A lactate-SREBP2 signaling axis drives tolerogenic dendritic cell maturation and promotes cancer progression.

Conventional dendritic cells (DCs) are essential mediators of antitumor immunity. As a result, cancers have developed poorly understood mechanisms to render DCs dysfunctional within the tumor microenvironment (TME). After identification of CD63 as a specific surface marker, we demonstrate that mature regulatory DCs (mregDCs) migrate to tumor-draining lymph node tissues and suppress DC antigen cross-presentation in trans while promoting T helper 2 and regulatory T cell differentiation. Transcriptional and metabolic studies showed that mregDC functionality is dependent on the mevalonate biosynthetic pathway and its master transcription factor, SREBP2. We found that melanoma-derived lactate activates SREBP2 in tumor DCs and drives conventional DC transformation into mregDCs via homeostatic or tolerogenic maturation. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promoted antitumor CD8+ T cell activation and suppressed melanoma progression. CD63+ mregDCs were found to reside within the lymph nodes of several preclinical tumor models and in the sentinel lymph nodes of patients with melanoma. Collectively, this work suggests that a tumor lactate-stimulated SREBP2-dependent program promotes CD63+ mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME.

Gli2 Facilitates Tumor Immune Evasion and Immunotherapeutic Resistance by Coordinating Wnt Ligand and Prostaglandin Signaling.

Therapeutic resistance to immune checkpoint blockade has been commonly linked to the process of mesenchymal transformation (MT) and remains a prevalent obstacle across many cancer types. An improved mechanistic understanding for MT-mediated immune evasion promises to lead to more effective combination therapeutic regimens. Herein, we identify the Hedgehog transcription factor, Gli2, as a key node of tumor-mediated immune evasion and immunotherapy resistance during MT. Mechanistic studies reveal that Gli2 generates an immunotolerant tumor microenvironment through the upregulation of Wnt ligand production and increased prostaglandin synthesis. This pathway drives the recruitment, viability, and function of granulocytic myeloid-derived suppressor cells (PMN-MDSCs) while also impairing type I conventional dendritic cell, CD8 + T cell, and NK cell functionality. Pharmacologic EP2/EP4 prostaglandin receptor inhibition and Wnt ligand inhibition each reverses a subset of these effects, while preventing primary and adaptive resistance to anti-PD-1 immunotherapy, respectively. A transcriptional Gli2 signature correlates with resistance to anti-PD-1 immunotherapy in stage IV melanoma patients, providing a translational roadmap to direct combination immunotherapeutics in the clinic. SIGNIFICANCE: Gli2-induced EMT promotes immune evasion and immunotherapeutic resistance via coordinated prostaglandin and Wnt signaling.

Impact of Antimicrobial Stewardship Program Intervention Acceptance on Hospital Length of Stay.

Background: Inappropriate antibiotic use is a major public health concern. Excessive exposure to antibiotics results in the proliferation of multidrug-resistant bacteria, increase in potentially avoidable adverse drug reactions, healthcare utilization, and cost. Currently, systematic reviews and controlled trials assessing the effects of antimicrobial stewardship programs (ASP) on hospital length of stay (LOS), mortality, and cost-savings are conflicting. Some studies reported a significant cost-savings driven by shorter hospital LOS while the others found no effect and, in some cases, prolonged LOS. Shortening the time to appropriate therapy and reducing unnecessary days of therapy have been shown to reduce hospital LOS. Objective: The purpose of this study was to evaluate the effects of prescriber acceptance to ASP interventions on hospital LOS. Methods: Between January 2018 and December 2019, 764 charts were retrospectively reviewed for patients who received antimicrobial treatment and in whom an ASP intervention was performed. Patients were allocated into 2 groups: those whose ASP interventions were accepted and those whose were rejected. Provider responses were then documented within 24 hours of being communicated. The primary outcome was hospital LOS. Secondary outcomes included 30-day readmission rates and inpatient antimicrobial duration of therapy (DOT). Results: There were 384 patients with an accepted ASP intervention and 380 with a denied intervention. Baseline characteristics were similar between both groups, except for a difference in the types of intervention performed (P < 0.001). The median hospital LOS for patients in the accepted intervention group was 6.5 days compared to 7 days in the rejected intervention group (P = 0.009). Antimicrobial DOT was also shorter in the accepted intervention group (5 vs 7 days; P < 0.001). There was no difference in 30-day readmission rates (P = 0.98). Conclusion: Prescriber acceptance to ASP interventions decreases hospital LOS and antimicrobial DOT without affecting 30-day readmission rates.

A SREBF2-dependent gene program drives an immunotolerant dendritic cell population during cancer progression.

Dendritic cells (cDCs) are essential mediators of anti-tumor immunity. Cancers have developed mechanisms to render DCs dysfunctional within the tumor microenvironment. Utilizing CD63 as a unique surface marker, we demonstrate that mature regulatory DCs (mregDCs) suppress DC antigen cross-presentation while driving T H 2 and regulatory T cell differentiation within tumor-draining lymph node tissues. Transcriptional and metabolic studies show that mregDC functionality is dependent upon the mevalonate biosynthetic pathway and the master transcription factor, SREBP2. Melanoma-derived lactate activates DC SREBP2 in the tumor microenvironment (TME) and drives mregDC development from conventional DCs. DC-specific genetic silencing and pharmacologic inhibition of SREBP2 promotes anti-tumor CD8 + T cell activation and suppresses melanoma progression. CD63 + mregDCs reside within the sentinel lymph nodes of melanoma patients. Collectively, this work describes a tumor-driven SREBP2-dependent program that promotes CD63 + mregDC development and function while serving as a promising therapeutic target for overcoming immune tolerance in the TME. One Sentence Summary: The metabolic transcription factor, SREBF2, regulates the development and tolerogenic function of the mregDC population within the tumor microenvironment.

A global phylogeny of butterflies reveals their evolutionary history, ancestral hosts and biogeographic origins.

Butterflies are a diverse and charismatic insect group that are thought to have evolved with plants and dispersed throughout the world in response to key geological events. However, these hypotheses have not been extensively tested because a comprehensive phylogenetic framework and datasets for butterfly larval hosts and global distributions are lacking. We sequenced 391 genes from nearly 2,300 butterfly species, sampled from 90 countries and 28 specimen collections, to reconstruct a new phylogenomic tree of butterflies representing 92% of all genera. Our phylogeny has strong support for nearly all nodes and demonstrates that at least 36 butterfly tribes require reclassification. Divergence time analyses imply an origin ~100 million years ago for butterflies and indicate that all but one family were present before the K/Pg extinction event. We aggregated larval host datasets and global distribution records and found that butterflies are likely to have first fed on Fabaceae and originated in what is now the Americas. Soon after the Cretaceous Thermal Maximum, butterflies crossed Beringia and diversified in the Palaeotropics. Our results also reveal that most butterfly species are specialists that feed on only one larval host plant family. However, generalist butterflies that consume two or more plant families usually feed on closely related plants.

[Artificial intelligence and internal medicine: The example of hydroxychloroquine according to ChatGPT]. / Les intelligences artificielles conversationnelles en médecine interne : l'exemple de l'hydroxychloroquine selon ChatGPT.

Artificial intelligence (AI) using deep learning is revolutionizing several fields, including medicine, with a wide range of applications. Available since the end of 2022, ChatGPT is a conversational AI or "chatbot", using artificial intelligence to dialogue with its users in all fields. Through the example of hydroxychloroquine (HCQ), we discuss its use for patients, clinicians, or researchers, and discuss its performance and limitations, particularly in relation to algorithmic bias. If AI tools using deep learning do not dispense with the expertise and experience of a clinician (at least, for the moment), they have a potential to improve or simplify our daily practice.

SARS-CoV-2 Reinfection and Severity of the Disease: A Systematic Review and Meta-Analysis.

Since the discovery of SARS-CoV-2, changes in genotype and reinfection with different variants have been observed in COVID-19-recovered patients, raising questions around the clinical pattern and severity of primary infection and reinfection. In this systematic review, we summarize the results of 23 studies addressing SARS-CoV-2 reinfections. A total of 23,231 reinfected patients were included, with pooled estimated reinfection rates ranging from 0.1 to 6.8%. Reinfections were more prevalent during the Omicron variant period. The mean age of reinfected patients was 38.0 ± 6. years and females were predominant among reinfected patients (M/F = 0.8). The most common symptoms during the first and second infection were fever (41.1%), cough (35.7% and 44.6%), myalgia (34.5% and 33.3%), fatigue (23.8% and 25.6%), and headaches (24.4% and 21.4%). No significant differences of clinical pattern were observed between primary infection and reinfection. No significant differences in the severity of infection were observed between primary infection and reinfection. Being female, being a patient with comorbidities, lacking anti-nucleocapsid IgG after the first infection, being infected during the Delta and Omicron wave, and being unvaccinated were associated with a higher risk of reinfection. Conflicting age-related findings were found in two studies. Reinfection with SARS-CoV-2 suggests that natural immunity is not long-lasting in COVID-19 patients.

Usage of RePlay as a Take-Home System to Support High-Repetition Motor Rehabilitation After Neurological Injury.

Stroke is a leading cause of chronic motor disability. While physical rehabilitation can promote functional recovery, several barriers prevent patients from receiving optimal rehabilitative care. Easy access to at-home rehabilitative tools could increase patients' ability to participate in rehabilitative exercises, which may lead to improved outcomes. Toward achieving this goal, we developed RePlay: a novel system that facilitates unsupervised rehabilitative exercises at home. RePlay leverages available consumer technology to provide a simple tool that allows users to perform common rehabilitative exercises in a gameplay environment. RePlay collects quantitative time series force and movement data from handheld devices, which provide therapists the ability to quantify gains and individualize rehabilitative regimens. RePlay was developed in C# using Visual Studio. In this feasibility study, we assessed whether participants with neurological injury are capable of using the RePlay system in both a supervised in-office setting and an unsupervised at-home setting, and we assessed their adherence to the unsupervised at-home rehabilitation assignment. All participants were assigned a set of 18 games and exercises to play each day. Participants produced on average 698 ± 36 discrete movements during the initial 1 hour in-office visit. A subset of participants who used the system at home produced 1593 ± 197 discrete movements per day. Participants demonstrated a high degree of engagement while using the system at home, typically completing nearly double the number of assigned exercises per day. These findings indicate that the open-source RePlay system may be a feasible tool to facilitate access to rehabilitative exercises and potentially improve overall patient outcomes.

COVID-19: A Review of Potential Treatments (Corticosteroids, Remdesivir, Tocilizumab, Bamlanivimab/Etesevimab, and Casirivimab/Imdevimab) and Pharmacological Considerations.

Objectives: In light of the ongoing global pandemic, this paper reviews data on a number of potential and approved agents for COVID-19 disease management, including corticosteroids, remdesivir, tocilizumab, and monoclonal antibody combinations. Dose considerations, potential drug-drug interactions, and access issues are discussed. Key findings: Remdesivir is the first antiviral agent approved for the treatment of COVID-19, based on results from large clinical trials showing reduction in recovery time, faster clinical improvement, and decrease in time to discharge with remdesivir. Dexamethasone and tocilizumab have demonstrated mortality benefits in large, randomized controlled trials. Consequently, the use of corticosteroids has become the standard of care for hospitalized patients with severe or critical COVID-19, while tocilizumab is recommended for use in combination with a corticosteroid in certain hospitalized patients. Recently, monoclonal antibody combinations bamlanivimab/etesevimab and casirivimab/imdevimab received emergency use authorizations for use in non-hospitalized patients with mild-to-moderate COVID-19 at high risk of disease progression. Summary: As data from large clinical trials emerge, the paradigm of COVID-19 treatments has shifted significantly. The use of corticosteroids, remdesivir, and tocilizumab depend on disease severity. Emerging data on monoclonal antibody combinations are promising, but further data are required. Pharmacists can play a role in ensuring appropriate access, correct administration, and safe use of COVID-19 treatments and are encouraged to stay abreast of new developments.

Tumor-intrinsic NLRP3-HSP70-TLR4 axis drives premetastatic niche development and hyperprogression during anti-PD-1 immunotherapy.

The tumor-intrinsic NOD-, LRR- and pyrin domain-containing protein-3 (NLRP3) inflammasome-heat shock protein 70 (HSP70) signaling axis is triggered by CD8+ T cell cytotoxicity and contributes to the development of adaptive resistance to anti-programmed cell death protein 1 (PD-1) immunotherapy by recruiting granulocytic polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) into the tumor microenvironment. Here, we demonstrate that the tumor NLRP3-HSP70 axis also drives the accumulation of PMN-MDSCs into distant lung tissues in a manner that depends on lung epithelial cell Toll-like receptor 4 (TLR4) signaling, establishing a premetastatic niche that supports disease hyperprogression in response to anti-PD-1 immunotherapy. Lung epithelial HSP70-TLR4 signaling induces the downstream Wnt5a-dependent release of granulocyte colony-stimulating factor (G-CSF) and C-X-C motif chemokine ligand 5 (CXCL5), thus promoting myeloid granulopoiesis and recruitment of PMN-MDSCs into pulmonary tissues. Treatment with anti-PD-1 immunotherapy enhanced the activation of this pathway through immunologic pressure and drove disease progression in the setting of Nlrp3 amplification. Genetic and pharmacologic inhibition of NLRP3 and HSP70 blocked PMN-MDSC accumulation in the lung in response to anti-PD-1 therapy and suppressed metastatic progression in preclinical models of melanoma and breast cancer. Elevated baseline concentrations of plasma HSP70 and evidence of NLRP3 signaling activity in tumor tissue specimens correlated with the development of disease hyperprogression and inferior survival in patients with stage IV melanoma undergoing anti-PD-1 immunotherapy. Together, this work describes a pathogenic mechanism underlying the phenomenon of disease hyperprogression in melanoma and offers candidate targets and markers capable of improving the management of patients with melanoma.

Elimination of fibrin polymer formation or crosslinking, but not fibrinogen deficiency, is protective against diet-induced obesity and associated pathologies.

BACKGROUND: Obesity predisposes individuals to metabolic syndrome, which increases the risk of cardiovascular diseases, non-alcoholic fatty liver disease (NAFLD), and type 2 diabetes. A pathological manifestation of obesity is the activation of the coagulation system. In turn, extravascular fibrin(ogen) deposits accumulate in adipose tissues and liver. These deposits promote adiposity and downstream sequelae by driving pro-inflammatory macrophage function through binding the leukocyte integrin receptor αM ß2 . OBJECTIVES: An unresolved question is whether conversion of soluble fibrinogen to a crosslinked fibrin matrix is required to exacerbate obesity-driven diseases. METHODS: Here, fibrinogen-deficient/depleted mice (Fib- or treated with siRNA against fibrinogen [siFga]), mice expressing fibrinogen that cannot polymerize to fibrin (FibAEK ), and mice deficient in the fibrin crosslinking transglutaminase factor XIII (FXIII-) were challenged with a high-fat diet (HFD) and compared to mice expressing a mutant form of fibrinogen lacking the αM ß2 -binding domain (Fib𝛾390-396A ). RESULTS AND CONCLUSIONS: Consistent with prior studies, Fib𝛾390-396A mice were significantly protected from increased adiposity, NAFLD, hypercholesterolemia, and diabetes while Fib- and siFga-treated mice gained as much weight and developed obesity-associated pathologies identical to wildtype mice. FibAEK and FXIII- mice displayed an intermediate phenotype with partial protection from some obesity-associated pathologies. Results here indicate that fibrin(ogen) lacking αM ß2 binding function offers substantial protection from obesity and associated disease that is partially recapitulated by preventing fibrin polymer formation or crosslinking of the wildtype molecule, but not by reduction or complete elimination of fibrinogen. Finally, these findings support the concept that fibrin polymerization and crosslinking are required for the full implementation of fibrin-driven inflammation in obesity.

Eco-friendly fashion among generation Z: Mixed-methods study on price value image, customer fulfillment, and pro-environmental behavior.

Raising environmental awareness and product development are two separate and costly investments that many small and medium-sized fashion businesses cannot afford to achieve sustainability. Therefore, there is a need to determine which factors exert a more significant impact on consumer loyalty and purchase intention toward eco-friendly fashions. Thus, this study employs a mixed-methods approach with thematic analysis and the SEM-PLS technique to research how Vietnamese Gen Z's perceptions of product-service quality, environmental awareness, and pro-environmental behavior influence their purchase intention and loyalty toward eco-friendly fashion products. Most interviewees acknowledged that they primarily gained knowledge about eco-friendly fashion through social media platforms. The qualitative results further showed that their knowledge of and attitudes toward eco-friendly fashion practices were insufficient to convince young customers to afford eco-friendly fashion products. The SEM-PLS results of 313 participants show that while customers' perceived behavioral control plays a more significant role in stimulating purchase intention, only product-service quality factors impact loyalty. Hence, this study suggests that businesses should prioritize improving service and product quality rather than funding green marketing when targeting Vietnamese Gen Z in case of financial constraints. Government should prioritize financial and technological support for fashion firms to develop high-quality eco-friendly fashion to ensure the product availability.

Identification of Specific Coronary Artery Disease Phenotypes Implicating Differential Pathophysiologies.

Background and Aims: The roles of multiple risk factors of coronary artery disease (CAD) are well established. Commonly, CAD is considered as a single disease entity. We wish to examine whether coronary angiography allows to identify distinct CAD phenotypes associated with major risk factors and differences in prognosis. Methods: In a cohort of 4,344 patients undergoing coronary angiography at Heidelberg University Hospital between 2014 and 2016, cluster analysis of angiographic reports identified subgroups with similar patterns of spatial distribution of high-grade stenoses. Clusters were independently confirmed in 3,129 patients from the LURIC study. Results: Four clusters were identified: cluster one lacking critical stenoses comprised the highest percentage of women with the lowest cardiovascular risk. Patients in cluster two exhibiting high-grade stenosis of the proximal RCA had a high prevalence of the metabolic syndrome, and showed the highest levels of inflammatory biomarkers. Cluster three with predominant proximal LAD stenosis frequently presented with acute coronary syndrome and elevated troponin levels. Cluster four with high-grade stenoses throughout had the oldest patients with the highest overall cardiovascular risk. All-cause and cardiovascular mortality differed significantly between the clusters. Conclusions: We identified four phenotypic subgroups of CAD bearing distinct demographic and biochemical characteristics with differences in prognosis, which may indicate multiple disease entities currently summarized as CAD.

Medical students and the response to COVID-19: Educational preparedness and psychological impact of their involvement in communicating with patients' relatives.

OBJECTIVES: The COVID-19 pandemic has challenged without precedent both healthcare and educational systems worldwide. How medical students could and should be engaged in the response remains unclear. Medical students were asked to help with communicating with patients' relatives in our institution. Authors aimed: to (i) present the rapid implementation and assessment of a teaching/e-teaching lesson in the COVID-19 era; (ii) report an early evaluation of preparedness, mental health and well-being of students involved. METHODS: The lesson was elaborated at lockdown in France. The clinical guidance consisted of a voluntary lesson entitled: "How to communicate with relatives of hospitalized COVID-19 patients?". Students received an anonymous online questionnaire after two weeks. RESULTS: Sixty-six medical students were trained (32% face-to-face). The response rate was 64%. Most students informed relatives about the routine care of the patient (95%). Concerning the lesson, students assured to have had one (95%), considered it relevant (86%), and had used the educational content (81%). 33% were charged with unexpected missions (only 36% felt prepared). Most of them did not report any psychological impact, but some reported anxiety or sleep disorders with no difference between face-to-face/distance training. CONCLUSIONS: This pandemic may last. Communication ability is a key competence in medical curriculum and is more than ever essential. Distance learning technologies may provide a useful and accepted tool for medical students. We report on a rapid feedback on what can be expected or not from students in terms of mission and short-term psychological consequences.

Controlled growth of ultrasmall Cu2O clusters on TiO2nanoparticles by atmospheric-pressure atomic layer deposition for enhanced photocatalytic activity.

This work presents a gas-phase approach for the synthesis of Cu2O/TiO2powder-based photocatalysts using atomic layer deposition (ALD). The process is carried out in a fluidized bed reactor working at atmospheric pressure using (trimethylvinylsilyl)-hexafluoroacetulacetonate copper(I) as the Cu-precursor and H2O vapor as the oxidizer. The saturating regime of the chemical reactions and the linear growth of ALD are achieved. In combination with the unsaturated regime, the ALD approach enables the deposition of ultrasmall Cu2O clusters with average diameters in the range of 1.3-2.0 nm, narrow particle size distributions and tunable Cu2O loadings on P25 TiO2nanoparticles. The photocatalytic performance of Cu2O/TiO2photocatalysts is investigated by the degradation of organic dyes, including Rhodamine B (RhB), methyl orange, and methylene blue; the results demonstrate that the surface modification of TiO2nanoparticles by Cu2O nanoclusters significantly enhances the photocatalytic activity of TiO2. This is attributed to the efficient charge transfer between Cu2O and TiO2that reduces the charge recombination. The photocatalytic reaction mechanism is further investigated for the degradation of RhB, revealing the dominating role of holes, which contribute to both direct hole oxidation and indirect oxidation (i.e. via the formation of hydroxyl radicals). Our approach provides a fast, scalable and efficient process to deposit ultrasmall Cu2O clusters in a controllable fashion for surface engineering and modification.

Guidelines on enhanced recovery after pulmonary lobectomy

To establish recommendations for optimisation of the management of patients undergoing pulmonary lobectomy, particularly Enhanced Recovery After Surgery (ERAS). A consensus committee of 13 experts from the French Society of Anaesthesia and Intensive Care Medicine (Soci,t, franOaise d'anesth,sie et de r,animation, SFAR) and the French Society of Thoracic and Cardiovascular Surgery (Soci,t, franOaise de chirurgie thoracique et cardiovasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. Five domains were defined: 1) patient pathway and patient information; 2) preoperative management and rehabilitation; 3) anaesthesia and analgesia for lobectomy; 4) surgical strategy for lobectomy; and 5) enhanced recovery after surgery. For each domain, the objective of the recommendations was to address a number of questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). An extensive literature search on these questions was carried out and analysed using the GRADE® methodology. Recommendations were formulated according to the GRADE® methodology, and were then voted by all experts according to the GRADE grid method. The SFAR/SFCTCV guideline panel provided 32 recommendations on the management of patients undergoing pulmonary lobectomy. After two voting rounds and several amendments, a strong consensus was reached for 31 of the 32 recommendations and a moderate consensus was reached for the last recommendation. Seven of these recommendations present a high level of evidence (GRADE 1+), 23 have a moderate level of evidence (18 GRADE 2+ and 5 GRADE 2-), and 2 correspond to expert opinions. Finally, no recommendation was provided for 2 of the questions. A strong consensus was expressed by the experts to provide recommendations to optimise the whole perioperative management of patients undergoing pulmonary lobectomy.

Guidelines on enhanced recovery after pulmonary lobectomy.

OBJECTIVE: To establish recommendations for optimisation of the management of patients undergoing pulmonary lobectomy, particularly Enhanced Recovery After Surgery (ERAS). DESIGN: A consensus committee of 13 experts from the French Society of Anaesthesia and Intensive Care Medicine (Soci,t, franOaise d'anesth,sie et de r,animation, SFAR) and the French Society of Thoracic and Cardiovascular Surgery (Soci,t, franOaise de chirurgie thoracique et cardiovasculaire, SFCTCV) was convened. A formal conflict-of-interest policy was developed at the onset of the process and enforced throughout. The entire guidelines process was conducted independently of any industry funding. The authors were advised to follow the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to guide assessment of quality of evidence. METHODS: Five domains were defined: 1) patient pathway and patient information; 2) preoperative management and rehabilitation; 3) anaesthesia and analgesia for lobectomy; 4) surgical strategy for lobectomy; and 5) enhanced recovery after surgery. For each domain, the objective of the recommendations was to address a number of questions formulated according to the PICO model (Population, Intervention, Comparison, Outcome). An extensive literature search on these questions was carried out and analysed using the GRADE® methodology. Recommendations were formulated according to the GRADE® methodology, and were then voted by all experts according to the GRADE grid method. RESULTS: The SFAR/SFCTCV guideline panel provided 32 recommendations on the management of patients undergoing pulmonary lobectomy. After two voting rounds and several amendments, a strong consensus was reached for 31 of the 32 recommendations and a moderate consensus was reached for the last recommendation. Seven of these recommendations present a high level of evidence (GRADE 1+), 23 have a moderate level of evidence (18 GRADE 2+ and 5 GRADE 2-), and 2 correspond to expert opinions. Finally, no recommendation was provided for 2 of the questions. CONCLUSIONS: A strong consensus was expressed by the experts to provide recommendations to optimise the whole perioperative management of patients undergoing pulmonary lobectomy.

Genome Sequence of Vibrio natriegens Phage vB_VnaS-AQKL99.

Vibrio natriegens is a naturally occurring marine bacterium that is emerging as a microbiological model system. Here, we describe Aquatic Killer 99 (AQKL99), a novel phage that infects Vibrio natriegens 14048. The genome of the phage is 58,464 bp long, has a GC content of 45.9%, and contains 51 protein-coding genes.

Dispersal out of Wallacea spurs diversification of Pteropus flying foxes, the world's largest bats (Mammalia: Chiroptera).

AIM: Islands provide opportunities for isolation and speciation. Many landmasses in the Indo-Australian Archipelago (IAA) are oceanic islands, and founder-event speciation is expected to be the predominant form of speciation of volant taxa on these islands. We studied the biogeographic history of flying foxes, a group with many endemic species and a predilection for islands, to test this hypothesis and infer the biogeographic origin of the group. LOCATION: Australasia, Indo-Australian Archipelago, Madagascar, Pacific Islands. TAXON: Pteropus (Pteropodidae). METHODS: To infer the biogeographic history of Pteropus, we sequenced up to 6169 bp of genetic data from 10 markers and reconstructed a multilocus species tree of 34 currently recognized Pteropus species and subspecies with 3 Acerodon outgroups using BEAST and subsequently estimated ancestral areas using models implemented in BioGeoBEARS. RESULTS: Species-level resolution was occasionally low because of slow rates of molecular evolution and/or recent divergences. Older divergences, however, were more strongly supported and allow the evolutionary history of the group to be inferred. The genus diverged in Wallacea from its common ancestor with Acerodon; founder-event speciation out of Wallacea was a common inference. Pteropus species in Micronesia and the western Indian Ocean were also inferred to result from founder-event speciation. MAIN CONCLUSIONS: Dispersal between regions of the IAA and the islands found therein fostered diversification of Pteropus throughout the IAA and beyond. Dispersal in Pteropus is far higher than in most other volant taxa studied to date, highlighting the importance of inter-island movement in the biogeographic history of this large clade of large bats.