Miracle-dz/UniFAR-FTUs huggingface dataset:
Preparation of highly activated natural killer cells for advanced lung cancer therapy

Background: Natural killer (NK) cells can be used as an adoptive immunotherapy to treat cancer patients. Purpose: In this study, we evaluated the efficacy of highly activated NK (HANK) cell immunotherapy in patients with advanced lung cancer. Patients and methods: Between March 2016 and September 2017, we enrolled 13 patients who met the enrollment criteria. Donor peripheral blood monocytes were isolated from patients and the NK cells were expanded. After 12 days of culture, the cells were collected and infused intravenously on days 13 to 15. The enrolled patients received at least one course including three times of infusions. The lymphocyte subsets, cytokine production, and the expression of carcinoembryonic antigen (CEA) and thymidine kinase 1 (TK1) were measured before treatment and after the last infusion. Results: No side effects were observed. After a three-month follow-up, the percentage of patients who achieved stable disease and progressive disease was 84.6% and 15.4%. Moreover, the level of IFN-γ was significantly higher after treatment and the level of CEA decreased substantially. The overall immune function of the patients who received the NK cell therapy remained stable. Conclusion: This is the first study to describe the efficacy of NK cell therapy of patients with advanced lung cancer. These clinical observations demonstrated that NK cell is safe and efficient for advanced lung cancer therapy.
Familial glioblastoma clustering in adult patients: a case report of two non-twin siblings and review of the literature

Purpose: Familial glioblastoma multiforme (gbm) has been described in children with hereditary tumor syndromes. The occurrence of gbm in adult members of the same family and in the absence of tumor syndromes is extremely rare. We describe the cases of a brother and a sister with multifocal gbm diagnosed at the age of 63 years. We discuss three further paired gbm in adult patients from the literature. Patients and results: The sister was diagnosed with multifocal primary gbm in 2014 at the age of 63 years and 6 months. In 2018, her younger brother had to be operated on for a multifocal primary gbm at the age of 63 years and 9 months. Extended neuropathological examination revealed most markers to be similar, except for the percentage of O6-methylguanine-DNA methyltransferase promotor methylation, the presence of intratumoral immune cells and the immunohistochemical expression of C12ORF75. Comparison with further published cases of familial adult GBM reveals that most of these patients are male, about 65 years old and the tumor is localized predominantly in the left temporal lobe. Conclusion: Paired adult familial gbm occurs mainly in the elderly male patient with an integrative diagnosis of primary gbm. Whereas a statistical coincidence seems to be most likely in these rare cases, supplementary and improved genetic studies may identify pathogenetic causes of gbm.
Iron status and inherited haemoglobin disorders modify the effects of micronutrient powders on linear growth and morbidity among young Lao children in a double-blind randomised trial

Abstract Some studies found that providing micronutrient powder (MNP) causes adverse health outcomes, but modifying factors are unknown. We aimed to investigate whether Fe status and inherited Hb disorders (IHbD) modify the impact of MNP on growth and diarrhoea among young Lao children. In a double-blind controlled trial, 1704 children of age 6–23 months were randomised to daily MNP (with 6 mg Fe plus fourteen micronutrients) or placebo for about 36 weeks. IHbD, and baseline and final Hb, Fe status and anthropometrics were assessed. Caregivers provided weekly morbidity reports. At enrolment, 55·6 % were anaemic; only 39·3 % had no sign of clinically significant IHbD. MNP had no overall impact on growth and longitudinal diarrhoea prevalence. Baseline Hb modified the effect of MNP on length-for-age (LAZ) (P for interaction = 0·082). Among children who were initially non-anaemic, the final mean LAZ in the MNP group was slightly lower (–1·93 (95 % CI –1·88, –1·97)) v. placebo (–1·88 (95 % CI –1·83, –1·92)), and the opposite occurred among initially anaemic children (final mean LAZ –1·90 (95 % CI –1·86, –1·94) in MNP v. –1·92 (95 % CI –1·88, –1·96) in placebo). IHbD modified the effect on diarrhoea prevalence (P = 0·095). Among children with IHbD, the MNP group had higher diarrhoea prevalence (1·37 (95 % CI 1·17, 1·59) v. 1·21 (95 % CI 1·04, 1·41)), while it was lower among children without IHbD who received MNP (1·15 (95 % CI 0·95, 1·39) v. 1·37 (95 % CI 1·13, 1·64)). In conclusion, there was a small adverse effect of MNP on growth among non-anaemic children and on diarrhoea prevalence among children with IHbD.
Influence of Patient Setting and Dedicated Limb Salvage Efforts on Outcomes in Charcot-Related Foot Ulcer

Charcot neuroarthropathy is a devastating consequence of diabetes mellitus and peripheral neuropathy. Because of its rarity, the condition is often misdiagnosed or poorly managed. When misadventure occurs, patients with Charcot neuroarthropathy can suffer ulceration, infection, amputation, and death. When patients have Charcot-related foot ulcers, the risks are amplified. Utilizing advanced electronic medical record analysis, a 30-month investigation was undertaken to determine if patients with diabetes mellitus and a concomitant diagnosis of Charcot-related foot ulcer were at greater risk of complications because of location setting of initial treatment for their condition. Charcot foot–related ulcers that are diagnosed in the outpatient setting had established foot specialist care. The outpatient management of the condition lead to a significant reduction in the amount of admissions to a higher acuity setting. However, patient outcomes did not vary once established and dedicated limb salvage efforts were employed. In this large contemporary population managed in a tertiary health system, patients with Charcot-related foot ulcer had negative outcomes when they were initially treated in an inpatient setting and had a significantly greater likelihood of readmission as compared with individuals who had established focused limb salvage care.
Association Between Food and Drug Administration Advisory Committee Recommendations and Agency Actions, 2008-2015.

Policy Points Food and Drug Administration (FDA) advisory committee recommendations and the agency's final actions exhibit high rates of agreement, with cases of disagreement tending to reflect the proposed action type and degree of advisory committee consensus. In the case of disagreements, the FDA tended to be less likely than its advisory committees to approve new products, approve new supplemental indications, or enact new safety changes. These findings raise important issues regarding the factors that differentially shape decision making by advisory committees and the FDA as an agency, including institutional or reputational concerns. CONTEXT The Food and Drug Administration (FDA) convenes advisory committees to provide external scientific counsel on potential agency actions and to inform regulatory decision making. The degree to which advisory committees and their respective agency divisions disagree on recommendations has not been well characterized across product and action types. METHODS We examined public documents from FDA advisory committee meetings and medical product databases for all FDA advisory committee meetings from 2008 through 2015. We classified the 376 voting meetings in that period by medical product, regulatory, and advisory committee meeting characteristics. We used multivariable logistic regression to determine the associations between these characteristics and discordance between the advisory committee's recommendations and the FDA's final actions. FINDINGS Twenty-two percent of the FDA's final actions were discordant with the advisory committee's recommendations. Of these, 75% resulted in the FDA making more restrictive decisions after favorable committee recommendations, and 25% resulted in the agency making less restrictive decisions after unfavorable committee recommendations. Discordance was associated with lower degrees of advisory committee consensus and was more likely for agency actions focused on medical product safety than for novel approvals or supplemental indications. Statements by public speakers, advisory committee conflicts of interest, and media coverage were not associated with discordance between the committee and the agency. CONCLUSIONS The FDA disagrees with the recommendation of its advisory committees a minority of the time, and in these cases it tends to be less likely to approve new products or supplemental indications and take safety actions. Deviations from recommendations thus offer an opportunity to understand the factors influencing decisions made by both the agency and its expert advisory groups.
Progress in mucosal immunization for protection against pneumococcal pneumonia

ABSTRACT Introduction: Lower respiratory tract infections are the fourth cause of death worldwide and pneumococcus is the leading cause of pneumonia. Nonetheless, existing pneumococcal vaccines are less effective against pneumonia than invasive diseases and serotype replacement is a major concern. Protein antigens could induce serotype-independent protection, and mucosal immunization could offer local and systemic immune responses and induce protection against pneumococcal colonization and lung infection. Areas covered: Immunity induced in the experimental human pneumococcal carriage model, approaches to address the physiological barriers to mucosal immunization and improve delivery of the vaccine antigens, different strategies already tested for pneumococcal mucosal vaccination, including live recombinant bacteria, nanoparticles, bacterium-like particles, and nanogels as well as, nasal, pulmonary, sublingual and oral routes of vaccination. Expert opinion: The most promising delivery systems are based on nanoparticles, bacterial-like particles or nanogels, which possess greater immunogenicity than the antigen alone and are considered safer than approaches based on living cells or toxoids. These particles can protect the antigen from degradation, eliminating the refrigeration need during storage and allowing the manufacture of dry powder formulations. They can also increase antigen uptake, control release of antigen and trigger innate immune responses.
Active learning: Evidence from basic science classes

The study examined the effects of active learning techniques on the teaching and learning outcomes of students’ in basic science in South-west, Nigeria. The study is a quasi-experimental of pre-test, post-test control groups design. A sample of 400 Junior Secondary School Two Students was purposively selected from two States in the South-west, Nigeria, specifically Ekiti and Ondo States. Four hypotheses were formulated to guide the study. Basic Science Achievement Test and Teachers’ Instructional Packages were used to collect data for the study. The data collected were analyzed using mean, standard deviation, t-test and analysis of variance. The results revealed that the three forms of active-learning techniques (problem-solving learning technique, cooperative learning technique and discussion learning technique) improved students learning of Basic Science significantly. It is recommended that teachers should be more proactive in the use of these teaching techniques so as to enrich students’ knowledge of science.
Effects of a behavioral medicine intervention on pain, health, and behavior among community-dwelling older adults: a randomized controlled trial

Purpose The aim of the study was to evaluate the effects of an intervention, based on a behavioral medicine approach in physical therapy (BMPI), on pain-related disability and physical performance as well as on pain severity, pain catastrophizing, physical activity levels, falls efficacy, and health-related quality of life (HRQL) by comparing the effects to standard care. Patients and methods The study was a pragmatic randomized controlled trial with a two-group design and included measurements preintervention and postintervention and a 12-week follow-up. In total, 105 older adults, aged >75 years with chronic musculoskeletal pain living alone at home and dependent on formal care to manage their everyday lives, were included in the study. All statistical analyses were performed using an intention to treat approach. Results The intervention, based on a behavioral medicine approach, compared to usual care, had a positive effect on pain-related disability, pain severity, level of physical activity, HRQL, management of everyday life, and self-efficacy. Conclusion BMPI can be a suitable evidence-based intervention for community-dwelling older adults, even for those who are very old and frail. BMPI can support and promote an active aging and “age in place” for the target population, which is currently the main goal of all interventions in this field.
The burden of preventable hospitalizations before and after implementation of the health transformation plan in a hospital in west of Iran

Abstract Background: Increased number of preventable hospitalizations (PHs) for ambulatory care sensitive conditions (ACSCs) represents less efficiency and low access to outpatient and primary health care, leading to waste of health system resources. Aim: The purpose of this study is to assess the quality of outpatient and primary health care using the rate of PHs for ACSCs and to estimate the economic burden of ASCS before and after the implementation of the health transformation plan (HTP) in Iran. Methods: This research was a before–after quasi-experimental study. The study population included all patients hospitalized in the largest general hospital of Kurdistan province with five diseases such as asthma, diabetes, hypertension, congestive heart failure, and chronic obstructive pulmonary disease in 2014 (before the implementation of the HTP) and 2015 (after the implementation of the HTP). Data were analyzed by SPSS v.20 using Chi-square test. Findings: Total number of hospitalizations before and after the implementation of the HTP was 1501 and 1405, respectively. Moreover, the proportion of PHs in all types of the hospital admissions before and after the implementation of the HTP was 47% and 49%, respectively. There was no statistically significant difference between the number of PHs before and after the HTP. In total, PHs imposed 885 798 US$ and 9920 bed-days on health system before and after the implementation of the HTP. Conclusion: Despite the previous expectations of policy makers for improving quality, efficiency, and access to primary health care through implementation of the HTP, proportion of PHs is considerable and it imposes a lot of costs and bed-days on the health system both before and after the HTP.
The origin of pointing: Evidence for the touch hypothesis

From infancy to adulthood, pointing gestures are produced and interpreted as though they originate in touch. Pointing gestures play a foundational role in human language, but up to now, we have not known where these gestures come from. Here, we investigated the hypothesis that pointing originates in touch. We found, first, that when pointing at a target, children and adults oriented their fingers not as though trying to create an “arrow” that picks out the target but instead as though they were aiming to touch it; second, that when pointing at a target at an angle, participants rotated their wrists to match that angle as they would if they were trying to touch the target; and last, that young children interpret pointing gestures as if they were attempts to touch things, not as arrows. These results provide the first substantial evidence that pointing originates in touch.
Review: brain neurobiology of gambling disorder based on rodent models

: Different literature reviews of gambling disorder (GD) neurobiology have been focused on human studies, others have focused on rodents, and others combined human and rodent studies. The main question of this review was: which are the main neurotransmitters systems and brain structures relevant for GD based on recent rodent studies? This work aims to review the experimental ﬁ ndings regarding the rodent´s neurobiology of GD. A search in the Pub Med database was set (October 2012 – October 2017) and 162 references were obtained. After screening, 121 references were excluded, and only 41 references remained from the initial output. More, other 25 references were added to complement (introduction section, neuroanatomical descriptions) the principal part of the work. At the end, a total of 66 references remained for the review. The main conclusions are: 1) according to studies that used noninvasive methods for drug administration, some of the neurotransmitters and receptors involved in behaviors related to GD are: muscarinic, N-methyl-D-aspartate (NMDA), cannabinoid receptor 1 (CB 1 ), cannabinoid receptor 2 (CB 2 ), dopamine 2 receptor (D 2 ), dopamine 3 receptor (D 3 ), and dopamine 4 receptor (D 4 ); 2) moreover, there are other neurotransmitters and receptors involved in GD based on studies that use invasive methods of drug administration (eg, brain microinjection); example of these are: serotonin 1A receptor (5-HT 1A ), noradrenaline receptors, gamma-aminobutyric acid receptor A (GABA A ), and gamma-aminobutyric acid receptor B (GABA B ); 3) different brain structures are relevant to behaviors linked to GD, like: amygdala (including basolateral amygdala (BLA)), anterior cingulate cortex (ACC), hippocampus, infralimbic area, insular cortex (anterior and rostral agranular), nucleus accumbens (NAc), olfactory tubercle (island of Calleja), orbitofrontal cortex (OFC), medial prefrontal cortex (mPFC), prefrontal cortex (PFC) – subcortical network, striatum (ventral) and the subthalamic nucleus (STN); and 4) the search for GD treatments should consider this diversity of receptor/neurotransmitter systems and brain areas.
Using prequestions to enhance learning from reading passages: the roles of question type and structure building ability

ABSTRACT Answering questions before learning something (“prequestions”) enhances learning. However, these benefits usually occur for information that was asked in the prequestions (i.e. prequestioned material), and not for non-prequestioned material. We reasoned that this narrow benefit may be due to the fact that studies typically use fairly simple prequestions that have a clear answer within one part of the learning material – isolative prequestions. We explored the effects of integrative prequestions that required participants to make connections across different parts of a reading passage. Experiment 1 showed the usual benefit of isolative prequestions on prequestioned but not on non-prequestioned material, but no benefit of integrative prequestions. However, in Experiment 2 when participants were given instructions to seek the answers while reading, integrative prequestions benefited learning of both prequestioned and non-prequestioned material. Individual differences in structure building positively predicted performance, but did not interact with the effects of prequestions.
[Identification of a novel SYNGAP1 mutation in a child with intellectual disability].

OBJECTIVE To report on a child with mental retardation caused by SYNGAP1 gene mutation. METHODS Peripheral blood samples were collected from the proband and her parents. High throughput sequencing (HTS) was employed for screening for potential mutation in the patient. Suspected mutation was validated by Sanger sequencing of the child and her parents. RESULTS By HTS, a previously unknown mutation [c.1656C>A (p.C552*)] was found in exon 10 of the SYNGAP1 gene in the proband. Sanger sequencing confirmed the heterozygous nature of the mutation and that neither of her parents carried the same mutation. CONCLUSION The dysmorphism and developmental delay of the child were probably due to the pathogenic mutation of the SYNGAP1 gene. HTS can facilitate elucidation of the genetic etiology with efficiency, which has great significance in the diagnosis, treatment and prognosis of the child.
High-affinity carboxyl-graphene oxide-based SPR aptasensor for the detection of hCG protein in clinical serum samples

Background The use of functionalized graphene oxide (fGO) has led to a new trend in the sensor field, owing to its high sensitivity with regards to sensing characteristics and easy synthesis procedures. Methods In this study, we developed an ultra-sensitive carboxyl-graphene oxide (carboxyl-GO)-based surface plasmon resonance (SPR) aptasensor using peptides to detect human chorionic gonadotropin (hCG) in clinical serum samples. The carboxyl-GO based SPR aptasensor provided high affinity and stronger binding of peptides, which are great importance to allow for a non-immunological label-free mechanism. Also, it allows the detection of low concentrations of hCG, which are in turn considered to be important clinical parameters to diagnose ectopic pregnancies and paraneoplastic syndromes. Results The high selectivity of the carboxyl-GO-based SPR aptasensor for hCG recombinant protein was verified by the addition of the interfering proteins bovine serum albumin (BSA) and human serum albumin (HSA), which did not affect the sensitivity of the sensor. The carboxyl-GO-based chip can enhance the assay efficacy of interactions between peptides and had a high affinity binding for a ka of 17×106 M−1S−1. The limit of detection for hCG in clinical serum samples was 1.15 pg/mL Conclusion The results of this study demonstrated that the carboxyl-GO-based SPR aptasensor had excellent sensitivity, affinity and selectivity, and thus the potential to be used as disease-related biomarker assay to allow for an early diagnosis, and possibly a new area in the field of biochemical sensing technology.
Effect of Pulmonary Rehabilitation (PR) Program in Patients with Interstitial Lung Disease (ILD)-Indian scenario.

Introduction Interstitial Lung diseases (ILD) are group of disorders wherein due to varied etiologies, interstitium goes into progressive inflammation or fibrosis. Although, the awareness has improved but the therapy is still facing challenges. Pulmonary Rehabilitation (PR) is a worthy modality, which not only supports but also imparts evident benefits in these patients. Material and Methods The study is a retrospective observational study conducted over a period of 2 years at Pulmonary Rehabilitation center, a private clinic setup on patients with different restrictive lung diseases like interstitial lung diseases, neuromuscular disorders and post-surgical patients. A total of 100 patients were enrolled, out of which 21 patients were lost to follow up. The study population included 34% males and 66 % females with a mean age of 56.3 ± 14.2 years. 24 patients required oxygen support (where SpO2< 90% at baseline). Outcome measures were assessed in these patients at the time of enrollment into the program (0 week) and at the end of the program (8 weeks). Effect of PR programme was then analyzed with appropriate statistical methods. Results Overall, statistically significant benefits were noted in 6 Minute walk distance (6MWD), muscle strength, dyspnea and Quality of life with 8 weeks. The mean 6 MWTD was 297.9 meters pre PR, which improved to 359.7 meters at the completion of 8 weeks post PR. Mean difference was 61.8 meters, which was found to be statistically significant (p value<0.001) Improvement in muscle strength of different upper and lower limb muscle groups were noted. Also, significant improvement in comprehensive score of Chronic Respiratory Diseases Questionnaire (CRDQ) scores was documented. Statistically significant improvement was found in the dyspnea, fatigue and emotional components. However, mastery components did not show statistically significant change. Conclusion PR has proven to be a very useful modality in the management of restrictive lung diseases, especially with the known limitations of pharmacological options to treat this disabling chronic lung diseases, even with those with evident type I respiratory failure at the beginning.