Miracle-dz/UniFAR-FTUs huggingface dataset:
Pembrolizumab in Microsatellite-Instability-High Advanced Colorectal Cancer.

BACKGROUND Programmed death 1 (PD-1) blockade has clinical benefit in microsatellite-instability-high (MSI-H) or mismatch-repair-deficient (dMMR) tumors after previous therapy. The efficacy of PD-1 blockade as compared with chemotherapy as first-line therapy for MSI-H-dMMR advanced or metastatic colorectal cancer is unknown. METHODS In this phase 3, open-label trial, 307 patients with metastatic MSI-H-dMMR colorectal cancer who had not previously received treatment were randomly assigned, in a 1:1 ratio, to receive pembrolizumab at a dose of 200 mg every 3 weeks or chemotherapy (5-fluorouracil-based therapy with or without bevacizumab or cetuximab) every 2 weeks. Patients receiving chemotherapy could cross over to pembrolizumab therapy after disease progression. The two primary end points were progression-free survival and overall survival. RESULTS At the second interim analysis, after a median follow-up (from randomization to data cutoff) of 32.4 months (range, 24.0 to 48.3), pembrolizumab was superior to chemotherapy with respect to progression-free survival (median, 16.5 vs. 8.2 months; hazard ratio, 0.60; 95% confidence interval [CI], 0.45 to 0.80; P = 0.0002). The estimated restricted mean survival after 24 months of follow-up was 13.7 months (range, 12.0 to 15.4) as compared with 10.8 months (range, 9.4 to 12.2). As of the data cutoff date, 56 patients in the pembrolizumab group and 69 in the chemotherapy group had died. Data on overall survival were still evolving (66% of required events had occurred) and remain blinded until the final analysis. An overall response (complete or partial response), as evaluated with Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, was observed in 43.8% of the patients in the pembrolizumab group and 33.1% in the chemotherapy group. Among patients with an overall response, 83% in the pembrolizumab group, as compared with 35% of patients in the chemotherapy group, had ongoing responses at 24 months. Treatment-related adverse events of grade 3 or higher occurred in 22% of the patients in the pembrolizumab group, as compared with 66% (including one patient who died) in the chemotherapy group. CONCLUSIONS Pembrolizumab led to significantly longer progression-free survival than chemotherapy when received as first-line therapy for MSI-H-dMMR metastatic colorectal cancer, with fewer treatment-related adverse events. (Funded by Merck Sharp and Dohme and by Stand Up to Cancer; KEYNOTE-177 ClinicalTrials.gov number, NCT02563002.).
PD-L1 Expression in 65 Conjunctival Melanomas and Its Association with Clinical Outcome

Conjunctival melanoma (CM) iss a rare and aggressive tumour that is increasing in frequency. The prognostic value of PD-L1 expression, alone or in combination with CD8 and PD-1 expression and the BRAF and NRAS status, has not been determined in CM to date. We evaluated the expression of PD-L1, CD8, PD-1 in CM and investigated whether there was an association between the expression of these markers and the BRAF and NRAS molecular profile as well as some clinico-pathological criteria. A total of sixty-five CM were assessed for PD-L1, PD-1, and CD8 expression by immunohistochemistry (IHC) and for BRAF and NRAS genomic alterations using molecular biology techniques and anti-BRAF and anti-NRAS antibodies. PD-L1 expression in tumour cells (TC) was very low or absent but detected in tumour-infiltrating immune cells (IC). A correlation was observed between the expression of PD-L1, CD8, and PD-1 in IC. No correlation between PD-L1 expression (in tumour and/or immune cells) and BRAF or NRAS mutations was observed. PD-L1 expression in IC correlated with a higher pTNM stage and PD-L1 expression in TC with worse disease-specific survival. PD-L1 expression is a potential prognostic biomarker that correlates with poor prognosis in CM patients.
Moral Sensitivity, Empathy and Prosocial Behavior: Implications for Humanization of Nursing Care

Humanization of nursing is related to certain social and moral variables. Moral sensitivity, empathy, and prosocial behavior help understand a situation and make decisions that benefit the patient. The objective of this study is to find out how these variables are related, and define the differences in moral sensitivity, empathy, and prosocial behavior in humanization of nursing. We also analyzed the mediating role of empathy in the relationship between moral sensitivity and prosocial behavior. The sample was made up of 330 Spanish nurses aged 22 to 56, who completed the HUMAS Scale and adapted versions of the Basic Empathy Scale, the Moral Sensitivity Questionnaire, and the Prosocial Behavior Scale. Descriptive analyses, bivariate correlations and multiple mediation models were calculated. The results found significantly different mean scores between all the groups in responsibility and moral strength, cognitive empathy, and prosocial behavior, and in moral burden, the differences were in the high-humanization-score group compared to the low-score group. Furthermore, the mediation models showed the mediating effect of cognitive empathy between the responsibility, strength, and moral burden factors on prosocial behavior, but not of affective empathy. The study concluded that humanization in nursing is closely related to moral sensitivity, cognitive empathy, and prosocial behavior. This facilitates a helping, caring, and understanding attitude toward patient needs, but without the affective flooding that affective empathy can lead to.
Slow Blink Eye Closure in Shelter Cats Is Related to Quicker Adoption

Simple Summary Slow blinking is a type of interaction between humans and cats that involves a sequence of prolonged eye narrowing movements being given by both parties. This interspecific social behaviour has recently been studied empirically and appears to be a form of positive communication for cats, who are more likely to approach a previously unfamiliar human after such interactions. We investigated whether slow blinking can also affect human preferences for cats in a shelter environment. We measured whether cats’ readiness to respond to a human-initiated slow blink interaction was associated with rates of rehoming in the shelter. We also examined cats’ propensity to slow blink when they were anxious around humans or not. We demonstrated that cats that responded to human slow blinking by using eye closures themselves were rehomed quicker than cats that closed their eyes less. Cats that were initially identified as more nervous around humans also showed a trend towards giving longer total slow blink movements in response to human slow blinking. Our results suggest that the cat slow blink sequence is perceived as positive by humans and may have a dual function in cats, occurring in both affiliative and submissive situations. Abstract The process of domestication is likely to have led to the development of adaptive interspecific social abilities in animals. Such abilities are particularly interesting in less gregarious animals, such as cats. One notable social behaviour that cats exhibit in relation to humans is the slow blink sequence, which our previous research suggests can function as a form of positive communication between cats and humans. This behaviour involves the production of successive half blinks followed by either a prolonged narrowing of the eye or an eye closure. The present study investigates how cat (n = 18) slow blink sequences might affect human preferences during the adoption of shelter cats. Our study specifically tested (1) whether cats’ propensity to respond to human-initiated slow blinking was associated with their speed of rehoming from a shelter environment, and (2) whether cats’ anxiety around humans was related to their tendency to slow blink. Our experiments demonstrated that cats that showed an increased number of and longer eye closures in response to human slow blinks were rehomed faster, and that nervous cats, who had been identified as needing desensitisation to humans, tended to spend more time producing slow blink sequences in response to human slow blinks than a non-desensitisation group. Collectively, these results suggest that the cat slow blink sequence is perceived as positive by humans and may have a dual function—occurring in both affiliative and submissive contexts.
Characterization of Preferred Crystal Nucleation Sites on Mica Surfaces

Rates of heterogeneous nucleation can be greatly increased not only through control of the chemistry of a surface, but also of its topography. Following previous work in which we showed that scratching a mica surface significantly enhances crystal nucleation from vapor, we here use a new experimental approach to understand better the effect of topography on crystal nucleation. The compounds carbon tetrabromide, camphor, norbornane, and hexachloroethane were deposited from vapor onto mica sheets containing various surface defects, and their nucleation was studied using optical microscopy. Following subsequent evaporation of the crystals, examination of the sites where these had nucleated with a scanning electron microscope enabled the nature of each material’s preferred nucleation sites to be determined, and all four compounds appeared to exhibit a strong preference for sites characterized by delamination of the layered mica structure. Indeed, comparison of the four compounds on the same mica substrates sh.
Obesity as a Possible Risk Factor for Pediatric Sensorineural Hearing Loss

Childhood hearing loss impacts linguistic, academic, social, and psychologic development, and may have lasting implications for future workforce performance. Current evidence for obesity as a pediatric sensorineural hearing loss (SNHL) risk factor is intriguing but equivocal. We hypothesized that obesity is associated with a higher risk of SNHL. We additionally examined whether underweight is associated with a higher risk of SNHL.
Occurrence and Characteristics of Extended-Spectrum β-Lactamase-Producing Escherichia coli from Dairy Cattle, Milk, and Farm Environments in Peninsular Malaysia

The emergence and spread of antimicrobial resistance genes and resistant bacteria do not recognize animal, human, or geographic boundaries. Addressing this threat requires a multidisciplinary approach involving human, animal, and environmental health (One Health) sectors. This is because antimicrobial agents used in veterinary medicine have been reported to be the same or similar to those in human medicine use. Extended-spectrum β-lactamase (ESBL) E. coli is a growing public health problem worldwide, and the agri-food industry is increasingly becoming a source of clinically important ESBL bacteria. Accordingly, the aim of this study was to investigate the occurrence and characteristics of ESBL-producing E. coli from dairy cattle, milk, and the farm environment. E. coli isolates were identified by their 16sRNA, and their ESBL production was confirmed using ESBL–CHROMagar media and the double disk diffusion method. Genotypes of ESBL producers were characterized using multiplex polymerase chain reaction (mPCR) assay. It was found that 18 (4.8%) of the total samples were positive for ESBL-producing E. coli. Of these, 66.7% were from milk, and 27.8% and 5.5% were from the farm environment and faecal samples, respectively. Predominant ESBL genotypes identified were a combination of both TEM and CTX-M in eight out of 18 (44.4%) isolates. Four (22.2%) isolates produced the CTX-M gene, two (11.1%) isolates produced the TEM gene, and four (22.2%) remaining isolates produced the ESBL genes other than TEM, SHV, CTX-M, and OXA. The SHV and OXA gene were not detected in all 18 isolates. In all, there were four profiles of genetic similarity. The occurrence of these genotypes in indicator organisms from dairy cattle, milk, and the farm environment further re-enforced the potential of food-animals as sources of ESBL-producing E. coli infection in humans via the food chain. Thus, there is the need for the adoption of a tripartite One Health approach in surveillance and monitoring to control antimicrobial resistance.
NAD+ is not utilized as a co-factor for DNA ligation by human DNA ligase IV

Abstract As nucleotidyl transferases, formation of a covalent enzyme-adenylate intermediate is a common first step of all DNA ligases. While it has been shown that eukaryotic DNA ligases utilize ATP as the adenylation donor, it was recently reported that human DNA ligase IV can also utilize NAD+ and, to a lesser extent ADP-ribose, as the source of the adenylate group and that NAD+, unlike ATP, enhances ligation by supporting multiple catalytic cycles. Since this unexpected finding has significant implications for our understanding of the mechanisms and regulation of DNA double strand break repair, we attempted to confirm that NAD+ and ADP-ribose can be used as co-factors by human DNA ligase IV. Here, we provide evidence that NAD+ does not enhance ligation by pre-adenylated DNA ligase IV, indicating that this co-factor is not utilized for re-adenylation and subsequent cycles of ligation. Moreover, we find that ligation by de-adenylated DNA ligase IV is dependent upon ATP not NAD+ or ADP-ribose. Thus, we conclude that human DNA ligase IV cannot use either NAD+ or ADP-ribose as adenylation donor for ligation.
Ecophysiological models for global invaders: Is Europe a big playground for the African clawed frog?

One principle threat prompting the worldwide decline of amphibians is the introduction of nonindigenous amphibians. The African Clawed Frog, Xenopus laevis, is now one of the widest distributed amphibians occurring on four continents with ongoing range expansion including large parts of Europe. Species distribution models (SDMs) are essential tools to predict the invasive risk of these species. Previous efforts have focused on correlative approaches but these can be vulnerable to extrapolation errors when projecting species' distributions in nonnative ranges. Recent developments emphasise more robust process-based models, which use physiological data like critical thermal limits and performance, or hybrid models using both approaches. Previous correlative SDMs predict different patterns in the potential future distribution of X. laevis in Europe, but it is likely that these models do not assess its full invasive potential. Based on physiological performance trials, we calculate size and temperature-dependent response surfaces, which are scaled to geographic performance layers matching the critical thermal limits. We then use these ecophysiological performance layers in a standard correlative SDM framework to predict the potential distribution in southern Africa and Europe. Physiological performance traits (standard metabolic rate and endurance time of adult frogs) are the main drivers for the predicted distribution, while the locomotor performance (maximum velocity and distance moved in 200 ms) of adults and tadpoles have low contributions.
Potassium isotopic heterogeneity in subducting oceanic plates

High-precision K isotopic measurements identify crustal inputs to the mantle and controls on oceanic K cycle. Oceanic crust and sediments are the primary K sinks for seawater, and they deliver considerable amounts of K to the mantle via subduction. Historically, these crustal components were not studied for K isotopes because of the lack of analytical precision to differentiate terrestrial variations. Here, we report a high-precision dataset that reveals substantial variability in oceanic plates and provides further insights into the oceanic K cycle. Sixty-nine sediments worldwide yield a broad δ41K range from −1.3 to −0.02‰. The unusually low values are indicative of release of heavy K during continental weathering and uptake of light K during submarine diagenetic alteration. Twenty samples of altered western Pacific crust from ODP Site 801 display δ41K from −0.60 to −0.05‰, averaging at −0.32‰. Our results indicate that submarine alteration of oceanic plates is essential for generating the high-δ41K signature of seawater. These regionally varying subducting components are heterogeneous K inputs to the mantle.
A bird’s-eye view of brain activity in socially interacting mice through mobile edge computing (MEC)

Illuminating neural event of interests on the head shows the direct link between brain activity and behaviors in group of mice. Social cognition requires neural processing, yet a unifying method linking particular brain activities and social behaviors is lacking. Here, we embedded mobile edge computing (MEC) and light emitting diodes (LEDs) on a neurotelemetry headstage, such that a particular neural event of interest is processed by the MEC and subsequently an LED is illuminated, allowing simultaneous temporospatial visualization of that neural event in multiple, socially interacting mice. As a proof of concept, we configured our system to illuminate an LED in response to gamma oscillations in the basolateral amygdala (BLA gamma) in freely moving mice. We identified (i) BLA gamma responses to a spider robot, (ii) affect-related BLA gamma during conflict, and (iii) formation of defensive aggregation under a threat by the robot, and reduction of BLA gamma responses in the inner-located mice. Our system can provide an intuitive framework for examining brain-behavior connections in various ecological situations and population structures.
Microcalorimetric determination of the enthalpy of sublimation of benzoic acid and anthracene

A Calvet microcalorimeter has been utilized to determine the sublimation enthalpy of benzoic acid and anthracene. The vapor pressures measured by Knudsen effusion weight‐loss method over the temperature ranges 338–383°K and 353–432°K were, respectively, log10p(torr)=(12.175 ± 0.047) − (4501 ± 17)/T, for benzoic acid, and log10p(torr)=(12.616 ± 0.062) − (5277 ± 24)/T, for anthracene. The Gibbs energy functions for C6H5COOH and C14H10 gaseous molecules have been estimated.
Translational control of coronaviruses

Abstract Coronaviruses represent a large family of enveloped RNA viruses that infect a large spectrum of animals. In humans, the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) is responsible for the current COVID-19 pandemic and is genetically related to SARS-CoV and Middle East respiratory syndrome-related coronavirus (MERS-CoV), which caused outbreaks in 2002 and 2012, respectively. All viruses described to date entirely rely on the protein synthesis machinery of the host cells to produce proteins required for their replication and spread. As such, virus often need to control the cellular translational apparatus to avoid the first line of the cellular defense intended to limit the viral propagation. Thus, coronaviruses have developed remarkable strategies to hijack the host translational machinery in order to favor viral protein production. In this review, we will describe some of these strategies and will highlight the role of viral proteins and RNAs in this process.
Enhancing water resistance of welded dowel wood joints by acetylated lignin

Low molecular mass acetylated organosolv lignin from wheat straw and from depolymerised low sulphur organosolv wood lignin have been shown to markedly improve both the water resistance and the mechanical performance of welded dowel wood joints. The acetylated oligomers distribution and extent of acetylation of the two lignins were determined by Matrix assisted laser desorption ionization-time-of-flight mass spectrometry. Extensive acetylation was confirmed by CP-MAS 13C NMR spectrometry. Force–displacement measurements on welded dowel joints to which acetylated wood lignins were added showed a ductile behaviour. This is due to the interpenetration of the elastic acetylated lignin network into the more rigid composite network of the welded interphase.
Sensitive quantification of dipicolinic acid from bacterial endospores in soils and sediments

Summary Endospore‐forming bacteria make up an important and numerically significant component of microbial communities in a range of settings including soils, industry, hospitals and marine sediments extending into the deep subsurface. Bacterial endospores are non‐reproductive structures that protect DNA and improve cell survival during periods unfavourable for bacterial growth. An important determinant of endospores withstanding extreme environmental conditions is 2,6‐pyridine dicarboxylic acid (i.e. dipicolinic acid, or DPA), which contributes heat resistance. This study presents an improved HPLC‐fluorescence method for DPA quantification using a single 10‐min run with pre‐column Tb3+ chelation. Relative to existing DPA quantification methods, specific improvements pertain to sensitivity, detection limit and range, as well as the development of new free DPA and spore‐specific DPA proxies. The method distinguishes DPA from intact and recently germinated spores, enabling responses to germinants in natural samples or experiments to be assessed in a new way. DPA‐based endospore quantification depends on accurate spore‐specific DPA contents, in particular, thermophilic spores are shown to have a higher DPA content, meaning that marine sediments with plentiful thermophilic spores may require spore number estimates to be revisited. This method has a wide range of potential applications for more accurately quantifying bacterial endospores in diverse environmental samples.
The Effect of Non-Personalised Tips on the Continued Use of Self-Monitoring mHealth Applications

Chronic tinnitus, the perception of a phantom sound in the absence of corresponding stimulus, is a condition known to affect patients’ quality of life. Recent advances in mHealth have enabled patients to maintain a ‘disease journal’ of ecologically-valid momentary assessments, improving patients’ own awareness of their disease while also providing clinicians valuable data for research. In this study, we investigate the effect of non-personalised tips on patients’ perception of tinnitus, and on their continued use of the application. The data collected from the study involved three groups of patients that used the app for 16 weeks. Groups A & Y were exposed to feedback from the start of the study, while group B only received tips for the second half of the study. Groups A and Y were run by different supervisors and also differed in the number of hospital visits during the study. Users of Group A and B underwent assessment at baseline, mid-study, post-study and follow-up, while users of group Y were only assessed at baseline and post-study. It is seen that the users in group B use the app for longer, and also more often during the day. The answers of the users to the Ecological Momentary Assessments are seen to form clusters where the degree to which the tinnitus distress depends on tinnitus loudness varies. Additionally, cluster-level models were able to predict new unseen data with better accuracy than a single global model. This strengthens the argument that the discovered clusters really do reflect underlying patterns in disease expression.