Miracle-dz/UniFAR-FTUs huggingface dataset:
Therapeutic plasma exchange clears circulating soluble PD-L1 and PD-L1-positive extracellular vesicles

Background Trans-acting programmed death-ligand 1 (PD-L1) derives from malignant cells in three known forms. High levels of secreted splice variant PD-L1 (sPD-L1), ADAM10/ADAM17-shed sPD-L1, and PD-L1-positive extracellular vesicles (evPD-L1) each predict poor prognosis and limited response to PD-(L)1 checkpoint inhibitors in cancer. To our knowledge, no clinical intervention has reduced any of these circulating forms of extracellular PD-L1. Here, we explore therapeutic plasma exchange (TPE) as a treatment to reduce circulating extracellular PD-L1. Results In patients with melanoma, sPD-L1 levels above 0.277 ng/mL predicted inferior overall survival. In patients undergoing TPE for non-malignant indications, each TPE session removed a mean 70.8% sPD-L1 and 73.1% evPD-L1 detectable in plasma. TPE also reduced total and ADAM10-positive extracellular vesicles. Conclusion Here, we report the first known clinical intervention to remove either sPD-L1 or evPD-L1 from plasma in vivo. TPE reduces plasma sPD-L1 and evPD-L1 in vivo and may have a role in treatment with immunotherapy. TPE may also prove useful in patients with other extracellular vesicle-related conditions.
Demonstrating the Benefits of Predictive Bayesian Dose–Response Relationships Using Six Exposure Studies of Cryptosporidium parvum

A conventional dose–response function can be refitted as additional data become available. A predictive dose–response function in contrast does not require a curve‐fitting step, only additional data and presents the unconditional probabilities of illness, reflecting the level of information it contains. In contrast, the predictive Bayesian dose–response function becomes progressively less conservative as more information is included. This investigation evaluated the potential for using predictive Bayesian methods to develop a dose–response for human infection that improves on existing models, to show how predictive Bayesian statistical methods can utilize additional data, and expand the Bayesian methods for a broad audience including those concerned about an oversimplification of dose–response curve use in quantitative microbial risk assessment (QMRA). This study used a dose–response relationship incorporating six separate data sets for Cryptosporidium parvum. A Pareto II distribution with known priors was applied to one of the six data sets to calibrate the model, while the others were used for subsequent updating. While epidemiological principles indicate that local variations, host susceptibility, and organism strain virulence may vary, the six data sets all appear to be well characterized using the Bayesian approach. The adaptable model was applied to an existing data set for Campylobacter jejuni for model validation purposes, which yielded results that demonstrate the ability to analyze a dose–response function with limited data using and update those relationships with new data. An analysis of the goodness of fit compared to the beta‐Poisson methods also demonstrated correlation between the predictive Bayesian model and the data.
Nanoparticles Presenting Potent TLR7/8 Agonists Enhance Anti-PD-L1 Immunotherapy in Cancer Treatment

Cancer immunotherapy can be augmented with toll-like receptor agonist (TLRa) adjuvants, which interact with immune cells to elicit potent immune activation. Despite their potential, use of many TLRa compounds has been limited clinically due to their extreme potency and lack of pharmacokinetic control, causing systemic toxicity from unregulated systemic cytokine release. Herein, we overcome these shortcomings by generating poly(ethylene glycol)–poly(lactic acid) (PEG–PLA) nanoparticles (NPs) presenting potent TLR7/8a moieties on their surface. The NP platform allows precise control of TLR7/8a valency and resulting surface presentation through self-assembly using nanoprecipitation. We hypothesize that the pharmacokinetic profile of the NPs minimizes systemic toxicity, localizing TLR7/8a presentation to the tumor bed and tumor-draining lymph nodes. In conjunction with antiprogrammed death-ligand 1 (anti-PD-L1) checkpoint blockade, peritumoral injection of TLR7/8a NPs slows tumor growth, extends survival, and decreases systemic toxicity in comparison to the free TLR7/8a in a murine colon adenocarcinoma model. These NPs constitute a modular platform for controlling pharmacokinetics of immunostimulatory molecules, resulting in increased potency and decreased toxicity.
Inter-Population Differences and Seasonal Dynamic of the Bacterial Gut Community in the Endangered Land Snail Helix pomatia (Gastropoda: Helicidae)

ABSTRACT Among the multifaceted environmental factors, the bacterial community ingested with soil and food might play an important role in physiological processes of terrestrial gastropods, with consequences on population dynamics and species distribution patterns. Therefore, we investigated the bacterial gut community structure and seasonal dynamic in three populations of the protected endangered land snail Helix pomatia. The PCR-DGGE fingerprinting analysis followed by Nonmetric Multidimensional Scaling (NMDS) showed that Gamma-and Alphaproteobacteria were common to all populations, while Mollicutes and Betaproteobacteria were population specific. Allochthonous strains might be transiently abundant in the gut of foraging snails with respect to habitat conditions. Autochthonous strains were permanently present in the gut, even after expulsion of the gut content at hibernation beginning. Some of these permanent strains are known to have ice-nucleating activity, which is consistent with the limited cold hardiness in this species. Snails that did not enter hibernation despite being exposed to winter conditions had a poor bacterial community. In conclusion, the bacterial community structure differed between habitats and physiological states, and might be important for physiological processes and survival. Further studies should focus on the individual variation in bacterial community and investigate how it is affected by environmental changes.
Physical activity on days with and without soccer practice in 12-13-year-old boys

ABSTRACT Introduction: Majority of children are unable to meet the recommended 60min of daily moderate to vigorous physical activity (MVPA). Even participation into organized sport may not guarantee that recommended amount of activity is reached. Objectives: Purpose of this study was to examine the amount and intensity of physical activity (PA) on days with and without practices and to find out whether daytime PA preceding soccer practice is associated with certain practice-time PA intensity level. Methods: Daily light, moderate and vigorous PA of 18 boys between 12 and 13 years of age engaged in soccer was measured for 9 days with and without soccer practices with wrist-worn Polar A300 activity meter. In addition, PA during practices was extracted and compared to PA preceding the practice session. Results: The daily MVPA was twice as high on days with training as compared to days without training both on weekdays (mean difference ± 95% confidence interval = 67 min ± 14 min) and on weekend (63 min ± 36 min). PA preceding soccer practice had a positive correlation with all PA intensity levels during practice (r = 0.34–0.84, p < 0.05–0.01). Conclusion: Physical activity should be promoted especially on days without organized practices and children should be encouraged to be physically active throughout the day as this was not found to compromise their activity during training.
Colitis cystica profunda mimicking mucinous adenocarcinoma of the rectum diagnosed by endoscopic submucosal dissection

A 48-year-old man presented to our hospital with complaints of fresh rectal bleeding. He was intellectually disabled and often inserted his fingers into the anus after defecation. Laboratory investigations demonstrated lowered hemoglobin level (9.3g/dL; normal range 13.5– 17.5g/dL). Colonoscopy showed a polypoid submucosal tumor-like elevated lesion with redness and rough surface, along with erosion in the lower rectum (▶Fig. 1 a, b). Endoscopic ultrasonography (EUS) showed hypoechoic and several anechoic cystic lesions in the submucosa, without invasion of the muscularis propria (▶Fig. 1 c). Magnetic resonance imaging (MRI) showed peripheral contrast-enhanced cystic lesions in the lower rectum. Regional lymphadenitis in the lower rectum was not seen on MRI (▶Fig. 2). Boring biopsy was suggestive of mucinous adenocarcinoma. After obtaining informed consent, we performed endoscopic submucosal dissection (ESD) for complete en bloc resection to confirm the preoperative diagnosis (▶Fig. 1d, ▶Fig. 3 a, ▶Video 1). Histological examination revealed colitis cystica profunda (CCP) with no evidence of dysplasia or malignancy (▶Fig. 3b, c). The patient progressed well after ESD and was discharged 7 days postoperatively. The patient was treated conservatively to improve bowel habits. CCP is a rare benign disease characterized by mucin-filled cysts beneath the muscularis mucosa [1]. Knowledge of this pathological entity is important as it can mimic a well-differentiated adenocarcinoma of the rectum and therefore could lead to unnecessary surgical resection [2]. EUS, computed tomography, and MRI are useful for diagnosis of CCP [3, 4]; however, the definitive diagnosis is based on endoscopic biopsies, which should be large and deep enough to include the submucosal layer, or resected surgical E-Videos
A Review on The Processing and Analysis of Next-generation RNA-seq Data

With the rapid development of the next-generation sequencing(NGS) technology,high-throughput RNA sequencing or RNA-seq is becoming a key experimental approach in the study of gene expression and transcriptome.The overwhelming amount of RNA-seq data brings new opportunities and challenges for bioinformatics.The efficient and effective processing and analysis of RNA-seq data is becoming the bottleneck for turning the possibilities provided by the new technology into real scientific discovery.A general description of the typical RNA-seq protocol was given.A complete review of major methods and available software in the processing and analysis of RNA-seq data were presented,using the Illumina/Solexa platform as an example.Questions that are still open and awaiting further research are also discussed.
Baroclinic Instability of a Rotating Hadley Cell

Abstract The stability of a thin fluid layer between two rotating plates which are subjected to a horizontal temperature gradient is studied. First, the solution for the stationary basic state is obtained in a closed form. This solution identifies Ekman and thermal layers adjacent to the plates and interior temperature and velocity fields which are almost linear functions of height. Then the stability of that basic state with respect to infinitesimal zonal waves is analyzed via the solution of the complete viscous linear equations for the perturbations. The character of the growth rates is found to be similar to the growth rates of the classical baroclinic waves. The neutral stability curves for these waves possessed a knee in the Rossby-Taylor number plane to the left of which all perturbations are stable. The region of instability is found to depend on the Prandtl number, the vertical stratification parameter, and both the meridional and zonal wavenumbers. It is found in general that the flow is unstabl.
Interventions to optimise transitional care coordination for older people living with dementia and concomitant multimorbidity and their caregivers: A systematic review

Background: People living with dementia and multimorbidity are frequent uses of health, amplifying risk of fragmented care when moving between care settings. Objectives: This Systematic review aims to identify interventions to support transitional care for older people living with dementia and multimorbidity, and their caregivers. Methods: A systematic search from January 2000-2018 of academic databases for studies which implemented a transitional care intervention for older people living with dementia and multimorbidity, and their caregivers. Results: Out of 6053 identified citations, 11 studies and 13 papers were included. These studies included 1861 people living with dementia, mean age 80 years and 1503 caregivers, mean age of 69 years. Narrative synthesis identifed six elements of care that optimise outcomes; unmet needs; depression; education and support; physical decline; poor quality of life and; access and knowledge of community services. Conclusion: This review demonstrates the paucity of interventions available to reduce impact and experiences of transitions for this vulnerable population. The need is increasing for further research and development in transitional care.
The possible effect of silver nanoparticles on glyceraldehyde‐3‐phosphate dehydrogenase activity and formation of amyloid‐like aggregates in MCF‐7 cell line

Silver nanoparticles (AgNPs) are widely used in medicine, however, the underlying mechanisms of their action on cellular signaling have not been completely determined, and fundamental studies are required to clarify them. We aimed to investigate AgNPs effects on glyceraldehyde‐3‐phosphate dehydrogenase (GAPDH) as both the internal control gene and the redox‐sensitive enzyme involved in apoptosis‐related pathways and the formation of amyloid aggregates. To achieve this purpose, MCF‐7 cells were treated with different concentrations (0, 3, 22, and 200 μg/ml) of AgNPs and then cell viability, generation of reactive oxygen species (ROS), induction of apoptosis, expression of GAPDH gene, the formation of amyloid aggregates, and GAPDH activity were assessed. The results indicated that treatment with AgNPs significantly reduced cell viability and increased apoptosis in a dose‐dependent manner. The ROS levels increased at lower concentrations of AgNPs (up to 22 μg/ml) and during short‐term exposure (30 min). The level of GAPDH gene expression was significantly upregulated by 1.22, 1.47, and 1.56 fold, in the concentrations of 3, 22, and 200 μg/ml, respectively. The amount of amyloid aggregates was significantly increased in a dose‐dependent manner. The results of enzyme activity showed that AgNPs were affected on the activity of GAPDH protein, however, it has fluctuated that could not be interpreted by our limited data. In conclusion, our results suggested that AgNPs could affect the GAPDH gene expression and enzyme activity, therefore the selection of GAPDH as a gene and protein internal control in the (AgNPs)‐related studies requires careful consideration. Additionally, AgNPs may cause apoptosis due to the increase in the production of amyloid aggregates.
Evaluation of TP53 Codon 72, P21 Codon 31, and MDM2 SNP309 Polymorphisms in Iranian Patients with Acute Lymphocytic Leukemia.

Background The tumor suppressing protein p53 and its downstream effector p21 play important roles in cell cycle regulation. Deficiency or deactivation of these proteins as a result of gene alterations has been indicated in several cancers. Such genetic variations could be considered as susceptibility indicators in acute lymphocytic leukemia (ALL). Therefore, we investigated the associations between ALL risk and TP53 codon 72, p21 codon 31, and MDM2 SNP309 polymorphisms in an Iranian population. Methods Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the MDM2 T309G (rs2279744), TP53 codon Arg72Pro (rs1042522), and p21 Ser31Arg (rs1801270) single nucleotide polymorphisms (SNPs). This study was performed in 115 ALL patients and 115 healthy controls in Khuzestan province in southwest Iran. Results In the control group and ALL patients, p21 Ser/Arg, and MDM2 TG and GG genotypes were associated with significant 1.81-fold (95% confidence interval CI= 1.008-3.267; P < 0.05), 11.07-fold (95% CI= 5.10-24.05; P < 0.0001), and 19.41-fold (95% CI= 8.56-43.99; P < 0.0001) increased risks for ALL, respectively. The TP53 72 Arg allele was significantly more prevalent in ALL patients (56.96%) than in control subjects (47.39%), and was significantly associated with ALL (OR= 1.47; 95% CI = 1.017-2.121, P < 0.05). Conclusion The MDM2T309G and the p21 Ser31Arg SNPs indicate a significantly increased risk for developing ALL in Khuzestan province.
Reproductive senescence and energetic metabolism of human luteinized granulosa cells: is it all about ATP? A prospective cohort and critical view

Abstract Mitochondria are known to play a key role in the regulation of reproductive capacity. Senescence is known to impair mitochondrial function and, ultimately, cellular energetic metabolism. Therefore, as women age, a deficient energy supply is likely to affect oocyte quality. The analysis of granulosa cells is considered a valuable noninvasive strategy to assess factors implicated in oocyte competence. Thus, we conducted an observational prospective cohort to evaluate the impact of aging on energy production by luteinized granulosa cells (LGCs). The control group comprised 13 young oocyte donors, whereas the comparison group included 13 infertile women over 38 years of age undergoing in vitro fertilization. Women with diseases that could potentially impact mitochondrial function were excluded. No differences were detected in the ATP levels in LGCs from young donors and infertile patients of advanced reproductive age (1.9 ± 0.99 picomoles in the control group vs. 2.1 ± 0.59 picomoles; p-value = .139). Likewise, the ATP levels in our series did not correlate with either oocyte number or maturity. Despite the similar ATP levels in LGCs, an age effect on the bioenergetic status cannot be excluded. Energy metabolism is very complex, and ATP does not seem to be the most important and reliable parameter.
Research Reports: Size Difference Among 16S rRNA Genes From Endosymbiontic Bacteria Found in Testes of Heliothis Virescens, H. Subflexa, (Lepidoptera: Noctuidae) and Backcross Sterile Male Moths

Experimentally induced interspecific matings between Heliothis virescens male and H. subflexa female moths result in sterile male and fertile female offspring. The fertile female progeny can be backcrossed with H. virescens males to produce more sterile male and fertile female offspring. Successive generations of backcross female progeny continue to produce sterile male and fertile female offspring when backcrossed to H. virescens males. Backcross sterile males readily mate with wild-type H. virescens females under field conditions. Backcross male sterility is of interest for its potential to suppress populations of the pest moth Heliothis virescens. Rickettsia-like organisms have been observed in the testes of backcross sterile males and the two parental species of Heliothis. Prokaryotic endosymbionts have been associated with hybrid sterility in other insects. Therefore, we investigated Heliothis endosymbionts via an analysis of their PCR-amplified rRNA genes (rDNA). Prokaryotic-specific primers were used to amplify 16S rDNA from aseptically removed testes. PCR reactions without testes extract were negative. Endosymbionts from H. virescens and H. subflexa were genetically different. The size of PCR-amplified 16S rDNA indicates that endosymbionts in backcross sterile males originate from H. subflexa. Sterile males have essentially a H. virescens nuclear genome as a result of backcrossing. We propose that backcross male sterility results from an incompatibility between the maternally inherited endosymbiont type found in the cytoplasm and the predominantly paternal genetic material found in the nucleus.
Acupuncture for patients with chronic pruritus: protocol of a systematic review and meta-analysis

Introduction Chronic pruritus (CP) frequently occurs in many skin and systemic diseases, and adversely affects quality of life. This systematic review aims to evaluate treatment effects of acupuncture on CP. Methods and analysis An electronic and manual search will be conducted for all acupuncture treatments for CP, from the inception date of predefined database up to 28 February 2020. Databases include PubMed, Embase, Springer, Web of Science, the Cochrane Library, the World Health Organization International Clinical Trial Registration Platform, the Chinese Medicine Database, the China National Knowledge Infrastructure, the Chinese Biomedical Literature Database, the China Science Journal Database and the Wanfang Database. Other sources, including existing systematic reviews, conference proceedings and reference lists of identified publications will also be searched. Additionally, any clinical randomised controlled trials related to acupuncture treatment for CP, regardless of the publication status and language limitations, will be included. Study selection, data extraction and research quality assessments will be conducted independently by two researchers. The primary outcome measures include the Visual Analogue Scale, Urdu 5D-Itch Scale or other validated scales implemented after at least 2 weeks of treatment. Secondary outcomes include the effective rate, Quality of Life Scale (eg, the EQ-5D third level, the Dermatology Life Quality Index, etc.), Pittsburgh Sleep Quality Index, recurrence rate during the follow-up period and adverse events. If possible, meta-analyses will be performed using RevMan V.5. 3 statistical software; otherwise, a descriptive analysis or subgroup analysis will be conducted. The results will be presented as the risk ratio of the binary data and the mean difference (MD) or standardised MD of the continuous data. Ethics and dissemination This systematic review protocol does not require formal ethical approval because the data are not personalised. It will be published in peer-reviewed journals and presented at international academic conferences. PROSPERO registration number CRD42019136727.
Role of microRNAs in myogenesis and their effects on meat quality in pig — A review

The demand for food is increasing day by day because of the increasing global population. Therefore, meat, the easiest and largely available source of protein, needs to be produced in large amounts with good quality. The pork industry is a significant shareholder in fulfilling the global meat demands. Notably, myogenesis-development of muscles during embryogenesis- is a complex mechanism which culminates in meat production. But the molecular mechanisms which govern the myogenesis are less known. The involvement of miRNAs in myogenesis and meat quality, which depends on factors such as myofiber composition and intramuscular fat contents which determine the meat color, flavor, juiciness, and water holding capacity, are being extrapolated to increase both the quantity and quality of pork. Various kinds of microRNAs (miRNAs), miR-1, miR-21, miR22, miR-27, miR-34, miR-127, miR-133, miR-143, miR-155, miR-199, miR-206, miR-208, miR-378, and miR-432 play important roles in pig skeletal muscle development. Further, the quality of meat also depends upon myofiber which is developed through the expression of different kinds of miRNAs at different stages. This review will focus on the mechanism of myogenesis, the role of miRNAs in myogenesis, and meat quality with a focus on the pig.