Host tracheal and intestinal microbiomes inhibit Coccidioides growth in vitro.

Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia, leading to inappropriate antibiotic treatment. The soil Bacillus subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides, while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2×GYE (GYE) and Columbia colistin and nalidixic acid with 5% sheep's blood agar inhibited the growth of Coccidioides, but microbiota grown on chocolate agar did not. Partial depletion of the microbiota through antibiotic disk diffusion revealed diminished inhibition and comparable growth of Coccidioides to controls. To characterize the bacteria grown and identify potential candidates contributing to the inhibition of Coccidioides, 16S rRNA sequencing was performed on tracheal and intestinal agar cultures and murine lung extracts. We found that the host bacteria likely responsible for this inhibition primarily included Lactobacillus and Staphylococcus. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo. IMPORTANCE: Coccidioidomycosis is caused by a fungal pathogen that invades the host lungs, causing respiratory distress. In 2019, 20,003 cases of Valley fever were reported to the CDC. However, this number likely vastly underrepresents the true number of Valley fever cases, as many go undetected due to poor testing strategies and a lack of diagnostic models. Valley fever is also often misdiagnosed as bacterial pneumonia, resulting in 60%-80% of patients being treated with antibiotics prior to an accurate diagnosis. Misdiagnosis contributes to a growing problem of antibiotic resistance and antibiotic-induced microbiome dysbiosis; the implications for disease outcomes are currently unknown. About 5%-10% of symptomatic Valley fever patients develop chronic pulmonary disease. Valley fever causes a significant financial burden and a reduced quality of life. Little is known regarding what factors contribute to the development of chronic infections and treatments for the disease are limited.

Engram reactivation mimics cellular signatures of fear.

Engrams, or the physical substrate of memory, recruit heterogeneous cell types. Targeted reactivation of neurons processing discrete memories drives the behavioral expression of memory, though the underlying landscape of recruited cells and their real-time responses remain elusive. To understand how artificial stimulation of fear affects intra-hippocampal neuron-astrocyte dynamics as well as their behavioral consequences, we express channelrhodopsin-2 in an activity-dependent manner within dentate gyrus neurons while recording both cell types with fiber photometry in hippocampal ventral CA1 across learning and memory. Both cell types exhibit shock responsiveness, with astrocytic calcium events uniquely modulated by fear conditioning. Optogenetic stimulation of a hippocampus-mediated engram recapitulates coordinated calcium signatures time locked to freezing, mirroring those observed during natural fear memory recall. Our findings reveal cell-type-specific dynamics in the hippocampus during freezing behavior, emphasizing neuronal-astrocytic coupling as a shared mechanism enabling both natural and artificially induced memory retrieval and the behavioral expression of fear.

Evaluation of a psychoneurological symptom cluster in patients with breast or digestive cancer: a longitudinal observational study.

BACKGROUND: A psychoneurological symptom cluster composed of cancer-related fatigue, emotional distress, sleep difficulties, and pain is very common among patients with cancer. Cognitive difficulties are also frequently associated with this cluster. Network analyses allow for an in-depth understanding of the relationships between symptoms in a cluster. This paper details the study protocol of a longitudinal assessment of the psychoneurological symptom cluster in two distinct cohorts: breast cancer and digestive cancer survivors, using network analyses. METHODS: Over two years, the symptoms involved in the psychoneurological symptom cluster, along with other common symptoms (e.g., digestive symptoms, financial difficulties) and variables (i.e., self-compassion, coping strategies) will be assessed in two cohorts: breast cancer survivors (N = 240) and digestive cancer survivors (N = 240). Online questionnaires will be completed at baseline, then 6, 12 and 24 months later. Network analyses will be used to assess the configuration of the symptom cluster at each measurement time and in each cohort. Comparison of networks between two measurement times or between the two cohorts will also be done with network comparison tests. DISCUSSION: This study will enable a better understanding of the relationships between common symptoms endured by patients with cancer. The results will be employed to develop more cost-effective interventions which, ultimately, will significantly improve the quality of life of patients with breast or digestive cancer. TRIAL REGISTRATION: ClinicalTrials.gov (NCT05867966). Registered on the 27th of April 2023. url: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05867966 .

Hippocampal Engrams Generate Variable Behavioral Responses and Brain-Wide Network States.

Freezing is a defensive behavior commonly examined during hippocampal-mediated fear engram reactivation. How these cellular populations engage the brain and modulate freezing across varying environmental demands is unclear. To address this, we optogenetically reactivated a fear engram in the dentate gyrus subregion of the hippocampus across three distinct contexts in male mice. We found that there were differential amounts of light-induced freezing depending on the size of the context in which reactivation occurred: mice demonstrated robust light-induced freezing in the most spatially restricted of the three contexts but not in the largest. We then utilized graph theoretical analyses to identify brain-wide alterations in cFos expression during engram reactivation across the smallest and largest contexts. Our manipulations induced positive interregional cFos correlations that were not observed in control conditions. Additionally, regions spanning putative "fear" and "defense" systems were recruited as hub regions in engram reactivation networks. Lastly, we compared the network generated from engram reactivation in the small context with a natural fear memory retrieval network. Here, we found shared characteristics such as modular composition and hub regions. By identifying and manipulating the circuits supporting memory function, as well as their corresponding brain-wide activity patterns, it is thereby possible to resolve systems-level biological mechanisms mediating memory's capacity to modulate behavioral states.

Host tracheal and intestinal microbiomes inhibit Coccidioides growth in vitro.

Coccidioidomycosis, also known as Valley fever, is a disease caused by the fungal pathogen Coccidioides. Unfortunately, patients are often misdiagnosed with bacterial pneumonia leading to inappropriate antibiotic treatment. Soil bacteria B. subtilis-like species exhibits antagonistic properties against Coccidioides in vitro; however, the antagonistic capabilities of host microbiota against Coccidioides are unexplored. We sought to examine the potential of the tracheal and intestinal microbiomes to inhibit the growth of Coccidioides in vitro. We hypothesized that an uninterrupted lawn of microbiota obtained from antibiotic-free mice would inhibit the growth of Coccidioides while partial in vitro depletion through antibiotic disk diffusion assays would allow a niche for fungal growth. We observed that the microbiota grown on 2xGYE (GYE) and CNA w/ 5% sheep's blood agar (5%SB-CNA) inhibited the growth of Coccidioides, but that grown on chocolate agar does not. Partial depletion of the microbiota through antibiotic disk diffusion revealed that microbiota depletion leads to diminished inhibition and comparable growth of Coccidioides growth to controls. To characterize the bacteria grown and narrow down potential candidates contributing to the inhibition of Coccidioides, 16s rRNA sequencing of tracheal and intestinal agar cultures and murine lung extracts was performed. The identity of host bacteria that may be responsible for this inhibition was revealed. The results of this study demonstrate the potential of the host microbiota to inhibit the growth of Coccidioides in vitro and suggest that an altered microbiome through antibiotic treatment could negatively impact effective fungal clearance and allow a niche for fungal growth in vivo.

Novel Frizzled-specific antibody-based Wnt mimetics and Wnt superagonists selectively activate WNT/ß-catenin signaling in target tissues.

WNTs are essential factors for stem cell biology, embryonic development, and for maintaining homeostasis and tissue repair in adults. Difficulties in purifying WNTs and their lack of receptor selectivity have hampered research and regenerative medicine development. While breakthroughs in WNT mimetic development have overcome some of these difficulties, the tools developed so far are incomplete and mimetics alone are often not sufficient. Here, we developed a complete set of WNT mimetic molecules that cover all WNT/ß-catenin-activating Frizzleds (FZDs). We show that FZD1,2,7 stimulate salivary gland expansion in vivo and salivary gland organoid expansion. We further describe the discovery of a novel WNT-modulating platform that combines WNT and RSPO mimetics' effects into one molecule. This set of molecules supports better organoid expansion in various tissues. These WNT-activating platforms can be broadly applied to organoids, pluripotent stem cells, and in vivo research, and serve as bases for future therapeutic development.

Basolateral Amygdala Astrocytes Are Engaged by the Acquisition and Expression of a Contextual Fear Memory.

Astrocytes are key cellular regulators within the brain. The basolateral amygdala (BLA) is implicated in fear memory processing, yet most research has entirely focused on neuronal mechanisms, despite a significant body of work implicating astrocytes in learning and memory. In the present study, we used in vivo fiber photometry in C57BL/6J male mice to record from amygdalar astrocytes across fear learning, recall, and three separate periods of extinction. We found that BLA astrocytes robustly responded to foot shock during acquisition, their activity remained remarkably elevated across days in comparison to unshocked control animals, and their increased activity persisted throughout extinction. Further, we found that astrocytes responded to the initiation and termination of freezing bouts during contextual fear conditioning and recall, and this behavior-locked pattern of activity did not persist throughout the extinction sessions. Importantly, astrocytes do not display these changes while exploring a novel context, suggesting that these observations are specific to the original fear-associated environment. Chemogenetic inhibition of fear ensembles in the BLA did not affect freezing behavior or astrocytic calcium dynamics. Overall, our work presents a real-time role for amygdalar astrocytes in fear processing and provides new insight into the emerging role of these cells in cognition and behavior.SIGNIFICANCE STATEMENT We show that basolateral amygdala astrocytes are robustly responsive to negative experiences, like shock, and display changed calcium activity patterns through fear learning and memory. Additionally, astrocytic calcium responses become time locked to the initiation and termination of freezing behavior during fear learning and recall. We find that astrocytes display calcium dynamics unique to a fear-conditioned context, and chemogenetic inhibition of BLA fear ensembles does not have an impact on freezing behavior or calcium dynamics. These findings show that astrocytes play a key real-time role in fear learning and memory.

Comparison between the WHO-CFICPS and the PRISMA classification of safety-related events in a radiation oncology department.

INTRODUCTION: Describing Safety-Related Events (SREs) in a radiotherapy (RT) department and comparing WHO-CFICPS (World Health Organization's Conceptual Framework For The International Classification For Patient Safety) and PRISMA (Prevention and Recovery Information System for Monitoring and Analysis) methods for classifying SREs. METHODS: From February 2017 to October 2020, two Quality Managers (QMs) randomly classified 1173 SREs using 13 incident types of WHO-CFICPS. The same two QMs, reclassified the same SREs according to 20 PRISMA incident codes. Statistical analysis was performed to assess the association between the 13 incident types of WHO-CFICPS and the 20 PRISMA codes. The chi-squared and post-hoc tests using adjusted standardized residuals were applied to detect the association between the two systems. RESULTS: There was a significant association between WHO-CFICPS incident types and PRISMA codes (P < 0.001). Ninety-two percent of all SREs were categorized using 4 of 13 WHO-CFICPS incident types including Clinical Process/Procedure (n = 448, 38.2%), Clinical Administration (n = 248, 21.1%), Documentation (n = 226, 19.2%) and Resources/Organizational Management (n = 15,613.3%). According to PRISMA classification, 14 of the 20 codes were used to describe the same SREs. PRISMA captured 41 Humans Skill Slips from 226 not better defined WHO-CFICPS Documentation Incidents, 38 Human Rule-based behaviour Qualification from not better defined 447 Clinical Process/Procedure and 40 Organization Management priority events from 156 not better defined WHO-CFICPS Resources/Organizational Management events (P < 0.001). CONCLUSION: Although there was a significant association between WHO-CFICPS and PRISMA, The PRISMA method provides a more detailed insight into SREs compared to WHO-CFICPS in a RT department.

Correction: Civil war and death in Yemen: Analysis of SMART survey and ACLED data, 2012-2019.

[This corrects the article DOI: 10.1371/journal.pgph.0000581.].

Compliance with Barrier Gestures during COVID-19 Pandemic as a Function of the Context: A Longitudinal Observational Survey at the University of Liège.

During the COVID-19 pandemic, barrier gestures such as mask wearing, physical distancing, greetings without contact, one-way circulation flow, and hand sanitization were major strategies to prevent the spread of SARS-CoV-2, but they were only useful if consistently applied. This survey was a follow-up of the first survey performed in 2020 at the University of Liège. We aim to evaluate the compliance with these gestures on campuses and examine differences in the extent of the compliance observed in different educational activities and contexts. During 3.5 months, the counting of compliant and non-compliant behaviors was performed each week in randomly selected rooms. Using data collected during both surveys (2020 and 2021), binomial negative regression models of compliance depending on periods (teaching periods and exam sessions), type of rooms, and campuses were conducted to evaluate prevalence ratios of compliance. The percentage of compliance in this second survey was the highest for mask wearing and physical distancing during educational activities (90% and 88%, respectively) and lowest for physical distancing outside educational activities and hand sanitization (45% and 52%, respectively). Multivariate analyses revealed that the compliance with most gestures was significantly higher in teaching rooms than in hallways and restaurants and during exam sessions. The compliance with physical distancing was significantly higher (from 66%) in auditoriums, where students had to remain seated, than during practical works that allowed or required free movement. Therefore, the compliance with barrier gestures was associated with contextual settings, which should be considered when communicating and managing barrier gestures. Further studies should specify and confirm the determining contextual characteristics regarding the compliance with barrier gestures in times of pandemic.

Patients' self-triage for unscheduled urgent care: a preliminary study on the accuracy and factors affecting the performance of a Belgian self-triage platform.

BACKGROUND: Management of unscheduled urgent care is a complex concern for many healthcare providers. Facing the challenge of appropriately dispatching unscheduled care, primary and emergency physicians have collaboratively implemented innovative strategies such as telephone triage. Currently, new original solutions tend to emerge with the development of new technologies. We created an interactive patient self-triage platform, ODISSEE, and aimed to explore its accuracy and potential factors affecting its performance using clinical case scenarios. METHODS: The ODISSEE platform was developed based on previously validated triage protocols for out-of-hours primary care. ODISSEE is composed of 18 icons leading to algorithmic questions that finally provide an advised orientation (emergency or primary care services). To investigate ODISSEE performance, we used 100 clinical case scenarios, each associated with a preestablished orientation determined by a group of experts. Fifteen volunteers were asked to self-triage with 50 randomly selected scenarios using ODISSEE on a digital tablet. Their triage results were compared with the experts' references. RESULTS: The 15 participants performed a total of 750 self-triages, which matched the experts references regarding the level of care in 85.6% of the cases. The orientation was incorrect in 14.4%, with an undertriage rate of 1.9% and an overtriage rate of 12.5%. The tool's specificity and sensitivity to advise participants on the appropriate level of care were 69% (95% CI: 64-74) and 97% (95% CI: 95-98) respectively. When combined with advice on the level of urgency, the tool only found the correct orientation in 68.4% with 9.2% of undertriages and 22.4% of overtriages. Some participant characteristics and the types of medical conditions demonstrated a significant association with the tool performance. CONCLUSION: Self-triage apps, such as the ODISSEE platform, could represent an innovative method to allow patients to self-triage to the most appropriate level of care. This study based on clinical vignettes highlights some positive arguments regarding ODISSEE safety, but further research is needed to assess the generalizability of such tools to the population without equity issues.

Developing high-affinity decoy receptors to treat multiple myeloma and diffuse large B cell lymphoma.

Disease relapse and treatment-induced immunotoxicity pose significant clinical challenges for patients with hematological cancers. Here, we reveal distinctive requirements for neutralizing TNF receptor ligands APRIL and BAFF and their receptor activity in MM and DLBCL, impacting protein translation and production in MM cells and modulating the translation efficiency of the ATM interactor (ATMIN/ACSIZ). Therapeutically, we investigated the use of BCMA decoy receptor (sBCMA-Fc) as an inhibitor of APRIL and BAFF. While wild-type sBCMA-Fc effectively blocked APRIL signaling in MM, it lacked activity in DLBCL due to its weak BAFF binding. To expand the therapeutic utility of sBCMA-Fc, we engineered an affinity-enhanced mutant sBCMA-Fc fusion molecule (sBCMA-Fc V3) 4- and 500-fold stronger in binding to APRIL and BAFF, respectively. The mutant sBCMA-Fc V3 clone significantly enhanced antitumor activity against both MM and DLBCL. Importantly, we also demonstrated an adequate toxicity profile and on-target mechanism of action in nonhuman primate studies.

"Debriefing and Organizational Lessons Learned" (DOLL): A Qualitative Study to Develop a Classification Framework for Reporting Clinical Debriefing Results.

Background: The COVID-19 crisis has radically affected our healthcare institutions. Debriefings in clinical settings provide a time for the clinicians to reflect on the successes (pluses) and difficulties (deltas) encountered. Debriefings tend to be well-received if included in the broader management of the unit. The goal of this study was to develop a framework to categorize these debriefings and to assess its worthiness. Methods: A qualitative approach based on a grounded theory research method was adopted resulting in the "Debriefing and Organizational Lessons Learned" (DOLL) framework. Debriefings were conducted within two Emergency Departments of a Belgian University Hospital during an 8-week period. In the first step, three researchers used debriefing transcripts to inductively develop a tentative framework. During the second step, these three researchers conducted independent categorizations of the debriefings using the developed framework. In step 3, the team analyzed the data to understand the utility of the framework. Chi-square was conducted to examine the associations between the item types (pluses and deltas) and the framework's dimensions. Results: The DOLL is composed of seven dimensions and 13 subdimensions. Applied to 163 debriefings, the model identified 339 items, including 97 pluses and 242 deltas. Results revealed that there was an association between the frequency of pluses and deltas and the dimensions (p < 0.001). The deltas were mainly related to the work environment (equipment and maintenance) (p < 0.001) while the pluses identified tended to be related to the organization of the unit (communication and roles) (p < 0.001). With leadership's support and subsequent actions, clinicians were more enthusiastic about participating and the researchers anecdotally detected a switch toward a more positive organizational learning approach. Conclusion: The framework increases the potential value of clinical debriefings because it organizes results into actionable areas. Indeed, leadership found the DOLL to be a useful management tool. Further research is needed to investigate how DOLL may work in non-crisis circumstances and further apply the DOLL into incident reporting and risk management process of the unit.

Consensus on the Objectives of an Educational Intervention for Patients with Oropharyngeal Dysphagia and Their Informal Caregivers: A Delphi Study.

Purpose: In the absence of literature allowing for an evidence-based approach to therapeutic patient education (TPE) in Oropharyngeal Dysphagia (OD), this study aims to reach a consensus of experts on the content of a competency framework of an educational program for OD patients and their informal caregivers (ICGs). Methods: We used the Delphi consensus-building method. Four categories of experts were recruited: 12 patients, 17 ICGs, 46 healthcare professionals (HCP) (experienced in OD, not necessarily certified in TPE), and 19 experts in TPE (trained individuals to set up and run TPE programs not necessarily HCPs). The content of the questionnaire of the first round (R) was established according to the result of a scoping review and the opinion of an expert committee. We carried out three rounds. In R1 and R2, we collected the opinions on the relevance (7-point Likert-type scale) and on comprehensiveness (YES/No question and asking participants to propose additional content). Participants were also invited to leave comments on each objective. In R3, we asked the participants to give their opinion about the relevance of the objectives again and asked them to rank the themes from highest to lowest priority. Results: Objectives were considered relevant for all participants if they reached consensus when the interquartile (IQR) ≤ 1, and if the median indicated agreement (Mdn ≥ 6) (6= appropriate, 7 = totally appropriate). Following three rounds, the final content of the educational program is composed of 23 educational objectives organized in 13 themes with an agreement about relevance amongst all participants (Mdn ≥ 6; IQR ≤ 1). The comprehensiveness criterion received also a consensus (IQR ≤ 1). The participants ranked the theme "normal swallowing vs difficulty swallowing" as the highest priority. Conclusion: This Delphi study resulted in a consensus, on the content of a competency framework of an educational program for OD patients and their ICGs. Further steps are needed to construct learning activities based on these objectives before testing their feasibility and efficacy.

Training of radiotherapy professionals: status, content, satisfaction and improvement suggestions in the Greater Region.

BACKGROUND: The initial training of Radiation Oncology professionals can vary widely across Europe. The aim of this study was to assess the status and content of the initial training programs currently implemented in the Greater Region: Lorraine (Nancy, France), Saarland (Homburg, Germany), Luxembourg, and Liège (Wallonia, Belgium). METHODS: A survey was developed to investigate (1) the overall satisfaction, learning objectives, and teaching methods used during initial training programs and (2) the perceptions of the importance of key professional competencies as described by the CanMEDS (a framework that identifies and describes the abilities physicians require to effectively meet the health care needs of the people they serve). In addition, open-ended questions were used to elicit opinions on room for improvement. Participants (N = 38) were physicians (radiation oncologists (RO) seniors and residents) and radiation therapists (RTTs). RESULTS: Only 21.1% of the respondents declared having acquired all the competencies required for their professional practice during their initial training. Heterogeneity in teaching methods was noted within professional programs but there is no difference between those from RO and RTT in the teaching of technical and relational skills. Relational skills were not addressed in a range of 39.5-57.9% of respondent's curricula. More practical lessons were deemed necessary to improve radiotherapy (RT) training programs. CONCLUSIONS: Radiation oncology professionals expressed the need for more practical teaching, especially in the training of non-technical skills. Regarding the perceived importance of professional aptitudes, radiation oncology professionals highlighted medical and relational skills as the most important competencies.

A 2-month field cohort study of SARS-CoV-2 in saliva of BNT162b2 vaccinated nursing home workers.

Background: Nursing home (NH) residents have been severely affected during the COVID-19 pandemic because of their age and underlying comorbidities. Infection and outbreaks in NHs are most likely triggered by infected workers. Screening for asymptomatic NH workers can prevent risky contact and viral transmission to the residents. This study examined the effect of the BNT162b2 mRNA COVID­19 (Comirnaty®; BioNTech and Pfizer) vaccination on the saliva excretion of SARS-CoV-2 among NH workers, through weekly saliva RT-qPCR testing. Methods: A 2-month cohort study was conducted among 99 NHs in the Walloon region (Belgium), at the start of February 2021. Three groups of workers, i.e., non-vaccinated (n = 1618), one-dosed vaccinated (n = 1454), and two-dosed vaccinated (n = 2379) of BNT162b2 mRNA COVID­19 vaccine, were followed-up weekly. Their saliva samples were used to monitor the shedding of SARS-CoV-2. All positive samples were sequenced and genotyped to identify the circulating wild-type virus or variants of concern. Results: The protection fraction against the excretion of the SARS-CoV-2 in the saliva samples of the workers after the second dose is estimated at 0.90 (95% CI: 0.18; 0.99) at 1 week and 0.83 (95% CI: 0.54; 0.95) at 8 weeks. We observe more circulating SARS-CoV-2 and a greater variability of viral loads in the unvaccinated group compared to those of the vaccinated group. Conclusions: This field cohort study advances our knowledge of the efficacy of the mRNA BNT162b2 COVID-19 vaccine on the viral shedding in the saliva specimens of vaccinated NH workers, contributing to better decision-making in public health interventions and management.

Clinical prediction models for diagnosis of COVID-19 among adult patients: a validation and agreement study.

BACKGROUND: Since the beginning of the pandemic, hospitals have been constantly overcrowded, with several observed waves of infected cases and hospitalisations. To avoid as much as possible this situation, efficient tools to facilitate the diagnosis of COVID-19 are needed. OBJECTIVE: To evaluate and compare prediction models to diagnose COVID-19 identified in a systematic review published recently using performance indicators such as discrimination and calibration measures. METHODS: A total of 1618 adult patients present at two Emergency Department triage centers and for whom qRT-PCR tests had been performed were included in this study. Six previously published models were reconstructed and assessed using diagnostic tests as sensitivity (Se) and negative predictive value (NPV), discrimination (Area Under the Roc Curve (AUROC)) and calibration measures. Agreement was also measured between them using Kappa's coefficient and IntraClass Correlation Coefficient (ICC). A sensitivity analysis has been conducted by waves of patients. RESULTS: Among the 6 selected models, those based only on symptoms and/or risk exposure were found to be less efficient than those based on biological parameters and/or radiological examination with smallest AUROC values (< 0.80). However, all models showed good calibration and values above > 0.75 for Se and NPV but poor agreement (Kappa and ICC < 0.5) between them. The results of the first wave were similar to those of the second wave. CONCLUSION: Although quite acceptable and similar results were found between all models, the importance of radiological examination was also emphasized, making it difficult to find an appropriate triage system to classify patients at risk for COVID-19.

Distinction of Lymphoma from Sarcoidosis on 18F-FDG PET/CT: Evaluation of Radiomics-Feature-Guided Machine Learning Versus Human Reader Performance.

Sarcoidosis and lymphoma often share common features on 18F-FDG PET/CT, such as intense hypermetabolic lesions in lymph nodes and multiple organs. We aimed at developing and validating radiomics signatures to differentiate sarcoidosis from Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL). Methods: We retrospectively collected 420 patients (169 sarcoidosis, 140 HL, and 111 DLBCL) who underwent pretreatment 18F-FDG PET/CT at the University Hospital of Liege. The studies were randomly distributed to 4 physicians, who gave their diagnostic suggestion among the 3 diseases. The individual and pooled performance of the physicians was then calculated. Interobserver variability was evaluated using a sample of 34 studies interpreted by all physicians. Volumes of interest were delineated over the lesions and the liver using MIM software, and 215 radiomics features were extracted using the RadiomiX Toolbox. Models were developed combining clinical data (age, sex, and weight) and radiomics (original and tumor-to-liver TLR radiomics), with 7 different feature selection approaches and 4 different machine-learning (ML) classifiers, to differentiate sarcoidosis and lymphomas on both lesion-based and patient-based approaches. Results: For identifying lymphoma versus sarcoidosis, physicians' pooled sensitivity, specificity, area under the receiver-operating-characteristic curve (AUC), and accuracy were 0.99 (95% CI, 0.97-1.00), 0.75 (95% CI, 0.68-0.81), 0.87 (95% CI, 0.84-0.90), and 89.3%, respectively, whereas for identifying HL in the tumor population, it was 0.58 (95% CI, 0.49-0.66), 0.82 (95% CI, 0.74-0.89), 0.70 (95% CI, 0.64-0.75) and 68.5%, respectively. Moderate agreement was found among observers for the diagnosis of lymphoma versus sarcoidosis and HL versus DLBCL, with Fleiss κ-values of 0.66 (95% CI, 0.45-0.87) and 0.69 (95% CI, 0.45-0.93), respectively. The best ML models for identifying lymphoma versus sarcoidosis showed an AUC of 0.94 (95% CI, 0.93-0.95) and 0.85 (95% CI, 0.82-0.88) in lesion- and patient-based approaches, respectively, using TLR radiomics (plus age for the second). To differentiate HL from DLBCL, we obtained an AUC of 0.95 (95% CI, 0.93-0.96) in the lesion-based approach using TLR radiomics and 0.86 (95% CI, 0.80-0.91) in the patient-based approach using original radiomics and age. Conclusion: Characterization of sarcoidosis and lymphoma lesions is feasible using ML and radiomics, with very good to excellent performance, equivalent to or better than that of physicians, who showed significant interobserver variability in their assessment.

University population-based prospective cohort study of SARS-CoV-2 infection and immunity (SARSSURV-ULiège): a study protocol.

INTRODUCTION: For a safe and sustainable return to normal functioning of academic activities in higher education, objective-driven testing strategies that are flexible and rapidly adaptable are essential to effectively monitor and respond to new developments of the COVID-19 pandemic. To date, prospective longitudinal research on SARS-CoV-2 antibody testing in saliva and seroprevalence in higher education contexts is substantially lacking, limiting our understanding of COVID-19 prevalence, incidence and nature of the immune response to SARS-CoV-2 at various stages of the infection and vaccination. To address this lack of evidence, a prospective population-based cohort study (SARSSURV-ULiège) has recently been started. METHODS AND ANALYSIS: Students (n=1396) and staff members (n=1143) of the University of Liège are followed up over more than 1 year. All participants are required to complete anamnestic, clinical and vaccine hesitancy questionnaires for medical histories and undertaken treatments. Previous proven or suspected SARS-CoV-2 infection is also registered. In phase 1, weekly saliva samples to perform RT-qPCR to detect SARS-CoV-2 and monthly COVID-19 serological rapid test results are collected. Once being positive to either saliva RT-qPCR assay for SARS-CoV-2 presence or to serological test, the participant is invited to enter phase 2. If participants get vaccinated during the study period, they are invited to phase 2. In this second phase, besides weekly saliva self-test, depending on the participants' profiles, both gargle and blood samples are collected to obtain various biological data to measure the presence of neutralising antibodies against SARS-CoV-2, determine the magnitude and the duration of antibody responses over time. ETHICS AND DISSEMINATION: The study has received the approval from the University Hospital of Liège Ethics Committee (reference number 2021/96, dated 26 March 2021). Potential protocol amendments will be presented to the Research Ethics Committee. The findings of the present study will be presented at scientific conferences and the results published in peer-review publications. Weekly reports will be submitted to the risk assessment group and the risk management group against COVID-19 of the university to enable a timely public health action if necessary.

Civil war and death in Yemen: Analysis of SMART survey and ACLED data, 2012-2019.

Conflict in Yemen has displaced millions and destroyed health infrastructure, resulting in the world's largest humanitarian disaster. The objective of this paper is to examine mortality in Yemen to determine whether it has increased significantly since the conflict began in 2015 compared to the preceding period. We analysed 91 household surveys using the Standardized Monitoring and Assessment of Relief and Transitions methodology, covering 2,864 clusters undertaken from 2012-2019, and deaths from Armed Conflict Location & Event Data Project database covering the conflict period 2015-2019. We used a Poisson-Gamma model to estimate pre-conflict (µp, baseline value) and conflict period (µc) mean death rates using household survey data from 2012-2019. To analyse changes in the distribution of deaths and estimate nationwide excess deaths, we applied pre- and post-conflict death rates to total population numbers. Further, we tested for association between excess death and security levels by governorate. The national estimated crude death rate/10,000 in the conflict period was 0.20 (95% CI: 0.17, 0.24), which is meaningfully higher than the estimated baseline rate of 0.19 (95% CI: 0.17, 0.22). Applying the conflict period rate to the Yemeni population, we estimated 168,212 excess deaths that occurred between 2015 and 2019. There was an 17.8% increase in overall deaths above the baseline during the conflict period. A large share (67.2%) of the excess deaths were due to combat-related violence. At the governorate level, posterior crude death rate varied across the country, ranging from 0.03 to 0.63 per 10,000 per day. Hajjah, Ibb, and Al Jawf governorates presented the highest total excess deaths. Insecurity level was not statistically associated with excess deaths. The health situation in Yemen was poor before the crisis in 2015. During the conflict, intentional violence from air and ground strikes were responsible for more deaths than indirect or non-violent causes. The provision of humanitarian aid by foreign agencies may have helped contain increases in indirect deaths from the conflict.