10) and brother–brother (BB) pairs (ρ = 0.07). On average, BB pairs had higher GMC than SS pairs and older siblings had higher GMC than younger siblings. Further, those with lower body mass index (BMI) and higher PF had higher GMC. There was also a significant interaction between age and PF with GMC. Siblings from the rainforest region demonstrated higher GMC than those from sea level and high-altitude siblings demonstrated lower GMC than their sea-level peers. Conclusion: These results demonstrate statistically significant sibling resemblance in GMC. Age, BMI, PF and geographical area were significant correlates of GMC.
Identification of regulatory elements from nascent transcription using dREG

Our genomes encode a wealth of transcription initiation regions (TIRs) that can be identified by their distinctive patterns of actively elongating RNA polymerase. We previously introduced dREG to identify TIRs using PRO-seq data. Here we introduce an efficient new implementation of dREG that uses PRO-seq data to identify both uni- and bidirectionally transcribed TIRs with 70% improvements in accuracy, 3-4-fold higher resolution, and >100-fold increases in computational efficiency. Using a novel strategy to identify TIRs based on their statistical confidence reveals extensive overlap with orthogonal assays, yet also reveals thousands of additional weakly-transcribed TIRs that were not identified by H3K27ac ChIP-seq or DNase-I-hypersensitivity. Novel TIRs discovered by dREG were often associated with RNA polymerase III initiation, bound by pioneer transcription factors, or located in broad domains marked by repressive chromatin modifications. We provide a web interface to dREG that can be used by the scientific community (http://dREG.DNASequence.org).
Impact of a stress management program on weight loss, mental health and lifestyle in adults with obesity: a randomized controlled trial.

AIM To evaluate the impact of a stress management program on weight loss, depression, anxiety and stress as well as on the adoption of healthy lifestyle in adults with obesity. METHODS Adults with obesity who sought help for weight loss at a medical obesity clinic were consecutively enrolled in the study and were randomly assigned to the intervention or control group. All participants received standard instructions for a healthy lifestyle. The intervention group attended an 8-week stress management program that comprised diaphragmatic breathing, progressive muscle relaxation, guided visualization and instructions about healthy nutrition/dietary habits. Anthropometric parameters were assessed and several questionnaires were completed by all participants, at the beginning and at the end of the study. RESULTS A total of 45 adults (mean age±SD 45.7±10.55 years) with obesity were enrolled in the study; 22 in the intervention group and 23 in the control group. Participants in the two groups were matched for age and BMI. Participants in the intervention group achieved a significantly larger reduction in BMI compared to the control group (ΔBMI -3.1 vs. -1.74 kg/m2 respectively, P<0.001). In addition, they displayed ameliorated depression and anxiety scores and a reduction in the health locus of control based on chance.
FURIN Inhibition Reduces Vascular Remodeling and Atherosclerotic Lesion Progression in Mice

Objective— Atherosclerotic coronary artery disease is the leading cause of death worldwide, and current treatment options are insufficient. Using systems-level network cluster analyses on a large coronary artery disease case-control cohort, we previously identified PCSK3 (proprotein convertase subtilisin/kexin family member 3; FURIN) as a member of several coronary artery disease–associated pathways. Thus, our objective is to determine the role of FURIN in atherosclerosis. Approach and Results— In vitro, FURIN inhibitor treatment resulted in reduced monocyte migration and reduced macrophage and vascular endothelial cell inflammatory and cytokine gene expression. In vivo, administration of an irreversible inhibitor of FURIN, &agr;-1-PDX (&agr;1-antitrypsin Portland), to hyperlipidemic Ldlr−/− mice resulted in lower atherosclerotic lesion area and a specific reduction in severe lesions. Significantly lower lesional macrophage and collagen area, as well as systemic inflammatory markers, were observed. MMP2 (matrix metallopeptidase 2), an effector of endothelial function and atherosclerotic lesion progression, and a FURIN substrate was significantly reduced in the aorta of inhibitor-treated mice. To determine FURIN’s role in vascular endothelial function, we administered &agr;-1-PDX to Apoe−/− mice harboring a wire injury in the common carotid artery. We observed significantly decreased carotid intimal thickness and lower plaque cellularity, smooth muscle cell, macrophage, and inflammatory marker content, suggesting protection against vascular remodeling. Overexpression of FURIN in this model resulted in a significant 67% increase in intimal plaque thickness, confirming that FURIN levels directly correlate with atherosclerosis. Conclusions— We show that systemic inhibition of FURIN in mice decreases vascular remodeling and atherosclerosis. FURIN-mediated modulation of MMP2 activity may contribute to the atheroprotection observed in these mice.
Improvement in sleep outcomes with a 17β-estradiol–progesterone oral capsule (TX-001HR) for postmenopausal women

Abstract Objective: The aim of the study was to evaluate the effects of TX-001HR, a single-capsule 17β-estradiol–progesterone on sleep parameters in postmenopausal women with vasomotor symptoms (VMS) using the Medical Outcomes Study (MOS)-Sleep scale questionnaire in the REPLENISH trial. Methods: In the REPLENISH trial (NCT01942668), women were randomized to one of four doses of TX-001HR or placebo, and the 12-item MOS-Sleep questionnaire (secondary endpoint) was self-administered at baseline, week 12, and months 6 and 12. Changes from baseline in the MOS-Sleep total score and 7 subscale scores were analyzed for treatment groups versus placebo at all time points. Somnolence was also collected as an adverse event. Results: Women (mean age 55 y) were randomized to TX-001HR (estradiol/ progesterone [E2/P4] [mg/mg]) doses: 1/100 (n = 415), 0.5/100 (n = 424), 0.5/50 (n = 421), 0.25/50 (n = 424), or placebo (n = 151). TX-001HR significantly improved MOS-Sleep total score, Sleep Problems Index II subscale, and sleep disturbance subscale versus placebo at all time points, except with 0.25 mg E2/50 mg P4 at week 12. Differences in LS mean changes between TX-001HR and placebo for MOS-Sleep total scores ranged from −6.5 to −7.6 at 12 months (all; P ≤ 0.001). All doses of TX-001HR significantly improved the Sleep Problems Index I subscale at all time points. The sleep somnolence subscale significantly improved from baseline with 0.5 mg E2/100 mg P4 and 0.5 mg E2/50 mg P4 at month 12. The incidence of somnolence as a treatment-emergent adverse event ranged from 0.2% to 1.2% versus 0% with placebo. Conclusion: TX-001HR significantly improved MOS-Sleep parameters from baseline to week 12, which was sustained for up to 12 months, and was associated with a very low incidence of somnolence.
Ground reaction force metrics are not strongly correlated with tibial bone load when running across speeds and slopes: Implications for science, sport and wearable tech

Introduction Tibial stress fractures are a common overuse injury resulting from the accumulation of bone microdamage due to repeated loading. Researchers and wearable device developers have sought to understand or predict stress fracture risks, and other injury risks, by monitoring the ground reaction force (GRF, the force between the foot and ground), or GRF correlates (e.g., tibial shock) captured via wearable sensors. Increases in GRF metrics are typically assumed to reflect increases in loading on internal biological structures (e.g., bones). The purpose of this study was to evaluate this assumption for running by testing if increases in GRF metrics were strongly correlated with increases in tibial compression force over a range of speeds and slopes. Methods Ten healthy individuals performed running trials while we collected GRFs and kinematics. We assessed if commonly-used vertical GRF metrics (impact peak, loading rate, active peak, impulse) were strongly correlated with tibial load metrics (peak force, impulse). Results On average, increases in GRF metrics were not strongly correlated with increases in tibial load metrics. For instance, correlating GRF impact peak and loading rate with peak tibial load resulted in r = -0.29±0.37 and r = -0.20±0.35 (inter-subject mean and standard deviation), respectively. We observed high inter-subject variability in correlations, though most coefficients were negligible, weak or moderate. Seventy-six of the 80 subject-specific correlation coefficients computed indicated that higher GRF metrics were not strongly correlated with higher tibial forces. Conclusions These results demonstrate that commonly-used GRF metrics can mislead our understanding of loading on internal structures, such as the tibia. Increases in GRF metrics should not be assumed to be an indicator of increases in tibial bone load or overuse injury risk during running. This has important implications for sports, wearable devices, and research on running-related injuries, affecting >50 scientific publications per year from 2015–2017.
KCNQ1 rescues TMC1 plasma membrane expression but not mechanosensitive channel activity

Transmembrane channel‐like protein isoform 1 (TMC1) is essential for the generation of mechano‐electrical transducer currents in hair cells of the inner ear. TMC1 disruption causes hair cell degeneration and deafness in mice and humans. Although thought to be expressed at the cell surface in vivo, TMC1 remains in the endoplasmic reticulum when heterologously expressed in standard cell lines, precluding determination of its roles in mechanosensing and pore formation. Here, we report that the KCNQ1 Kv channel forms complexes with TMC1 and rescues its surface expression when coexpressed in Chinese Hamster Ovary cells. TMC1 rescue is specific for KCNQ1 within the KCNQ family, is prevented by a KCNQ1 trafficking‐deficient mutation, and is influenced by KCNE β subunits and inhibition of KCNQ1 endocytosis. TMC1 lowers KCNQ1 and KCNQ1‐KCNE1 K+ currents, and despite the surface expression, it does not detectably respond to mechanical stimulation or high salt. We conclude that TMC1 is not intrinsically mechano‐ or osmosensitive but has the capacity for cell surface expression, and requires partner protein(s) for surface expression and mechanosensitivity. We suggest that KCNQ1, expression of which is not thought to overlap with TMC1 in hair cells, is a proxy partner bearing structural elements or a sequence motif reminiscent of a true in vivo TMC1 hair cell partner. Discovery of the first reported strategy to rescue TMC1 surface expression should aid future studies of the TMC1 function and native partners.
Particulate Matter and Traffic-Related Exposures in Relation to Breast Cancer Survival

Background: Although particulate matter (PM) has not been consistently associated with breast cancer risk, two studies have reported harmful associations for breast cancer survival. We examined PM exposures and breast cancer survival in two U.S.-based prospective cohort studies. Methods: The Nurses' Health Study (NHS) and NHSII are cohorts with detailed data on medical history, lifestyle factors, and causes of death. Women with Stage I–III breast cancer (n = 8,936) were followed through June 2014. Residential PM was estimated using spatio-temporal models. We performed Cox regression to estimate hazard ratios (HR) of breast cancer–specific mortality and all-cause mortality for 10 μg/m3 increases in post-diagnosis PM. Results: There were 1,211 breast cancer–specific deaths. Overall, PM was not associated with breast cancer–specific mortality [PM2.5: HR, 1.09; 95% confidence interval (CI), 0.87–1.36; PM2.5-10: HR, 1.03; 95% CI, 0.85–1.24; PM10: HR, 1.05; 95% CI, 0.89–1.24], but was associated with modest increases in all-cause mortality (PM2.5: HR, 1.12; 95% CI, 0.96–1.30; PM2.5-10: HR, 1.12; 95% CI, 1.00–1.24; PM10: HR, 1.09; 95% CI, 1.01–1.18). However, among participants with Stage I disease, PM2.5 was associated with higher breast cancer–specific mortality (HR, 1.64; 95% CI, 1.11–2.43). Conclusions: PM was not associated with breast cancer–specific death overall; however, higher PM was associated with all-cause mortality. Higher PM2.5 was associated with higher breast cancer–specific mortality among patients with Stage I breast cancer even after adjustment. Impact: Studies on ambient PM and breast cancer survival demonstrate that PM2.5 may have broader health effects than previously recognized and warrants further research on breast tumor progression.
Following Their Lead? Connecting Mainstream Media Use to Black Women’s Gender Beliefs and Sexual Agency

Although media exposure has emerged as a significant predictor of consumers’ sexual decision making, less is known about the mechanisms involved and about the dynamics of these relations for adults, in general, and for African American adults, in particular. To address these gaps, we used structural equation modeling (SEM) to test whether heterosexual Black women’s endorsement of traditional gender and sexual roles mediates connections between their consumption of four mainstream media (music videos, reality TV programming, movies, and women’s magazines) and three dimensions of their sexual well-being (sexual assertiveness, sexual inhibition, and sexual deception). We surveyed 594 heterosexual Black women aged 17 to 55 who were undergraduate and graduate students at two universities (one historically Black university and one predominantly White institution). Results confirmed expectations, such that greater media consumption was associated with greater support of traditional gender and sexual roles; in turn, endorsing these roles predicted lower levels of sexual assertiveness, greater sexual inhibition, and more frequent use of sexual dishonesty to retain a partner. We discuss implications of these findings for psychology and sexuality research and also for Black women’s sexual relationships.
CMV-Specific Immune Response—New Patients, New Insight: Central Role of Specific IgG during Infancy and Long-Lasting Immune Deficiency after Allogenic Stem Cell Transplantation

Although the existing paradigm states that cytomegalovirus (CMV) reactivation is under the control of the cellular immune response, the role of humoral and innate counterparts are underestimated. The study analyzed the host–virus interaction i.e., CMV-immune response evolution during infection in three different clinical situations: (1) immunodeficient CMV-positive human leukocyte antigen (HLA)-matched bone marrow recipients after immunoablative conditioning as well as immunocompetent, (2) adult, and (3) infant with primary immune response. In the first situation, a fast and significant decrease of specific immunity was observed but reconstitution of marrow-derived B and natural killer (NK) cells was observed prior to thymic origin of T cells. The lowest CMV-IgG (93.2 RU/mL) was found just before CMV viremia. It is noteworthy that the sole and exclusive factor of CMV-specific immune response is a residual recipient antibody class IgG. The CMV-quantiferon increase was detected later, but in the first phase, phytohemagglutinin (PHA)-induced IFN-γ release was significantly lower than that of CMV-induced (“indeterminate” results). It corresponds with the increase of NK cells at the top of lymphocyte reconstitution and undetected CMV-specific CD8 cells using a pentamer technique. In immunocompetent adult (CMV-negative donor), the cellular and humoral immune response increased in a parallel manner, but symptoms of CMV mononucleosis persisted until the increase of specific IgG. During infancy, the decrease of the maternal CMV-IgG level to 89.08 RU/mL followed by clinical sequel, i.e., CMV replication, were described. My observations shed light on a unique host-CMV interaction and CMV-IgG role: they indicate that its significant decrease predicts CMV replication. Before primary cellular immune response development, the high level of residual CMV-IgG (about >100 R/mL) from mother or recipient prevents virus reactivation. The innate immune response and NK-dependent IFN-secretion should be further investigated.
Lag Phase Is a Dynamic, Organized, Adaptive, and Evolvable Period That Prepares Bacteria for Cell Division

Lag is a temporary period of nonreplication seen in bacteria that are introduced to new media. Despite latency being described by Müller in 1895, only recently have we gained insights into the cellular processes characterizing lag phase. ABSTRACT Lag is a temporary period of nonreplication seen in bacteria that are introduced to new media. Despite latency being described by Müller in 1895, only recently have we gained insights into the cellular processes characterizing lag phase. This review covers literature to date on the transcriptomic, proteomic, metabolomic, physiological, biochemical, and evolutionary features of prokaryotic lag. Though lag is commonly described as a preparative phase that allows bacteria to harvest nutrients and adapt to new environments, the implications of recent studies indicate that a refinement of this view is well deserved. As shown, lag is a dynamic, organized, adaptive, and evolvable process that protects bacteria from threats, promotes reproductive fitness, and is broadly relevant to the study of bacterial evolution, host-pathogen interactions, antibiotic tolerance, environmental biology, molecular microbiology, and food safety.