Miracle-dz/UniFAR-FTUs huggingface dataset:
TIPE2 Induced the Proliferation, Survival, and Migration of Lung Cancer Cells Through Modulation of Akt/mTOR/NF-κB Signaling Cascade

Lung cancer represents the most common cause of cancer deaths in the world, constituting around 11.6% of all new cancer cases and 18.4% of cancer-related deaths. The propensity for early spread, lack of suitable biomarkers for early diagnosis, as well as prognosis and ineffective existing therapies, contribute to the poor survival rate of lung cancer. Therefore, there is an urgent need to develop novel biomarkers for early diagnosis and prognosis which in turn can facilitate newer therapeutic avenues for the management of this aggressive neoplasm. TIPE2 (tumor necrosis factor-α-induced protein 8-like 2), a recently identified cytoplasmic protein, possesses enormous potential in this regard. Immunohistochemical analysis showed that TIPE2 was significantly upregulated in different stages and grades of lung cancer tissues compared to normal lung tissues, implying its involvement in the positive regulation of lung cancer. Further, knockout of TIPE2 resulted in significantly reduced proliferation, survival, and migration of human lung cancer cells through modulation of the Akt/mTOR/NF-κB signaling axis. In addition, knockout of TIPE2 also caused arrest in the S phase of the cell cycle of lung cancer cells. As tobacco is the most predominant risk factor for lung cancer, we therefore evaluated the effect of TIPE2 in tobacco-mediated lung carcinogenesis as well. Our results showed that TIPE2 was involved in nicotine-, nicotine-derived nitrosamine ketone (NNK)-, N-nitrosonornicotine (NNN)-, and benzo[a]pyrene (BaP)-mediated lung cancer through inhibited proliferation, survival, and migration via modulation of nuclear factor kappa B (NF-κB)- and NF-κB-regulated gene products, which are involved in the regulation of diverse processes in lung cancer cells. Taken together, TIPE2 possesses an important role in the development and progression of lung cancer, particularly in tobacco-promoted lung cancer, and hence, specific targeting of it holds an enormous prospect in newer therapeutic interventions in lung cancer. However, these findings need to be validated in the in vivo and clinical settings to fully establish the diagnostic and prognostic importance of TIPE2 against lung cancer.
Time reference, morphology and prototypicality: tense production in stroke aphasia and semantic dementia in Greek

ABSTRACT The present study aims at investigating verb inflection in aphasia and semantic dementia. In particular, it addresses the contribution of time reference and morphological complexity. Moreover, it investigates whether the lexical properties of the verb, such as argument structure and lexical aspect interact with the production of tense. Ten individuals with (different types of) stroke aphasia and five individuals with semantic dementia and their respective control groups conducted a sentence completion task. Three tenses were tested: past perfective, past imperfective and present. All tenses had to be produced with three different verb classes, which differed with respect to syntactic and semantic properties: unergative, unaccusative and transitive verbs. The findings imply problems with marking aspect and an interaction between inflection and lexical aspect but no effect of morphological complexity or across the board difficulties with reference to the past in aphasia. Moreover, the results suggest problems with inflection in semantic dementia, an interaction between inflection and lexical aspect and a selective difficulty with imperfective tenses. The study contributes to a better understanding of inflection problems in aphasia and it provides evidence for inflection problems in semantic dementia.
Percutaneous Endoscopic Gastrostomy versus Nasogastric Tube Feeding: Oropharyngeal Dysphagia Increases Risk for Pneumonia Requiring Hospital Admission

Background: Aspiration pneumonia is the most common cause of death in patients with percutaneous endoscopic gastrostomy (PEG) and nasogastric tube (NGT) feeding. This study aimed to compare PEG versus NGT feeding regarding the risk of pneumonia, according to the severity of pooling secretions in the pharyngolaryngeal region. Methods: Patients were stratified by endoscopic observation of the pooling secretions in the pharyngolaryngeal region: control group (<25% pooling secretions filling the pyriform sinus), pharyngeal group (25–100% pooling secretions filling the pyriform sinus), and laryngeal group (pooling secretions entering the laryngeal vestibule). Demographic data, swallowing level scale score, and pneumonia requiring hospital admission were recorded. Results: Patients with NGT (n = 97) had a significantly higher incidence of pneumonia (episodes/person-years) than those patients with PEG (n = 130) in the pharyngeal group (3.6 ± 1.0 vs. 2.3 ± 2.1, P < 0.001) and the laryngeal group (3.8 ± 0.5 vs. 2.3 ± 2.2 vs, P < 0.001). The risk of pneumonia was significantly higher in patients with NGT than in patients with PEG (adjusted hazard ratio = 2.85, 95% CI: 1.46–4.98, P < 0.001). Cumulative proportion of pneumonia was significantly higher in patients with NGT than with PEG for patients when combining the two groups (pharyngeal + laryngeal groups) (P = 0.035). Conclusion: PEG is a better choice than NGT feeding due to the decrease in risk of pneumonia requiring hospital admission, particularly in patients with abnormal amounts of pooling secretions accumulation in the pyriform sinus or leak into the laryngeal vestibule.
Obesity And Obstetric Anesthesia: Current Insights

Abstract Obesity is a significant global health problem. It results in a higher incidence of complications for pregnant women and their neonates. Cesarean deliveries are more common in obese parturients as well. The increased burden of comorbidities seen in this population, such as obstructive sleep apnea, necessitates antepartum anesthetic consultation. These patients pose unique challenges for the practicing anesthesiologist and may benefit from optimization prior to delivery. Complications from anesthesia and overall morbidity and mortality are higher in this population. Neuraxial anesthesia can be challenging to place in the obese parturient, but is the preferred anesthetic for cesarean delivery to avoid airway manipulation, minimize aspiration risk, prevent fetal exposure to volatile anesthetic, and decrease risk of post-partum hemorrhage from volatile anesthetic exposure. Monitoring and positioning of these patients for surgery may pose specific challenges. Functional labor epidural catheters can be topped up to provide conditions suitable for surgery. In the absence of a working epidural catheter, a combined spinal epidural anesthetic is often the technique of choice due to relative ease of placement versus a single shot spinal technique as well as the ability to extend the anesthetic through the epidural portion. For cesarean delivery with a vertical supraumbilical skin incision, a two-catheter technique may be beneficial. Concern for thromboembolism necessitates early mobilization and a multimodal analgesic regimen can help accomplish this. In addition, thromboprophylaxis is recommended in this population after delivery—especially cesarean delivery. These patients also need close monitoring in the post-partum period when they are at increased risk for several complications.
Predictors of Emergency Department Use among Individuals with Current or Previous Experience of Homelessness

This study assessed the contributions of predisposing, enabling, and needs factors in predicting emergency department (ED) use among 270 individuals with current or previous experience of homelessness. Participants were recruited from three different types of housing (shelter, temporary housing and permanent housing) in Montreal, Quebec (Canada). They were interviewed at baseline (T0), and again 12 months after recruitment (T1). Longitudinal data analyses were conducted on associations between a set of baseline predictors (T0) with the dependent variable (ED users vs. non-users) from T1. Predictors were identified according to the Gelberg–Andersen Behavioral Model. Findings revealed two needs factors associated with ED use: having a substance use disorder (SUD) and low perceived physical health. Two enabling factors, use of ambulatory specialized services and stigma, were also related to ED use. No predisposing factors were retained in the model, and ED use was not associated with type of housing. Improvements are needed in SUD and physical health management in order to reduce ED use, as well as interventions aimed at stigma prevention for this vulnerable population.
Forty Years Since the Structural Elucidation of Platelet-Activating Factor (PAF): Historical, Current, and Future Research Perspectives

In the late 1960s, Barbaro and Zvaifler described a substance that caused antigen induced histamine release from rabbit platelets producing antibodies in passive cutaneous anaphylaxis. Henson described a ‘soluble factor’ released from leukocytes that induced vasoactive amine release in platelets. Later observations by Siraganuan and Osler observed the existence of a diluted substance that had the capacity to cause platelet activation. In 1972, the term platelet-activating factor (PAF) was coined by Benveniste, Henson, and Cochrane. The structure of PAF was later elucidated by Demopoulos, Pinckard, and Hanahan in 1979. These studies introduced the research world to PAF, which is now recognised as a potent phospholipid mediator. Since its introduction to the literature, research on PAF has grown due to interest in its vital cell signalling functions and more sinisterly its role as a pro-inflammatory molecule in several chronic diseases including cardiovascular disease and cancer. As it is forty years since the structural elucidation of PAF, the aim of this review is to provide a historical account of the discovery of PAF and to provide a general overview of current and future perspectives on PAF research in physiology and pathophysiology.
How Does Biological Maturation and Training Experience Impact the Physical and Technical Performance of 11–14-Year-Old Male Basketball Players?

This study (1) investigated the effects of age, maturity status, anthropometrics, and years of training on 11–14-year-old male basketball players’ physical performance and technical skills development, and (2) estimated the contribution of maturity status and training years on players’ physical and technical performances. The sample consisted of 150 participants, average age 13.3 ± 0.7 years, grouped by early, average, and late maturation. Biological maturation, anthropometry, and training data were collected using standard procedures. Measures of physical performance assessed included: aerobic fitness, abdominal muscular strength and endurance, static strength, lower body explosive power, upper body explosive power, speed, and agility and body control. Basketball-specific technical skills were also recorded. Analysis of variance (ANOVA) and analysis of covariance (ANCOVA) were used to compare group differences. Results indicated that early maturers were taller, heavier, and had greater strength, power, speed, and agility (p < 0.05). When controlling for age, height, and body mass, early maturers remained stronger, quicker, and more agile (p < 0.05). They were also more skillful in the speed shot shooting test (p < 0.05). Apart from tests of aerobic fitness, abdominal muscular strength and endurance, and lower body explosive power, maturity status was the primary contributor to the variance in the physical performance tests. Years of training was the primary contributor to the variance in the technical skills tests. Whilst physical performance was dependent on maturity status, technical skills were influenced by years of training. Since both biological maturation and years of training play an important role in basketball performance, we recommend that coaches consider the effects of these two confounders when recruiting and selecting youth basketballers.
Intraspecific Variation within the Utricularia amethystina Species Morphotypes Based on Chloroplast Genomes

Utricularia amethystina Salzm. ex A.St.-Hil. & Girard (Lentibulariaceae) is a highly polymorphic carnivorous plant taxonomically rearranged many times throughout history. Herein, the complete chloroplast genomes (cpDNA) of three U. amethystina morphotypes: purple-, white-, and yellow-flowered, were sequenced, compared, and putative markers for systematic, populations, and evolutionary studies were uncovered. In addition, RNA-Seq and RNA-editing analysis were employed for functional cpDNA evaluation. The cpDNA of three U. amethystina morphotypes exhibits typical quadripartite structure. Fine-grained sequence comparison revealed a high degree of intraspecific genetic variability in all morphotypes, including an exclusive inversion in the psbM and petN genes in U. amethystina yellow. Phylogenetic analyses indicate that U. amethystina morphotypes are monophyletic. Furthermore, in contrast to the terrestrial Utricularia reniformis cpDNA, the U. amethystina morphotypes retain all the plastid NAD(P)H-dehydrogenase (ndh) complex genes. This observation supports the hypothesis that the ndhs in terrestrial Utricularia were independently lost and regained, also suggesting that different habitats (aquatic and terrestrial) are not related to the absence of Utricularia ndhs gene repertoire as previously assumed. Moreover, RNA-Seq analyses recovered similar patterns, including nonsynonymous RNA-editing sites (e.g., rps14 and petB). Collectively, our results bring new insights into the chloroplast genome architecture and evolution of the photosynthesis machinery in the Lentibulariaceae.
Stepped-wedge trials should be classified as research for the purpose of ethical review

Background: All studies classified as research involving human participants require research ethics review. Most regulation and guidance on ethical oversight of research involving human participants was written for pharmacotherapy interventions. Interpretation of such guidance for cluster-randomized trials and stepped-wedge trials, which commonly evaluate complex non-therapeutic interventions such as knowledge translation, public health, or health service delivery interventions, can pose challenges to researchers and regulators. Current guidance: The Ottawa Statement on the Ethical Design and Conduct of Cluster-Randomized Trials provides guidance on the ethical oversight and consent procedures for cluster-randomized trials, and while not explicit, this includes stepped-wedge trials. Yet, stepped-wedge trials have unique characteristics that differentiate them from standard cluster-randomized trials. In particular, they can be used to evaluate knowledge translation interventions within the context of a routine health system rollout; they may have a non-randomized design; and the decision to implement the intervention is not always made by the researcher. Many stepped-wedge trials do not undergo ethical review and do not report trial registration. This suggests that those undertaking these studies and research ethics committees perceive them as non-research activities. Recommendations: Through an ethical analysis of two case studies, we argue that stepped-wedge trials, like parallel arm cluster trials, are systematic investigations designed to produce generalizable knowledge. We contend that stepped-wedge trials usually include human research participants, which may be patients, health care providers, or both. Stepped-wedge trials are therefore research involving human participants for the purpose of ethical review. Nevertheless, the use of a waiver or alteration of consent may be appropriate in many stepped-wedge trials due to the infeasibility of obtaining informed consent and the low-risk nature of the interventions. To ensure that traditional ethical principles such as respect for persons are upheld, these studies must undergo research ethics review.
Inhibition of Amyloid β Aggregation Using Optimized Nano Encapsulated Formulations of Plant Extracts with High Metal Chelator Activities.

BACKGROUND The role of Fe+2, Cu+2 and Zn+2 in facilitating aggregation of Amyloid β (Aβ) and consequently, the progression of Alzheimer's disease (AD) is well established. OBJECTIVE Development of non-toxic metal chelators is an emerging era in the treatment of AD, in which complete success has not been fully achieved. The purpose of this study was to determine plant extracts with high metal chelator activity and low toxicity and to encapsulate them in nano-micellar systems with the ability to pass through the Blood Brain Barrier (BBB). METHOD Extracts of 36 different Anatolian plants were prepared, total phenolic and flavonoid contents were determined, and the extracts with high content were examined for their Fe+2, Cu+2 and Zn+2 chelating activities. Apolipoprotein E4 (Apo E) decorated nano-formulations of active extracts were prepared using Poly (Lactide-co-Glycolide) (PLGA) (final product ApoEPLGA) to provide BBB penetrating property. RESULTS Verbascum flavidum aqueous extract was found as the most active sample, incubation of which, with Aβ before and after metal-induced aggregation, resulted in successful inhibition of aggregate formation, while re-solubilization of pre-formed aggregates was not effectively achieved. The same results were obtained using ApoEPLGA. CONCLUSION An optimized metal chelator nano-formulation with BBB penetrating ability was prepared and presented for further in-vivo studies.
Mechanical and Tribological Properties of Layered Materials Under High Pressure: Assessing the Importance of Many-Body Dispersion Effects.

The importance of many-body dispersion effects in layered materials subjected to high external loads is evaluated. State-of-the-art many-body dispersion density functional theory calculations performed for graphite, hexagonal boron nitride, and their hetero-structures were used to fit the parameters of a classical registry-dependent interlayer potential. Using the latter, we performed extensive equilibrium molecular dynamics simulations and studied the mechanical response of homogeneous and heterogeneous bulk models under hydrostatic pressures up to 30 GPa. Comparison with experimental data demonstrates that the reliability of the many-body dispersion model extends deep into the sub-equilibrium regime. Friction simulations demonstrate the importance of many-body dispersion effects for the accurate description of the tribological properties of layered materials interfaces under high pressure.
Children and Adults with Refractory Acute Graft-versus-Host Disease Respond to Treatment with the Mesenchymal Stromal Cell Preparation “MSC-FFM”—Outcome Report of 92 Patients

(1) Background: Refractory acute graft-versus-host disease (R-aGvHD) remains a leading cause of death after allogeneic stem cell transplantation. Survival rates of 15% after four years are currently achieved; deaths are only in part due to aGvHD itself, but mostly due to adverse effects of R-aGvHD treatment with immunosuppressive agents as these predispose patients to opportunistic infections and loss of graft-versus-leukemia surveillance resulting in relapse. Mesenchymal stromal cells (MSC) from different tissues and those generated by various protocols have been proposed as a remedy for R-aGvHD but the enthusiasm raised by initial reports has not been ubiquitously reproduced. (2) Methods: We previously reported on a unique MSC product, which was generated from pooled bone marrow mononuclear cells of multiple third-party donors. The products showed dose-to-dose equipotency and greater immunosuppressive capacity than individually expanded MSCs from the same donors. This product, MSC-FFM, has entered clinical routine in Germany where it is licensed with a national hospital exemption authorization. We previously reported satisfying initial clinical outcomes, which we are now updating. The data were collected in our post-approval pharmacovigilance program, i.e., this is not a clinical study and the data is high-level and non-monitored. (3) Results: Follow-up for 92 recipients of MSC-FFM was reported, 88 with GvHD ≥°III, one-third only steroid-refractory and two-thirds therapy resistant (refractory to steroids plus ≥2 additional lines of treatment). A median of three doses of MSC-FFM was administered without apparent toxicity. Overall response rates were 82% and 81% at the first and last evaluation, respectively. At six months, the estimated overall survival was 64%, while the cumulative incidence of death from underlying disease was 3%. (4) Conclusions: MSC-FFM promises to be a safe and efficient treatment for severe R-aGvHD.
SYK Targeting Represents a Potential Therapeutic Option for Relapsed Resistant Pediatric ETV6-RUNX1 B-Acute Lymphoblastic Leukemia Patients

The presence of the chromosomal rearrangement t(12;21)(ETV6-RUNX1) in childhood B-acute lymphoblastic leukemia (B-ALL) is an independent predictor of favorable prognosis, however relapses still occur many years later after stopping therapy, and patients often display resistance to current treatments. Since spleen tyrosine kinase (SYK), a cytosolic nonreceptor tyrosine kinase interacting with immune receptors, has been previously associated with malignant transformation and cancer cell proliferation, we aimed to assess its role in ETV6-RUNX1 cell survival and prognosis. We evaluated the effects on cell survival of three SYK inhibitors and showed that all of them, in particular entospletinib, are able to induce cell death and enhance the efficacy of conventional chemotherapeutics. By using reverse phase protein arrays we next revealed that activated SYK is upregulated at diagnosis in pediatric ETV6-RUNX1 patients who will experience relapse, and, importantly, hyperactivation is maintained at a high level also at relapse occurrence. We thus treated primary cells from patients both at diagnosis and relapse with the combination entospletinib + chemotherapeutics and observed that SYK inhibition is able to sensitize resistant primary cells to conventional drugs. Entospletinib could thus represent a new therapeutic option supporting conventional chemotherapy for relapsed ETV6-RUNX1 patients, and these evidences encourage further studies on SYK for treatment of other relapsed resistant acute lymphoblastic leukemia (ALL) subgroups.
Changes in the prevalence of chronic conditions associated with abdominal obesity between 1999 and 2014

To examine the trends in chronic conditions after accounting for temporal differences in body mass index (BMI) and waist circumference (WC). Pooled cycles (1999‐2014) of the U.S. National Health and Nutrition Examination Survey (NHANES) were analysed (n = 36 959). The models were adjusted for caloric intake, smoking, medications use and physical activity. The prevalence of diabetes increased in women with general or abdominal obesity (BMI*time; WC*time, P < .05), but there were no differences in men. For hypertension, independent of BMI, the prevalence was not different over time in both sexes (P > .05), whereas for a given WC, there was a decrease in the prevalence over time in women (WC*time, P = .05). For dyslipidemia, independent of BMI, the prevalence decreased in men, whereas for a given WC, there was a decrease in the prevalence in both sexes (P < .05). Over the same time frame, blood pressure, low‐density lipoprotein and triglycerides decreased, while plasma glucose increased independent of general and abdominal obesity (P < .001). The relationship between obesity and chronic conditions has changed over time. There may be other changes that have altered how obesity is related with metabolic health markers over time. Further investigation is needed to better understand the current causes of chronic conditions.