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Objectives: Night eating syndrome (NES) is classified as a delay of food intake, reflected by consuming large amounts after the evening meal or ingesting food after sleep onset (DSM-5). This article aims to describe NES experience, awareness, narratives, and behavior from the perspectives of patients with NES in light of their history of traumatic life events. Method: Semi-structured interviews based on the phenomenological approach were conducted with 18 women (aged 19–60) diagnosed with NES. Results: The analysis raised two themes: 1. References to NES as an experience that represents the darker sides of patients’ behaviors and involves helplessness, contempt, self-loathing, and a loss of control. Patients also related to difficult memories concerning sexual, physical, and emotional abuse. 2. References to the comforting side of NES patients’ behaviors that involves soothing, regulating, emotional disconnecting, and a sense of calm, control, and the ability to function. Conclusion: Findings present the relationship between traumatic life events, dissociation, and EDs. Clinically, they highlight the importance of an early assessment and a traumatic life history and suggest giving special treatment attention to the role of dissociation and night eating as regulatory mechanisms in the therapeutic process and alliance.

Abstract Among the most successful Lessepsian invaders is the symbiont-bearing benthic foraminifera Amphistegina lobifera. In its newly conquered habitat, this prolific calcifier and ecosystem engineer is exposed to environmental conditions that exceed the range of its native habitat. To disentangle which processes facilitated the invasion success of A. lobifera into the Mediterranean Sea we analyzed a ~ 1400 bp sequence fragment covering the SSU and ITS gene markers to compare the populations from its native regions and along the invasion gradient. The genetic variability was studied at four levels: intra-genomic, population, regional and geographical. We observed that the invasion is not associated with genetic differentiation, but the invasive populations show a distinct suppression of intra-genomic variability among the multiple copies of the rRNA gene. A reduced genetic diversity compared to the Indopacific is observed already in the Red Sea populations and their high dispersal potential into the Mediterranean appears consistent with a bridgehead effect resulting from the postglacial expansion from the Indian Ocean into the Red Sea. We conclude that the genetic structure of the invasive populations reflects two processes: high dispersal ability of the Red Sea source population pre-adapted to Mediterranean conditions and a likely suppression of sexual reproduction in the invader. This discovery provides a new perspective on the cost of invasion in marine protists: The success of the invasive A. lobifera in the Mediterranean Sea comes at the cost of abandonment of sexual reproduction.

Nikita Naicker,1 Hylton Rodel,2 Rubeshan Perumal,1 Yashica Ganga,2 Mallory Bernstein,2 Ntombi Benede,2 Salim Abdool Karim,1,3 Nesri Padayacthi,1,3 Alex Sigal,2,4,5 Kogieleum Naidoo1,3 1Centre for the AIDS Programme of Research in South Africa (CAPRISA), Durban, South Africa; 2Africa Health Research Institute, Durban, South Africa; 3MRC-CAPRISA HIV-TB Pathogenesis and Treatment Research Unit, Doris Duke Medical Research Institute; University of KwaZulu-Natal, Durban, South Africa; 4School of Laboratory Medicine and Medical Sciences; University of KwaZulu-Natal, Durban, South Africa; 5Max Planck Institute for Infection Biology, Berlin, GermanyCorrespondence: Nikita Naicker, Doris Duke Medical Research Institute, 2nd Floor, 719 Umbilo Road, Durban, 4041, South Africa, Tel +27843011636, Email nikita.naicker@caprisa.orgIntroduction: Current TB treatment regimens are pathogen-directed and can be severely compromised by the development of drug resistance. Metformin has been proposed as an adjunctive therapy for TB, however relatively little is known about how metformin modulates the cellular interaction between Mtb and macrophages. We aimed to characterize how metformin modulates Mtb growth within macrophages.Methods: We utilized live cell tracking through time-lapse microscopy to better understand the biological effect of metformin in response to Mtb infection. Furthermore, the potent first-line anti-TB drug, isoniazid, was used as a comparator and as a companion drug.Results: Metformin caused a 14.2-fold decrease in Mtb growth compared to the untreated control. Metformin combined with isoniazid controlled Mtb growth is slightly better than isoniazid alone. Metformin demonstrated the ability to regulate the cytokine and chemokine response over a 72 hour period, better than isoniazid only.Conclusion: We provide novel evidence that metformin controls mycobacterial growth by increasing host cell viability, and a direct and independent pro-inflammatory response to Mtb. Understanding the impact of metformin on Mtb growth within macrophages will advance our current knowledge on metformin as an adjunctive therapy, providing a new host-directed approach to TB treatment.Keywords: metformin, tuberculosis, host-directed therapy, INH, adjunctive therapy

The paper presents the "Smart City" pilot project from the point of view of the benefits of public-private partnership for each participant in the joint activity aimed at optimizing urban infrastructure. The role of the state and the private sector in the transformation of the city into a single "smart" system is defined. Indicators of the state's expectations from the implementation of the pilot project are given. The forms of public-private partnership contracts and the degree of their applicability on the example of a concession agreement are considered. The possibility of realization of public-private partnership in certain areas of concession agreements is examined. The probable future of the Smart City project activities after its completion from the point of view of the development of public-private partnership principles is determined. The strategic importance of the Smart City project implementation and, separately, of the PPP principle for the optimization of public relations is revealed.

Environmental disturbances resulting from anthropogenic energy pollution are intensely growing and represent a concern for the marine environment. Benthic organisms are the significant fauna exposed to this kind of pollution; among them, foraminifera are largely used as pollution bioindicators in marine environments, but studies on the effects induced by electrical stimulation are not documented. In the present research, we evaluated the effects of short-term different electric current densities on the viability of benthic foraminiferal species Amphistegina lessonii by checking the pseudopodial activity and defined the threshold electrical density range. After 3 days of treatment, A. lessonii stimulated with a constant current showed pseudopodial activity at a lower electric current density (0.29, 0.86 μA/cm2) up to 24 h. With increasing stimulation time, the percentages of pseudopodial activity decreased. The pseudopodial activity was absent at high current densities (5.71, 8.57 μA/cm2). The viability of A. lessonii exposed to a pulsed current was higher at a low and middle electric current density (from 0.29 to 5.71 μA/cm2) than at a high electric current density (from 11.43 to 20 μA/cm2). Based on these preliminary results, the selected benthic foraminiferal species seems to better stand pulsed currents than constant ones. These first experiments might provide useful information for the definition of the appropriate electrical density threshold to avoid side effects on a part of the benthic community.

Contemporary reconstruction algorithms yield the potential of reducing radiation exposure by denoising coronary computed tomography angiography (CCTA) datasets. We aimed to assess the reliability of coronary artery calcium score (CACS) measurements with an advanced adaptive statistical iterative reconstruction (ASIR-CV) and model-based adaptive filter (MBAF2) designed for a dedicated cardiac CT scanner by comparing them to the gold-standard filtered back projection (FBP) calculations. We analyzed non-contrast coronary CT images of 404 consecutive patients undergoing clinically indicated CCTA. CACS and total calcium volume were quantified and compared on three reconstructions (FBP, ASIR-CV, and MBAF2+ASIR-CV). Patients were classified into risk categories based on CACS and the rate of reclassification was assessed. Patients were categorized into the following groups based on FBP reconstructions: 172 zero CACS, 38 minimal (1–10), 87 mild (11–100), 57 moderate (101–400), and 50 severe (4003, 4.0 (0.0–103.5) mm3 using ASIR-CV, and 5.0 (0.0–118.5) mm3 with MBAF2+ASIR-CV (all comparisons p < 0.001). The concomitant use of ASIR-CV and MBAF2 may allow the reduction of noise levels while maintaining similar CACS values as FBP measurements.

The paper examines the prospects for the design and introduction of artificial intelligence technologies in Russia’s economic system. Based on official rankings of the globe’s leading organizations and the tools of economic and mathematical modeling, we have assessed the impact of artificial intelligence technologies on the level of competitiveness of the national economy. The obtained results indicate a rather strong impact of artificial intelligence technologies on the level of competitiveness of the national economy. We have also analyzed the current level of development of artificial intelligence technologies in the Russian Federation, and pointed out significant risks and threats caused by the introduction of these technologies. The development of artificial intelligence technologies can lead to the fact that, at some point, human capital might cease to be necessary in the economy; simply put, human capital will become an unnecessary factor in economic development. In order for humanity to cope with the challenges, driven by the development of artificial intelligence technologies, the implementation of intelligent information systems should not be thoughtless; their implementation should be reasonable and extremely careful. Furthermore, we suggest how to make the use of artificial intelligence technologies in Russia’s economy more efficient. The conclusion is that, first of all, Russia should develop artificial intelligence technologies in relation to the real sector of the economy in order to increase the competitiveness of domestic goods and services and achieve the goal of import substitution. Artificial intelligence technologies should aim at improving the performance of the public health service.

Today, there is an urgent need to use distance technologies in education. The significant disadvantages of e-learning are students’ low self-motivation, and the insufficient level of formed social communication skills. The above disadvantages can be largely overcome with interactive teaching methods and appropriate information technologies in the educational process. A correct approach in including interactive technologies in e-learning provides significant positive effects. One of the main challenges in using interactive technologies in e-learning is how to organize efficient remote dialogue and joint work of the participants. The paper analyzes information technologies recommended at various stages of organizing and designing interactive learning technologies. When working in groups, students can use online services such as Google Sheets, Google Docs, and Google Slides. These services greatly facilitate the work on a joint project and help the project team prepare for its successful presentation. Since many e-learning platforms cannot provide high-quality communication for participants, video conferencing services and social networks should supplement them. E-learning platforms should ensure that learners work effectively on common tasks using interactive learning technologies. We believe that every modern e-learning platform should contain a software module similar in functionality to Google Docs, Google Sheets, and Google Slides. It will make it possible to successfully implement all stages of organizing and designing interactive learning technologies. We can evaluate the efficiency of the forms of conducting classes using mathematical modeling, in particular, game-theoretic modeling. To assess the efficiency of the traditional and interactive forms of conducting classes, it is advisable to use an antagonistic (matrix) game and a cooperative game, correspondingly.

The evaluation of the efficiency of an investment project implemented in the real economy is impossible without assessing its environmental implications. The justification of investment projects may apply modern specialized software. Such software products do not provide an opportunity to fully automate the preparation of the environmental section of the business plan. The authors believe that it is wise to introduce automation into the development of the environmental section of the investment project business plan through an appropriate intelligent information system (expert system). Processing input data requested by the system with various prompts and explanations, the expert system should form the environmental section of the business plan. The proposed system should play the role of a consultant in the field of environmental legislation. It should offer the user a list of environmental protection measures corresponding to their project. The design and application of the expert system will lead to several positive effects: faster development of project materials, improved quality of planning, reduced number of mistakes, lower cost of assessment, increased confidence in the environmental section of the business plan by third-party participants, increased literacy of users of the expert system in the field of environmental protection.

Forrest B Fernandez,1 Adrian Ong,1 Anthony P Martin,1 C William Schwab,2 Tom Wasser,3 Christopher A Butts,4 Amanda R McNicholas,1 Alison L Muller,1 Charles F Barbera,5 Rachael Trupp,5 Adam P Sigal5 1Trauma and Surgical Critical Care Reading Hospital, Reading, PA, USA; 2Trauma and Surgical Critical Care, Hospital of the University of Pennsylvania, Philadelphia, PA, USA; 3Complete Statistical Services, Macungie, PA, USA; 4Philadelphia College of Osteopathic Medicine, Philadelphia, PA, USA; 5Department of Emergency Medicine, Reading Hospital, Reading, PA, USACorrespondence: Adam P SigalDepartment of Emergency Medicine, Reading Hospital, 6th Avenue and Spruce Street, P.O. Box 16052, West Reading, PA 19611, USATel +1 484 628 3636Email adam.sigal@towerhealth.orgBackground: Geriatric patients are at increased risk of injury following low-energy mechanisms and are less tolerant of injury. Current criteria for trauma team activation (TTA) often miss these injuries. We evaluated a novel triage process for an expedited Emergency Medicine Physician evaluation protocol (T3) for at-risk geriatric sub-populations not meeting trauma team activation (TTA) criteria.Methods: Retrospective review of injured patients (≥65 years) from a Level II Trauma Center with an Injury Severity Score (ISS < 16), prior to (Pre-T3, Jan 2007-Oct 2009), and after (Post-T3, Jan 2010-Oct 2012), implementation of T3, as well as a contemporary period (CP, Jan 2013-Oct 2015). Demographics, physiologic variables, and timeliness of care were measured. Rates of ICU admission, operative procedures and lengths of stay and in-hospital mortality were compared for all periods. Logistic regression analysis determined variables independently associated with mortality.Results: Post-T3, 49.2% of geriatric registry patients underwent T3 with a reduction in key time intervals. Median time to evaluation (42.1 mins vs 61.7 min, p

The evaluation of the effects of pollution (e.g., Hg pollution) is a difficult task and relies mostly on biomonitoring based on bioindicators. The application of biomarkers may represent a complementary or alternative approach in environmental biomonitoring. Mercury is known to pose a significant health hazard due to its ability to cross cellular membranes, bioaccumulate, and biomagnify. In the present research, the effects of short-term (i.e., 24 h) Hg exposure in the symbiont-bearing benthic foraminiferal species Amphistegina lessonii are evaluated using several biomarkers (i.e., proteins and enzymes). Mercury leads to significant changes in the biochemistry of cells. Its effects are mainly associated with oxidative stress (i.e., production of reactive oxygen species: ROS), depletion of glutathione (GSH), and alteration of protein synthesis. Specifically, our findings reveal that exposure to Hg leads to the consumption of GSH by GPx and GST for the scavenging of ROS and the activation of antioxidant-related enzymes, including SOD and GSH-enzymes (GST, GSR, GPx, and Se-GPx), that are directly related to a defense mechanism against ROS. The Hg exposure also activates the MAPK (e.g., p-p38) and HSP (e.g., HSP 70) pathways. The observed biochemical alterations associated with Hg exposure may represent effective and reliable proxies (i.e., biomarkers) for the evaluation of stress in A. lessonii and lead to a possible application for the detection of early warning signs of environmental stress in biomonitoring.

Members of societies involved in an intractable conflict usually consider costs that stem from the continuation of the conflict as unavoidable and even justify for their collective existence. This perception is well-anchored in widely shared conflict-supporting narratives that motivate them to avoid information that challenges their views about the conflict. However, since providing information about such major costs as a method for moderating conflict-related views has not been receiving much attention, in this research, we explore this venue. We examine what kind of costs, and under what conditions, exposure to major costs of a conflict affects openness to information and conciliatory attitudes among Israeli Jews in the context of the intractable Israeli–Palestinian conflict. Study 1 (N = 255) revealed that interventions based on messages providing information on mental health cost, economic cost, and cost of the conflict to Israeli democracy had (almost) no significant effect on perceptions of the participants of these prices, openness to new information about the conflict, or support for conciliatory policies. However, the existing perceptions that participants had about the cost of the conflict to Israeli democracy were positively associated with openness to alternative information about the conflict and support for conciliatory policies. Therefore, in Study 2 (N = 255), we tested whether providing information about future potential costs to the two fundamental characteristics of Israel, a democracy or a Jewish state, created by the continuation of the conflict, will induce attitude change regarding the conflict. The results indicate that information on the future cost to the democratic identity of Israel significantly affected the attitude of the participants regarding the conflict, while the effect was moderated by the level of religiosity. For secular participants, this manipulation created more openness to alternative information about the conflict and increased support for conciliatory policies, but for religious participants, it backfired. We discuss implications for the role of information about losses and the relationship between religiosity and attitudes regarding democracy and conflict.

The establishment of sustainable coastal industries requires better temporal and spatial monitoring of heavy metal (HM) pollutants, even at low concentrations and during pulse-release events, before their accumulation becomes hazardous for local ecosystems or for the use of seawater in desalination (for drinking water). Foraminifera, unicellular marine organism, build their shells by sequential addition of chambers made of calcite, which contains impurities reflecting the composition of the growth medium. Therefore, the chemical composition of each chamber reflects HM in the ambient water at the time of calcification. To test the applicability of single-chamber analyses of foraminifera shells as a tool for HM monitoring in seawater, we conducted culturing experiments to calibrate the relationship of zinc and lead in foraminiferal shells and the ambient seawater. Two species of the cosmopolitan genus Amphistegina were cultured under a range of concentrations of both metals and two temperatures. We show that concentrations of zinc and lead in shells increase linearly with metal concentration in seawater with no difference between species and no effect of temperature. Our experiments further show that the concentrations in seawater can be directly inferred from concentrations in the shells at least up to the levels representing chronic pollution for both metals (68 ug/L for Zn and 8 ug/L for Pb). Combined with their high abundances in all marine environments and good preservation of their shells in sediments, our results demonstrate that foraminifera represent a powerful natural recording system offering high spatial and temporal resolution, allowing the establishment of historical baselines and detection of confined or short-term events of HM release, which could escape traditional monitoring methods.

One of the challenges in monitoring the marine coastal environments is quantifying the magnitude and duration of pollution events. This study introduces a new concept of defining heavy metal (HM) baseline assessment levels (BALs) in coastal environments using foraminiferal shells. We demonstrated the potential of this approach by examining a nature reserve along the Mediterranean coast of Israel. Our previous investigation of this site in 2013–2014 using foraminiferal single-chamber LA-ICPMS created a large dataset consisting of HM measurements of two species, Lachlanella and Pararotalia calcariformata. This database was used to establish the BAL of Zn, Cu and Pb, associated with anthropogenic sources. In February 2021, a significant tar pollution event affected the entire Mediterranean coast of Israel, derived from an offshore oil spill. This event provided a unique opportunity to test the applicability of the foraminiferal BAL by comparing it to whole-shell ICPMS measurements of the two species collected in winter and summer 2021. Results reveal a significant increase (2–34-fold) in the three HMs between 2013–2014 and 2021, with Pb/Ca displaying the most prominent increase in both species. This suggests a possible linkage between the oil spill event and the significantly elevated metal/Ca ratios in 2021.

Desalination plants along the Mediterranean Israeli coastline currently provide ~587 million m3 drinking water/year, and their production is planned to increase gradually. Production of drinking water is accompanied by a nearly equivalent volume of brine discharge with a salinity of ~80 that is twice the normal, which can potentially impact marine ecosystems. The goal of this study was to examine whether benthic foraminifera, a known sensitive marine bio-indicator, are affected by this brine-discharge. For that, we investigated the seasonal and cumulative effect of brine discharges of three operating desalination facilities along the Israeli coast. Those facilities are located in Ashkelon, Hadera, and Sorek. The brine-discharge in the first two desalination plants is associated with thermal pollution, while the Sorek facility entails increased salinity but no thermal pollution. In four seasonal cruises during one year, we collected surface sediment samples in triplicates by grabs from the outfall (near the discharge site), and from a non-impacted control station adjacent to each study site. Our results highlight that the most robust responses were observed at two out of three desalination shallow sites (Ashkelon and Hadera), where the brine was discharged directly from a coastal outfall and was accompanied with thermal pollution from the nearby power plants. The total foraminiferal abundance and diversity were, generally, lower near the outfalls, and increased towards the control stations. Moreover, changes in the relative abundances of selected species indicate their sensitivity to the brine discharge. The most noticeable response to exclusively elevated salinity was detected at Sorek discharge site, where we observed a sharp decline in organic-cemented agglutinated benthic foraminifera, suggesting that these are particularly sensitive to elevated salinity. The herein study contribute new insights into the effect of brine discharge from desalination plants, on benthic foraminifera, and propose a scientifically-based ecological monitoring tool that can help stakeholders.

Malaria diagnosis based on microscopy is impaired by the gradual disappearance of experienced microscopists in non-endemic areas. Aside from the conventional diagnostic methods, fluorescence flow cytometry technology using Sysmex XN-31, an automated haematology analyser, has been registered to support malaria diagnosis. The aim of this prospective, monocentric, non-interventional study was to evaluate the diagnostic accuracy of the XN-31 for the initial diagnosis or follow-up of imported malaria cases compared to the reference malaria tests including microscopy, loop mediated isothermal amplification, and rapid diagnostic tests. Over a one-year period, 357 blood samples were analysed, including 248 negative and 109 positive malaria samples. Compared to microscopy, XN-31 showed sensitivity of 100% (95% CI: 97.13–100) and specificity of 98.39% (95% CI: 95.56–100) for the initial diagnosis of imported malaria cases. Moreover, it provided accurate species identification asfalciparumor non-falciparumand parasitaemia determination in a very short time compared to other methods. We also demonstrated that XN-31 was a reliable method for patient follow-up on days 3, 7, and 28. Malaria diagnosis can be improved in non-endemic areas by the use of dedicated haematology analysers coupled with standard microscopy or other methods in development, such as artificial intelligence for blood slide reading. Given that XN-31 provided an accurate diagnosis in 1 min, it may reduce the time interval before treatment and thus improve the outcome of patient who have malaria.

Adam Sigal,1 Anthony Martin,1 Adrian Ong2 1Department of Emergency Medicine, 2Department of Surgery, Trauma Section, The Reading Hospital, West Reading, PA, USA Objective: To understand the translation of one innovation in trauma care from the military to the civilian setting, the adoption of topical hemostatic agents in the Emergency Medical Services (EMS) community and in Trauma Centers in Pennsylvania. Method: We utilized an anonymous electronic survey of EMS Agency Administrative Officers and Trauma Center Coordinators. Results: We received responses from 23% (93/402) Advanced Life Support and Air Medical agencies in the State. Of the EMS agencies that responded, 46.6% (61/131) stock hemostatic products, with 55.5% (44/79) carrying QuickClot® Combat Gauze®. Of the agencies that carried hemostatic products, 50% utilized them at least once in the prior 6 months and 59% over the past 12 months. Despite the infrequent number of applications, prehospital providers ranked themselves as somewhat skilled and comfortable both with the application of the products and the indications for their use. Conclusion: Our survey found that 46.6% of the respondents indicated they carry hemostatic products, a much greater number than found on prior surveys of EMS agencies. There is a steady acceptance by EMS of new innovations in trauma care although more work is needed in translating the exact role of hemostatic agents in the civilian setting. Keywords: hemostatic, dressing, trauma, prehospital, trauma care, EMS

Proteins are essential to life, and the evaluation of their content, identification, and modification represents a fundamental assay in biochemistry research. Different analytical techniques and protocols have been specifically designed but have rarely been compared. Here, we test and compare a variety of methodologies and treatments for the quantification of proteins in Amphistegina lessonii, a larger symbiont-bearing benthic foraminiferal species. These analyses specifically include (a) lysis buffer (homemade vs. RIPA), (b) protein assays (Lowry, BCA, and Bradford), (c) ultrasonic bath treatment, and (d) protein staining (silver staining vs. Coomassie blue). On the basis of the comparative outcome, we suggest using the homemade lysis buffer, Lowry or BCA assays, ultrasonic bath treatment, and silver stain to maximize the extraction and characterization of protein for A. lessonii. This protocol might be suitable and extended to other benthic foraminiferal species, including the smaller ones.

Women now surpass men in overall rates of college graduation in many industrialized countries, but sex segregation in fields of study persists. In a world where gender norms have changed but gender stereotypes remain strong, we argue that men’s and women’s attitudes and orientations toward fields of study in college are less constrained by gendered institutions than is the ranking of these fields. Accordingly, the sex segregation in the broader choice set of majors considered by college applicants may be lower than the sex segregation in their first preference field of study selection. With unique data on the broader set of fields considered by applicants to elite Israeli universities, we find support for this theory. The factors that drive the gender gap in the choice of field of study, in particular labor market earnings, risk aversion, and the sex composition of fields, are weaker in the broad set of choices than in the first choice. The result is less segregation in considered majors than in the first choice and, more broadly, different gender patterns in the decision process for the set of considered majors and for the first choice. We consider the theoretical implications of these results.

The eastern Mediterranean is a hotspot of biological invasions. Numerous species of Indo-pacific origin have colonized the Mediterranean in recent times, including tropical symbiont-bearing foraminifera. Among these is the species Pararotalia calcariformata. Unlike other invasive foraminifera, this species was discovered only two decades ago and is restricted to the eastern Mediterranean coast. Combining ecological, genetic and physiological observations, we attempt to explain the recent invasion of this species in the Mediterranean Sea. Using morphological and genetic data, we confirm the species attribution to P. calcariformata McCulloch 1977 and identify its symbionts as a consortium of diatom species dominated by Minutocellus polymorphus. We document photosynthetic activity of its endosymbionts using Pulse Amplitude Modulated Fluorometry and test the effects of elevated temperatures on growth rates of asexual offspring. The culturing of asexual offspring for 120 days shows a 30-day period of rapid growth followed by a period of slower growth. A subsequent 48-day temperature sensitivity experiment indicates a similar developmental pathway and high growth rate at 28°C, whereas an almost complete inhibition of growth was observed at 20°C and 35°C. This indicates that the offspring of this species may have lower tolerance to cold temperatures than what would be expected for species native to the Mediterranean. We expand this hypothesis by applying a Species Distribution Model (SDM) based on modern occurrences in the Mediterranean using three environmental variables: irradiance, turbidity and yearly minimum temperature. The model reproduces the observed restricted distribution and indicates that the range of the species will drastically expand westwards under future global change scenarios. We conclude that P. calcariformata established a population in the Levant because of the recent warming in the region. In line with observations from other groups of organisms, our results indicate that continued warming of the eastern Mediterranean will facilitate the invasion of more tropical marine taxa into the Mediterranean, disturbing local biodiversity and ecosystem structure.

Textularia agglutinans d'Orbigny is a non-symbiont bearing and comparatively large benthic foraminiferal species with a widespread distribution across all oceans. In recent years, its populations have considerably expanded along the Israeli Mediterranean coast of the eastern Levantine basin. Despite its exceptionally widespread occurrence, no molecular data have yet been obtained. This study provides the first ribosomal DNA sequences of T. agglutinans complemented with morphological and ecological characterization, which are based on material collected during environmental monitoring of the hard bottom habitats along the Israeli Mediterranean coast, and from the Gulf of Elat (northern Red Sea). Our phylogenetic analyses reveal that all specimens from both provinces belong to the same genetic population, regardless their morphological variability. These results indicate that modern population of T. agglutinans found on the Mediterranean coast of Israel is probably Lessepsian. Our study also reveals that T. agglutinans has an epiphytic life mode, which probably enabled its successful colonization of the hard bottom habitats, at the Mediterranean coast of Israel, which consist of a diverse community of macroalgae. Our study further indicates that the species does not tolerate high SST (> 35°C), which will probably prevent its future expansion in the easternmost Mediterranean in light of the expected rise in temperatures.

Background: Sensitive and easy-to-perform methods for the diagnosis of malaria are not yet available. Improving the limit of detection and following the requirements for certification are issues to be addressed in both endemic and non-endemic settings. The aim of this study was to test whether loop-mediated isothermal amplification of DNA (LAMP) may be an alternative to microscopy or real-time PCR for the screening of imported malaria cases in non-endemic area. Results: 310 blood samples associated with 829 suspected cases of imported malaria were tested during a one year period. Microscopy (thin and thick stained blood slides, reference standard) was used for the diagnosis. Real-time PCR was used as a standard of truth, and LAMP (Meridian Malaria Plus) was used as an index test in a prospective study conducted following the Standards for Reporting Diagnosis Accuracy Studies. In the 83 positive samples, species identification was P. falciparum (n = 66), P. ovale (n = 9), P. vivax (n = 3) P. malariae (n = 3) and 2 co-infections with P. falciparum + P.malariae. Using LAMP methods, 93 samples gave positive results, including 4 false-positives. Sensitivity, specificity, positive predictive value and negative predictive value for LAMP tests were 100%, 98.13%, 95.51%, and 100% compared to PCR. Conclusion: High negative predictive value, and limit of detection suggest that LAMP can be used for screening of imported malaria cases in non-endemic countries when expert microscopists are not immediately available. However, the rare occurrence of non-valid results and the need for species identification and quantification of positive samples preclude the use of LAMP as a single reference method.

The Mediterranean Sea is considered as one of the hotspots of marine bioinvasions, largely due to the influx of tropical species migrating through the Suez Canal, so-called Lessepsian migrants. Several cases of Lessepsian migration have been documented recently, however, little is known about the ecological characteristics of the migrating species and their aptitude to colonize the new areas. This study focused on Red Sea soritids, larger symbiont-bearing benthic foraminifera (LBF) that are indicative of tropical and subtropical environments and were recently found in the Israeli coast of the Eastern Mediterranean. We combined molecular phylogenetic analyses of soritids and their algal symbionts as well as network analysis of Sorites orbiculus Forskål to compare populations from the Gulf of Elat (northern Red Sea) and from a known hotspot in Shikmona (northern Israel) that consists of a single population of S. orbiculus. Our phylogenetic analyses show that all specimens found in Shikmona are genetically identical to a population of S. orbiculus living on a similar shallow water pebbles habitat in the Gulf of Elat. Our analyses also show that the symbionts found in Shikmona and Elat soritids belong to the Symbiodinium clade F5, which is common in the Red Sea and also present in the Indian Ocean and Caribbean Sea. Our study therefore provides the first genetic and ecological evidences that indicate that modern population of soritids found on the Mediterranean coast of Israel is probably Lessepsian, and is less likely the descendant of a native ancient Mediterranean species.

Abstract Background There is a high burden of hepatitis B virus (HBV) in West Africa. Over the past 20 years, West African immigration to the United States (U.S.) has been increasing. Prevalence of HBV infection in West Africa has been reported to be as high as 5–10%. Methods We sought to understand knowledge and attitudes of and barriers and facilitators to HBV screening, vaccination, and treatment in a cohort of West African immigrants in the Bronx living with or at risk for HBV through a series of one-on-one qualitative interviews. We interviewed 23 West African immigrants and analyzed transcripts for recurring themes using Applied Thematic Analysis. We situated our analysis in the socioecological model (SEM) and adhered to the consolidated criteria for reporting qualitative research (COREQ). Results Multiple themes emerged, most prominently themes relating to HBV knowledge/awareness, trust in U.S. healthcare providers and the U.S. healthcare system, positive social support improving healthcare access, knowledge sharing, stigma towards those with HBV, issues concerning immigration status, insurance status, and access to healthcare services. Conclusion Raising awareness of HBV, addressing social and structural barriers such as stigma and health insurance, and improving access to culturally sensitive programs among West African communities are needed to increase HBV screening, vaccination, and linkage to care.

Abstract Background Identifying lifestyle factors that independently or jointly lower dementia risk is a public health priority given the limited treatment options available to patients. In this cohort study, we examined the associations between Mediterranean or Dietary Approaches to Stop Hypertension (DASH) diet adherence and cardiorespiratory fitness (CRF) with later-life dementia, and assessed whether the associations between dietary pattern and dementia are modified by CRF. Methods Data are from 9,095 adults seeking preventive care at the Cooper Clinic (1987–1999) who completed a 3-day dietary record and a maximal exercise test. Alzheimer’s disease and related disorders or senile dementia (i.e., all-cause dementia) was identified from Medicare administrative claims (1999–2019). Illness-death models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations between Mediterranean or DASH diet adherence (primary exposure), CRF (secondary exposure), and all-cause dementia, adjusted for demographic and clinical factors. An interaction term was included between diet score and CRF to assess effect modification by CRF. Results The mean age at baseline was 50.6 (standard deviation [SD]: 8.4) years, and a majority of the study sample were men (77.5%) and White (96.4%). 1449 cases of all-cause dementia were identified over a mean follow-up of 9.2 (SD: 5.8) years. Neither Mediterranean nor DASH diet adherence was associated with dementia risk in fully adjusted models (HR per SD of Mediterranean diet score: 1.00, 95% CI: 0.94, 1.05; HR per SD of DASH diet score: 1.02, 95% CI: 0.96, 1.08). However, participants with higher CRF had a decreased hazard of dementia (HR, per metabolic equivalent of task [MET] increase, Mediterranean model: 0.95, 95% CI: 0.92, 0.98; HR, per MET increase, DASH model: 0.96, 95% CI: 0.92, 0.97). No effect modification by CRF was observed in the association between diet and dementia. Conclusions In this sample of apparently healthy middle-aged adults seeking preventive care, higher CRF at midlife was associated with a lower risk of all-cause dementia, though adherence to a Mediterranean or DASH diet was not, and CRF did not modify the diet-dementia association. CRF should be emphasized in multimodal interventions for dementia prevention and investigated among diverse samples.

Background: Sacral nerve stimulation (SNS) is a minimally invasive surgical procedure used to treat refractory constipation in children. While its efficacy in improving symptoms has been studied, its effect on colonic motor function remains unclear. This case series explores SNS’s impact on colonic motor function in pediatric patients with idiopathic constipation, using high-resolution colonic manometry (HRCM). Methods: Four pediatric patients with chronic idiopathic constipation underwent SNS placement for intractable symptoms and were subsequently evaluated via HRCM. Clinical characteristics, comorbidities, treatment regimens, and outcomes were reviewed. HRCM was conducted during the SNS-off and SNS-on phases. The motility index (MI) was measured during the SNS-off (fasting and postprandial) and SNS-on phases. Results: Four pediatric patients aged 8 to 21 years met the inclusion criteria. In three patients, SNS-induced high-amplitude propagating contractions (HAPCs) were noted, and in one patient, low-amplitude propagating contractions (LAPCs) were noted. In one patient, propagating contractions were induced only when SNS was turned on. MI changes with SNS-on were variable among different patients with an increase in MI in two patients after turning SNS on and a decrease in the other two compared with baseline. Adverse effects following SNS placement remained minimal across all cases. Conclusion: This case series is the first to report SNS effects on colonic motility evaluated by HRCM in pediatrics. We demonstrate that propagating colonic contractions are promptly induced when SNS is turned on. Although the initial effects of SNS on colonic motility were observable, additional investigation is necessary to comprehend the fundamental mechanisms and long-term effectiveness of SNS in pediatric patients.

Abstract Background Multiple lines of evidence support peripheral organs in the initiation or progression of Lewy body disease (LBD), a spectrum of neurodegenerative diagnoses that include Parkinson’s Disease (PD) without or with dementia (PDD) and dementia with Lewy bodies (DLB). However, the potential contribution of the peripheral immune response to LBD remains unclear. This study aims to characterize peripheral immune responses unique to participants with LBD at single-cell resolution to highlight potential biomarkers and increase mechanistic understanding of LBD pathogenesis in humans. Methods In a case–control study, peripheral mononuclear cell (PBMC) samples from research participants were randomly sampled from multiple sites across the United States. The diagnosis groups comprise healthy controls (HC, n = 159), LBD (n = 110), Alzheimer’s disease dementia (ADD, n = 97), other neurodegenerative disease controls (NDC, n = 19), and immune disease controls (IDC, n = 14). PBMCs were activated with three stimulants (LPS, IL-6, and IFNa) or remained at basal state, stained by 13 surface markers and 7 intracellular signal markers, and analyzed by flow cytometry, which generated 1,184 immune features after gating. Results The model classified LBD from HC with an AUROC of 0.87 ± 0.06 and AUPRC of 0.80 ± 0.06. Without retraining, the same model was able to distinguish LBD from ADD, NDC, and IDC. Model predictions were driven by pPLCγ2, p38, and pSTAT5 signals from specific cell populations under specific activation. The immune responses characteristic for LBD were not associated with other common medical conditions related to the risk of LBD or dementia, such as sleep disorders, hypertension, or diabetes. Conclusions and Relevance Quantification of PBMC immune response from multisite research participants yielded a unique pattern for LBD compared to HC, multiple related neurodegenerative diseases, and autoimmune diseases thereby highlighting potential biomarkers and mechanisms of disease.

Abstract Background Exposure to climate change events like wildfires can lead to health and mental health problems. While conceptual frameworks have been hypothesized describing the potential relationship between disaster exposure and substance use, the association remains under-researched and unquantified. Methods We constructed a quantitative portrayal of one proposed conceptual framework that focuses on the intermediary role of anxiety. We used the Monte Carlo simulation to estimate the impact of wildfire exposure on opioid misuse outcomes through increased anxiety. We searched for and extracted prior empirical evidence on the associations between wildfire anxiety and anxiety-opioid misuse. Three scenarios were devised: in S1 the impact of wildfire on opioid misuse was limited to increasing anxiety incidence; in S2 we also considered the additive role of altered anxiety phenotype; and in S3 we further considered the role of increased opioid-related consequences of pre-existing anxiety due to wildfire exposure. Results Models show that the prevalence of opioid misuse post-wildfire may rise to 6.0%-7.2% from a baseline of 5.3%. In S1, the opioid misuse prevalence ratio was 1.12 (95% uncertainty interval [UI]: 1.00 – 1.27). The two exploratory scenarios, with less stringent assumptions, yielded prevalence ratios of 1.23 (95% UI: 1.00 – 1.51) and 1.34 (95% UI: 1.11 – 1.63). Conclusions Our modeling study suggests that exposure to wildfires may elevate opioid misuse through increasing anxiety incidence and severity. This can lead to substantial health burdens, possibly beyond the duration of the wildfire event, which may offset recent gains in opioid misuse prevention.

Abstract Differential diagnosis is a crucial aspect of medical practice, as it guides clinicians to accurate diagnoses and effective treatment plans. Traditional resources, such as medical books and services like UpToDate, are constrained by manual curation, potentially missing out on novel or less common findings. This paper introduces and analyzes two novel methods to mine etiologies from scientific literature. The first method employs a traditional Natural Language Processing (NLP) approach based on syntactic patterns. By using a novel application of human-guided pattern bootstrapping patterns are derived quickly, and symptom etiologies are extracted with significant coverage. The second method utilizes generative models, specifically GPT-4, coupled with a fact verification pipeline, marking a pioneering application of generative techniques in etiology extraction. Analyzing this second method shows that while it is highly precise, it offers lesser coverage compared to the syntactic approach. Importantly, combining both methodologies yields synergistic outcomes, enhancing the depth and reliability of etiology mining.

Abstract Plekhm2 is a protein regulating endosomal trafficking and lysosomal distribution. We recently linked a recessive inherited mutation in PLEKHM2 to a familial form of dilated cardiomyopathy and left ventricular non-compaction. These patients’ primary fibroblasts exhibited abnormal lysosomal distribution and autophagy impairment. We therefore hypothesized that loss of PLEKHM2 impairs cardiac function via autophagy derangement. Here, we characterized the roles of Plekhm2 in the heart using global Plekhm2 knockout (PLK2-KO) mice and cultured cardiac cells. Compared to littermate controls (WT), young PLK2-KO mice exhibited no difference in heart function or autophagy markers but demonstrated higher basal AKT phosphorylation. Older PLK2-KO mice had body and heart growth retardation and increased LC3II protein levels. PLK2-KO mice were more vulnerable to fasting and, interestingly, impaired autophagy was noted in vitro, in Plekhm2-deficient cardiofibroblasts but not in cardiomyocytes. PLK2-KO hearts appeared to be less sensitive to pathological hypertrophy induced by angiotensin-II compared to WT. Our findings suggest a role of Plekhm2 in murine cardiac autophagy. Plekhm2 deficiency impaired autophagy in cardiofibroblasts, but the autophagy in cardiomyocytes is not critically dependent on Plekhm2. The absence of Plekhm2 in mice appears to promote compensatory mechanism(s) enabling the heart to manage angiotensin-II-induced stress without detrimental consequences.

Abstract Prognosis determines major decisions regarding treatment for critically ill patients. Statistical models have been developed to predict the probability of survival and other outcomes of intensive care. Although they were trained on the characteristics of large patient cohorts, they often do not represent very old patients (age ≥ 80 years) appropriately. Moreover, the heterogeneity within this particular group impairs the utility of statistical predictions for informing decision-making in very old individuals. In addition to these methodological problems, the diversity of cultural attitudes, available resources as well as variations of legal and professional norms limit the generalisability of prediction models, especially in patients with complex multi-morbidity and pre-existing functional impairments. Thus, current approaches to prognosticating outcomes in very old patients are imperfect and can generate substantial uncertainty about optimal trajectories of critical care in the individual. This article presents the state of the art and new approaches to predicting outcomes of intensive care for these patients. Special emphasis has been given to the integration of predictions into the decision-making for individual patients. This requires quantification of prognostic uncertainty and a careful alignment of decisions with the preferences of patients, who might prioritise functional outcomes over survival. Since the performance of outcome predictions for the individual patient may improve over time, time-limited trials in intensive care may be an appropriate way to increase the confidence in decisions about life-sustaining treatment.

Abstract Wildfire smoke exposure leads to poorer health among those with pre‐existing conditions such as asthma. Particulate matter in wildfire smoke can worsen asthma control, cause acute exacerbations, and increase health resource utilization (HRU) and costs. Research to date has been retrospective with few opportunities to project changes in underlying asthma control and HRU given exposure to wildfire smoke. Using a microsimulation of 5,000 Californians with asthma, we calculated changes in asthma control distribution, risk of exacerbation, and HRU and cost outcomes in the 16 weeks during and after a wildfire. The model was calibrated against empirical values on asthma control distribution and increased HRU after exposure to wildfire smoke. Without smoke exposure, 48% of the cohort exhibited complete or well control of asthma, and 8% required acute healthcare per cycle. Following two consecutive weeks of wildfire smoke, complete or well control of asthma fell to 27%, with an additional 4% HRU. This corresponds to total additional $601,250 in all‐cause medical costs and eight fewer quality‐adjusted life years over 16 weeks of model time. Our model found increased asthma health and cost burden due to wildfire smoke that were aligned with empirical evidence from a historic wildfire event. This study establishes a framework for a more nuanced understanding of asthma impacts from wildfire smoke that can help inform the development of public health policies to mitigate harm and promote resilience among asthma patients in the face of climate change.

This study investigates the impact of the abrupt transition to emergency remote learning (ERT), specifically focusing on teachers’ cognitive resources and technological resources both before and during ERT. The sample comprised 1,071 teachers: before ERT (53.0%), during ERT (47.0%). Five questionnaires were administered. Results indicated that teachers surveyed during ERT, compared to their counterparts surveyed before ERT, exhibited significantly elevated attitudes toward information and communication technology (ICT), increased usage of the online environment for teaching and use of computers for communication. Additionally, the degree of readiness for educational change significantly contributed to the teachers’ changed attitudes toward ICT.

IntroductionThe insulin-like growth factor (IGF) system plays a key role in regulating growth and invasiveness in epithelial ovarian cancer (EOC) and is considered a promising therapeutic target. EOC is an immunosuppressive disease, although there are limited data about the involvement of the IGF1R system in the anti-tumor immune response in the EOC microenvironment.MethodsIn the current study, we hypothesized that IGF 1 receptor (IGF1R) involvement in the maturation of dendritic cells (DC) with the co-inhibition of IGF1R and PD-1 would affect the EOC microenvironment.ResultsWe found that DC pretreated with IGF1R inhibitor resulted in fewer EOC cells. Moreover, in vivo experiments conducted with an EOC mouse model, with anti-PD-1/IGF1R combined, resulted in lower tumor weight compared to individual treatments. Additionally, anti-PD-1/IGF1R treatment increased DC by 34% compared with AEW-541 and 40% with anti-PD-1. The combined treatment increased CD8+ T-cell levels compared to AEW-541 alone. RNA-seq data analysis indicated that anti-PD-1/IGF1R led to a more potent immune response, as reflected by altered gene expression levels related to anti-tumor immune response, compared with either treatment alone.DiscussionThese findings provide novel evidence that IGF1R axis inhibition combined with PD-1 blockade may be an effective therapeutic strategy for selected EOC patient populations.

BackgroundIL-26 is a key mediator of pulmonary host defense given its abundant expression in human airways and its established antibacterial properties. Moreover, recent studies indicate that IL-26 can also inhibit viral replication. Along these lines, we have previously reported an increase in the plasma concentration of IL-26 among patients with acute COVID-19 that is linked to harmful hyperinflammation. Nevertheless, it is still unclear whether this systemic increase in IL-26 relates to disease severity, sex, comorbidities, viral load, or the innate immune response in acute COVID-19.MethodsIL-26 was quantified using ELISA in plasma samples from a large cohort of well-characterized patients with acute COVID-19 (n=178) and healthy controls (n=30). The plasma concentrations of SARS-CoV-2 nucleocapsid and spike protein, as well as those of IFN-α2a, IFN-β, and IFN-γ, were determined using electrochemiluminescence immunoassay. The concentration of double-stranded DNA was determined using fluorometry.ResultsThe plasma concentration of IL-26 was increased in patients with severe/critical COVID-19, particularly among males and patients with comorbid obstructive lung disease. Moreover, the concentration of IL-26 displayed positive correlations with length of hospital stay, as well as with systemic markers of viral load, antiviral immunity, and extracellular DNA.ConclusionsSystemic IL-26 is involved in severe COVID-19, especially in males and patients with comorbid obstructive lung disease. These findings argue that systemic IL-26 has pathogenic and antiviral relevance, as well as biomarker potential.

IntroductionThis study investigates the dynamics of intranational intergroup contact between Arab and Jewish students in a higher education institution in Israel. Guided by the contact hypothesis, the research examines the gap between students’ willingness for intergroup closeness and their reported actual intergroup interactions.MethodsUsing a cross-sectional survey design, quantitative data were collected from a total of 733 Arab and Jewish students at two timepoints: in 2016 (n = 419) and in 2023 (n = 314). All students were studying to become physical education teachers.ResultsThe findings revealed both persistent challenges and encouraging trends in intergroup relationships. Despite reported willingness for meaningful connections, the students’ reported actual intergroup interactions remained limited. A significant increase in willingness for academic and friendship relationships was observed from 2016 to 2023, suggesting the potential for constructive change. Arab students consistently reported higher willingness for closeness and more frequent interactions than their Jewish counterparts.DiscussionThese findings underscore the importance of structured interventions in higher education settings to foster meaningful intergroup relations, amidst broader societal challenges.

IntroductionIn this study, we report a novel therapeutic approach redirecting antigen-specific CD4+ T cells recognizing a hybrid insulin peptide (BDC2.5 T cell receptor (TCR) transgenic CD4+ T cells) to attract and suppress islet-specific CD8+ T cells T cells in the non-obese diabetic (NOD) mouse model, and prevent the development of autoimmune diabetes.MethodsPurified BDC2.5 CD4+ T cells were induced to differentiate into regulatory T cells (Tregs). The Tregs were then electroporated with mRNA encoding chimeric human β2 microglobulin (hβ2m) covalently linked to insulin B chain amino acids 15-23 (designated INS-eTreg) or islet-specific glucose-6-phosphatase related protein (IGRP) peptide 206-214 (designated IGRP-eTreg). Immunoregulatory functions of these engineered regulatory T cells (eTregs) were tested by in vitro assays and in vivo co-transfer experiments with β-cell-antigen-specific CD8+ T cells in NOD.Scid mice or by adoptive transfer into young, pre-diabetic NOD mice.ResultsThese eTregs were phenotyped by flow cytometry, and shown to have high expression of FoxP3, as well as other markers of Treg function, including IL-10. They suppressed polyclonal CD4+ T cells and antigen-specific CD8+ T cells (recognizing insulin or IGRP), decreasing proliferation and increasing exhaustion and regulatory markers in vitro. In vivo, eTregs reduced diabetes development in co-transfer experiments with pathogenic antigen-specific CD8+ T cells (INS-CD8+ or IGRP-CD8+ cells) into NOD.Scid mice. Finally, when the eTreg were injected into young NOD mice, they reduced insulitis and prevented spontaneous diabetes in the recipient mice.ConclusionOur results suggest a novel therapeutic strategy to protect NOD mice by targeting antigen-specific cytotoxic CD8+ T cells, using redirected antigen-specific CD4+ Treg cells, to suppress autoimmune diabetes. This may suggest an innovative therapy for protection of people at risk of development of type 1 diabetes.

Background Prompt diagnosis of bacteremia in the emergency department (ED) is of utmost importance. Nevertheless, the average time to first clinical laboratory finding range from 1 to 3 days. Alongside a myriad of scoring systems for occult bacteremia prediction, efforts for applying artificial intelligence (AI) in this realm are still preliminary. In the current study we combined an AI algorithm with a Natural Language Processing (NLP) algorithm that would potentially increase the yield extracted from clinical ED data. Methods This study involved adult patients who visited our emergency department and at least one blood culture was taken to rule out bacteremia. Using both tabular and free text data, we built an ensemble model that leverages XGBoost for structured data, and logistic regression (LR) on a word-analysis technique called bag-of-words (BOW) Term Frequency-Inverse Document Frequency (TF-IDF), for textual data. All algorithms were designed in order to predict the risk for bacteremia with ED patients whose blood cultures were sent to the laboratory. Results The study cohort comprised 94,482 individuals, of whom 52% were males. The prevalence of bacteremia in the entire cohort was 9.7%. The model trained on the tabular data yielded an area under the curve (AUC) of 73.7% for XGBoost, while the LR that was trained on the free text achieved an AUC of 71.3%. After checking a range of weights, the best combination was for 55% weight on the XGBoost prediction and 45% weight on the LR prediction. The final model prediction yielded an AUC of 75.6%. Conclusion Harnessing artificial intelligence to the task of bacteremia surveillance in the ED settings by a combination of both free text and tabular data analysis improved predictive performance compared to using tabular data alone. We recommend that future AI applications based on our findings should be assimilated into the clinical routines of ED physicians.

BackgroundThe COVID-19 pandemic underscored the challenge of swiftly disseminating research findings to a global audience. Language barriers further exacerbated disparities in access to timely scientific information, particularly for non-English speaking communities. The majority of COVID-19 research was published in English, limiting accessibility for Spanish-speaking populations. ObjectiveThis paper aims to assess the reach and effectiveness of AccesoCovid.com, a platform designed to disseminate up-to-date COVID-19 research in both English and Spanish, addressing the language gap in scientific communication. MethodsAccesoCovid.com was developed through a partnership between the University of California, San Francisco (UCSF) and Universidad Nacional Autónoma de México (UNAM). The website’s performance and user engagement were evaluated using Google Analytics over a span of 2 years. Key metrics included user language preference, geographical distribution, and site traffic. The website summarized and translated 1032 articles on various COVID-19 topics, such as “Pharmaceutical Interventions and Vaccines.” ResultsFrom February 2021 to February 2023, the platform attracted 57,000 users. Of the 43,000 unique new visitors, 84.2% (n=36,219) hailed from Spanish-speaking regions. The majority accessed the site organically through search engines, with 88.4% (n=38,000) of users arriving this way, while 5000 (11.6%) users accessed the site directly. Most users (n=30,894, 72.1%) preferred the Spanish version of the site. The website’s most accessed category was “Pharmaceutical Interventions and Vaccines,” followed by “Clinical Presentation and Management” and “Mental Health.” Regarding language distribution, 72.1% (n=30,894) of users primarily used Spanish; 21.4% (n=9215) used English; and 6.7% (n=2891) spoke other languages, including Portuguese, Chinese, and German. Geographically, the website attracted visitors from 179 countries, with the highest visitor counts from Mexico (n=12,342, 28.7%), Spain (n=6405, 14.9%), the United States (n=4416, 10.3%), and Peru (n=3821, 8.9%). ConclusionsAccesoCovid.com successfully bridged a critical language gap in the dissemination of COVID-19 research. Its success underscores the pressing need for multilingual scientific resources. The platform demonstrated significant user engagement and reach, particularly in Spanish-speaking countries. This highlights the potential for similar platforms to ensure equitable access to scientific knowledge across diverse linguistic communities. Future efforts should focus on expanding to other languages and conducting formal evaluations to enhance user satisfaction and impact.

Summary: Background: It is unknown if early COVID-19 monoclonal antibody (mAb) therapy can reduce risk of Long COVID. The mAbs amubarvimab/romlusevimab were previously demonstrated to reduce risk of hospitalization/death by 79%. This study assessed the impact of amubarvimab/romlusevimab on late outcomes, including Long COVID. Methods: Non-hospitalized high-risk adults within 10 days of COVID-19 symptom onset enrolled in a randomized, double-blind, placebo-controlled phase 2/3 trial of amubarvimab/romlusevimab for COVID-19 treatment. Late symptoms, assessed using a participant-completed symptom diary, were a pre-specified exploratory endpoint. The primary outcome for this analysis was the composite of Long COVID by participant self-report (presence of COVID-19 symptoms as recorded in the diary at week 36) or hospitalization or death by week 36. Inverse probability weighting (IPW) was used to address incomplete outcome ascertainment, giving weighted risk ratios (wRR) comparing amubarvimab/romlusevimab to placebo. Findings: Participants received amubarvimab/romlusevimab (n = 390) or placebo (n = 390) between January and July 2021. Median age was 49 years, 52% were female, 18% Black/African American, 49% Hispanic/Latino, and 9% COVID-19-vaccinated at entry. At week 36, 103 (13%) had incomplete outcome ascertainment, and 66 (17%) on amubarvimab/romlusevimab and 92 (24%) on placebo met the primary outcome (wRR = 0.70, 95% confidence interval (CI) 0.53–0.93). The difference was driven by fewer hospitalizations/deaths with amubarvimab/romlusevimab (4%) than placebo (13%). Among 652 participants with available diary responses, 53 (16%) on amubarvimab/romlusevimab and 44 (14%) on placebo reported presence of Long COVID. Interpretation: Amubarvimab/romlusevimab treatment, while highly effective in preventing hospitalizations/deaths, did not reduce risk of Long COVID. Additional interventions are needed to prevent Long COVID. Funding: National Institute of Allergy and Infectious Diseases of the National Institutes of Health. Amubarvimab and romlusevimab supplied by Brii Biosciences.

Abstract Introduction Multiple sclerosis (MS) is a chronic autoimmune disease of the central nervous system characterized by neuroinflammation, demyelination and axonal loss. Cannabis, an immunomodulating agent, is known for its ability to treat MS effectively. However, due to variations in the profile of secondary metabolites, especially cannabinoids, among cannabis cultivars, the effectiveness of cannabis treatment can vary, with significant variability in the effects on different biological parameters. For screening available cultivars, cellular in vitro as well as pre-clinical in vivo assays, are required to evaluate the effectiveness of the wide range of chemical variability that exists in cannabis cultivars. This study evaluated comparatively three chemically diverse cannabis cultivars, CN2, CN4 and CN6, containing different ratios of phytocannabinoids, for their neuroinflammatory activity in MS model. Materials and methods In vitro experiments were performed with lipopolysaccharide (LPS)-activated BV-2 microglia and primary glial cells to evaluate the effect of different cannabis cultivars on nitric oxide (NO) and inflammatory cytokines, as well as inducible nitric oxide synthase (iNOS) protein expression. An in vivo experiment using the experimental autoimmune encephalomyelitis (EAE) MS model was conducted using Myelin oligodendrocyte glycoprotein (MOG) as the activating peptide. The cannabis extracts of the cultivars CN2, CN4, CN6 or vehicle, were intraperitoneally injected with clinical scores given based on observed symptoms over the course of study. At the end of the experiment, the mice were sacrificed, and splenocyte cytokine secretion was measured using ELISA. Lumbar sections from the spinal cord of treated MS mice were evaluated for microglia, astrocytes and CD4+ cells. Results Extracts of the CN2 cultivar contained tetrahydrocannabinolic acid (THCA) and tetrahydrocannabinol (THC) without cannabidiol (CBD), and a number of monoterpenes. CN4 contained cannabidiolic acid (CBDA) and tetrahydrocannabidiolic acid (THCA), with significant amounts of THC: CBD in a 1:1 ratio, as well as sesquiterpenes and some monoterpenes; and CN6 contained primarily CBDA and THCA, as well as THC and CBD in a 2:1 ratio, with some sesquiterpenes and no monoterpenes. All extracts were not cytotoxic in glial cells up to 50 µg/ml. Dose dependent inhibition of LPS-induced BV2 as well as primary microglial NO secretion confirmed the anti-inflammatory and anti-oxidative activity of the three cannabis cultivars. CN2 but not CN4 reduced both astrocytosis and microglial activation in lumbar sections of EAE mice. In contrast, CN4 but not CN2 significantly decreased the secretion of TNFα and Interferon γ (IFNγ) in primary splenocytes extracted from EAE mice. Conclusions While both cannabis cultivars, CN2 and CN4, significantly reduced the severity of the clinical signs throughout the course of the study, they modulated different inflammatory mediators and pathways, probably due to differences in their phytocannabinoid composition. This demonstrates the differential potential of cannabis cultivars differing in chemotype to regulate neuroinflammation and their potential to treat MS.

Abstract Background Thromboelastometry (TEM) provides a comprehensive overview of the entire coagulation process and has not been evaluated in heatstroke‐induced coagulopathies in dogs. Objectives To determine the diagnostic and prognostic utility of TEM in dogs with heatstroke. Animals Forty‐two client‐owned dogs with heatstroke. Methods Prospective observational study. Blood samples for intrinsic and extrinsic TEM (INTEM and EXTEM, respectively) were collected at presentation and every 12 to 24 hours for 48 hours. Coagulation phenotype (hypo‐, normo‐, or hypercoagulable) was defined based on TEM area under the 1st derivative curve (AUC). Results Case fatality rate was 31%. Median TEM variables associated with death (P

Abstract In this two-center prospective cohort study of children on ECMO, we assessed a panel of plasma brain injury biomarkers using exploratory factor analysis (EFA) to evaluate their interplay and association with outcomes. Biomarker concentrations were measured daily for the first 3 days of ECMO support in 95 participants. Unfavorable composite outcome was defined as in-hospital mortality or discharge Pediatric Cerebral Performance Category > 2 with decline ≥ 1 point from baseline. EFA grouped 11 biomarkers into three factors. Factor 1 comprised markers of cellular brain injury (NSE, BDNF, GFAP, S100β, MCP1, VILIP-1, neurogranin); Factor 2 comprised markers related to vascular processes (vWF, PDGFRβ, NPTX1); and Factor 3 comprised the BDNF/MMP-9 cellular pathway. Multivariable logistic models demonstrated that higher Factor 1 and 2 scores were associated with higher odds of unfavorable outcome (adjusted OR 2.88 [1.61, 5.66] and 1.89 [1.12, 3.43], respectively). Conversely, higher Factor 3 scores were associated with lower odds of unfavorable outcome (adjusted OR 0.54 [0.31, 0.88]), which is biologically plausible given the role of BDNF in neuroplasticity. Application of EFA on plasma brain injury biomarkers in children on ECMO yielded grouping of biomarkers into three factors that were significantly associated with unfavorable outcome, suggesting future potential as prognostic instruments.

Abstract Very old critically ill patients pose a growing challenge for intensive care. Critical illness and the burden of treatment in the intensive care unit (ICU) can lead to a long-lasting decline of functional and cognitive abilities, especially in very old patients. Multi-complexity and increased vulnerability to stress in these patients may lead to new and worsening disabilities, requiring careful assessment, prevention and rehabilitation. The potential for rehabilitation, which is crucial for optimal functional outcomes, requires a systematic, multi-disciplinary approach and careful long-term planning during and following ICU care. We describe this process and provide recommendations and checklists for comprehensive and timely assessments in the context of transitioning patients from ICU to post-ICU and acute hospital care, and review the barriers to the provision of good functional outcomes.

Abstract Background Violence against nurses is common. Previous research has recommended further development of the measurement of violence against nurses and integration of the individual and ward-related factors that contribute to violence against hospital nurses. This study was designed to address these issues by investigating the associations between violence, the listening climate of hospital wards, professional burnout, and perceived quality of care. For this purpose, we used a new operationalization of the violence concept. Methods We sought nurses to participate in the study through social media which yielded 765 nurses working in various healthcare systems across Israel who volunteered to complete a self-administered online questionnaire. 80% of the sample were hospital nurses, and 84.7% were female. The questionnaire included validated measures of burnout, listening climate, and quality of care. Instead of using the traditional binary measure of exposure to violence to capture the occurrence and comprehensive impact of violence, this study measured the incremental load of violence to which nurses are subjected. Results There were significant correlations between violence load and perceived quality of care and between constructive and destructive listening climates and quality of care. Violence load contributed 14% to the variance of burnout and 13% to the variance of perceived quality of care. The ward listening climate moderated the relationship between burnout and quality of care. Conclusions The results of this study highlight the impact of violence load among nurses and the ward listening climate on the development of burnout and on providing quality care. The findings call upon policymakers to monitor violence load and allocate resources to foster supportive work environments to enhance nurse well-being and improve patient care outcomes.

Abstract Squamous cell carcinomas (SCCs) are common and aggressive malignancies. Immune check point blockade (ICB) therapy using PD-1/PD-L1 antibodies has been approved in several types of advanced SCCs. However, low response rate and treatment resistance are common. Improving the efficacy of ICB therapy requires better understanding of the mechanism of immune evasion. Here, we identify that the SCC-master transcription factor TP63 suppresses interferon-γ (IFNγ) signaling. TP63 inhibition leads to increased CD8+ T cell infiltration and heighten tumor killing in in vivo syngeneic mouse model and ex vivo co-culture system, respectively. Moreover, expression of TP63 is negatively correlated with CD8+ T cell infiltration and activation in patients with SCC. Silencing of TP63 enhances the anti-tumor efficacy of PD-1 blockade by promoting CD8+ T cell infiltration and functionality. Mechanistically, TP63 and STAT1 mutually suppress each other to regulate the IFNγ signaling by co-occupying and co-regulating their own promoters and enhancers. Together, our findings elucidate a tumor-extrinsic function of TP63 in promoting immune evasion of SCC cells. Over-expression of TP63 may serve as a biomarker predicting the outcome of SCC patients treated with ICB therapy, and targeting TP63/STAT/IFNγ axis may enhance the efficacy of ICB therapy for this deadly cancer.

Abstract SARS-CoV-2 clearance requires adaptive immunity but the contribution of neutralizing antibodies and T cells in different immune states is unclear. Here we ask which adaptive immune responses associate with clearance of long-term SARS-CoV-2 infection in HIV-mediated immunosuppression after suppressive antiretroviral therapy (ART) initiation. We assembled a cohort of SARS-CoV-2 infected people in South Africa (n = 994) including participants with advanced HIV disease characterized by immunosuppression due to T cell depletion. Fifty-four percent of participants with advanced HIV disease had prolonged SARS-CoV-2 infection (>1 month). In the five vaccinated participants with advanced HIV disease tested, SARS-CoV-2 clearance associates with emergence of neutralizing antibodies but not SARS-CoV-2 specific CD8 T cells, while CD4 T cell responses were not determined due to low cell numbers. Further, complete HIV suppression is not required for clearance, although it is necessary for an effective vaccine response. Persistent SARS-CoV-2 infection led to SARS-CoV-2 evolution, including virus with extensive neutralization escape in a Delta variant infected participant. The results provide evidence that neutralizing antibodies are required for SARS-CoV-2 clearance in HIV-mediated immunosuppression recovery, and that suppressive ART is necessary to curtail evolution of co-infecting pathogens to reduce individual health consequences as well as public health risk linked with generation of escape mutants.

Abstract Airborne transmission of SARS-CoV-2 aerosol remains contentious. Importantly, whether cough or breath-generated bioaerosols can harbor viable and replicating virus remains largely unclarified. We performed size-fractionated aerosol sampling (Andersen cascade impactor) and evaluated viral culturability in human cell lines (infectiousness), viral genetics, and host immunity in ambulatory participants with COVID-19. Sixty-one percent (27/44) and 50% (22/44) of participants emitted variant-specific culture-positive aerosols 95%). There is considerable heterogeneity in potential infectiousness i.e., only 29% of participants were probably highly infectious (produced culture-positive aerosols

We demonstrate a compact ion beam device capable of accelerating H+ and D+ ions up to 75 keV energy, onto a solid target, with sufficient beam current to study fusion reactions. The ion beam system uses a microwave driven plasma source to generate ions that are accelerated to high energy with a direct current (DC) acceleration structure. The plasma source is driven by pulsed microwaves from a solid-state radiofrequency (RF) amplifier, which is impedance matched to the plasma source chamber at the S-band frequency in the range of 2.4–2.5 GHz. The plasma chamber is held at high positive DC potential and is isolated from the impedance matching structure (at ground potential) by a dielectric-filled gap. To facilitate the use of high-energy-particle detectors near the target, the plasma chamber is biased to a high positive voltage, while the target remains grounded. A target loaded with deuterium is used to study D-D fusion and a B4C or LaB6 target is used to study p-11B fusion. Detectors include solid-state charged particle detector and a scintillation fast neutron detector. The complete ion beam system can fit on a laboratory table and is a useful tool for teaching undergraduate and graduate students about the physics of fusion.

ABSTRACTObjective: Irritable bowel syndrome (IBS) is a prevalent gastrointestinal disorder associated with reduced quality of life and psychological distress (PD) including anxiety and depression. The mechanisms linking IBS to PD are unclear. Previous studies showed that body image and self-criticism may be contributory factors. Thus, the objective of this study was to test the potential mediating roles of these factors in the relationship between IBS and PD.Method: 507 adults participated, including 142 with IBS (Mean age = 31.9, SD = 11.7), and 365 healthy peers (Mean age = 26.2, SD = 6.4), ranging in age from 18 to 75. The majority of participants were women (78%). Self-report measures assessed IBS status, body appreciation, body dissatisfaction, self-criticism, sociodemographic status, depression, and anxiety. Path analysis tested the hypothesized mediation model.Results: IBS participants reported greater PD, lower body appreciation, higher body dissatisfaction, and higher self-criticism than controls. Body appreciation and self-criticism sequentially mediated the link between IBS status and both depression and anxiety. IBS was associated with reduced body appreciation, which in turn was linked to heightened self-criticism, thereby leading to elevated psychological distress.Conclusion: Results suggest IBS negatively impacts body image appreciation, fostering self-critical judgments that exacerbate psychological symptoms. This study is the first to demonstrate a significant association between body appreciation and IBS, specifically highlighting this relationship. Findings clarify the psychosocial pathways at play in the comorbidity of mental health issues in IBS. Physicians and other health professionals are advised to detect women with IBS who are distressed, and to offer them appropriate intervention to prevent downstream consequences.