Miracle-dz/UniFAR-FTUs huggingface dataset:
Pembrolizumab as first line treatment of Merkel cell carcinoma patients – a case series of patients with various co-morbidities

Merkel cell carcinoma (MCC) is a rare but highly aggressive neuroendocrine skin cancer associated with a high mortality rate in advanced stages [1,2]. For patients with nonresectable advanced/metastatic MCC, chemotherapy has been the systemic treatment of choice with high response rates albeit seldom durable and linked with significant toxicities [3,4]. Increased insight into the biology and immunological interplay has identified MCC as an immunogenic disease [5,6], and results from two phase 2 trials targeting the PD-1/L1 pathway have been promising [7,8]. A recent report by Nghiem et al. confirmed previous findings with longer follow up after administering the PD-1 antagonist pembrolizumab as first line therapy for 50 patients with advanced-stage MCC [9]. The objective response rate (ORR) remained at 56%, the 24-month progression free survival (PFS) rate was 48.3%, the median overall survival (OS) was not reached and the OS rate at 24months was 68%. Meanwhile, there is a concern that the published results do not apply to real-world patients with MCC since the treated patients were much younger and without significant co-morbidities known to be risk factors for MCC patients. We have treated seven patients with advanced MCC with pembrolizumab as first line therapy at our institution and with this report wish to investigate the efficacy and tolerability in a real-world setting.
Harnessing Cross-Reactive CD8+ TRM Cells for Long-Standing Protection Against Influenza A Virus

As of today, influenza A virus infection is very much a health issue for the human population. Over a 100 years have passed since the 1918 influenza pandemic that caused the deaths of tens of millions of people over the world, but despite this we have not been able to develop an efficient vaccine that can protect the population. Since they first became available, >60 years ago, commercial vaccines all primarily induce an antibody response targeting the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA). The vaccine is the most effective method of protecting the population against influenza infection available today, nevertheless the U.S. Centers for Disease Control and Prevention estimated the efficiency to be ranging between 20% and 60% over the last years (12,33,40,48,60). The major underlying reason for this is the ever-evolving influenza A virus. Genetic drift results in changes of the surface proteins, making it impossible for antibodies to recognize and neutralize newly evolved virus. As a result, there is an annual need for re-evaluation and possibly re-formulation of the vaccine in an attempt to match the circulating strains. An alternative to the antibody-mediated immunity, targeting the variable HA and NA, is to induce cellular immunity targeting the highly conserved internal influenza proteins. Nineteen years ago from Peter C. Doherty’s laboratory, Christensen et al. published a study illustrating the capacity and critical role of CD8 T cells in heterosubtypic protection, an article that has become one of the cornerstones when discussing the important role of CD8 T cells in cross protection against respiratory viruses (8). The data presented in that article clearly demonstrated that by generating a large number of influenza-specific CD8 T cells, protection against influenza A challenge was improved, not only against homosubtypic strains, but also against heterosubtypic influenza strains where seroimmunity was lacking. Specifically, the T cell immune response was boosted by re-infection with serologically different influenza strains that shared the same CD8 T cell nucleoprotein (NP) epitope. When an influenzaspecific CD8 T cell population was present before challenge, limited expansion of the CD8 T cell population was required, thus not only protecting against the virus infection but also limiting immunopathology. The article also illustrated that pre-existing cellular immunity have limitations. Despite high numbers of cross-reactive CD8 T cells, present as early as 1-day postchallenge, viral titers did not differ from groups with no T cell immunity. This pinpointed another important fact, the CD8 T cell response will first be activated after the influenza virus has infected its host. Since this publication in 2000, substantial effort has been put into understanding the basic foundations necessary for designing a vaccine generating a long-lasting cross-protective CD8 T cell population.
rMAPS2: an update of the RNA map analysis and plotting server for alternative splicing regulation

Abstract The rMAPS2 (RNA Map Analysis and Plotting Server 2) web server, freely available at http://rmaps.cecsresearch. org/, has provided the high-throughput sequencing data research community with curated tools for the identification of RNA binding protein sites. rMAPS2 analyzes differential alternative splicing or CLIP peak data obtained from high-throughput sequencing data analysis tools like MISO, rMATS, Piranha, PIPE-CLIP and PARalyzer, and then, graphically displays enriched RNA-binding protein target sites. The initial release of rMAPS focused only on the most common alternative splicing event, skipped exon or exon skipping. However, there was a high demand for the analysis of other major types of alternative splicing events, especially for retained intron events since this is the most common type of alternative splicing in plants, such as Arabidopsis thaliana. Here, we expanded the implementation of rMAPS2 to facilitate analyses for all five major types of alternative splicing events: skipped exon, mutually exclusive exons, alternative 5′ splice site, alternative 3′ splice site and retained intron. In addition, by employing multi-threading, rMAPS2 has vastly improved the user experience with significant reductions in running time, ∼3.5 min for the analysis of all five major alternative splicing types at once.
Why Are People Loyal to Live Stream Channels? The Perspectives of Uses and Gratifications and Media Richness Theories

Live stream services have emerged as a highly profitable Internet application in recent years with rapidly growing audiences for this form of instant and interactive Internet media. This study applies media richness theory along with uses and gratifications theory to predict user loyalty to live stream services. The proposed model is empirically evaluated using survey data collected from 295 users responding about their perception of such services. Empirical results show that perceived media richness and gratifications such as entertainment and sociability are antecedents of loyalty, while immediate feedback is the most salient facet of perceived media richness. The results provide further useful insights for service providers and streamers to build loyal user bases.
π-π-Stacked Poly(ε-caprolactone)-b-poly(ethylene glycol) Micelles Loaded with a Photosensitizer for Photodynamic Therapy

To improve the in vivo stability of poly(ε-caprolactone)-b-poly(ethylene glycol) (PCL-PEG)-based micelles and cargo retention by π-π stacking interactions, pendant aromatic rings were introduced by copolymerization of ε-caprolactone with benzyl 5-methyl-2-oxo-1,3-dioxane-5-carboxylate (TMC-Bz). It was shown that the incorporation of aromatic rings yielded smaller micelles (18–30 nm) with better colloidal stability in PBS than micelles without aromatic groups. The circulation time of i.v. injected micelles containing multiple pendant aromatic groups was longer (t½-α: ~0.7 h; t½-β: 2.9 h) than that of micelles with a single terminal aromatic group (t½ < 0.3 h). In addition, the in vitro partitioning of the encapsulated photosensitizer (meta-tetra(hydroxyphenyl)chlorin, mTHPC) between micelles and human plasma was favored towards micelles for those that contained the pendant aromatic groups. However, this was not sufficient to fully retain mTHPC in the micelles in vivo, as indicated by similar biodistribution patterns of micellar mTHPC compared to free mTHPC, and unequal biodistribution patterns of mTHPC and the host micelles. Our study points out that more detailed in vitro methods are necessary to more reliably predict in vivo outcomes. Furthermore, additional measures beyond π-π stacking are needed to stably incorporate mTHPC in micelles in order to benefit from the use of micelles as targeted delivery systems.
Trace Elements, PPARs, and Metabolic Syndrome

Metabolic syndrome (MetS) is a constellation of metabolic derangements, including central obesity, insulin resistance, hypertension, glucose intolerance, and dyslipidemia. The pathogenesis of MetS has been intensively studied, and now many factors are recognized to contribute to the development of MetS. Among these, trace elements influence the structure of proteins, enzymes, and complex carbohydrates, and thus an imbalance in trace elements is an independent risk factor for MetS. The molecular link between trace elements and metabolic homeostasis has been established, and peroxisome proliferator-activated receptors (PPARs) have appeared as key regulators bridging these two elements. This is because on one hand, PPARs are actively involved in various metabolic processes, such as abdominal adiposity and insulin sensitivity, and on the other hand, PPARs sensitively respond to changes in trace elements. For example, an iron overload attenuates hepatic mRNA expression of Ppar-α; zinc supplementation is considered to recover the DNA-binding activity of PPAR-α, which is impaired in steatotic mouse liver; selenium administration downregulates mRNA expression of Ppar-γ, thereby improving lipid metabolism and oxidative status in the liver of high-fat diet (HFD)-fed mice. More importantly, PPARs’ expression and activity are under the control of the circadian clock and show a robust 24 h rhythmicity, which might be the reasons for the side effects and the clinical limitations of trace elements targeting PPARs. Taken together, understanding the casual relationships among trace elements, PPARs’ actions, and the pathogenesis of MetS is of great importance. Further studies are required to explore the chronopharmacological effects of trace elements on the diurnal oscillation of PPARs and the consequent development of MetS.
B cells and multiple sclerosis spinal cord pathology

© 2020 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made. COMMENTARY
"If we do not look for it, we do not see it": Clinicians' experiences and understanding of identifying post-traumatic stress disorder in adults with autism and intellectual disability.

BACKGROUND Individuals with autism spectrum disorder (ASD) and intellectual disability (ID) are at increased risk of potentially traumatic events and may be at increased risk of post-traumatic stress disorder (PTSD). However, knowledge regarding identification of PTSD in this population is limited. The aim of this study was to investigate clinical experience regarding PTSD and trauma assessment in individuals with co-occurring ASD and ID. METHOD Interpretative phenomenological analysis was used to explore experiences of identifying PTSD in this population among 18 mental health clinicians working with ASD and ID. RESULTS Informants viewed PTSD in individuals with ASD and ID as equivalent to PTSD in the general population, but with causes and expressions potentially differing. Several factors were described to contribute to challenges in identification. CONCLUSIONS Trauma may have severe impact in individuals with ASD and ID. Multidimensional, individualized assessment strategies seem necessary to recognize PTSD or trauma-related symptoms in this population.
Mass-Spectrometry-Based Identification of Synthetic Drug Isomers Using Infrared Ion Spectroscopy

Infrared ion spectroscopy (IRIS), a mass-spectrometry-based technique exploiting resonant infrared multiple photon dissociation (IRMPD), has been applied for the identification of novel psychoactive substances (NPS). Identification of the precise isomeric forms of NPS is of significant forensic relevance since legal controls are dependent on even minor molecular differences such as a single ring-substituent position. Using three isomers of fluoroamphetamine and two ring-isomers of both MDA and MDMA, we demonstrate the ability of IRIS to distinguish closely related NPS. Computationally predicted infrared (IR) spectra are shown to correspond with experimental spectra and could explain the molecular origins of their distinctive IR absorption bands. IRIS was then used to investigate a confiscated street sample containing two unknown substances. One substance could easily be identified by comparison to the IR spectra of reference standards. For the other substance, however, this approach proved inconclusive due to incomplete mass spectral databases as well as a lack of available reference compounds, two common analytical limitations resulting from the rapid development of NPS. Most excitingly, the second unknown substance could nevertheless be identified by using computationally predicted IR spectra of several potential candidate structures instead of their experimental reference spectra.
Mucin-Derived O-Glycans Act as Endogenous Fiber and Sustain Mucosal Immune Homeostasis via Short-Chain Fatty Acid Production in Rat Cecum.

BACKGROUND Intestinal mucins escape digestion and enter the large bowel where they are degraded by the microbiota. To what extent and how mucins impact large-bowel physiology remain unclear. OBJECTIVE This study examined the large-bowel fermentation characteristics of mucins and mucin-derived O-glycan sugars and whether they affect gut immunity. METHODS Mucin secretion from the terminal ileum was determined from feces of ileorectostomized male Wistar rats (age 6 wk) fed an AIN76-based control diet (CD) for 15 d (experiment 1). Normal male Wistar rats (age 6 wk; 4 wk for experiment 4) were fed CD ± porcine stomach mucin (PM) at 6 or 12 g/kg diet, equivalent to 1.5 and 3 times the daily mucin secretion, for 14 d (experiment 2); CD ± N-acetylglucosamine (GlcNAc), fucose, or N-acetylneuraminic acid at 10 g/kg diet for 14 d (experiment 3); or CD ± PM (15 g/kg diet) or GlcNAc (10 g/kg diet) for 29 d (experiment 4). SCFAs, microbial composition, and cecal O-glycan content were assessed. IgA+ plasma cells and regulatory T cells and inflammatory cytokine expression in the cecum were evaluated (experiment 4). RESULTS Daily mucin secretion corresponded to 43.2 μmol of O-glycans. Cecal O-glycan contents were comparable between CD- and PM-fed rats. PM-fed rats harbored more mucin-degrading bacteria. Cecal concentrations of acetate (+37%) and n-butyrate (+73%) were higher in 12-g/kg PM diet-fed rats versus CD (P < 0.05). Among O-glycan sugars, only GlcNAc produced higher n-butyrate concentrations (+68%) versus CD (P < 0.05), with increased numbers of butyrate-producing bacteria. GlcNAc increased the abundance of IgA+ plasma cells (+29%) and regulatory T cells (+33%) versus CD, whereas PM increased IgA+ plasma cells (+25%) (all P < 0.05). GlcNAc and PM decreased expression of Tnfa (-30%, -40%) and Ifng (-30%, -70%) versus CD (all P < 0.05). CONCLUSIONS Mucin-derived O-glycans act as endogenous fiber and maintain mucosal immune homeostasis via large-bowel SCFA production in rats.
In Vitro Impact Testing to Simulate Implant-Supported Prosthesis Retrievability in Clinical Practice: Influence of Cement and Abutment Geometry

Cement-retained implant-supported prosthetics are gaining popularity compared to the alternative screw-retained type, a rise that serves to highlight the importance of retrievability. The aim of the present investigation is to determine the influence of luting agent, abutment height and taper angle on the retrievability of abutment–coping cementations. Abutments with different heights and tapers were screwed onto an implant and their cobalt-chrome copings were cemented on the abutments using three different luting agents. The removals were performed by means of Coronaflex®. The number of impulses and the forces were recorded and analyzed with a Kruskal–Wallis test. Harvard cement needed the highest number of impulses for retrieval, followed by Telio CS and Temp Bond. However, abutment height and taper showed a greater influence on the cap’s retrievability (p < 0.05). Long and tapered abutments provided the highest percentage of good retrievability. The influence of the luting agent and the abutment geometry on the cap’s retrieval performed by Coronaflex® reflects data from literature about the influence of the same factor on the maximum force reached during uniaxial tensile tests. The impulse force was slightly affected by the same factors.
Heart failure management in dialysis patients: Many treatment options with no clear evidence

Heart failure with reduced ejection fraction (HFrEF) impacts approximately 20% of dialysis patients and is associated with high mortality rates. Key issues discussed in this review of HFrEF management in dialysis include dialysis modality choice, vascular access, dialysate composition, pharmacological therapies, and strategies to reduce sudden cardiac death, including the use of cardiac devices. Peritoneal dialysis and more frequent or longer duration of hemodialysis may be better tolerated due to slower ultrafiltration rates, leading to less intradialytic hypotension and better volume control; dialysate cooling and higher dialysate calcium may also have benefits. While high‐quality evidence exists for many drug classes in the non‐dialysis population, dialysis patients were excluded from major trials, and only limited data exist for many medications in kidney failure patients. Despite limited evidence, beta blocker and angiotensin‐converting enzyme inhibitor or angiotensin receptor blocker use is common in dialysis. Similarly, devices such as implantable cardiac defibrillators (ICDs) and cardiac resynchronization therapy that have proven benefits in non‐dialysis HFrEF patients have not consistently been beneficial in the limited dialysis studies. The use of leadless pacemakers and subcutaneous ICDs can mitigate future hemodialysis access limitations. Additional research is critical to address knowledge gaps in treating maintenance dialysis patients with HFrEF.
Estudio comparado del pars stridens en las obreras de cinco nidos de Aphaenogaster senilis Mayr; 1853 (Hymenoptera, Formicidae)

In this paper we describe the stridulatory organ on workers of Aphaenogaster senilis, paying special attention to its pars stridens. We observe that it has the same morphological characteristics as other known Formicidae. Five ant-nests have been studied and we found significant differences between them in the length and the width of pars stridens. Workers of one ant-nest have the longest pars stridens, while the workers of another ant-nest have the widest. The distance between the ridges is similar for the five ant-nests. The head width is directly related to the body size ELMES, (1976). For this characteristic, we find significant differences since the workers of two of the ant-nests have shorter head sizes than those of the others, the workers of one of these nests have the longest pars stridens. 11 Alvarez 2/5/06 08:54 Página 93
Supplementation effect of thermotolerant yeast on nutrient utilization and rumen fermentation in Nellore lambs.

Abstract Eighteen Nellore ram lambs (23.65 ± 0.25 kg body weight, aged 6 months) were used for evaluation of test diets to determine nutrientdigestibility, plane of nutrition, nitrogen balance and rumen fermentation pattern. Lambs were fed finishing diets and assignedrandomly to one of three dietary treatments. Treatment diets were no yeast (CON; n = 6), with 1 g/kg mesophilic yeast MTCC­1813(MPY; n = 6) and with 1 g/kg thermotolerant yeast OBV­9 (TPY; n = 6). Dry matter intake (DMI), DMI (% b. wt.) and DMI/kgW0.75 were higher (P<0.01) for the TPY group than MPY and CON groups.Digestibility of DM, OM (P<0.05), CP, CF, NFE, aNDF, ADF, Hemicellulose (P<0.05) and Cellulose were higher (P<0.01) on TPY dietcompared to MPY and CON diets, indicating importance of thermotolerant yeast over mesophilic yeast. All Lambs were in positivenitrogen balance and was higher (P<0.01) on both TPY and MPY diets than CON diet. DCP, TDN and ME were significantly (P<0.01)higher on TPY diet, followed by MPY diet compared to CON diet. All the nitrogen fractions of rumen fluid (except food and protozoalnitrogen), pH and TVFA were higher (P<0.01) on TPY diet, compared to other two diets. Time of sampling also had significant(P<0.01) effect on concentration of all rumen nitrogen fractions and TVFA, which peaked at 4 h post feeding, while ammonia nitrogenand pH, peaked at 2 h post feeding irrespective of rations. The present study demonstrated the potential for supplementingtheromotolerant probiotic yeast by improving the digestibility of nutrients, intake and content of DCP, TDN and ME, positivenitrogen balance and rumen profiles without adverse effect on the health of Nellore ram lambs. Thus, incorporation of thermotolerantprobiotic yeast in straw based complete diet even when compared to mesophilic yeast, seems to be beneficial for livestock producers.Keywords: digestibility, N retention, ram lambs, rumen profiles
Mindfulness and Job Satisfaction Among Hospital Nurses: The Mediating Roles of Positive Affect and Resilience.

The current study aimed to explore the relationships between nurses' mindfulness and job satisfaction and the mediating roles of positive affect and resilience. A total of 1,043 Chinese hospital nurses completed self-report questionnaires from March to April 2019. Pearson's correlation analysis was used to identify the relationships among the four variables, and the bias-corrected bootstrap method was used to test the mediation hypotheses. The results revealed that nurses' mindfulness was at a medium-high level, whereas positive affect, resilience, and job satisfaction were at medium levels. The total scores and dimension scores of the four variables showed strong positive correlations, and nurses' mindfulness affected job satisfaction directly and indirectly through the intermediary roles of positive affect and resilience. Nursing managers should recognize the importance of mindfulness and incorporate mindfulness training into health promotion and employee management plans for hospital nurses. In addition, strategies should be implemented to cultivate positive affect and resilience. [Journal of Psychosocial Nursing and Mental Health Services, xx(x), xx-xx. ].