Miracle-dz/UniFAR-FTUs huggingface dataset:
Meningitis vaccines in children: what have we achieved and where next?

PURPOSE OF REVIEW This review highlights the recent impacts of vaccines against the major bacterial causes of meningitis in children, and the challenges for further prevention of bacterial meningitis, with a focus on Streptococcus pneumoniae, Neisseria meningitidis and group B Streptococcus. RECENT FINDINGS Conjugate vaccines against S. pneumoniae and N. meningitidis have resulted in dramatic reductions in bacterial meningitis globally where they have been used. Recent licensure and use of capsular group B meningococcal protein vaccines have further reduced meningococcal meningitis in infants, young children and adolescents for countries with endemic disease and during outbreaks. SUMMARY Existing vaccines to prevent bacterial meningitis in children should be utilized in countries with significant numbers of cases of pneumococcal and/or meningococcal meningitis. Vaccines, which are able to protect against more than 13 serotypes of S. pneumoniae are in clinical trials and should be able to further reduce pneumococcal meningitis cases. Cost effective meningococcal vaccines against non-A capsular groups are needed for low-resource countries. There remains an urgent need for a vaccine against group B Streptococcus, which is a major cause of neonatal meningitis globally and for which no vaccine currently exists.
Human Norovirus Cultivation in Nontransformed Stem Cell-Derived Human Intestinal Enteroid Cultures: Success and Challenges

Noroviruses, in the genus Norovirus, are a significant cause of viral gastroenteritis in humans and animals. For almost 50 years, the lack of a cultivation system for human noroviruses (HuNoVs) was a major barrier to understanding virus biology and the development of effective antiviral strategies. This review presents a historical perspective of the development of a cultivation system for HuNoVs in human intestinal epithelial cell cultures. Successful cultivation was based on the discovery of genetically-encoded host factors required for infection, knowledge of the site of infection in humans, and advances in the cultivation of human intestinal epithelial cells achieved by developmental and stem cell biologists. The human stem cell-derived enteroid cultivation system recapitulates the multicellular, physiologically active human intestinal epithelium, and allows studies of virus-specific replication requirements, evaluation of human host-pathogen interactions, and supports the pre-clinical assessment of methods to prevent and treat HuNoV infections.
Assessing the lymphoid tissue bioavailability of antiretrovirals in human primary lymphoid endothelial cells and in mice.

BACKGROUND The secondary lymphoid tissues (LTs), lymph nodes (LNs) and gut-associated lymphoid tissue (GALT) are considered reservoirs for HIV. Antiretrovirals (ARVs) have lower penetration into LT. In vitro models predictive of ARV LT penetration have not been established. OBJECTIVES To develop an in vitro model of LT bioavailability using human lymphoid endothelial cells (HLECs) and investigate its predictability with in vivo pharmacokinetic (PK) studies in mice. METHODS ARV bioavailability in HLECs was evaluated at the maximum plasma concentration (Cmax) observed in HIV-infected patients. ARVs were: abacavir, atazanavir, darunavir, dolutegravir, efavirenz, elvitegravir, emtricitabine, maraviroc, raltegravir, rilpivirine, ritonavir, tenofovir disoproxil fumarate and the PK booster cobicistat. The LT PK of representative drugs showing high (efavirenz), intermediate (dolutegravir) and low (emtricitabine) HLEC bioavailability was investigated in BALB/c mice given 50/10/30 mg/kg efavirenz/dolutegravir/emtricitabine orally, daily for 3 days. The concordance of in vitro and in vivo ARV bioavailability was examined. RESULTS ARVs showed high (>67th percentile; rilpivirine, efavirenz, elvitegravir and cobicistat), intermediate (67th-33rd percentile; ritonavir, tenofovir disoproxil fumarate, dolutegravir and maraviroc) and low (<33rd percentile; atazanavir, darunavir, raltegravir, emtricitabine and abacavir) HLEC bioavailability. The hierarchy of efavirenz, dolutegravir and emtricitabine bioavailability in LN, gut and brain tissues of mice was: efavirenz>dolutegravir>emtricitabine. CONCLUSIONS ARVs displayed distinct HLEC penetration patterns. PK studies of representative ARVs in LT of mice were concordant with HLEC bioavailability. These findings support further development of this approach and its translational predictability in humans.
Does natural birth have a circadian rhythm?

Abstract The aim of this study was to investigate whether natural birth has a circadian rhythm. The present study was planned as a retrospective descriptive study of the natural births performed in a Maternity and Children’s Diseases Training and Research Hospital in the north of Turkey between January 1 and December 31. The study included 723 (98.9%) cases of natural birth. It was found that the mean age of the women in the study sample was 26.84 ± 5.83 years and the mean gestational age was 38.98 ± 1.95 years. It was determined that the mean labour duration of the women was 12.47 ± 0.78 hours; of all births, 34.6% occurred between 08:00–16:00 hours, 38.2% occurred between 16:01–00:00 hours and 27.2% occurred between 00:01–07:59 hours. Considering the birth time in terms of month, it was observed that the most common birth month was July and the least common birth month was March. In accordance with the study data, it is observed that the labour process occurred at night in the day/night cycle and in the summer months at a higher rate. Impact statement What is already known on this subject? Chronological transitions are of critical importance for pregnancy. There are many mechanisms affecting Labour process. One of the most important mechanisms among these is the release and timing of foetal-maternal hormones. The chronological transitions are critical for a normal pregnancy and any temporary alteration may have detrimental effects for foetal development and/or maternal health What the results of this study add? It is observed that births occur at a higher rate at night hours in the day-night cycle and in summer months, and in terms of day, Wednesday is the most common birth day. Considering these results, although it is thought that the levels of hormones released at night lead the birth to occur mostly at night-time hours and non-fully developed thermoregulatory system and sympathetic nervous systems of foetus and sensitivity to temperature may be effective on the number of births in summer months, it is seen that the data are insufficient to reach this conclusion. What the implications are of these findings for clinical practice and/or further research? It is believed that the foetus has a biological clock. This is parallel to fluctuating levels of various hormones affecting labour and delivery, which may be a positive influence on the labour process itself. It seems that more study results are required in addition to these results.
A review of psychological treatments for vomiting associated with paediatric functional gastrointestinal disorders.

PURPOSE OF REVIEW Vomiting can be a primary symptom or associated with various other functional gastrointestinal disorders (FGIDs). The purpose of this review was to discuss the evidence for psychological treatments for vomiting in pediatric FGID. RECENT FINDINGS Vomiting of functional origin is an increasingly recognized symptom among children and adolescents. It is highly aversive and associated with disability and poor quality of life. Cognitive behavioral therapy, lifestyle modification (especially sleep), diaphragmatic breathing, and hypnosis can be helpful in preventing vomiting episodes and reducing disability. However, no randomized clinical trials have been performed. An evidence base for psychological treatments in children with vomiting of functional origin is highly needed. SUMMARY Increased evidence is demonstrating value and efficacy of incorporating psychogastroenterology practices into ongoing treatment plans for digestive conditions. Current psychological treatments are focused on prevention of vomiting through stress reduction and lifestyle modification, reduction of disability by limiting avoidance behaviours, as well as counteracting biological factors. However, psychological treatments have not been shown to be helpful during an acute vomiting episode. More research is needed to build an evidence base for psychological treatments in vomiting disorders.
Practical Application of Real-World Evidence in Developing Cancer Therapies.

One substantial limitation of randomized clinical trials (RCTs) relates to the stringent eligibility criteria that are typically used. As a result, only a small percentage of patients who face the disease under study are considered for RCT participation. Not surprisingly, this highly selected trial population often does not accurately reflect the patient population requiring treatment. Whereas this selectivity facilitates the interpretation of results by diminishing confounders, such as comorbid medical disease, concomitant medication interactions, and organ dysfunction, it also limits the generalizability of RCT results. Consequently, clinicians commonly treat patients who do not meet the entry criteria for the RCT of the most efficacious therapy. Physicians must therefore interpret and extrapolate existing data and use their discretion and judgment in making treatment decisions for individual patients. Medical training facilitates these analyses and, at the same time, there is tremendous subjectivity and discretion around many of these decision points.
The Effects of Virtual Reality on Motor Functions and Daily Life Activities in Unilateral Spastic Cerebral Palsy: A Single-Blind Randomized Controlled Trial.

Aim: This study was designed to investigate the effects of virtual reality (VR) through Kinect on both gross and fine motor functions and independence in daily living activities in children with unilateral spastic cerebral palsy (USCP). Materials and Methods: This study was designed as a single-blind, randomized, controlled trial. Sixty children with USCP were randomized and split equally between the VR intervention group (10 females and 20 males with a mean age of 10.5 ± 3.62 years) and the traditional occupational therapy (TOT) intervention group (13 females and 17 males with a mean age of 10.06 ± 3.24 years). Both groups were evaluated in terms of motor functioning via the Bruininks-Oseretsky Test of Motor Proficiency-Short Form (BOTMP-SF) and were assessed in accordance with independence in daily activities via the WeeFunctional Independence Measure (WeeFIM). Interventions were conducted for 8 weeks with the main objective of improving motor functions and independence in daily activities. Results: Total motor functions and total independence in daily lives in both groups improved after 8 weeks of intervention. A comparison between groups revealed significantly greater improvements in both gross and fine motor functions and daily activities in the VR group than in the TOT group (P < 0.001). Conclusion: The Kinect-based VR intervention approach is important to improving motor functions and independence in daily activities of children with USCP.
Direct Comparison of the Thickness Of The Parietal Peritoneum Using Peritoneal Biopsy and Ultrasonography of the Abdominal Wall in Patients Treated with Peritoneal Dialysis

Background: Long-term treatment with peritoneal dialysis (PD) results in peritoneal fibrosis. Peritoneal biopsies have been used to determine the severity of fibrosis. Ultrasonography (US) of the abdominal wall has been used to measure peritoneal thickness non-invasively. However, direct comparison of both methods in the same patient has never been done. Furthermore, the validity of US to measure peritoneal thickness has not been investigated. Methods: We performed 3 studies: 1) a human biopsy study to compare US measurement of peritoneal thickness with histological examination; 2) a human cadaver study to investigate the effect of removing the peritoneum on US results; and 3) a phantom study in which we used US to measure the thickness of membrane-like structures with a known thickness to investigate the influence of different US settings. Results: The median thickness in biopsies of the peritoneum was 113 μm (interquartile range [IQR] 72 –129 μm), while this was 370 μm (IQR 324 – 458 μm) when measured by US (p < 0.0001). The mean difference between the 2 measures was -257 μm (limits of agreement -4.6 and -511 μm). In the cadaver study, removal of the peritoneum did not have an effect on the presence or thickness of the hyperechoic line reported to represent the peritoneum. In the phantom study, results were highly dependent on frequency of the transducer, scan depth, and gain settings. Conclusions: Ultrasonography results differ markedly from histological measurement using peritoneal biopsies. However, the hyperechoic line generated by US represents the interface between 2 neighboring tissues and not a separate morphological structure. Moreover, its thickness is greatly influenced by user-defined US settings.
The Association of Provider and Practice Factors with HIV ART Adherence

Objective—While Anti-Retroviral Therapy (ART) is essential to patients with HIV, there is substantial variation in adherence nationally. We assess how provider and practice factors contribute to successful HIV ART adherence. Design—We used Medicaid Analytic Extract claims from 2008–2012. We attributed patients with HIV to the provider that provided the plurality of HIV-related services or primary care in a given year and assigned these providers to a medical practice based on the National Provider Identifier registry file. We fit successive linear hierarchical models with patient, provider, and practice characteristics to partition the variation in adherence driven by each factor. Our unit of analysis was the patient-year. Setting—14 US states with the highest HIV prevalence Participants—111,013 patient-years representing 60,496 Medicaid enrollees living with HIV attributed to 4,930 providers and 1,960 practices Main outcome measure—Percent of year individual patients were adherent to an ART regimen Results—Provider and practice random effects jointly explained 6.8% of variation in adherence with patient differences accounted for 45.2% of the variation. Patients seen by generalists and other specialists had a 1.6 (95%CI: 0.6–2.5) and 5.1 (95%CI: 4.1–6.1) percentage point greater adherence than those seen by infectious disease specialists (p<0.001). Every additional year a patient saw the same provider was associated with a 6% increase in adherence (95%CI:5.7–6.3). Conclusions—There is substantial variation in ART adherence attributable to providers and practices and between provider specialties. To improve ART adherence for patients living with HIV, structural aspects of care should be considered.
Association of School Residential PM2.5 with Childhood High Blood Pressure: Results from an Observational Study in 6 Cities in China

Objective: To investigate the association of long-term PM2.5 exposure with blood pressure (BP) outcomes in children aged 6–18 years, and to examine the population attributable risk (PAR) of PM2.5 exposure. Methods: A total of 53,289 participants aged 6–18 years with full record of age, sex, BP, height, and local PM2.5 exposure from a cross-sectional survey conducted in 6 cities of China in 2013 were involved in the present study. PM2.5 data from 18 January 2013 to 31 December 2013 were obtained from the nearest environmental monitoring station for each selected school. Two-level linear and logistic regression models were used to evaluate the influence of PM2.5 on children’s BP, and PAR was calculated in each sex and age group. Results: Participants had a mean age of 10.8 (standard deviation: 3.4) years at enrollment, 51.7% of them were boys. U-shaped trends along with increased PM2.5 concentration were found for both systolic blood pressure (SBP) and diastolic blood pressure (DBP), with the thresholds of 57.8 and 65.0 μg/m3, respectively. Both increased annual mean of PM2.5 concentration and ratio of polluted days were associated with increased BP levels and high blood pressure (HBP), with effect estimates for BP ranging from 2.80 (95% CI: −0.51, 6.11) mmHg to 5.78 (95% CI: 2.32, 9.25) mmHg for SBP and from 0.77 (95% CI: −1.98, 3.52) mmHg to 2.66 (−0.35, 5.66) mmHg for DBP, and the odds ratios for HBP from 1.21 (0.43, 3.38) to 1.92 (0.65, 5.67) in the highest vs. the lowest quartiles. Overall, 1.16% of HBP in our participants could be attributed to increased annual mean of PM2.5 concentration, while 2.82% could be attributed to increased ratio of polluted days. These proportions increased with age. Conclusions: The association between long-term PM2.5 exposure and BP values appeared to be U-shaped in Chinese children aged 6–18 years, and increased PM2.5 exposure was associated with higher risk of HBP.
Unravelling the Role of Trophoblastic-Derived Extracellular Vesicles in Regulatory T Cell Differentiation

Regulatory T cells (Treg) are mandatory elements in the maintenance of human pregnancy, but their de novo differentiation has not been completely exposed. HSPE1 chaperone expressing trophoblast cells may have a role in it. Trophoblast-derived extracellular vesicles (EVs), either at the feto–maternal interface or in circulation, target CD4+ T cells. We hypothesized that HSPE1-associated trophoblastic cell line (BeWo)-derived EVs are active mediators of Treg cell differentiation. We proved at first that recombinant HSPE1 promote human Treg cell differentiation in vitro. Developing a CRISPR-Cas9 based HSPE1 knockout BeWo cell line we could also demonstrate, that EV-associated HSPE1 induces Treg development. Next-generation sequencing of miRNA cargo of BeWo-EVs characterized the regulatory processes of Treg polarization. By the use of single-cell transcriptomics analysis, seven Treg cell subtypes were distinguished and we demonstrated for the first time that the expression level of HSPE1 was Treg subtype dependent, and CAPG expression is characteristic to memory phenotype of T cells. Our data indicate that HSPE1 and CAPG may be used as markers for identification of Treg subtypes. Our results suggest, that trophoblastic-derived iEVs-associated HSPE1 and miRNA cargo have an important role in Treg cell expansion in vitro and HSPE1 is a useful marker of Treg subtype characterization.
Intramolecular Domain Movements of Free and Bound pMHC and TCR Proteins: A Molecular Dynamics Simulation Study

The interaction of antigenic peptides (p) and major histocompatibility complexes (pMHC) with T-cell receptors (TCR) is one of the most important steps during the immune response. Here we present a molecular dynamics simulation study of bound and unbound TCR and pMHC proteins of the LC13-HLA-B*44:05-pEEYLQAFTY complex to monitor differences in relative orientations and movements of domains between bound and unbound states of TCR-pMHC. We generated local coordinate systems for MHC α1- and MHC α2-helices and the variable T-cell receptor regions TCR Vα and TCR Vβ and monitored changes in the distances and mutual orientations of these domains. In comparison to unbound states, we found decreased inter-domain movements in the simulations of bound states. Moreover, increased conformational flexibility was observed for the MHC α2-helix, the peptide, and for the complementary determining regions of the TCR in TCR-unbound states as compared to TCR-bound states.
Real-time Video Object Segmentation in the Compressed Domain Based on EM Clustering

Moving object segmentation in the compressed domain is fast and efficient compared to former segmentation in pixel domain.Recently some moving object segmentation algorithm in MPEG compressed domain have been reported.However,very few approaches have been proposed in the H.264 compressed domain.In this paper,a real-time video segmentation method in H.264 compressed domain is proposed.Firstly,the current frame is globally compensated in motion after the global motion estimation.Then the 4×4 motion vectors are processed by median filter and classification.Thirdly the non-zero motion vectors are applied by improved EM clustering segmentation algorithm.The performance of the proposed approach is illustrated by simulation carried on several test sequences.Experiment results show that the proposed algorithm can provide satisfactory real-time segmentation results both on static background and moving background video.
Is the Canadian Healthy Eating Index 2007 an Appropriate Diet Indicator of Metabolic Health? Insights from Dietary Pattern Analysis in the PREDISE Study

The objective of this study was to identify key elements from the 2007 Canada’s Food Guide that should be included in a diet quality score aiming to reflect the risk of metabolic syndrome (MetS). Dietary intakes of 998 adults (mean age: 43.2 years, 50% women) were used to obtain the Canadian Healthy Eating Index 2007 (C-HEI 2007) and Alternative Healthy Eating Index 2010 (AHEI) scores, as well as a dietary pattern (DP) generated by the reduced rank regression (RRR) method. Based on these three scores, a modified version of the C-HEI 2007 (Modified C-HEI) was then proposed. The prevalence ratio (PR) of MetS was examined across diet quality scores using multivariate binomial regression analysis. A higher AHEI, Modified C-HEI, and a lower score for DP were all associated with a significantly lower prevalence of MetS (PR = 0.42; 95% confidence interval (CI) 0.28, 0.64; PR = 0.39; 95% CI 0.23, 0.63; and PR = 0.48; 95% CI 0.31, 0.74, respectively), whereas C-HEI 2007 was not (PR = 0.68; 95% CI 0.47, 1.00). Results suggest that a Modified C-HEI that considers key elements from the C-HEI 2007 and the AHEI, as well the DP, shows that participants with a higher score are less likely to have MetS.
Effects of Exergames on Brain Dynamics in Women with Fibromyalgia: A Randomized Controlled Trial

Background: Exergames are non-immersive versions of virtual reality that involve physical exercise and have shown several benefits on physical fitness and quality of life in women with fibromyalgia. However, the effects on brain dynamics are still unknown. Aim: the aim was to evaluate the effects of a 24-week exergame intervention on resting brain dynamics in women with fibromyalgia in a single-blinded, randomized controlled trial. Methods: Fifty-six women with fibromyalgia were assessed for eligibility; 55 fulfilled the inclusion criteria. The exercise group completed a 24-week exergame-based intervention that focused on mobility, postural control, upper and lower limb coordination, aerobic fitness, and strength. This group received two 60-min sessions per week. We measured electroencephalographic (EEG) signals from 19 channels. Participants were also divided into two subgroups according to the duration of their symptoms. The intervention was more effective in the group with a shorter duration of symptoms, showing between-group differences in F8, T5 and T4. Conclusion: Exergames may lead to changes in brain dynamics that could be related to increased cerebral blood flow.