Miracle-dz/UniFAR-FTUs huggingface dataset:
Safety and tolerability of HIV-1 multiantigen pDNA vaccine given with IL-12 plasmid DNA via electroporation, boosted with a recombinant vesicular stomatitis virus HIV Gag vaccine in healthy volunteers in a randomized, controlled clinical trial

Background The addition of plasmid cytokine adjuvants, electroporation, and live attenuated viral vectors may further optimize immune responses to DNA vaccines in heterologous prime-boost combinations. The objective of this study was to test the safety and tolerability of a novel prime-boost vaccine regimen incorporating these strategies with different doses of IL-12 plasmid DNA adjuvant. Methods In a phase 1 study, 88 participants received an HIV-1 multiantigen (gag/pol, env, nef/tat/vif) DNA vaccine (HIV-MAG, 3000 μg) co-administered with IL-12 plasmid DNA adjuvant at 0, 250, 1000, or 1500 μg (N = 22/group) given intramuscularly with electroporation (Ichor TriGrid™ Delivery System device) at 0, 1 and 3 months; followed by attenuated recombinant vesicular stomatitis virus, serotype Indiana, expressing HIV-1 Gag (VSV-Gag), 3.4 ⊆ 107 plaque-forming units (PFU), at 6 months; 12 others received placebo. Injections were in both deltoids at each timepoint. Participants were monitored for safety and tolerability for 15 months. Results The dose of IL-12 pDNA did not increase pain scores, reactogenicity, or adverse events with the co-administered DNA vaccine, or following the VSV-Gag boost. Injection site pain and reactogenicity were common with intramuscular injections with electroporation, but acceptable to most participants. VSV-Gag vaccine often caused systemic reactogenicity symptoms, including a viral syndrome (in 41%) of fever, chills, malaise/fatigue, myalgia, and headache; and decreased lymphocyte counts 1 day after vaccination. Conclusions HIV-MAG DNA vaccine given by intramuscular injection with electroporation was safe at all doses of IL-12 pDNA. The VSV-Gag vaccine at this dose was associated with fever and viral symptoms in some participants, but the vaccine regimens were safe and generally well-tolerated. Trial registration Clinical Trials.gov NCT01578889.
Multistep coupling of preexisting local ferroic distortions in PbTiO3 above the Curie temperature

Temperature-dependent Raman spectroscopic analyses were performed for the prominent ferroelectric PbTiO3 in the temperature range 130–1040 K, focusing particularly on its paraelectric state above the Curie temperature K. The temperature evolution of the anomalous Raman scattering reveals that not only local ferroic distortions persist at temperatures well above , but also there is a sequence of different coupling processes preceding the appearance of long-range ferroelectric order at . Our results indicate that, similar to relaxor ferroelectrics, the paraelectric phase of PbTiO3 can be considered as an ergodic system of local ferroic distortions, which only on average appears to have cubic symmetry.
Modeling Entropic and Energetic Effects of Linker Length and Rigidity within Synthetic HIV-1 Antibodies designed to Bind Bivalently to Env Spikes

Due to the low density of envelope (Env) spikes on the surface of HIV-1, neutralizing IgG antibodies rarely bind bivalently using both antigen-binding arms (Fabs) to crosslink between spikes (inter-spike crosslinking), instead resorting to weaker monovalent binding that is more sensitive to Env mutations. Antibodies capable of bivalently binding within single Env trimers (intra-spike crosslinking) should exhibit increased neutralization potencies. Here we consider synthetic diFabs joined by varying lengths of rigid double-stranded DNA (dsDNA). We asked whether linkers with different rigidities could enhance diFab potency by modeling DNA-Fabs containing different combinations of rigid dsDNA and flexible single-stranded DNA (ssDNA) and created a model that predicts their neutralization potencies. Model predictions showed that although a long flexible polymer may be capable of bivalent binding, it exhibits weak neutralization due to the large loss in entropic degrees of freedom during bivalent binding. In contrast, the strongest neutralization potencies were predicted to require a rigid linker that optimally spanned the distance between two Fab binding sites on an Env trimer. These results inform the design of bivalent anti-HIV-1 therapeutics that utilize avidity effects to remain potent against HIV-1 in the face of the rapid mutation of Env spikes. Significance Effective antibody-mediated immune responses against pathogens involve tight binding to invading particles. IgG antibodies usually accomplish this by simultaneously binding two antigen-binding arms (Fabs) to a dense array of antigens on the pathogen – if one Fab dissociates, IgGs can remain attached through the second arm, enhancing the likelihood that the first Fab will reassociate. This avidity effect enables bivalent IgGs to achieve a higher apparent affinity for the pathogen than a monovalent Fab. HIV-1 foils this strategy by having few, highly-separated, Envelope spikes (Envs) on its surface for IgGs to bind. This forces most anti-HIV-1 antibodies to bind monovalently, causing IgGs to rapidly dissociate from mutated strains of HIV-1 that arise during infection. In this work, we explore the predicted efficacies of an array of synthetic antibodies that achieve avidity through bivalent binding to single trimeric Envs. We develop a model that uses the geometry of each synthetic antibody to predict its neutralization potency, quantifying how entropic effects determine neutralization potencies and presenting a way to theoretically design an optimal antibody-based reagent that can bind bivalently to HIV-1 Env in order to target the virus in the face of its rapid mutation.
Human Milk Casein and Whey Protein and Infant Body Composition over the First 12 Months of Lactation

Human milk (HM) influences infant feeding patterns and body composition (BC). This small proof-of concept longitudinal study investigated relationships between infant/maternal BC and HM casein, whey and total protein during the first 12 months of lactation. BC of breastfeeding dyads (n = 20) was measured at 2 (n = 15), 5 (n = 20), 9 (n = 19), and/or 12 (n = 18) months postpartum with ultrasound skinfolds (infants) and bioimpedance spectroscopy (infants/mothers). Proteins concentrations and 24-h milk intake were measured and calculated daily intakes (CDI) determined. Higher maternal weight, body mass index, fat-free mass, fat-free mass index, and fat mass index were associated with higher concentration of whey protein (p ≤ 0.034, n = 20). There were no associations between infant BC and concentrations of all proteins, and CDI of whey and total protein. Higher CDI of casein were associated with lower infant fat-free mass (p = 0.003, n = 18) and higher fat mass (p < 0.001), fat mass index (p = 0.001, n = 18), and % fat mass (p < 0.001, n = 18) measured with ultrasound skinfolds. These results show a differential effect of HM casein on development of infant BC during the first year of life, suggesting that there is a potential to improve outcome for the infant through interventions, such as continuation of breastfeeding during the first 12 months of life and beyond, which may facilitate favourable developmental programming that could reduce risk of non-communicable diseases later in life.
Adaptive Design: Results of 2012 Survey on Perception and Use

Adaptive designs are increasingly used in clinical trials. The Drug Information Association’s Adaptive Design Scientific Working Group (ADSWG) works to foster collaboration among regulatory agencies, academia, and pharmaceutical and biotech companies to further the science of adaptive clinical development. The ADSWG Survey Subteam has collected data on the usage of adaptive designs in clinical research from multiple sources, including a recent ADSWG survey regarding the perception and usage of adaptive designs in academia and industry for studies between 2008 and 2011, as well as barriers to usage; a literature review examining publications of adaptive design methodology and usage between 2000 and 2011; and a trial registry review of adaptive design references from 1996 to 2011. The comprehensive results of the ADSWG 2012 survey are provided in this article with comparisons to our previous 2008 survey, the literature and registry reviews, and recent surveys carried out by the US Food and Drug Administration (FDA) and the European Medicines Agency. Results of the ADSWG 2012 survey illustrate that industry and academia are showing more enthusiasm for adaptive trials, accompanied by an increase in the number of trials using designs described as less well understood in the FDA draft guidance on adaptive designs, published in 2010. The increased use of these methods in exploratory trials is consistent with the FDA draft guidance. The survey also identified several examples of successful marketing applications supported by confirmatory trials utilizing adaptive designs that were considered, at least at the time of the draft guidance, as less well understood . While some of the technological barriers to adaptive design usage identified in the 2008 survey are now less common, there are several important persistent barriers to usage. Organizations can help overcome these barriers through education, preplanning, and early engagement in discussions with the regulators.
Switching Divergences for Spectral Learning in Blind Speech Dereverberation

When recorded in an enclosed room, a sound signal will most certainly get affected by reverberation. This not only undermines audio quality, but also poses a problem for many human-machine interaction technologies that use speech as their input. In this paper, a new blind, two-stage dereverberation approach based in a generalized $\beta$-divergence as a fidelity term over a non-negative representation is proposed. The first stage consists of learning the spectral structure of the signal solely from the observed spectrogram, while the second stage is devoted to model reverberation. Both steps are taken by minimizing a cost function in which the aim is put either in constructing a dictionary or a good representation by changing the divergence involved. In addition, an approach for finding an optimal fidelity parameter for dictionary learning is proposed. An algorithm for implementing the proposed method is described and tested against state-of-the-art methods. Results show improvements for both artificial reverberation and real recordings.
The Prevalence and Risk Factors of Latent Tuberculosis Infection among Health Care Workers Working in a Tertiary Hospital in South Korea

Background The risk of tuberculosis (TB) infection among health care workers (HCWs) is higher than as noted among workers in the general population. The prevalence and risk factors of TB infection among HCWs were assessed in a tertiary hospital in South Korea, resulting in a conclusion of an intermediate TB burden within the country. Methods This cross-sectional study enrolled HCWs who underwent a QuantiFERON-TB Gold In-Tube (QFT-GIT) test to detect the presence of a latent TB infection (LTBI), in patients admitted to a tertiary hospital in South Korea in 2017. The departments of the hospital were divided into TB-related and TB-unrelated departments, which were based on the risk of exposure to TB patients. In this sense, the risk factors for LTBI, including current working in the TB-related departments, were analyzed. Results In this case, a total of 499 HCWs (54 doctors, 365 nurses and 80 paramedical personnel) were enrolled in this study. The median age of the subjects was 31 years (range, 20–67 years), 428 (85.8%) were female, and 208 (41.7%) were working in the TB-related departments. The prevalence of LTBI was 15.8% based on the QFT-GIT. Additionally, the prevalence of experience of exposure to pre-treatment TB patents was higher among HCWs working in the TB-related departments, than among HCWs working in the TB-unrelated departments (78.8% vs. 61.9%, p<0.001). However, there was no significant difference in the prevalence of LTBI between the two groups (17.3% vs. 14.8%, p=0.458). On a review of the multivariate analysis, only the factor of age was independently associated with an increased risk of LTBI (p=0.006). Conclusion Broadly speaking, the factor of age was associated with an increased risk of LTBI among the HCWs in South Korea. However, those workers current working in the TB-related departments was not associated with an increased risk of LTBI.
Perceptions on Support, Challenges and Needs among Parents of Children with Autism: the Serbian Experience.

BACKGROUND Autism spectrum disorders (ASD) significantly impact lives of affected individuals and their families. They confront daunting challenges and multiple demands in their daily life, when compared to parents of children with other disabilities or parents of typically developing children. SUBJECTS AND METHODS Participants completed The Caregiver Needs Survey, the survey intended for parents or primary caregivers of children with a diagnosis of ASD. During the study, 231 parents were interviewed; 167 mothers and 64 fathers. Parents were recruited from the patient database comprised of families from the two largest cities in Serbia. All of them were contacted before the study, either via phone or at the child's regular check-in visit. RESULTS Over 90 percent of the parents reported that additional support at schools, home, and improved relationships with service providers are necessary and important. The most important challenges related to care were child's communication difficulties, social interaction difficulties, and problems with daily living skills. The significant predictors of lower overall satisfaction were parent's higher education, having a first concern related to problems of the child's interaction with others or playing alone, and parent frustration with accessing services in the past 12 months. Greater overall satisfaction, on the other hand, was related to having an in-school tutor training or assistance in managing child's needs or implementing treatments, and having primary care doctor or pediatrician as a source of information on autism. CONCLUSIONS Future efforts to develop ASD-related policies and services should also take the following into consideration: the low level of awareness among caregivers and health care providers about the early signs of autism; disparities in access to services; educational problems and significant levels of dissatisfaction with the overall care and stigma.
Pharmacotherapeutic Follow-up and Pharmacogenetics of CYP2C9 and CYP3A4 in Antihypertensive Therapy: A Pilot Study in a Community Pharmacy

No pharmacogenetic studies have yet been conducted in community pharmacies, despite pharmacogenetics being an emerging discipline. Pharmacotherapeutic follow-up (PFU) was performed for 6 months in 37 patients receiving antihypertensive treatment, and they were genotyped for variant alleles *2 and *3 in the CYP2C9 gene and *1B in CYP3A4. Systolic blood pressure, cardiovascular risk, and adherence improved with PFU. Most of the interactions between drugs were represented by concurrent administration of statins and calcium channel blockers, which both use CYP3A4 for their metabolism. Heterozygotic patients for the CYP2C9*2 allele showed higher mean heart rate values after PFU than homozygous patients (73.4 ± 10.0 pulse/min vs 66.2 ± 10.6 pulse/min, respectively; P =.048). Carriers of CYP2C9*2 showed a tendency to less frequent negative outcomes associated with medication due to inefficacy than homozygous patients (50% vs 78.9%, respectively; P =.072). Pharmacogenetics and PFU can be used in community pharmacies to carry out a more exhaustive study of medication in hypertensive outpatients.
The role of protein disulphide isomerase AGR2 in the tumour niche

In recent years, the discovery of ‘tumour niche’, a microenvironment that favours tumour development has changed our perspective of cancer. This microenvironment generated by the tumour cells itself and surrounding cells is capable of providing essential elements for its growth. Consequently, the homoeostasis of the secretory pathway (SP) has become an essential player in cancer development. The SP not only promotes cellular adaptation to protein misfolding due to oncogenic transformation or challenging tumour niche but also allows tumour cells to produce specific secretomes. This impacts tumour cells in cis‐ or trans‐ as well as stromal cells in the tumour niche. In this context, the Anterior GRadient 2 (AGR2) protein has been identified as a key player. AGR2 is a protein disulphide isomerase that resides in the endoplasmic reticulum (ER) and mediates the formation of disulphide bonds, catalyses the cysteine‐based redox reactions and assists the quality control of proteins. AGR2 not only plays an essential role in the homoeostasis of the SP but also exerts pro‐oncogenic gain‐of‐function due to its reported mislocalisation in the tumour niche microenvironment. In this review, we summarise the dual role of AGR2, inside and outside the ER, on the tumour niche and its microenvironment.
Changes in Work Practices for Safe Use of Formaldehyde in a University-Based Anatomy Teaching and Research Facility

Anatomy teaching and research relies on the use of formaldehyde (FA) as a preservation agent for human and animal tissues. Due to the recent classification of FA as a carcinogen, university hospitals are facing a challenge to (further) reduce exposure to FA. The aim of this study was to reduce exposure to FA in the anatomy teaching and research facility. Workers participated in the development of improved work practices, both technical and organizational solutions. Over a period of 6 years mitigating measures were introduced, including improvement of a down-flow ventilation system, introduction of local exhaust ventilation, collection of drain liquid from displayed specimens in closed containers and leak prevention. Furthermore, some organizational changes were made to reduce the number of FA peak exposures. Stationary and personal air sampling was performed in three different campaigns to assess the effect of these new work practices on inhalation exposure to FA. Samples were collected over 8 h (full shift) and 15 min (task-based) to support mitigation of exposure and improvement of work practices. Air was collected on an adsorbent coated with 2,4-dinitrophenylhydrazine (DNPH) and analyzed by HPLC-UV. Geometric mean (GM) concentrations of FA in the breathing zone over a work-shift were 123 µg/m3 in 2012 and 114 µg/m3 in 2014, exceeding the workplace standard of 150 µg/m3 (8 h time-weighted average, TWA) on 46% of the workdays in 2012 and 38% of the workdays in 2014. This exposure was reduced to an average of 28.8 µg/m3 in 2017 with an estimated probability of exceeding the OEL of 0.6%. Task-based measurements resulted in a mean peak exposures of 291 µg/m3 in 2012 (n = 19) and a mean of 272 µg/m3 in 2014 (n = 21), occasionally exceeding the standard of 500 µg/m3 (15 min TWA), and were reduced to a mean of 88.7 µg/m3 in 2017 (n = 12) with an estimated probability of exceeding the OEL of 1.6%.
Limited Coverage of Hepatitis C Virus Testing in the United States, 2013–2017

In the US household population, hepatitis C virus testing coverage marginally increased between 2013 and 2017 among persons born between 1966 and 1994 (13.2% to 16.8%) and persons born between 1945 and 1965 (12.3% to 17.3%). Testing coverage remains limited and sociodemographic disparities were observed in both populations.
Lessons Learned in Multilingual Grounded Language Learning

Recent work has shown how to learn better visual-semantic embeddings by leveraging image descriptions in more than one language. Here, we investigate in detail which conditions affect the performance of this type of grounded language learning model. We show that multilingual training improves over bilingual training, and that low-resource languages benefit from training with higher-resource languages. We demonstrate that a multilingual model can be trained equally well on either translations or comparable sentence pairs, and that annotating the same set of images in multiple language enables further improvements via an additional caption-caption ranking objective.
Vitamin D deficiency in head and neck cancer patients – prevalence, prognostic value and impact on immune function

ABSTRACT Vitamin D deficiency is frequently observed in human cancer patients and a prognostic relevance could be shown for some entities. Additionally, it is known that vitamin D can stimulate the patients’ antitumor immunity. However, valid epidemiological data for head and neck squamous cell carcinoma (HNSCC) patients are sparse and functional studies on a possible connection between vitamin D and the patients’ immune system are missing. 25-OH vitamin D serum levels were analyzed in 231 HNSCC patients and 232 healthy controls and correlated with clinical data and patient survival. Intra- and peritumoral infiltration with T-cell, NK-cell and macrophage populations was analyzed in 102 HNSCC patients by immunohistochemistry. In 11 HNSCC patients, NK-cells were isolated before and after vitamin D substitution and analyzed for their cytotoxic activity directed against a HNSCC cell line. Vitamin D serum levels were significantly lower in HNSCC patients compared with healthy controls. Low vitamin D levels were associated with lymphatic metastasis and a negative HPV status and were a significant predictor of poor overall survival. HNSCC patients with severe vitamin D deficiency showed significantly altered intra- and peritumoral immune cell infiltrate levels. After vitamin D substitution, the patients’ NK cells showed a significant rise in cytotoxic activity. Taken together, we could show that Vitamin D deficiency is highly prevalent in HNSCC patients and is a predictor of poor survival. Vitamin D substitution used as an adjuvant in immune therapies such as cetuximab and nivolumab treatment could support antitumorigenic immune responses, thus contributing to the improvement of the patients’ prognosis in the context of a multimodal therapy.
Logging and soil nutrients independently explain plant trait expression in tropical forests.

Plant functional traits regulate ecosystem functions but little is known about how co-occurring gradients of land use and edaphic conditions influence their expression. We test how gradients of logging disturbance and soil properties relate to community-weighted mean traits in logged and old-growth tropical forests in Borneo. We studied 32 physical, chemical and physiological traits from 284 tree species in eight 1 ha plots and measured long-term soil nutrient supplies and plant-available nutrients. Logged plots had greater values for traits that drive carbon capture and growth, whilst old-growth forests had greater values for structural and persistence traits. Although disturbance was the primary driver of trait expression, soil nutrients explained a statistically independent axis of variation linked to leaf size and nutrient concentration. Soil characteristics influenced trait expression via nutrient availability, nutrient pools, and pH. Our finding, that traits have dissimilar responses to land use and soil resource availability, provides robust evidence for the need to consider the abiotic context of logging when predicting plant functional diversity across human-modified tropical forests. The detection of two independent axes was facilitated by the measurement of many more functional traits than have been examined in previous studies.