Miracle-dz/UniFAR-FTUs huggingface dataset:
Novel strategies in immune checkpoint inhibitor drug development: How far are we from the paradigm shift?

The development of immune checkpoint inhibitors (ICI) represents a major milestone in immune‐oncology. Over the years these agents have demonstrated efficacy in an increasing array of malignancies. Despite this success however, significant challenges remain. Novel approaches to both drug development and trial design are required to incorporate the unique pharmacokinetic and pharmacodynamic properties of ICIs. Further, it has also been established that the benefit of ICIs is limited to only a subset of patients. The molecular interactions between native immune cells and tumorigenesis and progression represent an active area of biomarker research, and elucidating the mechanisms of response and resistance is crucial to develop rational trial designs for the next wave of immune‐oncology (IO) clinical trials, particularly in patients with primary and/or acquired resistance. Efforts are now being made to integrate both biological and clinical information using novel multi‐omic approaches which are now being developed to further elucidate the molecular signatures associated with IO treatment response and resistance and enable rational drug development and trial design processes. As such, precision IO and the ability to deliver patient‐specific choices for ICI monotherapies or combination therapies has become an increasingly tangible goal. We herein describe the current landscape in ICI drug development and discuss the challenges and future directions in this exciting and evolving era in immune‐oncology.
Ecology, Structure, and Evolution of Shigella Phages.

Numerous bacteriophages-viruses of bacteria, also known as phages-have been described for hundreds of bacterial species. The Gram-negative Shigella species are close relatives of Escherichia coli, yet relatively few previously described phages appear to exclusively infect this genus. Recent efforts to isolate Shigella phages have indicated these viruses are surprisingly abundant in the environment and have distinct genomic and structural properties. In addition, at least one model system used for experimental evolution studies has revealed a unique mechanism for developing faster infection cycles. Differences between these bacteriophages and other well-described model systems may mirror differences between their hosts' ecology and defense mechanisms. In this review, we discuss the history of Shigella phages and recent developments in their isolation and characterization and the structural information available for three model systems, Sf6, Sf14, and HRP29; we also provide an overview of potential selective pressures guiding both Shigella phage and host evolution. Expected final online publication date for the Annual Review of Virology, Volume 7 is September 29, 2020. Please see http://www.annualreviews. org/page/journal/pubdates for revised estimates.
Long-Term Follow-Up Outcomes after Percutaneous US/CT-Guided Radiofrequency Ablation for cT1a-b Renal Masses: Experience from Single High-Volume Referral Center

Image-guided thermal ablations are increasingly applied in the treatment of renal cancers, under the guidance of ultrasound (US) or computed tomography (CT). Sometimes, multiple ablations are needed. The aim of the present study was to evaluate the long-term results in patients with renal mass treated with radiofrequency ablation (RFA) with both US and CT, with a focus on the multiple ablations rate. 149 patients (median age 67 years) underwent RFA from January 2008 to June 2015. Median tumor diameter was 25 mm (IQR 17–32 mm). Median follow-up was 54 months (IQR 44–68). 27 (18.1%) patients received multiple successful ablations, due to incomplete ablation (10 patients), local tumor progression (8 patients), distant tumor progression (4 patients) or multiple tumor foci (5 patients), with a primary and secondary technical efficacy of 100%. Complications occurred in 13 (8.7%) patients (6 grade A, 5 grade C, 2 grade D). 24 patients died during follow-up, all for causes unrelated to renal cancer. In conclusion, thermal ablations with the guidance of US and CT are safe and effective in the treatment of renal tumors in the long-term period, with a low rate of patients requiring multiple treatments over the course of their disease.
A quality evaluation of guidelines on five different viruses causing public health emergencies of international concern

This project aims to evaluate the methods and reporting quality of practice guidelines of five different viruses that have caused Public Health Emergencies of International Concern (PHEIC) over 20 past years: the severe acute respiratory syndrome coronavirus (SARS-CoV), Ebola virus, Middle East respiratory syndrome coronavirus (MERS-CoV), Zika virus and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We systematically searched databases, guideline websites and government health agency websites from their inception to February 02, 2020 to extract practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus, SARS-CoV-2 and the diseases they caused. The literature was screened independently by four researchers. Then, fifteen researchers evaluated the quality of included guidelines using the AGREE-II (Appraisal of Guidelines for Research and Evaluation II, for methodological quality) instrument and RIGHT (Reporting Items for practice Guidelines in Healthcare, for reporting quality) statement. Finally, a total of 81 guidelines were included, including 21 SARS-CoV guidelines, 11 Ebola virus (EBOV) guidelines, 9 MERS-CoV guidelines, 10 Zika Virus guidelines and 30 SARS-CoV-2 guidelines. The evaluation of the methodological quality indicated that the mean scores of each domain for guidelines of each virus were all below 60%, the scores for guidelines in the domains of “clarity of presentation” being the highest and in the “editorial independence” lowest. The mean reporting rate of each domain for guidelines of each virus was also less than 60%: the reporting rates for the domain “background” were highest, and for the domain “funding and interests” lowest. The methodological and reporting quality of the practice guidelines for SARS-CoV, Ebola virus, MERS-CoV, Zika virus and SARS-CoV-2 guidelines tend to be low. We recommend to follow evidence-based methodology and the RIGHT statement on reporting when developing guidelines.
Polyanilines as New Sorbents for Hydrocarbons Removal from Aqueous Solutions

Water remediation from hydrocarbons is crucial to reduce health risks. Numerous costly and, sometimes, sophisticated methods were proposed over the years. Herein, an innovative green procedure for porous polyanilines preparation is reported. Polyaniline (PANI) was synthesized by three different approaches ranging from traditional to more eco-friendly ones. Thermal, optical and morphological features of the resulting materials were investigated along with their surface properties. Finally, PANIs were tested as sorbents for hydrocarbons removal from waterbodies. Although an overall fast and high sorption efficiency is always observed, the effective hydrocarbons abatement performed by ‘green’ PANIs is particularly welcome in the context of environmental protection. Moreover, the sorption efficiency retention after five-run recycling tests suggests potential applications in wastewater remediation.
The impact of a benthic filter feeder: limitations imposed by physical transport of algae to the benthos

We used an acoustic Doppler profiler to investigate the hydrodynamics of a nearshore site in western Lake Erie, and we incorporated the measured parameters in numerical simulations of phytoplankton consumption by benthic zebra mussels (Dreissena polymorpha) to examine the link between pelagic production and benthic filter feeders. Daily-averaged eddy diffusivities varied from 105 to 104 m2·s1 at our site. Our simulations demonstrate that diffusivities of this order decrease near-bed algal biomass, while algal biomass in the pelagic remains relatively unaffected. Between 8% and 67% of the algal biomass in the water column could be consumed daily, depending on the shape and magnitude of the diffusivity profile. Correspondingly, in situ vertical biomass profiles showed a near-bed zone of algal depletion, but no impact was observed near the surface. The impact of the zebra mussel in nearshore regions is expected to be stronger than in deeper open water. The flow of algal biomass into the benthos was tightl.
Structural and Functional Characterization of the Tongue and Digestive Tract of Psammophis sibilans (Squamata, Lamprophiidae): Adaptive Strategies for Foraging and Feeding Behaviors

Abstract We describe the morphological adaptations of the tongue and gastrointestinal tract of the striped sand snake Psammophis sibilans and discuss their functional importance. Using standard histological, histochemical, and scanning electron microscopy techniques, we analyzed 11 adult snakes of both sexes. Our findings showed that the bifurcated non-papillate tongue exhibited chemoreceptive adaptions to squamate foraging behavior. The lingual apex tapered terminally with sensory spines, and the body of the tongue possesses a characteristic central odor–receptor chamber that might serve to trap and retain scent molecules. Furthermore, the intrinsic musculature showed interwoven and well-developed transverse, vertical and longitudinal muscle fibers that control contraction and retraction during probing and flicking. The esophagus displayed highly folded mucosa lined with columnar epithelium with goblet cells. In contrast, the stomach mucosa formed finger-like gastric rugae, encompassing tubular glands with dorsal gastric pits. The intestine is distinct from other vertebrates in lacking the crypts of Lieberkühn in the tunica mucosa and submucosa. The intestine mucosa is mostly arranged in interdigitating villi oriented perpendicular to the luminal surface. We extrapolated subtle variations for both acid and neutral mucopolysaccharides and glycoproteins localization as well as collagen fibers using histochemical analyses. The elaborate histo-morphological and functional adaptation of the tongue and digestive tract plays a pivotal role in foraging and feeding behavior.
Antinociceptive effects of ceftriaxone in formalin‐induced nociception

Ceftriaxone (CFX) is a β‐lactam antibiotic with analgesic properties. However, its role in the formalin‐induced nociception remains unknown. The purpose of this study was to investigate the antinociceptive effect of CFX in the 1% formalin test in rats. Formalin induced a typical nociceptive response (flinching behavior) of two phases. Local peripheral pretreatment (20 min) with CFX (400–800 μg/paw) slightly attenuated the flinching behavior in phase 2, but not phase 1. Acute intraperitoneal pretreatment (20 min) also reduced phase 2 of the formalin test. In both cases, CFX induced a dose‐dependent antinociception. We also tested the effect of CFX 1 day after its administration and in two schedules of repeated administration. One‐day pretreatment with CFX (50–400 mg/kg, ip) induced a dose‐dependent antinociceptive effect in formalin‐treated rats. Repeated administration (daily during 3 or 7 days) with CFX (50–400 mg/kg, ip) diminished formalin‐induced nociception. Results suggest that local or systemic as well as single or repeated administration of CFX reduces formalin‐induced nociception.
Predicting COVID-19 in China Using Hybrid AI Model

The coronavirus disease 2019 (COVID-19) breaking out in late December 2019 is gradually being controlled in China, but it is still spreading rapidly in many other countries and regions worldwide. It is urgent to conduct prediction research on the development and spread of the epidemic. In this article, a hybrid artificial-intelligence (AI) model is proposed for COVID-19 prediction. First, as traditional epidemic models treat all individuals with coronavirus as having the same infection rate, an improved susceptible–infected (ISI) model is proposed to estimate the variety of the infection rates for analyzing the transmission laws and development trend. Second, considering the effects of prevention and control measures and the increase of the public’s prevention awareness, the natural language processing (NLP) module and the long short-term memory (LSTM) network are embedded into the ISI model to build the hybrid AI model for COVID-19 prediction. The experimental results on the epidemic data of several typical provinces and cities in China show that individuals with coronavirus have a higher infection rate within the third to eighth days after they were infected, which is more in line with the actual transmission laws of the epidemic. Moreover, compared with the traditional epidemic models, the proposed hybrid AI model can significantly reduce the errors of the prediction results and obtain the mean absolute percentage errors (MAPEs) with 0.52%, 0.38%, 0.05%, and 0.86% for the next six days in Wuhan, Beijing, Shanghai, and countrywide, respectively.
Characterization of carbapenem‐resistant Klebsiella pneumoniae in a tertiary hospital in Fuzhou, China

The emergence of carbapenem‐resistant Klebsiella pneumoniae (CRKP) strains has led to increased mortality and morbidity rates. Tigecycline, a new class of broad‐spectrum glycyl‐tetracycline antibiotics, has been used to target multi‐ and pan‐drug‐resistant bacterial infections. This study aimed to assess the molecular characteristics of CRKP in a tertiary hospital, and its susceptibility to tigecycline, to create a reference for hospital infection control and clinical drug use.
SUMOylated PRC1 controls histone H3.3 deposition and genome integrity of embryonic heterochromatin

Chromatin integrity is essential for cellular homeostasis. Polycomb group proteins modulate chromatin states and transcriptionally repress developmental genes to maintain cell identity. They also repress repetitive sequences such as major satellites and constitute an alternative state of pericentromeric constitutive heterochromatin at paternal chromosomes (pat‐PCH) in mouse pre‐implantation embryos. Remarkably, pat‐PCH contains the histone H3.3 variant, which is absent from canonical PCH at maternal chromosomes, which is marked by histone H3 lysine 9 trimethylation (H3K9me3), HP1, and ATRX proteins. Here, we show that SUMO2‐modified CBX2‐containing Polycomb Repressive Complex 1 (PRC1) recruits the H3.3‐specific chaperone DAXX to pat‐PCH, enabling H3.3 incorporation at these loci. Deficiency of Daxx or PRC1 components Ring1 and Rnf2 abrogates H3.3 incorporation, induces chromatin decompaction and breakage at PCH of exclusively paternal chromosomes, and causes their mis‐segregation. Complementation assays show that DAXX‐mediated H3.3 deposition is required for chromosome stability in early embryos. DAXX also regulates repression of PRC1 target genes during oogenesis and early embryogenesis. The study identifies a novel critical role for Polycomb in ensuring heterochromatin integrity and chromosome stability in mouse early development.
Single-Tube Multimarker Assay for Estimating the Risk to Develop Preeclampsia.

BACKGROUND Preeclampsia (PE) affects 2%-8% of all pregnancies worldwide. The predictive value of the currently used maternal serum fms-like tyrosine kinase-1/ placental growth factor (sFlt-1/PlGF) test is < 40% for PE onset within 4 weeks. We aimed to develop an innovative multiplex assay to improve PE prediction. METHODS The 6PLEX assay combining the measurements of ADAM12, sENG, leptin, PlGF, sFlt-1, and PTX3 was developed for the Luminex® xMAP platform. Assay performance was evaluated using 61 serum samples drawn from 53 pregnant women between 180 and 275 gestational days: diagnosed PE cases, n = 4; cases with PE onset within 4-62 days after sampling, n = 25; controls, n = 32. The B·R·A·H·M·S Kryptor sFlt-1/PlGF test (Thermo Fisher Scientific, Hennigsdorf, Germany) was applied as an external reference. Alternative PE prediction formulae combining 6PLEX measurements with clinical parameters were developed. RESULTS There was a high correlation in sFlt-1/PlGF estimated for individual sera between the 6PLEX and B·R·A·H·M·S Kryptor immunoassays (Spearman's r = 0.93, P < 0.0001). The predictive power of the 6PLEX combined with gestational age and maternal weight at sampling reached AUC 0.99 (95% CI 0.97-1.00) with sensitivity 100.0% and specificity 96.9%. In all models, sFlt-1/PlGF derived from the B·R·A·H·M·S immunoassays exhibited the lowest AUC value (<0.87) and sensitivity (<80%) with broad confidence intervals (13%-92%). The estimated prognostic yield of the 6PLEX compared to the B·R·A·H·M·S assay was significantly higher (96.5% vs 73.7%; P = 0.0005). CONCLUSIONS The developed single-tube multimarker assay for PE risk estimation in combination with clinical symptoms reached high prognostic yield (96.5%) and exhibited superior performance compared to the sFlt-1/PlGF test.
Multimodality treatment in unresectable cholangiocarcinoma

Purpose Cholangiocarcinomas (CCs) are rare and highly malignant cancers. Although there are different treatment protocols for treatment of cholangiocarcinoma, we aimed to investigate a survival rate of patients with unresectable extrahepatic CCs (ECCs) receiving multimodality therapeutic protocol (MTP) (biliary drainage + external beam radiotherapy [EBRT] + brachytherapy and systemic chemotherapy). Similarly, we aimed to identify a relationship between survival time and associated factors in treatment outcome. Material and methods This retrospective study was performed on patients with ECC, who were referred to our university hospital between 2012 and 2015, and their imaging were diagnosed as unresectable. Patients underwent MTP including internal-external drainage catheter (F10-12) with insertion under fluoroscopy guidance, EBRT with 25-28 fractions and concurrent chemotherapy using capecitabine (Xeloda) 825 mg/m2 at the days of radiotherapy, followed by brachytherapy (BT) with iridium-192 (192Ir) or cobalt-60 (60Co) sources for 21 Gy in 3 consecutive days. Demographic variables, complications, laboratory tests, imaging findings, and survival time (OS – overall survival after diagnosis; CS – survival after catheter placement) were recorded. Results A total of 38 patients, with mean SD age = 58.08 (9.80) years, male = 22 (57.9%), were evaluated. According to Bismuth-Corlette classification, 15 (39.5%) were in stage IIIA, 5 (13.2%) were in stage IIIB, 10 (26.3%) were in stage IV, and 8 (21.2%) were undefined. Of those, 21 (55.3%), 15 (39.5%), and 17 (44.7%) were involved with liver parenchyma, great vessels, and regional lymph nodes, respectively. Mean SD of OS was 15.11 (8.10) months (median = 15; 95% CI: 13.25-16.69), and CS was 2-29 months (mean SD = 11.71 (7.29); median = 10; 95% CI: 10.05-13.37). Further analysis revealed a considerable decrease in OS and CS in those with an involvement of liver parenchyma, great vessels, regional lymph nodes, and Bismuth type IV. Conclusions Multimodality therapeutic approach in patients with inoperable ECCs could definitely improve their survival time and decrease complications. Survival time is significantly depending on tumor staging, gender, and involvement of liver parenchyma, great vessels, and regional lymph nodes.
Incidental learning of list membership is affected by serial position in the list

ABSTRACT Cowan, Donnell, and Saults [(2013). A list-length constraint on incidental item-to-item associations. Psychonomic Bulletin & Review, 20, 1253–1258] examined incidental memory of whether two words had occurred in the same list or different lists, after the lists had been presented with an orienting task that did not require memorisation. Performance was superior for 3-word lists compared to 6- or 9-word lists, with memory for the longer lists near chance levels. Here we re-examine this phenomenon with methodological modifications to ensure that learning was incidental: we removed potential clues that a memory test would follow, eliminated trials with special mnemonic cues related to the orienting task, eliminated participants who suspected a memory test according to a post-experimental questionnaire, used signal detection measures to distinguish between memory sensitivity and bias, and tested list length with the relative serial position controlled. Incidental memory formed primarily for the most recent part of each list, an effect that was stronger than that of list length. The new evidence helps to constrain theories about the relation between working memory and incidental learning. A capacity-limited approach to the incidental-learning process still is possible but must be modified compared to Cowan et al., and the evidence is favourable to other theoretical approaches as well.
Genetic Variation in Resistance to Bacterial Kidney Disease within and between Two Strains of Coho Salmon from British Columbia

Abstract Genetic variation in resistance to bacterial kidney disease (BKD) was investigated between and within the Robertson Creek and Kitimat River strains of coho salmon Oncorhynchus kisutch from British Columbia. For each strain, juvenile fish from 20 pairs of paternal half-sib families were inoculated with Renibacterium salmoninarum, the causative agent of BKD. Mortality due to BKD began 26 d after inoculation, and had reached a level of 68% when the experiment was terminated on day 113. Survival was greater (P = 0.08) and time to death (in days) was longer (P < 0.05) among juvenile coho salmon from the Kitimat River strain than among those from the Robertson Creek strain. The estimated sire component of survival heritability, based on binomial data, was 0.53 ± 0.16 (mean ± SE), which became 0.90 ± 0.26 when survival was considered to be a threshold trait. The sire component estimate of heritability of time to death was 0.26 ± 0.10. There was no consistent genetic correlation between fish weight and s.
Explaining change in content of life narratives over time

ABSTRACT Aiming to further the understanding of stability and change of the life story, we investigated memory age and valence of life events as possible factors influencing life narrative stability. Additionally, we examined personal memories that 145 participants ranging in age from 16 to 69 years had told four years earlier but omitted from their current life narratives. In particular, we tested the accessibility of these omitted memories and explored the reasons for omission from life narratives. Younger age of memories but not valence predicted omission. Further, omitted memories could be remembered when aided with memory prompts. Both remembering and including life events in the current life narrative appeared to be related to personal relevance at the time of telling, supporting prior research that emphasises the role of motivation, ongoing goals, and concerns for the construction of personal narratives.