Miracle-dz/UniFAR-FTUs huggingface dataset:
Validation of self-administered nasal swabs and postage for the isolation of Staphylococcus aureus

Staphylococcus aureus carriers are at higher risk of S. aureus infection and are a reservoir for transmission to others. Detection of nasal S. aureus carriage is important for both targeted decolonization and epidemiological studies. Self-administered nasal swabbing has been reported previously, but the effects of posting swabs prior to culture on S. aureus yield have not been investigated. A longitudinal cohort study was performed in which healthy volunteers were recruited, trained in the swabbing procedure and asked to take weekly nasal swabs for 6 weeks (median: 3 weeks, range 1–6 weeks). Two swabs were taken at each sampling episode and randomly assigned for immediate processing on arrival to the laboratory (Swab A) or second class postage prior to processing (Swab B). S. aureus was isolated using standard methods. A total of 95 participants were recruited, who took 944 swabs (472 pairs) over a median of 5 weeks. Of these, 459 swabs were positive for S. aureus. We found no significant difference (P=0.25) between 472 pairs of nasal self-swabs processed immediately or following standard postage from 95 study participants (51.4 % vs. 48.6 %, respectively). We also provide further evidence that persistent carriers can be detected by two weekly swabs with high degrees of sensitivity [92.3 % (95 % CI 74.8–98.8 %)] and specificity [95.6 % (95 % CI 84.8–99.3 %)] compared with a gold standard of five weekly swabs. Self-swabbing and postage of nasal swabs prior to processing has no effect on yield of S. aureus, and could facilitate large community-based carriage studies.
Hypomorphic conditional deletion of E11/Podoplanin reveals a role in osteocyte dendrite elongation

The transmembrane glycoprotein E11/Podoplanin (Pdpn) has been implicated in the initial stages of osteocyte differentiation. However, its precise function and regulatory mechanisms are still unknown. Due to the known embryonic lethality induced by global Pdpn deletion, we have herein explored the effect of bone‐specific Pdpn knockdown on osteocyte form and function in the post‐natal mouse. Extensive skeletal phenotyping of male and female 6‐week‐old Oc‐cre;Pdpnflox/flox (cKO) mice and their Pdpnflox/flox controls (fl/fl) has revealed that Pdpn deletion significantly compromises tibial cortical bone microarchitecture in both sexes, albeit to different extents (p < 0.05). Consistent with this, we observed an increase in stiffness in female cKO mice in comparison to fl/fl mice (p < 0.01). Moreover, analysis of the osteocyte phenotype by phalloidin staining revealed a significant decrease in the dendrite volume (p < 0.001) and length (p < 0.001) in cKO mice in which deletion of Pdpn also modifies the bone anabolic loading response (p < 0.05) in comparison to age‐matched fl/fl mice. Together, these data confirm a regulatory role for Pdpn in osteocyte dendrite formation and as such, in the control of osteocyte function. As the osteocyte dendritic network is known to play vital roles in regulating bone modeling/remodeling, this highlights an essential role for Pdpn in bone homeostasis.
Raising Standards for the Evaluation of Future Psoriasis Therapeutics: A Critical Checklist

The quality of life for a patient has been transformed in the last 15 years due to innovations that have resulted in better treatments for severe psoriasis, a chronic inflammatory cutaneous disease. Now, novel therapies for psoriasis need to reach a high standard in order to offer patients with psoriasis a genuine alternative. Here we outline a suggested critical checklist that will help industry sponsors, researchers, and clinicians evaluate novel therapeutics for psoriasis.
Use of 2-Octyl Cyanoacrylate Adhesive and Polyester Mesh for Wound Closure in Primary Knee Arthroplasty.

Wound closure in primary knee arthroplasty is important both for surgical success, by minimizing the risk of wound complications and infection, and for patient satisfaction with wound care and cosmesis. This article reports the use of a topical self-adhering, pressure-sensitive polyester mesh combined with 2-octyl cyanoacrylate adhesive for final skin closure of primary knee arthroplasty without external staples or sutures. During a 2.5-year period, 360 consecutive primary knee arthroplasty procedures (321 total knee arthroplasty procedures and 39 partial knee arthroplasty procedures) performed by 1 surgeon at 1 institution were reviewed. For all primary arthroplasty procedures, closure was performed with a standardized method. Final skin closure was performed with 2-octyl cyanoacrylate adhesive and polyester mesh. Patients returned at 6 weeks and 1 year postoperatively. The study found a 0.8% rate of superficial wound complications, no cases of dehiscence, no wound complications requiring operative irrigation and debridement, and no prosthetic joint infections. One patient had a reaction consistent with previously reported localized contact dermatitis that was believed to be related to the 2-octyl cyanoacrylate adhesive. In 2 cases, treatment with cephalexin was required, in 1 case for 2 small suture abscesses and in the other case for periincisional cellulitis. All wound complications resolved by 6 weeks. The results showed that 2-octyl cyanoacrylate adhesive and polyester mesh can be used successfully in the setting of primary knee arthroplasty for closure of high-tension knee arthroplasty wounds. This series found a 0.8% rate of superficial wound complications, no cases of dehiscence, and no infections. [Orthopedics. 2017; 40(5):e784-e787. ].
The Scottish school leavers cohort: linkage of education data to routinely collected records for mortality, hospital discharge and offspring birth characteristics

Purpose The Scottish school leavers cohort provides population-wide prospective follow-up of local authority secondary school leavers in Scotland through linkage of comprehensive education data with hospital and mortality records. It considers educational attainment as a proxy for socioeconomic position in young adulthood and enables the study of associations and causal relationships between educational attainment and health outcomes in young adulthood. Participants Education data for 284 621 individuals who left a local authority secondary school during 2006/2007–2010/2011 were linked with birth, death and hospital records, including general/acute and mental health inpatient and day case records. Individuals were followed up from date of school leaving until September 2012. Age range during follow-up was 15 years to 24 years. Findings to date Education data included all formal school qualifications attained by date of school leaving; sociodemographic information; indicators of student needs, educational or non-educational support received and special school unit attendance; attendance, absence and exclusions over time and school leaver destination. Area-based measures of school and home deprivation were provided. Health data included dates of admission/discharge from hospital; principal/secondary diagnoses; maternal-related, birth-related and baby-related variables and, where relevant, date and cause of death. This paper presents crude rates for all-cause and cause-specific deaths and general/acute and psychiatric hospital admissions as well as birth outcomes for children of female cohort members. Future plans This study is the first in Scotland to link education and health data for the population of local authority secondary school leavers and provides access to a large, representative cohort with the ability to study rare health outcomes. There is the potential to study health outcomes over the life course through linkage with future hospital and death records for cohort members. The cohort may also be expanded by adding data from future school leavers. There is scope for linkage to the Prescribing Information System and the Scottish Primary Care Information Resource.
Electron-shuttling antibiotics structure bacterial communities by modulating cellular levels of c-di-GMP

Significance In cells residing within communities, limitation for electron acceptors (e.g., oxygen) leads to redox imbalance and hampers metabolism. Pseudomonas aeruginosa bacteria in biofilms produce antibiotics called phenazines that facilitate redox balancing. When phenazines and oxygen are not sufficiently available, P. aeruginosa biofilms increase production of ECM, which increases surface area-to-volume ratio and access to oxygen. Here, we describe RmcA, a protein that regulates matrix production in response to phenazine exposure. RmcA contains four sensing domains and two domains that modulate levels of a small-molecule inducer of matrix secretion. These results provide molecular insight into mechanisms underpinning the adaptability of P. aeruginosa biofilms, which likely contributes to their persistence in diverse hosts and clinical settings. Diverse organisms secrete redox-active antibiotics, which can be used as extracellular electron shuttles by resistant microbes. Shuttle-mediated metabolism can support survival when substrates are available not locally but rather at a distance. Such conditions arise in multicellular communities, where the formation of chemical gradients leads to resource limitation for cells at depth. In the pathogenic bacterium Pseudomonas aeruginosa PA14, antibiotics called phenazines act as oxidants to balance the intracellular redox state of cells in anoxic biofilm subzones. PA14 colony biofilms show a profound morphogenic response to phenazines resulting from electron acceptor-dependent inhibition of ECM production. This effect is reminiscent of the developmental responses of some eukaryotic systems to redox control, but for bacterial systems its mechanistic basis has not been well defined. Here, we identify the regulatory protein RmcA and show that it links redox conditions to PA14 colony morphogenesis by modulating levels of bis-(3′,5′)-cyclic-dimeric-guanosine (c-di-GMP), a second messenger that stimulates matrix production, in response to phenazine availability. RmcA contains four Per-Arnt-Sim (PAS) domains and domains with the potential to catalyze the synthesis and degradation of c-di-GMP. Our results suggest that phenazine production modulates RmcA activity such that the protein degrades c-di-GMP and thereby inhibits matrix production during oxidizing conditions. RmcA thus forms a mechanistic link between cellular redox sensing and community morphogenesis analogous to the functions performed by PAS-domain–containing regulatory proteins found in complex eukaryotes.
PTSD and cognitive symptoms relate to inhibition‐related prefrontal activation and functional connectivity

Posttraumatic stress disorder (PTSD) is associated with reduced executive functioning and verbal memory performance, as well as abnormal task‐specific activity in prefrontal cortex (PFC) and anterior cingulate cortices (ACC). The current study examined how PTSD symptoms and neuropsychological performance in combat veterans relates to (1) medial PFC and ACC activity during cognitive inhibition, and (2) task‐independent PFC functional connectivity.
Testing for linkage and Hardy‐Weinberg disequilibrium

This paper concerns several important points when testing for Hardy‐Weinberg equilibrium (HWE) and linkage disequilibrium (LD) in genetics. First, we challenge the necessity of using exclusively two‐sided tests for LD. Next, we show that the exact 2‐sided tests based on the most popular measures of LD are not equivalent, and neither are the standard statistical tests even though the 1‐sided tests are equivalent. We show how this results in different inference about LD for two data sets consisting of small groups of markers. Finally, we advocate the use of the conditional p‐value for both LD and HWE testing. An important advantage of this p‐value is that equivalent 1‐sided tests are transformed into equivalent 2‐sided tests.
An Evaluation of Local Features for Face Detection and Localization

Local features have the ability to overcome the major drawback of traditional, holistic object detection approaches, because they are inherently invariant to geometric deformation and pose; in addition scale and rotation invariance can be easily achieved as well. However, the selection of discriminative feature locations and local descriptions is a complex task that has not been generally solved. In case of face detection, features must possess the discriminative power to differentiate between facial parts and cluttered backgrounds while they have to remain person agnostic. A multitude of suggestions for selecting facial features for tracking or identification / recognition can be found in literature, most of which rely on semi-automatic or manual definition of the feature locations. In contrast, fully automatic feature selection and generic description approaches like SIFT and SURF have been shown to provide excellent performance for rigid as well as non-rigid registration and even for object class recognition. While quantitative evaluations exist that give a hint on the registration performance of the competing designs, these scenarios are not directly transferable to object detection. In this paper we provide qualitative and quantitative analysis of existing interest point detectors as well as local descriptions in the context of face detection and localization.
Cholinergic-Dependent Plateau Potential in Hippocampal CA1 Pyramidal Neurons

Cholinergic stimulation of the hippocampal formation results in excitation and/or seizure. We report here, using whole-cell patch-clamp techniques in the hippocampal slice (34–35°C), a cholinergic-dependent slow afterdepolarization (sADP) and long-lasting plateau potential (PP). In the presence of 20 μm carbachol, action potential firing evoked by weak intracellular current injection elicited an sADP that lasted several seconds. Increased spike firing evoked by stronger depolarizing stimuli resulted in long-duration PPs maintained close to −20 mV. Removal of either Na+ or Ca2+ from the external media, intracellular Ca2+([Ca2+]i) chelation with 10 mmbis(2-aminophenoxy)ethane-N,N,N′,N′-tetra-acetic acid, or the addition of 100 μmCd2+ to the perfusate abolished both the sADP and PP. The sADP was depressed and the PP was abolished by either 10 μm nimodipine or 1 μmω-conotoxin, whereas 1.2 μm tetrodotoxin was ineffective. The involvement of a Na+/Ca2+ exchanger was minimal because both the sADP and PP persisted after equimolar substitution of 50 mm Li+for Na+ in the external media or reduction of the bath temperature to 25°C. Finally, in the absence of carbachol the sADP and PP could not be evoked when K+ channels were suppressed, suggesting that depression of K+conductances alone was not sufficient to unmask the conductance. Based on these data, we propose that a Ca2+-activated nonselective cation conductance was directly enhanced by muscarinic stimulation. The sADP, therefore, represents activation of this conductance by residual [Ca2+]i, whereas the PP represents a novel regenerative event involving the interplay between high-voltage-activated Ca2+ channels and the Ca2+-activated nonselective cation conductance. This latter mechanism may contribute significantly to ictal depolarizations observed during cholinergic-induced seizures.
Inspiratory activation is not required for episodic hypoxia‐induced respiratory long‐term facilitation in postnatal rats

Episodic hypoxia causes repetitive inspiratory activation that induces a form of respiratory plasticity termed long‐term facilitation (LTF). While LTF is a function of the hypoxic exposures and inspiratory activation, their relative importance in evoking LTF is unknown. The aims of this study were to: (1) dissociate the relative roles played by episodic hypoxia and respiratory activation in LTF; and (2) determine whether the magnitude of LTF varies as a function of hypoxic intensity. We did this by examining the effects of episodic hypoxia in postnatal rats (15–25 days old), which unlike adult rats exhibit a prominent hypoxia‐induced respiratory depression. We quantified inspiratory phrenic nerve activity generated by the in situ working‐heart brainstem before, during and for 60 min after episodic hypoxia. We demonstrate that episodic hypoxia evokes LTF despite the fact that it potently suppresses inspiratory activity during individual hypoxic exposures (P < 0.05). Specifically, we show that after episodic hypoxia (three 5 min periods of 10% O2) respiratory frequency increased to 40 ± 3.3% above baseline values over the next 60 min (P < 0.001). Continuous hypoxia (15 min of 10% O2) had no lasting effects on respiratory frequency (P > 0.05). To determine if LTF magnitude was affected by hypoxic intensity, the episodic hypoxia protocol was repeated under three different O2 tensions. We demonstrate that the magnitude and time course of LTF depend on hypoxic severity, with more intense hypoxia inducing a more potent degree of LTF. We conclude that inspiratory activation is not required for LTF induction, and that hypoxia per se is the physiological stimulus for eliciting hypoxia‐induced respiratory LTF.
The impact of focusing a program to prevent heavier drinking on a pre-existing phenotype, the low level of response to alcohol.

BACKGROUND Heavy drinking is common during transitions from high school to college. Optimal programs for diminishing risks for high alcohol consumption often tailor the approach to the specific needs of students. This study describes the results of an Internet-based prevention protocol that tailors the information to the risk associated with a pre-existing phenotype, the Low level of Response (Low LR) to alcohol. METHODS Using stratified random assignment, 454 freshmen with Low and High LR values were assigned to 2 education groups (LR-based where all examples were given the context of the Low LR model of heavy drinking or a State Of The Art (SOTA) Group where the same lessons were taught but without an emphasis on LR) or a no-intervention Control Group. Individuals in the 2 education groups viewed 50-minute online videos once per week for 4 weeks. Changes in drinking patterns were assessed at Baseline, 4 weeks, and 8 weeks using a 2 (LR status) by 3 (education group) by 3 (time points) analysis of variance, with additional tests for ethnicity and sex. RESULTS Low LR participants tended to decrease their usual (p < 0.06) and maximum (p < 0.05) drinks per occasion most prominently when assigned to the LR-based protocol, while those with High LRs improved more in the SOTA Group. The most robust differences were seen when controlling for ethnicity. The effect sizes were small to medium. CONCLUSIONS These results support the advantages of carrying out prevention via the Internet and in tailoring the approach to a pre-existing phenotype.
The influence of income on health: views of an epidemiologist.

Income is related to health in three ways: through the gross national product of countries, the income of individuals, and the income inequalities among rich nations and among geographic areas. A central question is the degree to which these associations reflect a causal association. If so, redistribution of income would improve health. This paper discusses two ways in which income could be causally related to health: through a direct effect on the material conditions necessary for biological survival, and through an effect on social participation and opportunity to control life circumstances. The fewer goods and services are provided publicly by the community, the more important individual income is for health. Under present U.S. circumstances, a policy of counteracting growing income inequalities through the tax and benefit system and of public provision appears justified.
Loss of PFKFB4 induces cell death in mitotically arrested ovarian cancer cells

Taxanes represent some of the most commonly used chemotherapeutic agents for ovarian cancer treatment. However, they are only effective in approximately 40% of patients. Novel therapeutic strategies are required to potentiate their effect and improve patient outcome. A hallmark of many cancers is the constitutive activation of the PI3K/AKT pathway, which drives cell survival and metabolism. We discovered a striking decrease in AKT activity coupled with a significant reduction in glucose 6-phosphate and ATP levels during mitotic arrest in the majority of ovarian cancer cell lines tested, indicating a potential metabolic vulnerability. A high-content siRNA screen to detect novel metabolic targets in mitotically arrested ovarian cancer cells identified the glycolytic enzyme PFKFB4. PFKFB4 depletion increased caspase 3/7 activity, and levels of reactive oxygen species only in mitotically arrested cells, and significantly enhanced mitotic cell death after paclitaxel treatment. Depletion of PFKFB3 demonstrated a similar phenotype. The observation that some ovarian cancer cells lose AKT activity during mitotic arrest and become vulnerable to metabolic targeting is a new concept in cancer therapy. Thus, combining mitotic-targeted therapies with glycolytic inhibitors may act to potentiate the effects of antimitotics in ovarian cancer through mitosis-specific cell death.
The therapeutic effects of BMP-2 and IGF-1 on fracture healing in diabetic rats

Our objective is to explore the effects of BMP-2 and IGF-I in promoting fracture healing in diabetic rats. First 30 rats were made into fracture model with diabetes and randomly divided into 2 experimental groups, the rats in group A´ received insulin growth factor-1 (IGF-1) combined with fibrin glue and the rats in group B´ received bone morphogenetic protein-2 (BMP-2) combined with fibrin glue. The rats without any treatment after model establishment were set as control (group A). At 2, 4 and 6 weeks after the surgery, the X-ray of left lower limb was taken, the bone mineral density (BMD) of local fracture site and callus was detected, the fracture healing was observed, the tissue from the end of fracture was observed by hematoxylin-eosin (HE X-ray results showed that the callus was increased, the BMD values were slightly increased; RT-PCR results showed that the collagen type I in local callus was increased which was most significantly in 2nd week and there was no difference in 6th week. Compared with group B´, the collagen type I in local callus tissue in group A´ was slightly higher which was most significant in 2nd week and there was no difference in 6th week. In conclusion, under the same condition, IGF-I or BMP-2 combined with fibrin glue applying at the end of fracture can significantly improve the fracture healing, and IGF-1 has better effects. Local application of fibrin glue combined with BMP-2 or IGF-I for treating fracture in diabetic rats cannot effectively increase the BMD values in the fracture end and callus.
Hierarchical Linear Modeling of the relationship between Attitudinal and Instructional Variables and Mathematics Achievement

Students’ achievement in mathematics is often considered necessary for the success of the future of a country. Therefore, the training and preparation of students to do well in mathematics has become fundamental goal of education for most countries and more specifically in Ghana. Applying Hierarchical Linear Modeling on the Trends in International Mathematics and Science Study (TIMSS) 2007 data, the relationship between attitudinal and instructional variables and mathematics achievement among Ghana’s grade eight students was examined. Prior to the analyses, exploratory factor analyses were conducted for clusters of similar items to reduce the number of predictor variables. The results indicate that student’s gender, educational aspirations, self-confidence in mathematics, value for mathematics, and frequent use of some instructional variables were significant positive predictors at Level 1. Whiles amount of homework, years of teaching, major area of study were significant positive predictors, teaching license or certificate was a significant negative predictor at Level 2.