Miracle-dz/UniFAR-FTUs huggingface dataset:
A Diagnostic Biopsy-Adapted Immunoscore Predicts Response to Neoadjuvant Treatment and Selects Patients with Rectal Cancer Eligible for a Watch-and-Wait Strategy

Purpose: No biomarker to personalize treatment in locally advanced rectal cancer (LARC) is currently available. We assessed in LARC whether a diagnostic biopsy-adapted immunoscore (ISB) could predict response to neoadjuvant treatment (nT) and better define patients eligible to an organ preservation strategy (“Watch-and-Wait”). Experimental Design: Biopsies from two independent cohorts (n1 = 131, n2 = 118) of patients with LARC treated with nT followed by radical surgery were immunostained for CD3+ and CD8+ T cells and quantified by digital pathology to determine ISB. The expression of immune-related genes post-nT was investigated (n = 64 patients). Results were correlated with response to nT and disease-free survival (DFS). The ISB prognostic performance was further assessed in a multicentric cohort (n = 73 patients) treated by Watch-and-Wait. Results: ISB positively correlated with the degree of histologic response (P < 0.001) and gene expression levels for Th1 orientation and cytotoxic immune response, post-nT (P = 0.006). ISB high identified patients at lower risk of relapse or death compared with ISB low [HR, 0.21; 95% confidence interval (CI), 0.06–0.78; P = 0.009]. Prognostic performance of ISB for DFS was confirmed in a validation cohort. ISB was an independent parameter, more informative than pre- (P < 0.001) and post-nT (P < 0.05) imaging to predict DFS. ISB combined with imaging post-nT discriminated very good responders that could benefit from organ preservation strategy. In the “Watch-and-Wait” cohort (n = 73), no relapse was observed in patients with ISB high (23.3%). Conclusions: ISB predicts response to nT and survival in patients with LARC treated by surgery. Its usefulness in the selection of patients eligible for a Watch-and-Wait strategy is strongly suggested.
Mapping of the FGF14:Nav1.6 complex interface reveals FLPK as a functionally active peptide modulating excitability

The voltage‐gated sodium (Nav) channel complex is comprised of pore‐forming α subunits (Nav1.1–1.9) and accessory regulatory proteins such as the intracellular fibroblast growth factor 14 (FGF14). The cytosolic Nav1.6 C‐terminal tail binds directly to FGF14 and this interaction modifies Nav1.6‐mediated currents with effects on intrinsic excitability in the brain. Previous studies have identified the FGF14V160 residue within the FGF14 core domain as a hotspot for the FGF14:Nav1.6 complex formation. Here, we used three short amino acid peptides around FGF14V160 to probe for the FGF14 interaction with the Nav1.6 C‐terminal tail and to evaluate the activity of the peptide on Nav1.6‐mediated currents. In silico docking predicts FLPK to bind to FGF14V160 with the expectation of interfering with the FGF14:Nav1.6 complex formation, a phenotype that was confirmed by the split‐luciferase assay (LCA) and surface plasmon resonance (SPR), respectively. Whole‐cell patch‐clamp electrophysiology studies demonstrate that FLPK is able to prevent previously reported FGF14‐dependent phenotypes of Nav1.6 currents, but that its activity requires the FGF14 N‐terminal tail, a domain that has been shown to contribute to Nav1.6 inactivation independently from the FGF14 core domain. In medium spiny neurons in the nucleus accumbens, where both FGF14 and Nav1.6 are abundantly expressed, FLPK significantly increased firing frequency by a mechanism consistent with the ability of the tetrapeptide to interfere with Nav1.6 inactivation and potentiate persistent Na+ currents. Taken together, these results indicate that FLPK might serve as a probe for characterizing molecular determinants of neuronal excitability and a peptide scaffold to develop allosteric modulators of Nav channels.
Recruitment variation in subtidal macrofouling assemblages of a Patagonian harbour (Argentina, south-western Atlantic)

The recruitment of subtidal macrofouling organisms was studied in the Patagonian harbour of Comodoro Rivadavia (Argentina, 45°51′35″S 67°27′23″W). Changes in coverage and density were analysed in the central 100 cm2 of upper and lower surfaces which were replaced monthly from January to December 2004. The fouling assemblage consisted of algae, spirorbid polychaetes, compound ascidians, hydrozoans, bryozoans and egg masses spawned by the small fish Helcogrammoides cunninghami. Monthly changes in richness and diversity of taxa on upper and lower surfaces were significantly correlated with sea surface temperature. Fouling assemblage structure differed significantly between upper and lower surfaces. Filamentous algae were dominant on upper surfaces, while filter-feeding invertebrates were more abundant on the lower surfaces of the experimental panels. The density of the spirorbid Romanchella scoresbyi was two orders of magnitude higher on lower than on upper surfaces. Its recruitment began in late winter, reaching maximum values in spring.
Diet of sympatric Brazilian caatinga peccaries (Tayassu tajacu and T. pecari)

Food habits of the Collared Peccary (Tayassu tajacu Linnaeus) have been well documented in the arid northern part of its range, where it feeds mainly on succulent plants (summary in Corn & Warren 1985). There is also a substantial amount of information on the diet of both this species and of the White-lipped Peccary (T. pecari Link) in the forested parts of their ranges (Bodmer 1989, Enders 1935, Kiltie 1981, Kiltie & Terborgh 1983, Leopold 1959). Both species seem to be primarily frugivorous in rain forest areas, being able to crack and digest hard seeds (Bodmer 1989). The occurrence of both species of peccaries in the caatinga, the vast xeric biome which covers most of north-eastern Brazil (Reis 1976), has been largely ignored in the recent literature (see Willig & Mares 1989), despite the fact that at least T. tajacu was originally widespread and is well known by local people even in the driest areas (Sick et al. 1987). Between March and July 1990 I was able to gather data on the food habits of both species in Serra da Capivara National Park (around 08? 26' S, 42? 19' W), a 1300 km2 reserve in south-eastern Piaui, Brazil. The area has been described by Emperaire (1989) and Olmos (1992). The park is covered by several xeric, deciduous plant associations from dry, open woodland to thorn scrub with cacti and terrestrial bromeliads. The climate is semi-arid, with a variable annual precipitation between 250 and 1270 mm which falls unpredictably between September and March. There is no permanent water course, only some springs, water-holes and man-made reservoirs. The study period covered the late rainy to early dry season of 1990, when most plants had not yet lost their leaves and were either flowering or fruiting. Because of the tangled vegetation, and nocturnal habits of the peccaries, the best way to collect data was to search for and follow the tracks of peccary
Can Wolbachia (Rickettsiaceae) explain female-biased sex ratios in mountain pine beetles (Coleoptera: Curculionidae)?

Abstract Wolbachia Hertig (Rickettsiales: Rickettsiaceae) is a genus of endosymbionts that are widespread in insects and can have important implications on population dynamics through cytoplasmic incompatibility or sex-ratio distortion. We considered Wolbachia as a possible explanation for female-biased sex ratios often observed in mountain pine beetle populations, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae: Scolytinae), a major pest species in western Canada whose most recent outbreak and range expansion has killed many millions of mature lodgepole pine, Pinus contorta var. latifolia Engelmann (Pinaceae). We used wsp primers to screen for Wolbachia in 10 mountain pine beetle populations with varying degrees of female bias in southeast British Columbia and southwest Alberta, Canada. We found no evidence of Wolbachia in these populations and suggest that other factors may explain the sex-ratio bias. Résumé Wolbachia Hertig (Rickettsiales: Rickettsiaceae) est un genre d’endosymbiontes répandus chez les insectes et pouvant avoir des conséquences importantes sur la dynamique des populations par le biais de l'incompatibilité cytoplasmique ou distorsion du rapport des sexes. Nous avons considéré Wolbachia comme une explication possible des rapports de sexe biaisés vers les femelles souvent observés dans les populations de dendroctones du pin ponderosa, Dendroctonus ponderosae Hopkins (Coleoptera: Curculionidae: Scolytinae), une des principales espèces de ravageurs dans l'ouest du Canada dont la plus récente éclosion et l'expansion de la distribution ont tué des millions de pins tordus matures, Pinus contorta var. latifolia Engelmann (Pinaceae). Nous avons utilisé des amorces wsp pour le dépistage de la bactérie Wolbachia dans 10 populations du dendroctone du pin ponderosa avec une gamme de biais du rapport des sexes dans le sud-est de la Colombie-Britannique et le sud-ouest de l'Alberta, Canada. Nous n'avons trouvé aucune preuve de Wolbachia dans ces populations et nous suggérons que d'autres facteurs peuvent expliquer le biais du rapport des sexes.
Mitochondrial DNA: more than an evolutionary bystander

Summary 1. The vast majority of studies employing mtDNA in evolutionary biology and ecology have used it as a means to infer demographic and historical patterns without pondering the underlying functional implications. In contrast, the biochemical and medical communities often aim to understand the influence of specific mtDNA mutations on mitochondrial functions, but rarely consider the evolutionary and ecological implications. 2. Ongoing research has shown that mtDNA mutations can profoundly affect mitochondrial function in humans and other animals. If the mutation (or set of mutations) is pathogenic, mitochondrial malfunction may be detected from early age. In nature, however, most mutations are not highly deleterious and may exist at intermediate frequency in populations. 3. In this review, we suggest that knowledge of the underlying biochemistry and functions of mitochondria can facilitate a more complete determination of the evolutionary dynamics of mtDNA and its influence on the life-history traits of organisms. With this approach, it is possible to use biochemistry to link the genotype with the phenotype. 4. After reviewing the literature, we conclude that there can be physiological and evolutionary trade-offs in the way that mitochondrial mutations can affect age classes and/or fitness components and that these effects may depend on the environment. Through these trade-offs, it may be possible for specific mtDNA mutations to have unequal fitness in different nuclear genetic backgrounds and also in different environments.
Can the growing of transgenic maize threaten protected Lepidoptera in Europe?

We evaluated whether protected European butterflies can potentially be at risk if transgenic maize is extensively grown in Central Europe. We explored potential consequences of both insect resistant (IR) and herbicide resistant (HR) transgenic maize. IR maize can produce pollen that is toxic to lepidopteran larvae, and this puts butterfly species at possible risk if the presence of young larvae coincides with maize flowering, during which large quantities of maize pollen can be deposited on vegetation. By considering the timing of maize flowering in Europe and the phenology of the protected Lepidoptera species, we found that 31 species had at least one generation where 50% of the larval stage overlapped with maize flowering, and 69 species for which first instar larvae were present during maize pollen shedding. HR maize allows high concentration herbicide treatments on fields without seasonal limitation, which can drastically reduce weed densities. In cases where such weed species are host plants for protected butterflies, reduced host plant/food availability can result, causing population decreases. By using published information, we first identified the important weed species in major maize‐growing European countries. Subsequently, we checked whether the host plants of protected Lepidoptera included species that are common maize weeds. We identified 140 protected species having food plants that are common weeds in one or more of the major European maize‐growing countries. If HR maize is grown in Europe, there is a potential hazard that their food plants will seriously decline, causing a subsequent decline of these protected species.
An Observational Study of the Behaviour of Captive Rehabilitant Sun Bears (Helarctos malayanus)

ABSTRACT Rehabilitant Malayan sun bears often remain in captivity for long periods of time and may experience significant welfare challenges including disability and persistent lip lesions. This study aimed to investigate whether short-term observations of behavior such as oral stereotypies are useful as noninvasive indicators of lip lesion pain, and whether behavior differs between able-bodied and disabled bears. Observations were collected from 21 captive, rehabilitant Malayan sun bears, of both sexes, a range of ages, and with lip lesions ranging in severity. Some also had disabilities. Oral stereotypy frequency was unrelated to lip lesion severity (p > 0.05), and no relationships with other behaviors were found; however, visual disabilities had significant effects on behavior. For example, visually disabled bears walked more than able-bodied bears (p = 0.003) or those with physical disabilities (p = 0.01). Further research on the feeding behavior of bears suffering from lip lesions may elucidate other potential behavioral indicators of pain. Researching effects of visual disabilities in bears with a larger sample size is also recommended to determine generalizable impacts in affected individuals and resulting welfare implications.
New Treatments in Spinal Muscular Atrophy: Positive Results and New Challenges

Spinal muscular atrophy (SMA) is one of the most common autosomal recessive diseases with progressive weakness of skeletal and respiratory muscles, leading to significant disability. The disorder is caused by mutations in the survival motor neuron 1 (SMN1) gene and a consequent decrease in the SMN protein leading to lower motor neuron degeneration. Recently, Food and Drug Administration (FDA) and European Medical Agency (EMA) approved the antisense oligonucleotide nusinersen, the first SMA disease-modifying treatment and gene replacement therapy by onasemnogene abeparvovec. Encouraging results from phase II and III clinical trials have raised hope that other therapeutic options will enter soon in clinical practice. However, the availability of effective approaches has raised up ethical, medical and financial issues that are routinely faced by the SMA community. This review covers the available data and the new challenges of SMA therapeutic strategies.
The effect of school exposure and personal contact on attitudes towards bullying and autism in schools: A cohort study with a control group

Research shows that the attitudes of children and adolescents towards bullying are influenced by the school environment and their peer groups. Given the increased vulnerability to bullying for autistic children, this study explored whether neurotypical children’s attitudes towards bullying and autism varied according to school exposure and personal contact with autistic people. Survey data were collected at the beginning and end of the school year from 775 children aged 11–12 years, from six schools: three with specialist centres for autism and three without. Participants read vignettes depicting bullying scenarios then completed measures of their attitudes in relation to the vignette and towards autism. Children from centre schools showed a greater increase in prosocial emotions towards bullying. For children from non-centre schools, an interaction showed a decrease in prosocial emotions except in response to social exclusion of an autistic child. Increases in personal contact showed a greater increase in positive attitudes towards autistic people. Explanations draw on theories of inter-group contact and social-moral reasoning. Results highlight the need for contact both at a personal level and through attending a school with an inclusive autism provision to increase understanding, improve attitudes towards autism and reduce tolerance for bullying. Lay abstract Autistic children are more likely than non-autistic children to be bullied at school. This study therefore explored whether the kind of school setting and the level of personal contact with autistic people can affect children’s attitudes towards bullying and autism. Surveys were completed at the beginning and end of the school year by 775 children aged 11–12 years, from six schools: three with specialist centres for autistic children and three without. Participants read stories describing bullying situations, then provided their views in relation to the story and in relation to autism. Children in schools with centres increased their feelings of anger, pity, sadness and shame in response to the bullying situations. In contrast, children in schools with no centre showed less sociable responses to bullying, except in response to a story describing an autistic child, being excluded by classmates. Furthermore, children who increased the time they spent with autistic individuals over the course of the year showed a greater rise in positive attitudes towards autistic people. This highlights the need for both personal contact and an inclusive school environment, to improve attitudes towards autism and reduce tolerance for bullying.
Using Tooth Rakes to Monitor Population and Sex Differences in Aggressive Behaviour in Bottlenose Dolphins (Tursiops truncatus)

This study investigated intraspecific tooth rake scarring, an established indicator of received aggression by conspecifics, on bottlenose dolphins (Tursiops truncatus) to gain knowledge of aggressive interactions. The differences in tooth rake scarring between male and female dolphins on the east coast of Scotland were examined, and overall levels of scarring were compared with dolphins on the west coast of Scotland (Sound of Barra and Hebrides). Photographs were examined for evidence of tooth rake scarring using four different methods. East coast males displayed significantly higher scarring percentages (i.e., body area covered by tooth rake scarring), numbers of dorsal fin rake directions (i.e., whether tooth rake scars were vertical, horizontal, diagonal, or curved), and nick percentage (i.e., amount of the dorsal fin missing due to nicks) than females. Differences also existed between the three areas, with bottlenose dolphins around the Sound of Barra showing significantly lower levels of dorsal fin rake directions than those on the east coast or Hebrides. Observed sex differences are likely the result of intrasexual conflict between males over access to females. However, other factors such as sex- or age-specific behaviours or sexual coercion of females may also be involved. Such information could potentially be used to differentiate between the sexes. The differences in dorsal fin scarring between these populations suggests differences in aggressive interactions, possibly indicating differences in social structure. The lower scarring levels seen in the Sound of Barra group may support the suggestion that bottlenose dolphins on the west coast belong to two communities. However, this variability in conspecific aggression may also be the result of different social behaviours, age or sex ratios, habitat, resources, or individual behavioural differences.
Use of Rifampin Compared with Isoniazid for the Treatment of Latent Tuberculosis Infection in Japan: A Bayesian Inference with Markov Chain Monte Carlo Method

Objective Treating latent tuberculosis infection (LTBI) is essential for eliminating the serious endemicity of tuberculosis. A shorter regimen is preferred to longer regimens because the former has better adherence with a better safety profile. However, lengthy treatment with isoniazid is still recommended in Japan. Based on the latest evidence, we switched from a conventional nine-month isoniazid regimen to a shorter four-month rifampin regimen for the treatment of LTBI. Methods To evaluate the safety and efficacy of the shorter regimen, we conducted Bayesian analyses using a stochastic mathematical model to calculate the posterior probabilities of several parameters. Patients Clinical data of 13 patients in the isoniazid group and 5 in the rifampin group were used for the Bayesian analyses. The outcomes measured were completion of the treatment, adverse effects, number of clinic visits, and medical costs. Results The medial posterior probability of the isoniazid group completing the treatment was 66% [95% credible interval (CrI) 43-89%], whereas that of the rifampin group was 86% (95% CrI 60-100%). The probability that the completion rate in the rifampin group was better than that in the isoniazid group was as high as 88% (95% CrI 0-100%). Other parameters, such as the number of clinical visits and duration of treatment, were better with rifampin therapy than with isoniazid therapy, with comparable medical costs. Conclusion Four months of rifampin therapy might be preferred to isoniazid for treating LTBI in Japan.
Temporal trends and mortality of post-ERCP pancreatitis in the United States: a nationwide analysis

Abstract Background Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis (PEP) is the most common and most serious complication of ERCP. Our aim was to estimate the nationwide incidence, temporal trends, and mortality of PEP in the United States and to establish risk factors associated with PEP development. Methods This was a retrospective cohort study analyzing Nationwide Inpatient Sample data from 2011 to 2017 using International Classification of Diseases codes. The primary outcomes were trends in PEP incidence and predictors of PEP development. Secondary outcomes were in-hospital mortality, length of hospital stay, and admission to the intensive care unit. Results Of 1 222 467 adult patients who underwent inpatient ERCP during the study period, 55 225 (4.5 %) developed PEP. The hospital admission rate of PEP increased by 15.3 %, from 7735 in 2011 to 8920 in 2017 (odds ratio [OR] 1.23, 95 % confidence interval [CI] 1.04 – 1.46; P = 0.02). The overall rate of mortality increased from 2.8 % of PEP cases in 2011 to 4.4 % in 2017 (OR 1.62, 95 %CI 1.10 – 2.38; P = 0.01). Multiple patient-related (alcohol use, cocaine use, obesity, chronic kidney disease, heart failure), procedure-related (therapeutic ERCP, sphincterotomy, pancreatic duct stent placement, sphincter of Oddi dysfunction), and hospital-related (teaching hospitals, hospitals located in the West and Midwest) factors that impact the occurrence of PEP were identified. Conclusions Our study showed rising hospital admission and mortality rates associated with PEP in the United States. This calls for a greater recognition of this life-threatening complication and amelioration of its risk factors, whenever possible.
Laser thermal therapy in the management of high-grade gliomas

Abstract Laser interstitial thermal therapy (LITT) is a minimally invasive therapy that have been used for brain tumors, epilepsy, chronic pain, and other spine pathologies. This therapy is performed under imaging and stereotactic guidance to precisely direct the probe and ablate the area of interest using real-time magnetic resonance (MR) thermography. LITT has gained popularity as a treatment for glioma because of its minimally invasive nature, small skin incision, repeatability, shorter hospital stay, and the possibility of receiving adjuvant therapy shortly after surgery instead of several weeks as required after open surgical resection. Several reports have demonstrated the usefulness of LITT in the treatment of newly-diagnosed and recurrent gliomas. In this review, we will summarize the recent evidence of this therapy in the field of glioma surgery and the future perspectives of the use of LITT combined with other treatment strategies for this devastating disease.