Miracle-dz/UniFAR-FTUs huggingface dataset:
Indications for hyperthermic intraperitoneal chemotherapy with cytoreductive surgery: a clinical practice guideline.

Objective The purpose of the present review was to provide evidence-based guidance about the provision of cytoreductive surgery (crs) with hyperthermic intraperitoneal chemotherapy (hipec) in the treatment of peritoneal cancers. Methods The guideline was developed by the Program in Evidence-Based Care together with the Surgical Oncology Program at Ontario Health (Cancer Care Ontario) through a systematic review of relevant literature, patient- and caregiver-specific consultation, and internal and external reviews. Results Recommendation 1a: For patients with newly diagnosed stage iii primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, hipec should be considered for those with at least stable disease after neoadjuvant chemotherapy at the time that interval crs (if complete) or optimal cytoreduction is achieved. Recommendation 1b: There is insufficient evidence to recommend the addition of hipec when primary crs is performed for patients with newly diagnosed advanced primary epithelial ovarian or fallopian tube carcinoma, or primary peritoneal carcinoma, outside of a clinical trial. Recommendation 2: There is insufficient evidence to recommend hipec with crs in patients with recurrent ovarian cancer outside the context of a clinical trial. Recommendation 3: There is insufficient evidence to recommend hipec with crs in patients with peritoneal colorectal carcinomatosis outside the context of a clinical trial. Recommendation 4: There is insufficient evidence to recommend hipec with crs for the prevention of peritoneal carcinomatosis in colorectal cancer outside the context of a clinical trial; however, hipec using oxaliplatin is not recommended. Recommendation 5: There is insufficient evidence to recommend hipec with crs for the treatment of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 6: There is insufficient evidence to recommend hipec with crs for the prevention of gastric peritoneal carcinomatosis outside the context of a clinical trial. Recommendation 7: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with malignant peritoneal mesothelioma; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol. Recommendation 8: There is insufficient evidence to recommend hipec with crs as a standard of care in patients with disseminated mucinous neoplasm in the appendix; however, patients should be referred to hipec specialty centres for assessment for treatment as part of an ongoing research protocol.
Characterisation and functional analysis of canine TLR5

In this study, we characterised the single exon TLR5 gene of the Chinese rural dog. Sequence analysis revealed a 2577 nucleotide-long open reading frame of canine TLR5, encoding an 858 amino acid-long protein. The putative amino acid sequence of canine TLR5 consisted of a signal peptide sequence, 15 LRR domains, a LRR C-terminal domain, a transmembrane domain and an intracellular Toll-IL-1 receptor domain. The amino acid sequence of the canine TLR5 protein shared 95.4% identity with vulpine, 72.2% with feline and 64.7% with human TLR5. Plasmids expressing canine TLR5 and NF-κB-luciferase were constructed and transfected into HEK293T cells. Expression was confirmed by indirect immunofluorescence assay. These HEK293T cells transfected with the canine TLR5- and NF-κB-luciferase plasmids signiﬁcantly responded to ﬂagellin from Salmonella enteritidis serovar Typhimurium, indicating that it is a functional TLR5 homolog. In response to stimulation with Salmonella enteritidis, the level of TLR5 mRNA significantly increased over the control in PBMCs at 4 h. The levels of IL-8, IL-6 and IL-1β also increased after exposure. The highest levels of TLR5, IL-8 and IL-1β expression were detected at 8, 4 and 12 h after stimulation, respectively. These results imply that the expression of canine TLR5 may participate in the immune response against bacterial pathogens.
Mental health during and after protests, riots and revolutions: A systematic review

Objectives: Protests, riots and revolutions have long been a part of human history and are increasing globally, yet their impact on mental health remains largely unknown. We therefore systematically reviewed studies on collective actions and mental health. Method: We searched PubMed, Web of Science, PsycINFO and CINAHL Plus for published studies from their inception until 1 January 2018. Study quality was rated using the Newcastle–Ottawa Scale. Results: We identified 52 studies (n = 57,487 participants) from 20 countries/regions. The prevalence of post-traumatic stress disorder ranged from 4% to 41% in riot-affected areas. Following a major protest, the prevalence of probable major depression increased by 7%, regardless of personal involvement in the protests, suggestive of community spillover effects. Risk factors for poorer mental health included female sex, lower socioeconomic status, exposure to violence, interpersonal conflicts, frequent social media use and lower resilience and social support. Nevertheless, two studies suggested that collective actions may reduce depression and suicide, possibly due to a collective cathartic experience and greater social cohesion within subpopulations. Conclusion: We present the first systematic review of collective actions and mental health, showing compelling evidence that protests even when nonviolent can be associated with adverse mental health outcomes. Health care professionals therefore need to be vigilant to the mental and psychological sequelae of protests, riots and revolutions. Further research on this emerging sociopolitical determinant of mental health is warranted.
Novel percutaneous dual-lumen cannula-based right ventricular assist device provides effective support for refractory right ventricular failure after left ventricular assist device implantation.

OBJECTIVES Right heart failure after left ventricular assist device (LVAD) implantation is associated with significant morbidity and mortality. A new generation of percutaneous right ventricular assist devices (RVADs) may mitigate the need for invasive surgical RVAD implantation. The purpose of this study was to evaluate the safety and efficacy of the Protek Duo (TandemLife, Pittsburgh, PA, USA) RVAD in patients who developed severe acute right heart failure in the intensive care unit after LVAD implantation. METHODS This was a retrospective cohort study of 27 patients who received a Protek Duo after LVAD implantation from January 2016 to March 2019 at our centre. The primary outcome of interest was survival to hospital discharge. Secondary outcomes included procedural success, device-related complications and conversion to a surgical RVAD. RESULTS The median age of patients was 63 years (interquartile range 58-71), 78% were men and 78% were Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profile 1 or 2. Patients were on a median of 2 inotropes and 2 pressors prior to Protek Duo insertion. The device successfully implanted on the first attempt in all patients a median of 1 day (interquartile range 1-2) after LVAD implantation and the median duration of support was 11 days (interquartile range 7-16). Device weaning occurred in 86% of patients, with 15% in-hospital mortality. Major complications related to the device included new moderate-to-severe tricuspid regurgitation (36%), haemolysis (14%) and cannula migration (7%). Three patients (11%) required conversion to surgical RVAD. Overall survival to 1 year was 81%. CONCLUSIONS The use of the Protek Duo as a percutaneous RVAD is a safe and feasible treatment for patients who develop acute right heart failure after LVAD implantation.
Endothelial sphingosine 1-phosphate receptors promote vascular normalization and antitumor therapy

Significance Tumor progression is dependent on angiogenesis, which supplies nutrients and enables gas exchange and metastatic dissemination. However, tumor vessels are dysfunctional and immature, which hinders the effectiveness of various therapeutics. Sphingosine 1-phosphate receptors in endothelial cells are essential for developmental angiogenesis and physiological functions such as the maintenance of the vascular barrier and vascular tone. This study shows that endothelial sphingosine 1-phosphate receptors determine the tumor vascular phenotype and maturation and that function of S1P receptor-1 is needed for tumor vascular normalization, which allows better blood circulation and enhances antitumor therapeutic efficacy in mouse models. Sphingosine 1-phosphate receptor-1 (S1PR1) is essential for embryonic vascular development and maturation. In the adult, it is a key regulator of vascular barrier function and inflammatory processes. Its roles in tumor angiogenesis, tumor growth, and metastasis are not well understood. In this paper, we show that S1PR1 is expressed and active in tumor vessels. Murine tumor vessels that lack S1PR1 in the vascular endothelium (S1pr1 ECKO) show excessive vascular sprouting and branching, decreased barrier function, and poor perfusion accompanied by loose attachment of pericytes. Compound knockout of S1pr1, 2, and 3 genes further exacerbated these phenotypes, suggesting compensatory function of endothelial S1PR2 and 3 in the absence of S1PR1. On the other hand, tumor vessels with high expression of S1PR1 (S1pr1 ECTG) show less branching, tortuosity, and enhanced pericyte coverage. Larger tumors and enhanced lung metastasis were seen in S1pr1 ECKO, whereas S1pr1 ECTG showed smaller tumors and reduced metastasis. Furthermore, antitumor activity of a chemotherapeutic agent (doxorubicin) and immune checkpoint inhibitor blocker (anti-PD-1 antibody) were more effective in S1pr1 ECTG than in the wild-type counterparts. These data suggest that tumor endothelial S1PR1 induces vascular normalization and influences tumor growth and metastasis, thus enhancing antitumor therapies in mouse models. Strategies to enhance S1PR1 signaling in tumor vessels may be an important adjunct to standard cancer therapy of solid tumors.
Cancer causes metabolic perturbations associated with reduced insulin-stimulated glucose uptake in peripheral tissues and impaired muscle microvascular perfusion

Cancer is often associated with poor glycemic control but the molecular mechanisms are unknown. The aim of this study was to elucidate tissue-specific contributions and molecular mechanisms underlying impaired glycemic regulation in cancer. Basal and insulin-stimulated glucose uptake in skeletal muscle and white adipose tissue (WAT), as well as hepatic glucose production, were determined in control and Lewis lung carcinoma (LLC) tumor-bearing C57BL/6 mice using isotopic tracers. Skeletal muscle microvascular perfusion was analyzed via a real-time contrast-enhanced ultrasound technique. Finally, the role of fatty acid turnover on glycemic control was determined by treating tumor-bearing insulin-resistant mice with nicotinic acid or etomoxir. LLC tumor-bearing mice displayed whole-body insulin resistance and glucose intolerance, which was restored by nicotinic acid or etomoxir. Insulin-stimulated glucose uptake was 30-40% reduced in skeletal muscle and WAT of mice carrying large tumors. Despite compromised glucose uptake, tumor-bearing mice displayed upregulated insulin-stimulated phosphorylation of TBC1D4Thr642 (+18%), AKTSer473 (+65%), and AKTThr308 (+86%) in muscle. Insulin caused a 70% increase in muscle microvascular perfusion in control mice, which was abolished in tumor-bearing mice. Additionally, tumor-bearing mice displayed increased (+45%) basal (not insulin-stimulated) hepatic glucose production. We show that cancer can result in marked perturbations on at least six metabolically essential functions; i) insulin’s blood-glucose-lowering effect, ii) glucose tolerance, iii) skeletal muscle and white adipose tissue insulin-stimulated glucose uptake, iv) intramyocellular insulin signaling, v) muscle microvascular perfusion, and vi) basal hepatic glucose production in mice. Additionally, we show that the mechanism causing cancer-induced insulin resistance may relate to fatty acid metabolism.
Impact of past climate warming on genomic diversity and demographic history of collared lemmings across the Eurasian Arctic

Significance Ongoing climate warming significantly impacts cold-adapted Arctic biota. One way to predict the biological consequences of Arctic warming in the future is to investigate biotic responses to past warming events. We use variation in mitochondrial and nuclear genomes in the collared lemming, a keystone species of the food web in tundra, to reconstruct demographic changes as a response to warming of the last interglacial and Holocene thermal optimum. We show that environmental change during Late Quaternary climate warming contracted distribution range, reduced effective population size, and decreased genetic diversity across the Eurasian Arctic except for West Beringia, a region in the extreme northeast of Eurasia. Thus, West Beringia represents a potential refugium for terrestrial Arctic species under ongoing climate warming. The Arctic climate was warmer than today at the last interglacial and the Holocene thermal optimum. To reveal the impact of past climate-warming events on the demographic history of an Arctic specialist, we examined both mitochondrial and nuclear genomic variation in the collared lemming (Dicrostonyx torquatus, Pallas), a keystone species in tundra communities, across its entire distribution in northern Eurasia. The ancestral phylogenetic position of the West Beringian group and divergence time estimates support the hypothesis of continental range contraction to a single refugial area located in West Beringia during high-magnitude warming of the last interglacial, followed by westward recolonization of northern Eurasia in the last glacial period. The West Beringian group harbors the highest mitogenome diversity and its inferred demography indicates a constantly large effective population size over the Late Pleistocene to Holocene. This suggests that northward forest expansion during recent warming of the Holocene thermal optimum did not affect the gene pool of the collared lemming in West Beringia but reduced genomic diversity and effective population size in all other regions of the Eurasian Arctic. Demographic inference from genomic diversity was corroborated by species distribution modeling showing reduction in species distribution during past climate warming. These conclusions are supported by recent paleoecological evidence suggesting smaller temperature increases and moderate northward forest advances in the extreme northeast of Eurasia during the Late Pleistocene-to-Holocene warming events. This study emphasizes the importance of West Beringia as a potential refugium for cold-adapted Arctic species under ongoing climate warming.
Effect of a dementia education intervention on the confidence and attitudes of general practitioners in Australia: a pretest post-test study

Objectives This study assessed the impact of a Dementia Education Workshop on the confidence and attitudes of general practitioner (GP) registrars (GPR) and GP supervisors (GPS) in relation to the early diagnosis and management of dementia. Design Pretest post-test research design. Setting Continuing medical education in Australia. Participants 332 GPR and 114 GPS. Interventions Registrars participated in a 3-hour face-to-face workshop while supervisors participated in a 2-hour-modified version designed to assist with the education and supervision of registrars. Main outcome measures The General Practitioners Confidence and Attitude Scale for Dementia was used to assess overall confidence, attitude to care and engagement. A t-test for paired samples was used to identify differences from preworkshop (T1) to postworkshop (T2) for each GP group. A t-test for independent samples was undertaken to ascertain differences between each workshop group. A Cohen’s d was calculated to measure the effect size of any difference between T1 and T2 scores. Results Significant increases in scores were recorded for Confidence in Clinical Abilities, Attitude to Care and Engagement between pretest and post-test periods. GPR exhibited the greatest increase in scores for Confidence in Clinical Abilities and Engagement. Conclusions Targeted educational interventions can improve attitude, increase confidence and reduce negative attitudes towards engagement of participating GPs.
Liquid biopsy in the era of immune-oncology. Is it ready for prime-time use for cancer patients?

BACKGROUND The emergence of immunotherapy in oncology requires the discovery, validation and subsequent adoption of robust, sensitive and specific predictive and prognostic biomarkers for daily practice. Until now, anti-PD-L1 immunohistochemistry (IHC) on tissue sections has been the only validated companion diagnostic test for first-line immunotherapy for advanced and metastatic cancer, notably non-small-cell lung cancer (NSCLC). However, detection of this biomarker presents limitations which have stimulated the development of other biomarkers and other approaches. Within this context, the use of a liquid biopsy (LB) could provide an important complementary or alternative added value to PD-L1 IHC. DESIGN In this review, we discuss how liquid biopsies (LBs) have been used in the field of immuno-oncology (I-O) to predict response, relapse or adverse advents for patients undergoing immune-checkpoint inhibitor (ICI) therapy (anti PD-1/PD-L1 and CTLA-4) and we highlight recent developments. Circulating tumor cells (CTCs), cell-free DNA (cfDNA), proteins and cytokines detected in plasma as well as circulating T-lymphocytes are discussed as potential sources for developing new I-O biomarkers. RESULTS The quantification of cfDNA as a predictive biomarker, as well as its sequencing for the determination of tumor mutational burden (TMB), is already well advanced. Additionally, the quantification of PD-L1 from CTCs, bound on exosomes or free in plasma, as well as the determination of cytokines, are also being actively investigated with promising results having recently been published. Lastly, analysis of T-lymphocytes, especially by analyzing the T-cell receptor, has recently emerged as a valuable biomarker that might become relevant for the prediction of response to ICIs. CONCLUSION While LBs have not yet been implemented in routine I-O clinical practice, recent promising data and rapidly advancing technologies indicate that this approach has the potential to soon personalize the clinical management of cancer patients receiving ICIs.
Cabbage looper (Trichoplusia ni Hübner) labial glands contain unique bacterial flora in contrast with their alimentary canal, mandibular glands, and Malpighian tubules

In recent years, several studies have examined the gut microbiome of lepidopteran larvae and how factors such as host plant affect it, and in turn, how gut bacteria affect host plant responses to herbivory. In addition, other studies have detailed how secretions of the labial (salivary) glands can alter host plant defense responses. We examined the gut microbiome of the cabbage looper (Trichoplusia ni) feeding on collards (Brassica oleracea) and separately analyzed the microbiomes of various organs that open directly into the alimentary canal, including the labial glands, mandibular glands, and the Malpighian tubules. In this study, the gut microbiome of T. ni was found to be generally consistent with those of other lepidopteran larvae in prior studies. The greatest diversity of bacteria appeared in the Firmicutes, Actinobacteria, Proteobacteria, and Bacteriodetes. Well‐represented genera included Staphylococcus, Streptococcus, Corynebacterium, Pseudomonas, Diaphorobacter, Methylobacterium, Flavobacterium, and Cloacibacterium. Across all organs, two amplicon sequence variants (ASVs) associated with the genera Diaphorobacter and Cloacibacterium appeared to be most abundant. In terms of the most prevalent ASVs, the alimentary canal, Malpighian tubules, and mandibular glands appeared to have similar complements of bacteria, with relatively few significant differences evident. However, aside from the Diaphorobacter and Cloacibacterium ASVs common to all the organs, the labial glands appeared to possess a distinctive complement of bacteria which was absent or poorly represented in the other organs. Among these were representatives of the Pseudomonas, Flavobacterium, Caulobacterium, Anaerococcus, and Methylobacterium. These results suggest that the labial glands present bacteria with different selective pressures than those occurring in the mandibular gland, Malpighian tubules and the alimentary canal. Given the documented effects that labial gland secretions and the gut microbiome can exert on host plant defenses, the effects exerted by the bacteria inhabiting the labial glands themselves deserve further study.
Influence of Arctic sea-ice variability on Pacific trade winds

Significance By 20th-century standards, the Central Pacific trade winds that drive the El Nino–Southern Oscillation feedback system to instability have been unusually strong in the 21st century. The annual summer melts of Arctic sea ice are up to twice as large in area as in the 20th century. Arctic sea ice, upper atmospheric circulation, surface wind, and sea-surface temperature data provide evidence that upper troposphere transport processes connect the increased summer losses of Arctic sea ice to the trade-wind and Central Pacific El Nino events characteristic of the present climate state. These results add to the evidence that loss of Arctic sea ice is having a major impact on climatic variability around the world. A conceptual model connecting seasonal loss of Arctic sea ice to midlatitude extreme weather events is applied to the 21st-century intensification of Central Pacific trade winds, emergence of Central Pacific El Nino events, and weakening of the North Pacific Aleutian Low Circulation. According to the model, Arctic Ocean warming following the summer sea-ice melt drives vertical convection that perturbs the upper troposphere. Static stability calculations show that upward convection occurs in annual 40- to 45-d episodes over the seasonally ice-free areas of the Beaufort-to-Kara Sea arc. The episodes generate planetary waves and higher-frequency wave trains that transport momentum and heat southward in the upper troposphere. Regression of upper tropospheric circulation data on September sea-ice area indicates that convection episodes produce wave-mediated teleconnections between the maximum ice-loss region north of the Siberian Arctic coast and the Intertropical Convergence Zone (ITCZ). These teleconnections generate oppositely directed trade-wind anomalies in the Central and Eastern Pacific during boreal winter. The interaction of upper troposphere waves with the ITCZ air–sea column may also trigger Central Pacific El Nino events. Finally, waves reflected northward from the ITCZ air column and/or generated by triggered El Nino events may be responsible for the late winter weakening of the Aleutian Low Circulation in recent years.