Miracle-dz/UniFAR-FTUs huggingface dataset:
Comparative safety of immune checkpoint inhibitors in cancer: systematic review and network meta-analysis

Abstract Objective To provide a complete toxicity profile, toxicity spectrum, and a safety ranking of immune checkpoint inhibitor (ICI) drugs for treatment of cancer. Design Systematic review and network meta-analysis. Data sources Electronic databases (PubMed, Embase, Cochrane Library, and Web of Science) were systematically searched to include relevant studies published in English between January 2007 and February 2018. Review methods Only head-to-head phase II and III randomised controlled trials comparing any two or three of the following treatments or different doses of the same ICI drug were included: nivolumab, pembrolizumab, ipilimumab, tremelimumab, atezolizumab, conventional therapy (chemotherapy, targeted therapy, and their combinations), two ICI drugs, or one ICI drug with conventional therapy. Eligible studies must have reported site, organ, or system level data on treatment related adverse events. High quality, single arm trials and placebo controlled trials on ICI drugs were selected to establish a validation group. Results 36 head-to-head phase II and III randomised trials (n=15 370) were included. The general safety of ICI drugs ranked from high to low for all adverse events was as follows: atezolizumab (probability 76%, pooled incidence 66.4%), nivolumab (56%, 71.8%), pembrolizumab (55%, 75.1%), ipilimumab (55%, 86.8%), and tremelimumab (54%, not applicable). The general safety of ICI drugs ranked from high to low for severe or life threatening adverse events was as follows: atezolizumab (49%, 15.1%), nivolumab (46%, 14.1%), pembrolizumab (72%, 19.8%), ipilimumab (51%, 28.6%), and tremelimumab (28%, not applicable). Compared with conventional therapy, treatment-related adverse events for ICI drugs occurred mainly in the skin, endocrine, hepatic, and pulmonary systems. Taking one ICI drug was generally safer than taking two ICI drugs or one ICI drug with conventional therapy. Among the five ICI drugs, atezolizumab had the highest risk of hypothyroidism, nausea, and vomiting. The predominant treatment-related adverse events for pembrolizumab were arthralgia, pneumonitis, and hepatic toxicities. The main treatment-related adverse events for ipilimumab were skin, gastrointestinal, and renal toxicities. Nivolumab had a narrow and mild toxicity spectrum, mainly causing endocrine toxicities. Integrated evidence from the pooled incidences, subgroup, and sensitivity analyses implied that nivolumab is the best option in terms of safety, especially for the treatment of lung cancer. Conclusions Compared with other ICI drugs used to treat cancer, atezolizumab had the best safety profile in general, and nivolumab had the best safety profile in lung cancer when taking an integrated approach. The safety ranking of treatments based on ICI drugs is modulated by specific treatment-related adverse events. Systematic review registration PROSPERO CRD42017082553.
Phlebosclerotic colitis

Abstract The aim of the current study was to enhance the awareness of phlebosclerotic colitis (PC) through our clinical experience. A retrospective review of 25 patients who were diagnosed as PC in our 2 affiliated hospitals from January 2013 to October 2017 was conducted. The patients were found at a mean age of 63.5 years, range 47 to 87years. The majority of patients were male (23 cases). Only 4 patients (16%, 4/25) had the history about long-term use of Chinese herbs and medical liquor. The most common symptoms were abdominal pain (40%) and intestinal obstruction (16%), followed by diarrhea (12%), and gastrointestinal bleeding (12%), etc. Three cases (12%) had no symptoms. The varying degrees of calcifications along the colon and mesenteric venous were found in all of their computed tomography (CT) images. The lesions mainly located in transverse and ascending colon (60%, 15/25). The terminal ileum, the whole colon and rectum involvement were also been found. Fourteen patients had the examination of colonoscopy which all presented characteristic dark purple-colored endoscopic findings. Conservative treatment with close follow-up was preferred in our group. Three cases had the surgery of colectomy due to the repeatedly intestinal obstruction, perforation. The PC was a very rare but characteristic entity with unclear etiopathogenesis. Examination of abdomen CT and colonoscopy could help you to make clinical diagnosis.
I dream of Gini: Quantifying inequality in otolaryngology residency interviews

Otolaryngology applicants routinely decry conflicting interview dates because this limits the number of interviews that one can attend, despite being offered an interview. Conversely, applicants also perceive that a large number of interviews are offered to a minority of applicants. We sought to verify and quantify the inequality in distribution of interviews attended.
Avatars in Pain: Visible Harm Enhances Mind Perception in Humans and Robots

Previous research has shown that when people read vignettes about the infliction of harm upon an entity appearing to have no more than a liminal mind, their attributions of mind to that entity increased. Currently, we investigated if the presence of a facial wound enhanced the perception of mental capacities (experience and agency) in response to images of robotic and human-like avatars, compared with unharmed avatars. The results revealed that harmed versions of both robotic and human-like avatars were imbued with mind to a higher degree, irrespective of the baseline level of mind attributed to their unharmed counterparts. Perceptions of capacity for pain mediated attributions of experience, while both pain and empathy mediated attributions of abilities linked to agency. The findings suggest that harm, even when it appears to have been inflicted unintentionally, may augment mind perception for robotic as well as for nearly human entities, at least as long as it is perceived to elicit pain.
Cytomorphometric Neutrophil and Monocyte Markers May Strengthen the Diagnosis of Sepsis

Background: The diagnosis of sepsis is challenging in the absence of a gold standard test. Recent studies have explored the role of neutrophil and monocyte volume, conductivity, and scatter (VCS), derived from automated hematology analyzers, in diagnosing sepsis. We assessed the diagnostic accuracy of VCS parameters in critically ill patients with sepsis. Methodology: In this prospective study, VCS parameters, procalcitonin, and C-reactive protein (CRP) were assessed in patients with proven sepsis (cases) and 2 control groups (intensive care unit [ICU] patients without sepsis and healthy blood donors). The diagnostic property of each test was explored by calculating sensitivity, specificity, negative and positive predictive values, and area under the curve (AUC). Results: The study included 65 patients with sepsis, 58 nonseptic ICU controls, and 98 blood donors. Procalcitonin and CRP were not significantly different (P > .06) between patients with sepsis and nonseptic patients. Mean (95% confidence interval [CI]) neutrophil volume (MNV) was significantly higher (P < .001) in patients with sepsis (165.5; 95%CI 161.6-169.4) than in nonseptic (157.3; 95%CI 154.6-160.1) patients and donors (148.9; 95%CI 147.9-150). A similar pattern was seen with mean monocyte volume (MMoV). Neutrophil and monocyte conductivity and scatter parameters were variably associated. The AUC was highest for MMoV (0.74) and lowest for CRP (0.62). Among all parameters, MNV and MMoV had the highest specificity of 85% and 80%, respectively. Conclusion: In critically ill patients with suspected sepsis, VCS parameters may help strengthen the diagnostic probability of sepsis. Future studies may explore the role of serial monitoring of VCS to track response to antimicrobial therapy.
Structural mechanisms for defective CFTR gating caused by the Q1412X mutation, a severe Class VI pathogenic mutation in cystic fibrosis

Electrophysiological characterization of Q1412X‐CFTR, a C‐terminal truncation mutation of cystic fibrosis transmembrane conductance regulator (CFTR) associated with the severe form of cystic fibrosis (CF), reveals a gating defect that has not been reported previously. Mechanistic investigations of the gating deficit in Q1412X‐CFTR suggest that the reduced open probability in Q1412X‐CFTR is the result of a disruption of the function of the second ATP binding site (or site 2) in the nucleotide binding domains (NBDs). Detailed comparisons of several mutations with different degrees of truncation in the C‐terminal region of NBD2 reveal the importance of the last two beta‐strands in NBD2 for maintaining proper gating functions. The results of the present study also show that the application of clinically‐approved drugs (VX‐770 and VX‐809) can greatly enhance the function of Q1412X, providing in vitro evidence for a therapeutic strategy employing both reagents for patients bearing Q1412X or similar truncation mutations.
Viral Acute Respiratory Illnesses in Young Infants Increase the Risk of Respiratory Readmission

Background: Respiratory viruses cause acute respiratory illness (ARI) in early childhood, but their effect on subsequent ARI admissions is not fully understood. This study aimed to determine the association between initial ARI admission because of viruses including human rhinovirus (HRV), respiratory syncytial virus (RSV), human adenovirus (HAdV) and human metapneumovirus (hMPV) and the risk of ARI readmission in children. Methods: Clinical information and nasopharyngeal swab samples were collected from children <2 years old at their initial ARI admission in Nha Trang, Vietnam, from January 2007 to April 2012. The incidence of ARI readmission during the follow-up period (initial admission to 5 years of age) was compared between children with and without 1 of 13 respiratory viruses (influenza virus A, influenza virus B, RSV, hMPV, parainfluenza virus-1, parainfluenza virus-2, parainfluenza virus-3 and parainfluenza virus-4, HRV, human coronavirus-229E, human coronavirus-OC43, HAdV and human bocavirus) at initial admission. Results: A total of 1941 children were enrolled in the study. Viruses were detected in 1254 (64.6%) children at enrollment; HRV, RSV, HAdV and hMPV were detected in 499 (25.7%), 439 (22.6%), 156 (8.0%) and 47 (2.4%) children, respectively. During the follow-up period (4572.7 person-years), 277 children were readmitted with ARI. Virus-related ARI initial admission was associated with an increased risk of ARI readmission for children who were initially admitted before 6 months of age (adjusted rate ratio, 1.6; 95% confidence interval: 1.1–2.5). HAdV (4.6; 1.8–11.9), hMPV (20.4; 6.2–66.9) and HRV (1.6; 1.0–2.4) were independently associated with the outcome. These associations were not observed for children whose initial admission occurred after 6 months of age. Conclusions: HAdV-, hMPV- and HRV-related initial ARI admissions, when occurring during early infancy, increased the risk of subsequent ARI-related readmission.
Transmission Cycle Analysis in a Leishmania infantum Focus: Infection Rates and Blood Meal Origins in Sand Flies (Diptera: Psychodidae)

ABSTRACT: An entomological study was conducted in a Leishmania infantum focus, including the identification of the sand fly species, the detection and the characterization of Leishmania DNA in female sand flies, and blood meal origins in engorged sand flies. A total of 643 sand flies (31% female, 69% male) was identified based on their morphological features or molecular markers. Ten different species were identified, with Phlebotomus perniciosus, the confirmed vector of L. infantum, being the most abundant (56%), P. papatasi in 25% of sand flies, the unique vector species of L. major, and P. longicuspis in 7% of cases, the suspected second vector of L. infantum. Moreover, the infection rate was 3.4% in P. perniciousus, P. papatasi, P. longicuspis, and Sergentomya minuta. Also, L. infantum was identified in five unfed P. perniciosus and two P. longicuspis. Our results suggest the vector role of P. perniciosus and P. longicuspis in the transmission cycle of L. infantum. The DNA of four mammalian species (human, rabbit, horse, and cow) was identified in the blood meals of sand flies, suggesting that these species are potential reservoirs of leishmaniasis, though it is not yet fully elucidated (especially for MON-24 and MON-80). We suggest the existence of different transmission cycles of L. infantum involving different species of sand flies and hosts.
Trait-based predation suitability offers insight into effects of changing prey communities

Increasing environmental pressures and human impacts are reshaping community structures and species interactions throughout all trophic levels. The morphological and behavioural characteristics of species communities contain key ecological information on why prey species appear attractive to predators but are rarely applied when exploring predator-prey (PP) relationships. Expanding our knowledge on how changing prey communities can alter the food resource suitability (RS) for predators is vital for understanding PP dynamics in changing ecosystems. Detailed predator diet data are commonly restricted to commercially important species and often not available over long temporal scales. To find out whether structural changes of prey communities impact the food RS for predator communities over space and time, we apply a novel framework to describe and interpret changes in predator diet-suitability based on predation-relevant traits of prey. We use information on described feeding links from the literature to compile the prey spectrum for each predator and subsequently translate the prey-species into a prey-trait spectrum. For each predator, we then calculate a frequency-based prey-trait affinity score and relate it to the available food resource pool, the community weighted means of prey traits, resulting in a prey-suitability measure. We aim to reveal whether a described multi-decadal change in the community structure of zoobenthos had an impact on the food suitability for the benthic-feeding fish in a coastal system of the Baltic Sea. We assess the direction of change in resource quality from the perspective of benthic-feeding fish and describe predator-specific responses to examine which species are likely to profit or be disadvantaged by changes in their prey spectrum. Furthermore, we test the relationship between functional diversity of prey communities and food suitability for predators, and whether predation linkage-structures are affected through prey community-changes. Our results show that changes in zoobenthic communities had a positive effect on the food suitability for most benthic-feeding fish, implying more suitable food resources. Species-specific responses of predators suggest varying plasticity to cope with prey assemblages of different trait compositions. Additionally, the functional diversity of zoobenthos had a positive effect on the food suitability for predator fish. The changing trait compositions of prey influenced the PP linkage-structure, indicating varying specialisation of benthic feeding fish towards available food resources. Our findings suggest that changing morphological characteristics of prey can impact food RS features for its predators. This approach enables long-term evaluation of prey quality characteristics where no detailed diet data is available and allows for cross-system comparison as it is not relying on taxonomic identities per se.
More than just co-workers: Presence of humanoid robot co-worker influences human performance

Does the presence of a robot co-worker influence the performance of humans around it? Studies of motor contagions during human-robot interactions have examined either how the observation of a robot affects a human’s movement velocity, or how it affects the human’s movement variance, but never both together. Performance however, has to be measured considering both task speed (or frequency) as well as task accuracy. Here we examine an empirical repetitive industrial task in which a human participant and a humanoid robot work near each other. We systematically varied the robot behavior, and observed whether and how the performance of a human participant is affected by the presence of the robot. To investigate the effect of physical form, we added conditions where the robot co-worker torso and head were covered, and only the moving arm was visible to the human participants. Finally, we compared these behaviors with a human co-worker, and examined how the observed behavioral affects scale with experience of robots. Our results show that human task frequency, but not task accuracy, is affected by the observation of a humanoid robot co-worker, provided the robot’s head and torso are visible.
In situ Immune Signatures and Microbial Load at the Nasopharyngeal Interface in Children With Acute Respiratory Infection

Acute respiratory infection (ARI) is the most frequent cause for hospitalization in infants and young children. Using multiplexed nCounter technology to digitally quantify 600 human mRNAs in parallel with 14 virus- and 5 bacterium-specific RNAs, we characterized viral and bacterial presence in nasopharyngeal aspirates (NPA) of 58 children with ARI and determined the corresponding in situ immune profiles. NPA contained different groups of organisms and these were classified into bacterial (n = 27), viral (n = 5), codetection [containing both viral and bacterial transcripts (n = 21), or indeterminate intermediate where microbial load is below threshold (n = 5)]. We then identified differentially expressed immune transcripts (DEITs) comparing NPAs from symptomatic children vs. healthy controls, and comparing children presenting NPAs with detectable microbial load vs. indeterminate. We observed a strong innate immune response in NPAs, due to the presence of evolutionarily conserved type I Interferon (IFN)-stimulated genes (ISG), which was correlated with total bacterial and/or viral load. In comparison with indeterminate NPAs, adaptive immunity transcripts discriminated among viral, bacterial, and codetected microbial profiles. In viral NPAs, B cell transcripts were significantly enriched among DEITs, while only type III IFN was correlated with viral load. In bacterial NPAs, myeloid cells and coinhibitory transcripts were enriched and significantly correlated with bacterial load. In conclusion, digital nCounter transcriptomics provide a microbial and immunological in situ “snapshot” of the nasopharyngeal interface in children with ARI. This enabled discrimination among viral, bacterial, codetection, and indeterminate transcripts in the samples using non-invasive sampling.
The eggstraordinary story of how life begins

More than 15 years have elapsed since the identification of phospholipase C ζ1 (PLCζ) from a genomic search for mouse testis/sperm‐specific PLCs. This molecule was proposed to represent the sperm factor responsible for the initiation of calcium (Ca2+) oscillations required for egg activation and embryo development in mammals. Supporting evidence for this role emerged from studies documenting its expression in all mammals and other vertebrate species, the physiological Ca2+ rises induced by injection of its messenger RNA into mammalian and nonmammalian eggs, and the lack of expression in infertile males that fail intracytoplasmic sperm injection. In the last year, genetic animal models have added support to its role as the long sought‐after sperm factor. In this review, we highlight the findings that demonstrated the role of Ca2+ as the universal signal of egg activation and the experimental buildup that culminated with the identification of PLCζ as the soluble sperm factor. We also discuss the structural–functional properties that make PLCζ especially suited to evoke oscillations in eggs. Lastly, we examine unresolved aspects of the function and regulation of PLCζ and whether or not it is the only sperm factor in mammalian sperm.
Overview of the History of the Cranial Nerves: From Galen to the 21st Century

Throughout history the description and classification of the cranial nerves has been linked to the development and characteristics of anatomy and the role that it played as a tool in providing rationality to medicine, together with social, cultural, religious, and philosophical factors. Anatomists were interested in the cranial nerves, but they disagreed on their number and their paths. We can divide the history of the cranial nerves into three different periods: the first, early or macroscopic period; the second or microscopic period; and the third period or ontogenesis and genoarchitecture. The main aim of this article is to show how the description and knowledge of the cranial nerves were developed in the course of these three periods, and to highlight the main changes produced and the factors related to these changes. We describe how the first period was mainly focused on establishing the definition, number and paths of the cranial nerves, through contributions ranging from Galen's studies in the second century to Sömmerring's Doctoral Dissertation in 1778 that described 12 cranial nerves for the first time. Then, the microscopic period was concentrated on the identification of the real nuclei of origin of the different cranial nerves located in the brain stem. Finally came the third period, or ontogenesis and genoarchitecture of the rhombecephalic and mesencephalic cranial nerve nuclei. Anat Rec, 302:381–393, 2019. © 2018 Wiley Periodicals, Inc.
Using meta‐omics of contaminated sediments to monitor changes in pathways relevant to climate regulation

Microbially mediated biogeochemical processes are crucial for climate regulation and may be disrupted by anthropogenic contaminants. To better manage contaminants, we need tools that make real-time causal links between stressors and altered microbial functions, and the potential consequences for ecosystem services such as climate regulation. In a manipulative field experiment, we used metatranscriptomics to investigate the impact of excess organic enrichment and metal contamination on the gene expression of nitrogen and sulfur metabolisms in coastal sediments. Our gene expression data suggest that excess organic enrichment results in (i) higher transcript levels of genes involved in the production of toxic ammonia and hydrogen sulfide and (ii) lower transcript levels associated with the degradation of a greenhouse gas (nitrous oxide). However, metal contamination did not have any significant impact on gene expression. We reveal the genetic mechanisms that may lead to altered productivity and greenhouse gas production in coastal sediments due to anthropogenic contaminants. Our data highlight the applicability of metatranscriptomics as a management tool that provides an immense breadth of information and can identify potentially impacted process measurements that need further investigation.