Nanopore adaptive sampling of a metagenomic sample derived from a human monkeypox case.

In 2022, a series of human monkeypox cases in multiple countries led to the largest and most widespread outbreak outside the known endemic areas. Setup of proper genomic surveillance is of utmost importance to control such outbreaks. To this end, we performed Nanopore (PromethION P24) and Illumina (NextSeq. 2000) Whole Genome Sequencing (WGS) of a monkeypox sample. Adaptive sampling was applied for in silico depletion of the human host genome, allowing for the enrichment of low abundance viral DNA without a priori knowledge of sample composition. Nanopore sequencing allowed for high viral genome coverage, tracking of sample composition during sequencing, strain determination, and preliminary assessment of mutational pattern. In addition to that, only Nanopore data allowed us to resolve the entire monkeypox virus genome, with respect to two structural variants belonging to the genes OPG015 and OPG208. These SVs in important host range genes seem stable throughout the outbreak and are frequently misassembled and/or misannotated due to the prevalence of short read sequencing or short read first assembly. Ideally, standalone standard Illumina sequencing should not be used for Monkeypox WGS and de novo assembly, since it will obfuscate the structure of the genome, which has an impact on the quality and completeness of the genomes deposited in public databases and thus possibly on the ability to evaluate the complete genetic reason for the host range change of monkeypox in the current pandemic.

Vaccine Nationalism Counterintuitively Erodes Public Trust in Leaders.

Global access to resources like vaccines is key for containing the spread of infectious diseases. However, wealthy countries often pursue nationalistic policies, stockpiling doses rather than redistributing them globally. One possible motivation behind vaccine nationalism is a belief among policymakers that citizens will mistrust leaders who prioritize global needs over domestic protection. In seven experiments (total N = 4,215 adults), we demonstrate that such concerns are misplaced: Nationally representative samples across multiple countries with large vaccine surpluses (Australia, Canada, United Kingdom, and United States) trusted redistributive leaders more than nationalistic leaders-even the more nationalistic participants. This preference generalized across different diseases and manifested in both self-reported and behavioral measures of trust. Professional civil servants, however, had the opposite intuition and predicted higher trust in nationalistic leaders, and a nonexpert sample also failed to predict higher trust in redistributive leaders. We discuss how policymakers' inaccurate intuitions might originate from overestimating others' self-interest.

Business culture and dishonesty in the banking industry.

Trust in others' honesty is a key component of the long-term performance of firms, industries, and even whole countries. However, in recent years, numerous scandals involving fraud have undermined confidence in the financial industry. Contemporary commentators have attributed these scandals to the financial sector's business culture, but no scientific evidence supports this claim. Here we show that employees of a large, international bank behave, on average, honestly in a control condition. However, when their professional identity as bank employees is rendered salient, a significant proportion of them become dishonest. This effect is specific to bank employees because control experiments with employees from other industries and with students show that they do not become more dishonest when their professional identity or bank-related items are rendered salient. Our results thus suggest that the prevailing business culture in the banking industry weakens and undermines the honesty norm, implying that measures to re-establish an honest culture are very important.

Increasing honesty in humans with noninvasive brain stimulation.

Honesty plays a key role in social and economic interactions and is crucial for societal functioning. However, breaches of honesty are pervasive and cause significant societal and economic problems that can affect entire nations. Despite its importance, remarkably little is known about the neurobiological mechanisms supporting honest behavior. We demonstrate that honesty can be increased in humans with transcranial direct current stimulation (tDCS) over the right dorsolateral prefrontal cortex. Participants (n = 145) completed a die-rolling task where they could misreport their outcomes to increase their earnings, thereby pitting honest behavior against personal financial gain. Cheating was substantial in a control condition but decreased dramatically when neural excitability was enhanced with tDCS. This increase in honesty could not be explained by changes in material self-interest or moral beliefs and was dissociated from participants' impulsivity, willingness to take risks, and mood. A follow-up experiment (n = 156) showed that tDCS only reduced cheating when dishonest behavior benefited the participants themselves rather than another person, suggesting that the stimulated neural process specifically resolves conflicts between honesty and material self-interest. Our results demonstrate that honesty can be strengthened by noninvasive interventions and concur with theories proposing that the human brain has evolved mechanisms dedicated to control complex social behaviors.

Value of PCR, Serology, and Blood Smears for Human Granulocytic Anaplasmosis Diagnosis, France.

We prospectively examined the effectiveness of diagnostic tests for anaplasmosis using patients with suspected diagnoses in France. PCR (sensitivity 0.74, specificity 1) was the best-suited test. Serology had a lower specificity but higher sensitivity when testing acute and convalescent samples. PCR and serology should be used in combination for anaplasmosis diagnosis.

Natalizumab as a Disease-Modifying Therapy in Chronic Inflammatory Demyelinating Polyneuropathy - A Report of Three Cases.

BACKGROUND: Several treatments are available to treat the immune-mediated chronic inflammatory demyelinating polyneuropathy (CIDP). Among these treatments, intravenous immunoglobulins, corticosteroids and plasma exchanges are validated and widely used. A few immunosuppressive drugs have been tried, but they had little efficiency. METHODS: We describe three CIDP patients treated by Natalizumab (acting against cellular adhesion and T-cell migration) after a failure of the validated treatments. RESULTS: We observed a long-term improvement in one patient, a dramatic improvement over a significant duration in another patient and stabilization in the last one. CONCLUSION: This open label study provides evidence for the value of Natalizumab as second-line treatment for individual patients with a high dependency on waning efficacy of first-line therapies. CIDP is characterized by heterogeneity of clinical phenotypes, electrophysiological and pathological features, and various variable courses types of evolution. The different responses to drugs of our patients are consistent with some reported cases and may reflect the spectrum of lesional mechanisms and the molecular dysfunctions in CIDP.

Farm, household, and farmer characteristics associated with changes in management practices and technology adoption among dairy smallholders.

This study explored whether technology adoption and changes in management practices were associated with farm structure, household, and farmer characteristics and to identify processes that may foster productivity and sustainability of small-scale dairy farming in the central highlands of Mexico. Factor analysis of survey data from 44 smallholders identified three factors-related to farm size, farmer's engagement, and household structure-that explained 70 % of cumulative variance. The subsequent hierarchical cluster analysis yielded three clusters. Cluster 1 included the most senior farmers with fewest years of education but greatest years of experience. Cluster 2 included farmers who reported access to extension, cooperative services, and more management changes. Cluster 2 obtained 25 and 35 % more milk than farmers in clusters 1 and 3, respectively. Cluster 3 included the youngest farmers, with most years of education and greatest availability of family labor. Access to a network and membership in a community of peers appeared as important contributors to success. Smallholders gravitated towards easy to implement technologies that have immediate benefits. Nonusers of high investment technologies found them unaffordable because of cost, insufficient farm size, and lack of knowledge or reliable electricity. Multivariate analysis may be a useful tool in planning extension activities and organizing channels of communication to effectively target farmers with varying needs, constraints, and motivations for change and in identifying farmers who may exemplify models of change for others who manage farms that are structurally similar but performing at a lower level.

Moral dilemmas and trust in leaders during a global health crisis.

Trust in leaders is central to citizen compliance with public policies. One potential determinant of trust is how leaders resolve conflicts between utilitarian and non-utilitarian ethical principles in moral dilemmas. Past research suggests that utilitarian responses to dilemmas can both erode and enhance trust in leaders: sacrificing some people to save many others ('instrumental harm') reduces trust, while maximizing the welfare of everyone equally ('impartial beneficence') may increase trust. In a multi-site experiment spanning 22 countries on six continents, participants (N = 23,929) completed self-report (N = 17,591) and behavioural (N = 12,638) measures of trust in leaders who endorsed utilitarian or non-utilitarian principles in dilemmas concerning the COVID-19 pandemic. Across both the self-report and behavioural measures, endorsement of instrumental harm decreased trust, while endorsement of impartial beneficence increased trust. These results show how support for different ethical principles can impact trust in leaders, and inform effective public communication during times of global crisis. PROTOCOL REGISTRATION STATEMENT: The Stage 1 protocol for this Registered Report was accepted in principle on 13 November 2020. The protocol, as accepted by the journal, can be found at https://doi.org/10.6084/m9.figshare.13247315.v1 .

Species and sex-specific chemosensory gene expression in Anopheles coluzzii and An. quadriannulatus antennae.

BACKGROUND: Olfactory cues drive mosquito behaviors such as host-seeking, locating sugar sources and oviposition. These behaviors can vary between sexes and closely related species. For example, the malaria vector Anopheles coluzzii is highly anthropophilic, whereas An. quadriannulatus is not. These behavioral differences may be reflected in chemosensory gene expression. METHODS: The expression of chemosensory genes in the antennae of both sexes of An. coluzzii and An. quadriannulatus was compared using RNA-seq. The sex-biased expression of several genes in An. coluzzii was also compared using qPCR. RESULTS: The chemosensory expression is mostly similar in the male antennae of An. coluzzii and An. quadriannulatus, with only a few modest differences in expression. A handful of chemosensory genes are male-biased in both species; the highly expressed gustatory receptor AgGr33, odorant binding proteins AgObp25, AgObp26 and possibly AgObp10. Although the chemosensory gene repertoire is mostly shared between the sexes, several highly female-biased AgOrs, AgIrs, and one AgObp were identified, including several whose expression is biased towards the anthropophilic An. coluzzii. Additionally, the expression of several chemosensory genes is biased towards An. coluzzii in both sexes. CONCLUSIONS: Chemosensory gene expression is broadly similar between species and sexes, but several sex- biased/specific genes were identified. These may modulate sex- and species-specific behaviors. Although the male behavior of these species remains poorly studied, the identification of sex- and species-specific chemosensory genes may provide fertile ground for future work.

Motivated misremembering of selfish decisions.

People often prioritize their own interests, but also like to see themselves as moral. How do individuals resolve this tension? One way to both pursue personal gain and preserve a moral self-image is to misremember the extent of one's selfishness. Here, we test this possibility. Across five experiments (N = 3190), we find that people tend to recall being more generous in the past than they actually were, even when they are incentivized to recall their decisions accurately. Crucially, this motivated misremembering effect occurs chiefly for individuals whose choices violate their own fairness standards, irrespective of how high or low those standards are. Moreover, this effect disappears under conditions where people no longer perceive themselves as responsible for their fairness violations. Together, these findings suggest that when people's actions fall short of their personal standards, they may misremember the extent of their selfishness, thereby potentially warding off threats to their moral self-image.

Describing adverse events in Swiss hospitalized oncology patients using the Global Trigger Tool.

BACKGROUND AND AIMS: The occurrence rate of adverse events (AEs) related to care among hospitalized oncology patients in Switzerland remains unknown. The primary objective of this study was to describe, for the first time, the occurrence rate, type, severity of harm, and preventability of AEs related to care, reported in health records of hospitalized hematological and solid-tumor cancer patients in three Swiss hospitals. METHODS: Using an adapted version of the validated Global Trigger Tool (GTT) from the Institute for Healthcare Improvement, we conducted a retrospective record review of patients discharged from oncology units over a 6-week period during 2018. Our convenience sample included all records from adult patients (≥18 years of age), diagnosed with cancer, and hospitalized (>24 hours). Per the GTT method, two trained nurses independently assessed patient records to identify AEs using triggers, and physicians from the included units analyzed the consensus of the two nurses. Together, they assessed the severity and preventability of each AE. RESULTS: From the sample of 224 reviewed records, we identified 661 triggers and 169 AEs in 94 of them (42%). Pain related to care was the most frequent AE (n = 29), followed by constipation (n = 17). AEs rates were 75.4 per 100 admissions and 106.6 per 1000 patient days. Most of the identified AEs (78%) caused temporary harm to the patient and required an intervention. Among AEs during hospitalization (n = 125), 76 (61%) were considered not preventable, 28 (22%) preventable, and 21 (17%) undetermined. CONCLUSION: About half of the hospitalized oncology patients suffered from at least one AE related to care during their hospitalization. Pain, constipation, and nosocomial infections were the most frequent AEs. It is, therefore, essential to identify AEs to guide future clinical practice initiatives to ensure patient safety.

Implementation of practice guidelines for antifungal therapy in a surgical intensive care unit and its impact on use and costs.

BACKGROUND: Considering the complexity of diagnosis, high costs of therapy and high morbidity and mortality of systemic fungal infections, antifungal therapy of intensive care patients should follow clearly defined guidelines. We outline the impact of a standardised practice of antifungal treatment in an interdisciplinary surgical intensive care unit of a university hospital. METHODS: Therapy was intended to be optimised by implementation of standardised practice guidelines supported by the clinical pharmacist. Costs for antifungal agents during a period of 18 months before and after implementation of the practice guidelines were compared, respectively. RESULTS: The intervention was associated with a significant decrease in use of antifungal agents. Analysis of data revealed a reduction in costs by 50%. This could substantially be attributed to the implementation of the practice guidelines. CONCLUSION: The implementation of standardised practice guidelines for antifungal therapy in intensive care units decreased the use of selected antifungal agents and resulted in substantial reduction in expenditure on antifungal agents.

Human papilloma virus-associated squamous cell carcinoma of the larynx in an 18-year-old woman.

BACKGROUND: Human papilloma virus (HPV)-associated malignancies are considered to be sexually transmitted diseases. METHODS: We report a HPV-positive larynx cancer in an 18-year-old female clarinet player, despite vaccination with the quadrivalent HPV-6-11-16-18-vaccine Gardasil (Merck Sharp & Dohme Corp., West Point, Pennsylvania). The patient showed no evidence of genito-oral infection but showed some evidence for oral-oral HPV transmission through the sharing of saliva-infested clarinet mouthpieces. A right vocal cord lesion of benign appearance was removed via free margin resection. RESULTS: Histopathology revealed a microinvasive squamous cell carcinoma inside a zone of high-grade dysplasia that was positive for HPV-45. No tumor recurrence was observed during a 4-year follow-up evaluation. CONCLUSION: Benign lesion appearance and quadrivalent HPV vaccine status do not exclude HPV-associated malignancies. In our patient, the Gardasil vaccine did not provide crossover protection against HPV 45 infection. HPV-associated disease may not necessarily be transmitted via sexual practice patterns alone.

Civic honesty around the globe.

Civic honesty is essential to social capital and economic development but is often in conflict with material self-interest. We examine the trade-off between honesty and self-interest using field experiments in 355 cities spanning 40 countries around the globe. In these experiments, we turned in more than 17,000 lost wallets containing varying amounts of money at public and private institutions and measured whether recipients contacted the owners to return the wallets. In virtually all countries, citizens were more likely to return wallets that contained more money. Neither nonexperts nor professional economists were able to predict this result. Additional data suggest that our main findings can be explained by a combination of altruistic concerns and an aversion to viewing oneself as a thief, both of which increase with the material benefits of dishonesty.

Lemierre Syndrome: Clinical Update and Protocol for a Systematic Review and Individual Patient Data Meta-analysis.

Lemierre syndrome usually affects otherwise healthy adolescents or young adults and occurs at an overall rate of 1 to 10 cases per million person-years with an estimated fatality rate of 4 to 9%. Diagnostic criteria remain debated and include acute neck/head bacterial infection (often tonsillitis caused by anaerobes at high potential for sepsis and vascular invasion, notably Fusobacterium necrophorum) complicated by local vein thrombosis, usually involving the internal jugular vein, and systemic septic embolism. Medical treatment is based on antibiotic therapy with anaerobic coverage, anticoagulant drugs and supportive care in case of sepsis. Surgical procedures can be required, including drainage of the abscesses, tissue debridement and jugular vein ligation. Evidence for clinical management is extremely poor in the absence of any adequately sized study with clinical outcomes. In this article, we illustrate two cases of Lemierre syndrome not caused by Fusobacterium necrophorum and provide a clinically oriented discussion on the main issues on epidemiology, pathophysiology and management strategies of this disorder. Finally, we summarize the study protocol of a proposed systematic review and individual patient data meta-analysis of the literature. Our ongoing work aims to investigate the risk of new thromboembolic events, major bleeding or death in patients diagnosed with Lemierre syndrome, and to better elucidate the role of anticoagulant therapy in this setting. This effort represents the starting point for an evidence-based treatment of Lemierre syndrome built on multinational interdisciplinary collaborative studies.

[Hemophagocytic Lymphohistiocytosis]. / Les lymphohistiocytoses hémophagocytaires.

Hemophagocytic Lymphohistiocytosis Abstract. Hemophagocytic lymphohistiocytosis (HLH) is a group of rare diseases characterized by over-activation of the immune system. They form two groups: primary and secondary HLH. Primary HLH are linked to mutations impairing lymphocyte cytotoxicity. Secondary HLH are triggered by infections, autoimmune diseases or neoplasia, the remaining cases being labeled idiopathic. HLH manifest as febrile states, cytopenias and hepatosplenomegaly. In the absence of treatment, they quickly lead to multiple organ failure. The diagnosis is currently based on the presence of several clinical and biological markers. Treatment consists of suppression of the triggering factor, organ support and immunosuppression. Primary forms, affecting a pediatric population, have been the subject of intense research, and are nowadays treated with established therapeutic protocols. Several recent retrospective studies have improved our knowledge of secondary HLH, which affects mostly adults and whose incidence seems to be increasing. Thus, new diagnostic criteria are currently being studied for secondary HLH, and several treatment protocols have just been published or are being evaluated.

Oxytocin improves "mind-reading" in humans.

BACKGROUND: The ability to "read the mind" of other individuals, that is, to infer their mental state by interpreting subtle social cues, is indispensable in human social interaction. The neuropeptide oxytocin plays a central role in social approach behavior in nonhuman mammals. METHODS: In a double-blind, placebo-controlled, within-subject design, 30 healthy male volunteers were tested for their ability to infer the affective mental state of others using the Reading the Mind in the Eyes Test (RMET) after intranasal administration of 24 IU oxytocin. RESULTS: Oxytocin improved performance on the RMET compared with placebo. This effect was pronounced for difficult compared with easy items. CONCLUSIONS: Our data suggest that oxytocin improves the ability to infer the mental state of others from social cues of the eye region. Oxytocin might play a role in the pathogenesis of autism spectrum disorder, which is characterized by severe social impairment.

Recursive partitioning for the prediction of cytochromes P450 2D6 and 1A2 inhibition: importance of the quality of the dataset.

The purpose of this study was to explore the use of detailed biological data in combination with a statistical learning method for predicting the CYP1A2 and CYP2D6 inhibition. Data were extracted from the Aureus-Pharma highly structured databases which contain precise measures and detailed experimental protocol concerning the inhibition of the two cytochromes. The methodology used was Recursive Partitioning, an easy and quick method to implement. The building of models was preceded by the evaluation of the chemical space covered by the datasets. The descriptors used are available in the MOE software suite. The models reached at least 80% of Accuracy and often exceeded this percentage for the Sensitivity (Recall), Specificity, and Precision parameters. CYP2D6 datasets provided 11 models with Accuracy over 80%, while CYP1A2 datasets counted 5 high-accuracy models. Our models can be useful to predict the ADME properties during the drug discovery process and are indicated for high-throughput screening.