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In 2021, the Israel Ministry of Health began a national hepatitis C elimination program. Implementing a World Health Organization goal, Israel’s program involved targeted screening, barrier minimization, workup simplification, awareness campaigns, and a patient registry. We evaluated program costs for testing and treatment. By May 15, 2023, the program had identified 865,382 at-risk persons, of whom 555,083 (64.3%) were serologically screened for hepatitis C virus (HCV), which was detected in 24,361 (4.4%). Among 20,928 serologically positive patients, viremia was detected in 13,379 (63.9%), of whom 10,711 (80%) were treated, and 4,618 (96.5%) of 4,786 persons receiving posttreatment HCV RNA testing had sustained virologic response. We estimated costs of ₪14,426 (new Israel shekel; ≈$3,606 USD) per person whose HCV infection was diagnosed and successfully treated. The program yielded screening and treatment in almost two thirds of the identified at-risk population. Although not eliminated, HCV prevalence will likely decrease substantially by the 2030 target.

This report summarises the SMARTCLAP research project, which employs a user-centred design approach to develop a revolutionary smart product service system. The system offers personalised motivation to encourage children with cerebral palsy to actively participate more during their occupational therapy sessions, while providing paediatric occupational therapists with an optimal tool to monitor children’s progress from one session to another. The product service system developed includes of a smart wearable device called DigiClap used to interact with a serious game in an Augmented Reality environment. The report highlights the research methodology used to advance the technology readiness level from 4 to 6, acknowledging the contribution of the consortium team and funding source. As part of the technology’s maturity process, DigiClap and the respective serious game were evaluated with target users, to identify the system’s impact in supporting the children’s overall participation and hand function, and to gather feedback from occupational therapists and caregivers on this novel technology. The outcomes of this study are discussed, highlighting limitations and lessons learned. The report also outlines future work and further funding for the sustainability of the project and to reach other individuals who have upper limb limitations. Ultimately, the potential of DigiClap and the overall achievements of this project are discussed.

Abstract Apical membrane antigen-1 (AMA1) is a conserved malarial vaccine candidate essential for the formation of tight junctions with the rhoptry neck protein (RON) complex, enabling Plasmodium parasites to invade human erythrocytes, hepatocytes, and mosquito salivary glands. Despite its critical role, extensive surface polymorphisms in AMA1 have led to strain-specific protection, limiting the success of AMA1-based interventions beyond initial clinical trials. Here, we identify an i-body, a humanised single-domain antibody-like molecule that recognises a conserved pan-species conformational epitope in AMA1 with low nanomolar affinity and inhibits the binding of the RON2 ligand to AMA1. Structural characterisation indicates that the WD34 i-body epitope spans the centre of the conserved hydrophobic cleft in AMA1, where interacting residues are highly conserved among all Plasmodium species. Furthermore, we show that WD34 inhibits merozoite invasion of erythrocytes by multiple Plasmodium species and hepatocyte invasion by P. falciparum sporozoites. Despite a short half-life in mouse serum, we demonstrate that WD34 transiently suppressed P. berghei infections in female BALB/c mice. Our work describes the first pan-species AMA1 biologic with inhibitory activity against multiple life-cycle stages of Plasmodium. With improved pharmacokinetic characteristics, WD34 could be a potential immunotherapy against multiple species of Plasmodium.

Abstract On October 7, 2023, Hamas terrorists attacked people in their homes, fields, and at a music festival in Israeli communities near the border with Gaza. More than 1,145 men, women, and children were killed, about 1,800 wounded were evacuated to hospitals in the country, and 253 infants, children, women, elderly, and men were abducted. This mass casualty incident (MCI) was the start of a war that is still ongoing. The Israeli medical system, which faced an overwhelming first 24 h, continues to take care of casualties, including those who are injured by missiles that target Israeli residential areas. Israel has a well-established trauma system, and as a result of the experience gained in this war, the system merited review. This was the topic of a meeting of leaders of the Israeli healthcare system, and it forms the basis of this report. The meeting and report provide a platform for presenting the trauma system management during the war, highlighting the strengths of the system as well as its challenges and lessons learned. The participants also brainstormed and discussed possibilities for future improvements.

Abstract Major depressive disorder (MDD) is the leading cause of disability worldwide, yet treatment selection still proceeds via “trial and error”. Given the varied presentation of MDD and heterogeneity of treatment response, the use of machine learning to understand complex, non-linear relationships in data may be key for treatment personalization. Well-organized, structured data from clinical trials with standardized outcome measures is useful for training machine learning models; however, combining data across trials poses numerous challenges. There is also persistent concern that machine learning models can propagate harmful biases. We have created a methodology for organizing and preprocessing depression clinical trial data such that transformed variables harmonized across disparate datasets can be used as input for feature selection. Using Bayesian optimization, we identified an optimal multi-layer dense neural network that used data from 21 clinical and sociodemographic features as input in order to perform differential treatment benefit prediction. With this combined dataset of 5032 individuals and 6 drugs, we created a differential treatment benefit prediction model. Our model generalized well to the held-out test set and produced similar accuracy metrics in the test and validation set with an AUC of 0.7 when predicting binary remission. To address the potential for bias propagation, we used a bias testing performance metric to evaluate the model for harmful biases related to ethnicity, age, or sex. We present a full pipeline from data preprocessing to model validation that was employed to create the first differential treatment benefit prediction model for MDD containing 6 treatment options.

WeedCube dataset consists of hyperspectral images of three crops (canola, soybean, and sugarbeet) and four invasive weeds species (kochia, common waterhemp, redroot pigweed, and common ragweed). Plants were grown in two separate greenhouses and plant canopies were captured from a top-down camera angle. A push-broom hyperspectral sensor in the visible near infrared region of 400–1000 nm was used for data collection. The dataset includes 160 calibrated images. The number of images can be further increased by selection of smaller region of interests (ROIs). Dataset is supplemented by Jupyter Notebook scripts that help in data augmentation, spectral pre-processing, ROI selection for points and images, and data visualization. The primary purpose of this dataset is to support weed classification or identification studies by enhancing existing training datasets and validating the generalization capabilities of existing models. Owing to the three-dimensional (3D) nature of hyperspectral images, this dataset can also be utilized by researchers and educators across various domains for the development and testing of deep learning algorithms, the creation of automated data processing pipelines effective for 3D data, the development of tools for 3D data visualization, the creation of innovative solutions for data compression, and addressing system memory issues associated with high-dimensional data.

Pigmented villonodular synovitis is an uncommon benign neoplastic proliferation associated with the synovium, bursa, or tendon sheaths; most commonly occurring in the third to fourth decade of life. It is rare in children and may be painful or painless. Magnetic resonance imaging is the diagnostic study of choice. In this report, the radiologic, ultrasound, and magnetic resonance imaging findings of pigmented villonodular synovitis of the flexor hallucis longus in a 12-year-old girl are discussed. We briefly review the surgical findings as well. To our knowledge, this is the first case report that simultaneously synthesizes the imaging findings of 3 diagnostic imaging modalities for optimal visualization and is the youngest reported case of pigmented villonodular synovitis of the flexor hallucis longus tendon.

Bipolar latissimus dorsi transfer has been considered a viable option for the restoration of elbow flexion in patients with large traumatic defects of the anterior arm compartment. Advantages of bipolar transfer of the latissimus include stabilization of the anterior shoulder joint in addition to recreating the biceps for a direct line of pull in restoring elbow flexion with minimal donor site morbidity. Previous literature in bipolar latissimus transfer has demonstrated good outcomes in elbow flexion against gravity, range of motion, and patient satisfaction. We present a step-by-step demonstration of a bipolar pedicled latissimus dorsi transfer for restoration of elbow function and soft-tissue coverage for large traumatic defects to the anterior compartment of the arm.

BackgroundThe COVID-19 pandemic led to several surges in the mass hospitalization rate. Extreme increases in hospital admissions without adequate medical resources may increase mortality. No study has addressed the impact of daily census of ventilated patients on mortality in the context of the pandemic in a nationwide setting. ObjectiveThis study aimed to determine whether daily census of ventilated patients affected COVID-19 mortality rates nationwide in Israel. MethodsWe conducted a cohort study using nationwide, public-domain, population-based COVID-19 data of hospitalized patients from an Israeli database from March 11, 2020, until February 11, 2021. We included all COVID-19 hospital admissions, classified as mild to severe per the Centers for Diseases Control and Prevention classification irrespective of whether they were mechanically ventilated. Outcome measures were daily death rates and death rates expressed as a percentage of ventilated patients. ResultsDuring the study period (338 days from March 11, 2020, to February 11, 2021), 715,743 patients contracted and were clinically confirmed as having COVID-19. Among them, 5577 (0.78%) patients died. In total, 3398 patients were ventilated because of severe COVID-19. Daily mortality correlated with daily census of ventilated patients (R2=0.828, P

Background: Microcytic anemia due to iron deficiency is the most common type of anemia in children in Israel and many parts of the world, and has been shown to have negative consequences for the cognitive performance. We aimed to examine the association between microcytic anemia at age 9–18 months and ADHD during childhood. Methods: This case-control study included healthy children aged 6–18 years at data collection (April 2020), insured by Clalit-Health-Services, and aged 9–18 months between June 2004 and December 2013, when a blood-count was performed. The study group included children diagnosed with ADHD based on the medical documentation of at least two consecutive stimulant prescriptions. A control group without any stimulant prescriptions was matched in a ratio of 1–3:1, by year of birth, sex and cultural background. Any microcytic anemia was defined as Hb

Objective To estimate the cost-effectiveness of craniotomy, compared with decompressive craniectomy (DC) in UK patients undergoing evacuation of acute subdural haematoma (ASDH).Design Economic evaluation undertaken using health resource use and outcome data from the 12-month multicentre, pragmatic, parallel-group, randomised, Randomised Evaluation of Surgery with Craniectomy for Patients Undergoing Evacuation-ASDH trial.Setting UK secondary care.Participants 248 UK patients undergoing surgery for traumatic ASDH were randomised to craniotomy (N=126) or DC (N=122).Interventions Surgical evacuation via craniotomy (bone flap replaced) or DC (bone flap left out with a view to replace later: cranioplasty surgery).Main outcome measures In the base-case analysis, costs were estimated from a National Health Service and Personal Social Services perspective. Outcomes were assessed via the quality-adjusted life-years (QALY) derived from the EuroQoL 5-Dimension 5-Level questionnaire (cost-utility analysis) and the Extended Glasgow Outcome Scale (GOSE) (cost-effectiveness analysis). Multiple imputation and regression analyses were conducted to estimate the mean incremental cost and effect of craniotomy compared with DC. The most cost-effective option was selected, irrespective of the level of statistical significance as is argued by economists.Results In the cost-utility analysis, the mean incremental cost of craniotomy compared with DC was estimated to be −£5520 (95% CI −£18 060 to £7020) with a mean QALY gain of 0.093 (95% CI 0.029 to 0.156). In the cost-effectiveness analysis, the mean incremental cost was estimated to be −£4536 (95% CI −£17 374 to £8301) with an OR of 1.682 (95% CI 0.995 to 2.842) for a favourable outcome on the GOSE.Conclusions In a UK population with traumatic ASDH, craniotomy was estimated to be cost-effective compared with DC: craniotomy was estimated to have a lower mean cost, higher mean QALY gain and higher probability of a more favourable outcome on the GOSE (though not all estimated differences between the two approaches were statistically significant).Ethics Ethical approval for the trial was obtained from the North West—Haydock Research Ethics Committee in the UK on 17 July 2014 (14/NW/1076).Trial registration number ISRCTN87370545.

Surveys for the tricolored blackbird (Agelaius tricolor), a California-listed threatened species, are needed to provide essential information about its status and distribution to support conservation efforts. Surveying for the species, however, poses challenges because of its colonial nesting habits, large flock sizes, and frequent interannual movements among colony sites. We present standardized approaches for tricolored blackbird surveys to accommodate a variety of goals, including determining potential for occurrence, detecting colonies, estimating population numbers, and assessing nesting success. Pre-survey research should assess overlap with the species’ geographic range and include database searches for recent and historical occurrences. Site surveys should assess availability of sufficient suitable foraging habitat (grasslands, irrigated pasture, shallow wetlands, agricultural fields) within 5 km of potential nesting habitat and nearby drinking water. Confirming presence or absence of nesting at a historical colony site, or at an area within the range of the tricolored blackbird that provides suitable nesting and foraging habitat, requires at least three surveys conducted about three weeks apart during the breeding season, generally April, May, and June in most of the species’ range. Colonies can be located by searching for foraging flocks and following them to colonies and by checking for nesting activity at suitable nesting substrates, especially those used in the past. Surveyors can estimate numbers from counts of foraging flocks departing and arriving at colonies, average density and area occupied by the nesting colony, and post-nesting density transects. Colony nesting success (i.e., whether a colony successfully fledged some young), is easily determined and is often the only feasible metric to attain on reproduction. Determining reproductive success (the average number of young fledged per occupied nest) may be feasible under ideal and intensive surveys but is impractical at many colonies due to accessibility limitations.

Objectives: Elderly patients with hematologic malignancies face the highest risk of severe COVID-19 outcomes. The infection's impact on different age groups remains unstudied in detail. Methods: We analyzed elderly patients (age groups: 65-70, 71-75, 76-80, and >80 years old) with hematologic malignancies included in the EPICOVIDEHA registry between January 2020 and July 2022. Univariable and multivariable Cox regression models were conducted to identify factors influencing death in COVID-19 patients with hematological malignancy. Results: The study included data from 3,603 elderly patients (aged 65 or older) with hematological malignancy, with a majority being male (58.1%) and a significant proportion having comorbidities. The patients were divided into four age groups, and the analysis assessed COVID-19 outcomes, vaccination status, and other variables in relation to age and pandemic waves. The 90-day survival rate for patients with COVID-19 was 71.2%, with significant differences between groups. The pandemic waves had varying impacts, with the first wave affecting patients over 80 years old, the second being more severe in 65-70, and the third being the least severe in all age groups. Factors contributing to 90-day mortality included age, comorbidities, lymphopenia, active malignancy, acute leukemia, less than three vaccine doses, severe COVID-19, and using only corticosteroids as treatment. Conclusion: These data underscore the heterogeneity of elderly hematological patients, highlight the different impacts of COVID-19 waves and the pivotal importance of vaccination, and may help in planning future healthcare efforts.

Healthcare Information Exchange (HIE) is becoming a fundamental operation in current healthcare systems. In such systems, electronic health records (EHRs) are digitally stored inside each medical centers and, sometimes, are required to be shared between various healthcare facilities (HCFs). Indeed, sharing patient information is crucial and might be vulnerable to power outages, data misuse, privacy or security violations, and an audit trail. Hence, researchers have focused recently on cutting-edge technologies to develop secure HIE systems and ensure data privacy during transactions. Among such technologies, blockchain and artificial intelligence (AI) occupy a vital role in researchers’ focuses and efforts to detect risky transactions in HIE systems, thus enhancing their security and privacy. While the blockchain allows HCFs to link to each other without requiring a central authority, AI models offer an additional security layer when sharing patient data between HCFs. This paper presents a survey about HIE systems, and the aim is two-fold: we first present the architecture of HIE systems along with their challenges; then, we categorize and classify the current state-the-art-techniques that show the potential of using blockchain and AI technologies in such systems.

Summary: Background: The COVID-19 pandemic heightened risks for individuals with hematological malignancies due to compromised immune systems, leading to more severe outcomes and increased mortality. While interventions like vaccines, targeted antivirals, and monoclonal antibodies have been effective for the general population, their benefits for these patients may not be as pronounced. Methods: The EPICOVIDEHA registry (National Clinical Trials Identifier, NCT04733729) gathers COVID-19 data from hematological malignancy patients since the pandemic's start worldwide. It spans various global locations, allowing comprehensive analysis over the first three years (2020–2022). Findings: The EPICOVIDEHA registry collected data from January 2020 to December 2022, involving 8767 COVID-19 cases in hematological malignancy patients from 152 centers across 41 countries, with 42% being female. Over this period, there was a significant reduction in critical infections and an overall decrease in mortality from 29% to 4%. However, hospitalization, particularly in the ICU, remained associated with higher mortality rates. Factors contributing to increased mortality included age, multiple comorbidities, active malignancy at COVID-19 onset, pulmonary symptoms, and hospitalization. On the positive side, vaccination with one to two doses or three or more doses, as well as encountering COVID-19 in 2022, were associated with improved survival. Interpretation: Patients with hematological malignancies still face elevated risks, despite reductions in critical infections and overall mortality rates over time. Hospitalization, especially in ICUs, remains a significant concern. The study underscores the importance of vaccination and the timing of COVID-19 exposure in 2022 for enhanced survival in this patient group. Ongoing monitoring and targeted interventions are essential to support this vulnerable population, emphasizing the critical role of timely diagnosis and prompt treatment in preventing severe COVID-19 cases. Funding: Not applicable.

This work presents a Monte Carlo Potts grain growth model in which the grain boundary (GB) energies depend on the GB inclination. The inclination is calculated using a linear smoothing approach developed by the authors. In bicrystal simulations with a shrinking grain, the grain changes shape to prefer low energy GB inclinations. However, in polycrystal simulations the preferred inclinations depend on the approach used to assign the triple junction (TJ) energies. Approaches that produce unimodal TJ energy distributions result in the expected behavior of preferring low energy GB inclinations. However, approaches that produce bimodal TJ energy distributions result in medium energy or even high energy inclinations being preferred. Overall, this study underscores the importance of TJs in anisotropic grain growth.

Abstract: Introduction: Using the job demands control support (JDCS) model, we examined the impact of introducing information and communication technologies (ICTs) on the working conditions of civil servants in a major public institution in Gabon. We hypothesized that perceived ICT usability moderates the temporal beneficial/detrimental (dis)continuity of job demands and job control before and after their introduction. For exploratory and complementary purposes, we also investigated changes in social support. Methods: To this end, we conducted a quantitative two-wave longitudinal study of 162 civil servants, with measures before and after the introduction of ICTs for one subsample, and compared them to another subsample for which ICTs had not already been introduced (control group). Results: At baseline (T1), the two subsamples were similar regarding JDCS variables; at follow-up (T2), civil servants without ICTs reported, on average, a slight increase in job demand and a strong decrease in job control, whereas civil servants with newly introduced ICTs reported unchanged levels of job demand and job control. Similar observations, albeit of a lesser magnitude, occurred for social support. The analyses revealed that perceived usability marginally moderated the temporal stability of job control, whereas high job control at T1 favored similarly high job control at T2 only when ICTs were perceived as very highly usable. Discussion and Conclusion: The discussion addresses the possible existence of a downward social comparison effect for civil servants without ICTs, suggests the likely role of coping strategies to explain the mixed results, examines the study contributions and limitations, and delineates practical implications.

The frequency of co-infections with bacterial or fungal pathogens has constantly increased among critically ill patients with coronavirus disease 2019 (COVID-19) during the pandemic. Candidemia was the most frequently reported invasive fungal co-infection. The onset of candidemia in COVID-19 patients was often delayed compared to non-COVID-19 patients. Additionally, Candida invasive infections in COVID-19 patients were more often linked to invasive procedures (e.g., invasive mechanical ventilation or renal replacement therapy) during the intensive care stay and the severity of illness rather than more “classic” risk factors present in patients without COVID-19 (e.g., underlying diseases and prior hospitalization). Moreover, apart from the increased incidence of candidemia during the pandemic, a worrying rise in fluconazole-resistant strains was reported, including a rise in the multidrug-resistant Candida auris. Regarding outcomes, the development of invasive Candida co-infection had a negative impact, increasing morbidity and mortality compared to non-co-infected COVID-19 patients. In this narrative review, we present and critically discuss information on the diagnosis and management of invasive fungal infections caused by Candida spp. in critically ill COVID-19 patients.

Abstract Psoriasis is a chronic, systemic inflammatory condition primarily affecting skin. While the role of the immune compartment (e.g., T cells) is well established, the changes in the skin compartment are more poorly understood. Using longitudinal skin biopsies (n = 375) from the “Psoriasis Treatment with Abatacept and Ustekinumab: A Study of Efficacy”(PAUSE) clinical trial (n = 101), we report 953 expression quantitative trait loci (eQTLs). Of those, 116 eQTLs have effect sizes that were modulated by local skin inflammation (eQTL interactions). By examining these eQTL genes (eGenes), we find that most are expressed in the skin tissue compartment, and a subset overlap with the NRF2 pathway. Indeed, the strongest eQTL interaction signal – rs1491377616-LCE3C – links a psoriasis risk locus with a gene specifically expressed in the epidermis. This eQTL study highlights the potential to use biospecimens from clinical trials to discover in vivo eQTL interactions with therapeutically relevant environmental variables.

Abstract Aims This scoping review examined the factors affecting access to dialysis for patients with end‐stage kidney disease in Sub‐Saharan Africa. Design Scoping review. Methods The scoping review is conducted following the Joanna Briggs Institute methodology for scoping reviews and modelled by Preferred Reporting Items for Systematic Reviews and Meta‐analyses extension for scoping review. Results A descriptive content analysis of 30 included articles revealed three main findings affecting access and use of dialysis: Health system–related factors, health provider–related factors and patient factors. Patient or Public Contribution Equity in renal replacement therapy access and use will require concerted advocacy for good public policy, healthcare delivery, workforce capacity and education.

This study examines the psychological repercussions of the COVID-19 pandemic on a medical team in an Israeli general hospital. The research explores the professional quality of life, burnout symptoms, secondary traumatic stress, and mindfulness among team members across three distinct phases of the pandemic. Analysis was conducted for different subgroups based on job roles and seniority, allowing for an evaluation of the phase-specific effects on ProQOL (Professional Quality of Life) and mindfulness. Results align with established crisis trajectories: honeymoon/heroic phases, inventory, disillusionment, and recovery. As a result of the prolonged pandemic and the need to change shifts and recruit staff to deal with the affected patients, it is an accumulative study not following the same person but the same ward and the same hospital. The findings suggest a negative correlation between compassion satisfaction and burnout, as well as between mindfulness and burnout/secondary traumatic stress. Unlike most studies, healthcare workers (HCWs) were less affected than doctors in all measures. This study highlights doctors’ vulnerability and underscores hospital management’s key role in promoting effective support for professional quality of life. This is especially important for male doctors facing distinct well-being challenges.

Abstract Background In order to reduce patient no-show, the Israeli government is promoting legislation that will allow Health Plans to require a co-payment from patients when reserving an appointment. It is hoped that this will create an incentive for patients to cancel in advance rather than simply not show up. The goal of this policy is to improve patient access to medical care and ensure that healthcare resources are utilized effectively. We explore this phenomenon to support evidence-based decision making on this issue, and to determine whether the proposed legislation is aligned with the findings of previous studies. Main body No-show rates vary across countries and healthcare services, with several strategies in place to mitigate the phenomenon. There are three key stakeholders involved: (1) patients, (2) medical staff, and (3) insurers/managed care organizations, each of which is affected differently by no-shows and faces a different set of incentives. The decision whether to impose financial penalties for no-shows should take a number of considerations into account, such as the fine amount, service type, the establishment of an effective fine collection system, the patient’s socioeconomic status, and the potential for exacerbating disparities in healthcare access. The limited research on the impact of fines on no-show rates has produced mixed results. Further investigation is necessary to understand the influence of fine amounts on no-show rates across various healthcare services. Additionally, it is important to evaluate the implications of this proposed legislation on patient behavior, access to healthcare, and potential disparities in access. Conclusion It is anticipated that the proposed legislation will have minimal impact on attendance rates. To achieve meaningful change, efforts should focus on enhancing medical service availability and improving the ease with which appointments can be cancelled or alternatively substantial fines should be imposed. Further research is imperative for determining the most effective way to address the issue of patient no-show and to enhance healthcare system efficiency.

Drug-induced tremor is a common side effect of lithium with an occurrence of approximately 25% of patients. Cessation of the offending drug can be difficult, and many medical treatments for drug-induced tremor are ineffective. Deep brain stimulation (DBS) has been shown in a limited number of case reports to effectively reduce drug-induced tremor, however, which remains an invasive therapeutic option. MR-guided focused ultrasound (MRgFUS) thalamotomy is an FDA-approved non-invasive treatment for essential tremor (ET). To the best of our knowledge, MRgFUS thalamotomy has never been reported to treat drug-induced tremor. Here, we present a case of a left-handed 55-year-old man with a progressive, medically refractory lithium-induced tremor of the bilateral upper extremities. The patient underwent MRgFUS thalamotomy targeting the right ventral intermediate nucleus (VIM) of the thalamus to treat the left hand. There was almost complete resolution of his left-hand tremor immediately following MRgFUS. There were no side effects. The patient continues to show excellent tremor control at 90-day follow-up and remains free from side effects. This case demonstrates MRgFUS thalamotomy as a possible novel treatment option to treat drug-induced tremor.

Evaluating archaeobotanical data from over 3.9 million seeds and 124,300 charcoal fragments across 330 archaeological site phases in Southwest Asia, we reconstruct the history of olive and grape cultivation spanning a period of 6,000 years. Combining charcoal and seed data enables investigation into both the production and consumption of olive and grape. The earliest indication for olive and grape cultivation appears in the southern Levant around ca. 5000 BC and 4th millennium BC respectively, although cultivation may have been practiced prior to these dates. Olive and grape cultivation in Southwest Asia was regionally concentrated within the Levant until 600 BC, although there were periodic pushes to the East. Several indications for climate influencing the history of olive and grape cultivation were found, as well as a correlation between periods of high population density and high proportions of olive and grape remains in archaeological sites. While temporal uncertainty prevents a detailed understanding of the causal mechanisms behind these correlations, we suggest that long distance trade in olives, grapes and their associated products was integral to the economic, social, and demographic trajectories of the region.

This paper presents the use of a Gaussian neighborhood mode filter for predicting grain growth in a manner similar to the solutions obtained by a Monte Carlo Potts model. This flexible grain growth model can quickly utilize modern, computationally optimized data science strategies on graphics processing units to simulate grain growth up to 100 times faster than the state-of-the-art, publicly available Monte Carlo Potts model. We show that, given the correct neighborhood, the mode filter can replicate normal grain growth in two or three dimensions. In addition, the paper briefly demonstrates the ability to model limited anisotropic in grain boundary energy and mobility. Anisotropic grain boundary energy is modeled by defining a weighted mode filter operation. Anisotropic grain boundary mobility is modeled by scaling and orienting the Gaussian neighborhood in a particular direction.

BackgroundTuberculosis (TB) and COVID-19 are the two leading causes of infectious disease mortality worldwide, and their overlap is likely frequent and inevitable. Previous research has shown increased mortality in TB/COVID-coinfected individuals, and emerging evidence suggests that COVID-19 may increase susceptibility to TB. However, the immunological mechanisms underlying these interactions remain unclear. In this study, we aimed to elucidate the impact of prior or concurrent COVID-19 infection on immune profiles of TB patients and those with other respiratory diseases (ORD).MethodsSerum and nasopharyngeal samples were collected from 161 Gambian adolescents and adults with either TB or an ORD. Concurrent COVID-19 infection was determined by PCR, while prior COVID-19 was defined by antibody seropositivity. Multiplex cytokine immunoassays were used to quantify 27 cytokines and chemokines in patient serum samples at baseline, and throughout treatment in TB patients.ResultsStrikingly, TB and ORD patients with prior COVID-19 infection were found to have significantly reduced expression of several cytokines, including IL-1β, TNF-α and IL-7, compared to those without (p0.035).ConclusionsOur findings demonstrate that COVID-19 infection alters the subsequent response to TB and ORDs, potentially contributing to pathogenesis. Further work is necessary to determine whether COVID-19 infection accelerates TB disease progression, though our results experimentally support this hypothesis.

Background: The objective of this paper is to discuss perceived clinical utility and impact on physician-patient relationship of a novel, artificial-intelligence (AI) enabled clinical decision support system (CDSS) for use in treating adults with major depression. Methods: A single arm, naturalistic follow-up study aimed at assessing the acceptability and useability of the software. Patients had a baseline appointment, followed by a minimum of two appointments with the CDSS. Study exit questionnaires and interviews were conducted to assess perceived clinical utility, impact on patient-physician relationship, and understanding and trust. 7 physicians and 17 patients, of which 14 completed, consented to participate. Results: 86 % of physicians (6/7) felt the information provided by the CDSS provided more comprehensive understanding of patient situations. 71 % (5/7) felt the information was helpful. 86 % of physicians (6/7) reported the AI/predictive model was useful when deciding treatment. 62 % of patients (8/13) reported improved care due to the tool, and 46 %(6/13) reported a significantly or somewhat improved physician-patient relationship 54 % reported no change. 71 % of physicians (5/7) and 62 % of patients (8/13) rated trusting the tool. Limitations: Small sample size and treatment changes prior to CDSS introduction limits ability to verify impact on outcomes. Conclusions: Qualitative results from 12 patient exit interviews are analyzed and presented. Findings suggest physicians perceived the tool as useful in conducting appointments and used it while deciding treatment. Physicians and patients generally found the tool trustworthy, and it may have positive effects on physician-patient relationships. (Study identifier: NCT04061642).

Cavum septum pellucidum (CSP) is a normal anatomical variant that is largely asymptomatic, though in rare cases can cause headache, developmental delay, and even acute hydrocephalus. There exist many surgical treatments in these symptomatic cases, though no one treatment has been deemed superior. In this report, we describe bilateral fenestration of the septum pellucidum with flexible endoscopy via a right frontal approach in a patient with exercise-induced headaches.The patient is a 17-year-old male who experienced headaches for six years that were progressively worsening with exercise and bearing down with associated emesis. Imaging evaluation demonstrated a CSP cyst. The decision was made to treat via bilateral septostomy with flexible endoscopy. He progressed appropriately and his headaches have now resolved.There is debate regarding if unilateral vs bilateral septostomy, placement of CSF diversion device, or performing endoscopic third ventriculostomy is superior. In this report, we present a case where bilateral septostomy in a patient with episodic headache yields complete resolution of symptoms.

Abstract Over a period of about 9 months, we conducted three serosurveys in the two major cities of Cameroon to determine the prevalence of SARS-COV-2 antibodies and to identify factors associated with seropositivity in each survey. We conducted three independent cross-sectional serosurveys of adult blood donors at the Central Hospital in Yaoundé (CHY), the Jamot Hospital in Yaoundé (JHY) and at the Laquintinie Hospital in Douala (LHD) who consented in writing to participate. Before blood sampling, a short questionnaire was administered to participants to collect their sociodemographic and clinical characteristics. We included a total of 743, 1202, and 1501 participants in the first (January 25–February 15, 2021), second (May 03–28, 2021), and third (November 29–December 31, 2021) surveys, respectively. The adjusted seroprevalence increased from 66.3% (95% CrI 61.1–71.3) in the first survey to 87.2% (95% CrI 84.0–90.0) in the second survey, and 98.4% (95% CrI 96.8–99.7) in the third survey. In the first survey, study site, participant occupation, and comorbid conditions were associated with SARS-CoV-2 seropositivity, whereas only study site remained associated in the second survey. None of the factors studied was significantly associated with seropositivity in the third survey. Together, the data suggest a rapid initial spread of SARS-CoV-2 in the study population, independent of the sociodemographic parameters assessed.

The activated carbon based on waste tea (WT-AC) was prepared using sulfuric acid as an activating agent at different concentrations (5%, 10%, 20%, and 30%). Suitable characteristics as adsorbent have revealed concentration at 30% of waste tea activated carbon (WT-AC4) yield better adsorption, whereby other parameters including bulk density, ash content, volatile matter content, and moisture content obtained are 0.301 g mL−1, 3.40%, 26.76%, and 4.34%, sequentially. Overall, WT-AC samples have shown a well-developed porous structure and are declared an amorphous region. Comparatively, the results of adsorption studies reveal iodine value of WT-AC4 is 593.41 mg g−1 and commercial activated carbon is 738.62 mg g−1, while in 100 mg L−1 of methylene blue, the percentage of removal along with adsorption capacity yield the value of 89.2% (1.78 mg g−1) and 97.6 (1.98 mg g−1), respectively. In 0.5 mg L−1 and 1.0 mg L−1 of cadmium ions, WT-AC4 achieved 100% removal in both concentrations compared to commercially activated carbon with only 88.9%, then dropped to 46.2%. Significantly, the activated carbon from waste tea at a concentration of 30% sulfuric acid could be used as a low-cost adsorbent to remove organic and inorganic pollutants.

It is widely believed that (1) children lose months of reading and math skills over summer vacation and that (2) inequality in skills grows much faster during summer than during school. Concerns have been raised about the replicability of evidence for these claims, but an impression may exist that nonreplicable findings are limited to older studies. After reviewing the 100-year history of nonreplicable results on summer learning, we compared three recent data sources (ECLS- K:2011, NWEA, and Renaissance) that tracked U.S. elementary students' skills through school years and summers in the 2010s. Most patterns did not generalize beyond a single test. Summer losses looked substantial on some tests but not on others. Score gaps—between schools and students of different income levels, ethnicities, and genders—grew on some tests but not on others. The total variance of scores grew on some tests but not on others. On tests where gaps and variance grew, they did not consistently grow faster during summer than during school. Future research should demonstrate that a summer learning pattern replicates before drawing broad conclusions about learning or inequality.

Commercial tests are often employed in clinical microbiology laboratories for antifungal susceptibility testing of filamentous fungi. Method-dependent epidemiological cutoff values (ECVs) have been defined in order to detect non-wild-type (NWT) isolates harboring resistance mechanisms. We reviewed the literature in order to find studies where commercial methods were used to evaluate for in vitro susceptibility of filamentous fungi and assess their ability to detect NWT isolates according to the available ECVs. Data were found for the gradient concentration strips Etest and MIC Test Strips (MTS), broth microdilution Sensititre YeastOne (SYO), Micronaut-AM and the agar dilution VIPcheck assays. Applying itraconazole, voriconazole and posaconazole Etest ECVs for A. fumigatus, Etest was able to detect 90.3% (84/93), 61.2% (90/147) and 86% (31/36) of isolates with known cyp51A mutations, respectively. Moreover, Etest also was able to detect 3/3 fks mutants using caspofungin ECVs and 2/3 micafungin mutant isolates. Applying the voriconazole and posaconazole SYO ECVs, 57.7% (67/116) and 100% (47/47) of mutants with known cyp51A substitutions were classified as NWT, respectively. VIPcheck detected 90.3% (159/176), 80.1% (141/176) and 66% (141/176)of mutants via itraconazole, voriconazole and posaconazole, respectively, whereas Micronaut-AM detected 88% (22/25). In conclusion, Etest posaconazole and itraconazole, as well as micafungin and caspofungin ECVs, detected A. fumigatus mutants. On the other hand, while the posaconazole SYO ECV was able to detect cyp51A mutants, similar data were not observed with the SYO voriconazole ECV.

Hodgkin lymphoma (HL) treatment increases the risk of lung cancer. Most HL survivors are not eligible for lung cancer screening (LCS) programmes developed for the general population, and the utility of these programmes has not been tested in HL survivors. We ran a LCS pilot in HL survivors to describe screening uptake, participant characteristics, impact of a decision aid and screen findings. HL survivors treated ≥5 years ago with mustine/procarbazine and/or thoracic radiation, were identified from a follow-up database and invited to participate. Participants underwent a low-dose CT (LDCT) reported using protocols validated for the general population. Two hundred and eighteen individuals were invited, 123 were eligible, 102 were screened (58% response rate): 58% female, median age 52 years, median 22 years since HL treatment. 91.4% were deemed to have made an informed decision; participation was not influenced by age, gender, years since treatment or deprivation. Only 3/35 ever-smokers met criteria for LCS through the programme aimed at the general population. Baseline LDCT results were: 90 (88.2%) negative, 10 (9.8%) indeterminate, 2 (2.0%) positive. Two 3-month surveillance scans were positive. Of 4 positive scans, 2 patients were diagnosed with small-cell lung cancer; 1 underwent curative surgery. Coronary artery calcification was detected in 36.3%, and clinically significant incidental findings in 2.9%. LDCT protocols validated in ever-smokers can detect asymptomatic early-stage lung cancers in HL survivors. This finding, together with screening uptake and low false positive rates, supports further research to implement LCS for HL survivors.

We generalize the familiar notion of periodicity in sequences to a new kind of pseudoperiodicity, and we prove some basic results about it. We revisit the results of a 2012 paper of Shevelev and reprove his results in a simpler and more unified manner, and provide a complete answer to one of his previously unresolved questions. We consider finding words with specific pseudoperiod and having the smallest possible critical exponent. Finally, we consider the problem of determining whether a finite word is pseudoperiodic of a given size, and show that it is NP-complete.

BackgroundDeep brain stimulation (DBS) is the primary surgical intervention for Parkinson’s disease (PD) patients with insufficient response to medication, significantly improving motor symptoms and quality of life. Despite FDA approval for over two decades, access to this therapy remains limited. This systematic review aims to evaluate the influence of gender, race/ethnicity, socioeconomic status, and age on health disparities associated with DBS for PD, providing an overview of current research in this field.MethodsA systematic literature search was conducted in PubMed/MEDLINE, Embase, Web of Science and Cochrane databases from 1960 to September 12th, 2023, following Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Studies that examine the disparities in accessing DBS among patients with PD were included, comparing different demographic factors. Findings were synthesized and presented narratively to identify and understand DBS disparities.ResultsAfter screening for relevance, 25 studies published between 1960 and 2023 were included, with 16 studies meeting full-text review criteria. While reviewing the references of the 16 articles, two additional studies were included, bringing the total number of included studies to 18. Most studies originated from the United States (44%). The identified studies were categorized as identifying disparities, understanding disparities, or reducing disparities. The majority focused on identifying disparities (72%), while fewer studies delved into understanding the underlying factors (28%). No studies evaluated strategies for reducing disparities. The findings indicate that elderly, female, and Black people, as well as those from low socioeconomic backgrounds and developing countries face greater obstacles in accessing DBS for PD.ConclusionThis study highlights factors contributing to disparities in DBS utilization for PD, including race, gender, and socioeconomic status. Public health policymakers, practitioners, and clinicians should recognize these inequalities and work toward reducing disparities, particularly among vulnerable populations.

Pineapple is widely grown in tropical countries, and the fruits are well-known for their unique flavor. The ideal stage of maturity, optimum storage temperature, congenial relative humidity, and adequate type of packaging are critical factors that determine the shelf life and quality of pineapple fruits. Therefore, this investigation was carried out to determine the effect of maturity stage and shrink-wrap packaging, along with ambient and low-temperature storage in order to determine the impact of these factors on extending the shelf life and quality of pineapple fruits. The results revealed that fruits with 75% yellow tubercles at the harvesting stored under ambient temperature had a shelf life of just 7 days compared to the fruits having 25% yellow tubercles subjected to shrink-wrap packaging, followed by low-temperature storage, which had a shelf life of 49 days. The findings of this study conclusively proved that harvesting pineapple fruits with 25% of yellow tubercles, followed by shrink-wrap packaging in 25 μ polyolefin film and subsequent storage in a cool chamber at 12–13 °C and 85% relative humidity can prolong the shelf life and will also maintain the quality of pineapple fruits.

ObjectivesThere is limited data regarding the prevalence of suicidal risk among physicians during COVID-19, and the risk factors relating to it. Dominant risk factors for suicide among physicians are depression and burnout. Maladaptive perfectionism may also serve as a profound risk factor for suicidality among physicians and may aggravate symptoms of distress under the challenges of COVID-19. This study aims to evaluate current suicidal risk, suicidal ideation, depression, and burnout before and during COVID-19 among physicians in Israel, and to identify the best sets of correlates between perfectionism and burnout, depression and suicidal ideation, during these time periods.MethodsA sample of 246 Israeli physicians (160 before COVID-19 and 86 during COVID-19) completed online surveys assessing lifetime suicidal risk, suicidal ideation during the last year and current suicidal ideation, depression, burnout symptoms and maladaptive perfectionism.ResultsMore than one-fifth of the sample (21.9%) reported high suicidal risk (Lifetime suicidal behaviors). More than one-fourth (27.2%) reported suicidal ideation during the last 12 months; and 13.4% reported suicidal ideation during the last 3 months. In addition, more than one-third (34.6%) exhibited moderate–severe levels of depressive symptoms and more than a half of the sample reported burnout symptoms. Maladaptive perfectionism was positively correlated with current suicidal ideation, burnout, and depression. Moderated serial mediation analysis demonstrated indirect effect of perfectionism on suicidal ideation by its impact on burnout and depression only during COVID-19. Before COVID-19, physicians were more likely to experience depressive symptoms.ConclusionPhysicians in Israel are at increased risk for depression and suicidal ideation, regardless of the COVID-19 pandemic. Maladaptive perfectionism was found to be a risk factor for burnout, depression, and suicidal ideation. During the first waves of the pandemic, physicians were less likely to experience depressive symptoms. However, among physicians who were characterized with high maladaptive perfectionism, depression served as a significant risk factor for suicidal ideation during the pandemic, which places these individuals at increased risk for suicidality. These results highlight the importance of implementing intervention programs among physicians to reduce suicidal risk and to better identify rigid perfectionism and depressive symptoms.

ABSTRACT Significant variation in minimal inhibitory concentrations (MIC) has been reported for amphotericin B (AMB) and C. auris, depending on the antifungal susceptibility testing (AFST) method. Although the Sensititre YeastOne (SYO) is widely used in routine laboratory testing, data regarding its performance for the AFST of C. auris are scarce. We tested AMB against 65 C. auris clinical isolates with the SYO and the reference methodology by the Clinical and Laboratory Standards Institute (CLSI). The essential agreement (EA, ±1 dilution) between the two methods and the categorical agreement (CA) based on the Centers for Disease Control and Prevention (CDC)’s tentative breakpoint of MIC ≥ 2 mg/L were determined. The SYO wild type upper limit value (WT-UL) was determined using the ECOFFinder. The modal (range) CLSI growth inhibitory MIC was lower than the SYO colorimetric MIC [1(0.25-1) versus 2(1-8) mg/L, respectively]). The CLSI-colorimetric SYO EA was 29% and the CA was 11% (89% major errors; MaE). MaE were reduced when the SYO WT-UL of 8 mg/L was used (0% MaE). Alternatively, the use of SYO growth inhibition endpoints of MIC-1 (75% growth inhibition) or MIC-2 (50% growth inhibition) resulted in 88% CA with 12% MaE and 97% CA with 3% MaE, respectively. In conclusion, SYO overestimated AMB resistance in C. auris isolates when colorimetric MICs, as per SYO instructions and the CDC breakpoint of 2 mg/L, were used. This can be improved either by using the method-specific WT-UL MIC of 8 mg/L for colorimetric MICs or by determining growth inhibition MIC endpoints, regardless of the color. IMPORTANCE Candida auris is an emerging and frequently multidrug-resistant fungal pathogen that accounts for life-threatening invasive infections and nosocomial outbreaks worldwide. Reliable AF is important for the choice of the optimal treatment. Commercial methods are frequently used without prior vigorous assessment. Resistance to AMB was over-reported with the commercial colorimetric method Sensititre YeastOne (SYO). SYO produced MICs that were 1 to 2 twofold dilutions higher than those of the reference CLSI method, resulting in 89% MaE. MaE were reduced using a SYO-specific colorimetric wild type upper limit MIC value of 8 mg/L (0%) or a 50% growth inhibition endpoint (3%).

Abstract Background Systemic infections caused by the black yeast-like fungus Exophiala dermatitidis are rare, but are associated with high mortality especially in immunocompromised patients. We report the first case of E. dermatitidis fungemia in a premature extremely low birth weight (ELBW) neonate who succumbed despite antifungal therapy with liposomal amphotericin (AMB) and fluconazole. A systematic review of all fungemia cases due to E. dermatitidis was also conducted aiming for a better understanding of the risk factors, treatment strategies and outcomes. Case presentation A male, ELBW premature neonate, soon after his birth, developed bradycardia, apnoea and ultimately necrotizing enterocolitis with intestinal perforation requiring surgical intervention. Meanwhile, he had also multiple risk factors for developing bloodstream infection, such as intubation, mechanical ventilation, central venous catheter (CVC), parenteral nutrition, empirical and prolonged antibiotic use. His blood cultures were positive, firstly for Acinetobacter junii and then for Klebsiella pneumoniae together with E. dermatitidis while on fluconazole prophylaxis and antibiotic empiric therapy. Despite the treatment with broad spectrum antibiotics, liposomal AMB and fluconazole, the newborn succumbed. A literature review identified another 12 E. dermatitidis bloodstream infections, mainly in patients with hematologic malignancies and solid organ transplant recipients (61%), with overall mortality 38% despite CVC removal and antifungal therapy. Conclusions Due to the rarity of E. dermatitidis infections, little is known about the characteristics of this yeast, the identification methods and the optimal therapy. Identification by common biochemical tests was problematic requiring molecular identification. Resolution of neonatal fungemia is difficult despite proper antifungal therapy especially in cases with multiple and severe risk factors like the present one. Therapeutic intervention may include CVC removal and treatment for at least 3 weeks with an azole (itraconazole or fluconazole after susceptibility testing) or AMB monotherapy but not echinocandins or AMB plus azole combination therapy.

ABSTRACT: Objective: Being a member of the dental profession is often associated with stress and high levels of burnout. Stress coping strategies may significantly help mediate burnout. The present cross-sectional study sought to examine the role of stress coping strategies on burnout, secondary traumatic stress, and compassion satisfaction amongst Israeli dentists. Methods: The study was carried out amongst Israeli dentists with the use of the following questionnaires: (1) the Professional Quality of Life Scale 5 (ProQOL), referring to burnout, compassion satisfaction, and level of secondary traumatic stress; (2) the Coping Inventory for Stressful Situations–Situation Specific Coping Inventory (CISS-SSC), referring to coping strategies (task-focused, emotion-focused, or avoidance-focused coping); and (3) demographic and professional variables (eg, specialisation, workload). Participants included 243 Israeli dentists. Univariate analyses and linear regressions were conducted to evaluate the relationships amongst coping strategies and burnout, secondary traumatic stress, and compassion satisfaction. Results: Female dentists had higher emotion-focused and avoidance coping scores than male dentists. Burnout could be explained by higher emotion-focused coping scores and lower task-focused and avoidance-focused coping. Secondary traumatic stress could be explained by higher emotion-focused scores, having fewer years of professional experience, and younger ages. Compassion satisfaction could be explained by lower emotion-focused coping as well as by higher task-focused coping and workload scores, specialisation, and gender. Conclusions: The findings suggest that emotional coping may cause dentists to be vulnerable to burnout and to secondary traumatic stress.

Summary: Background: Nirmatrelvir/ritonavir treatment decreases the hospitalisation rate in immunocompetent patients with COVID-19, but data on efficacy in patients with haematological malignancy are scarce. Here, we describe the outcome of nirmatrelvir/ritonavir treatment in a large cohort of the latter patients. Methods: This is a retrospective cohort study from the multicentre EPICOVIDEHA registry (NCT04733729) on patients with haematological malignancy, who were diagnosed with COVID-19 between January and September 2022. Patients receiving nirmatrelvir/ritonavir were compared to those who did not. A logistic regression was run to determine factors associated with nirmatrelvir/ritonavir administration in our sample. Mortality between treatment groups was assessed with Kaplan–Meier survival plots after matching all the patients with a propensity score. Additionally, a Cox regression was modelled to detect factors associated with mortality in patients receiving nirmatrelvir/ritonavir. Findings: A total of 1859 patients were analysed, 117 (6%) were treated with nirmatrelvir/ritonavir, 1742 (94%) were treated otherwise. Of 117 patients receiving nirmatrelvir/ritonavir, 80% had received ≥1 anti-SARS-CoV-2 vaccine dose before COVID-19 onset, 13% of which received a 2nd vaccine booster. 5% were admitted to ICU. Nirmatrelvir/ritonavir treatment was associated with the presence of extrapulmonary symptoms at COVID-19 onset, for example anosmia, fever, rhinitis, or sinusitis (aOR 2.509, 95%CI 1.448–4.347) and 2nd vaccine booster (aOR 3.624, 95%CI 1.619–8.109). Chronic pulmonary disease (aOR 0.261, 95%CI 0.093–0.732) and obesity (aOR 0.105, 95%CI 0.014–0.776) were not associated with nirmatrelvir/ritonavir use. After propensity score matching, day-30 mortality rate in patients treated with nirmatrelvir/ritonavir was 2%, significantly lower than in patients with SARS-CoV-2 directed treatment other than nirmatrelvir/ritonavir (11%, p = 0.036). No factor was observed explaining the mortality difference in patients after nirmatrelvir/ritonavir administration. Interpretation: Haematological malignancy patients were more likely to receive nirmatrelvir/ritonavir when reporting extrapulmonary symptoms or 2nd vaccine booster at COVID-19 onset, as opposed to chronic pulmonary disease and obesity. The mortality rate in patients treated with nirmatrelvir/ritonavir was lower than in patients with targeted drugs other than nirmatrelvir/ritonavir. Funding: EPICOVIDEHA has received funds from Optics COMMIT (COVID-19 Unmet Medical Needs and Associated Research Extension) COVID-19 RFP program by GILEAD Science, United States (Project 2020-8223).

BackgroundCerebrospinal fluid rhinorrhoea (CSFR) is a common complication following endonasal skull base surgery, a technique that is fundamental to the treatment of pituitary adenomas and many other skull base tumours. The CRANIAL study explored CSFR incidence and related risk factors, particularly skull base repair techniques, via a multicentre prospective observational study. We sought to use machine learning to leverage this complex multicentre dataset for CSFR prediction and risk factor analysis.MethodsA dataset of 865 cases - 725 transsphenoidal approach (TSA) and 140 expanded endonasal approach (EEA) - with cerebrospinal fluid rhinorrhoea as the primary outcome, was used. Relevant variables were extracted from the data, and prediction variables were divided into two categories, preoperative risk factors; and repair techniques, with 6 and 11 variables respectively. Three types of machine learning models were developed in order to predict CSFR: logistic regression (LR); decision tree (DT); and neural network (NN). Models were validated using 5-fold cross-validation, compared via their area under the curve (AUC) evaluation metric, and key prediction variables were identified using their Shapley additive explanations (SHAP) score.ResultsCSFR rates were 3.9% (28/725) for the transsphenoidal approach and 7.1% (10/140) for the expanded endonasal approach. NNs outperformed LR and DT for CSFR prediction, with a mean AUC of 0.80 (0.70-0.90) for TSA and 0.78 (0.60-0.96) for EEA, when all risk factor and intraoperative repair data were integrated into the model. The presence of intraoperative CSF leak was the most prominent risk factor for CSFR. Elevated BMI and revision surgery were also associated with CSFR for the transsphenoidal approach. CSF diversion and gasket sealing appear to be strong predictors of the absence of CSFR for both approaches.ConclusionNeural networks are effective at predicting CSFR and uncovering key CSFR predictors in patients following endonasal skull base surgery, outperforming traditional statistical methods. These models will be improved further with larger and more granular datasets, improved NN architecture, and external validation. In the future, such predictive models could be used to assist surgical decision-making and support more individualised patient counselling.

Abstract Background In 2005, Clalit Health Services (CHS), the largest health maintenance organization in Israel, initiated an intervention program aimed at reducing the prevalence rate of infantile anemia (IA). This study evaluated the progress made during the intervention (2005–2014) and its yield 5 years after it ended (2019). Methods The CHS database was retrospectively reviewed twice yearly from 2005 to 2014 for repetitive samples of children aged 9 to 18 months regarding the previous half-year interval, and a single sample in 2019. Data were collected on gender, ethnicity (Jewish/non-Jewish), socioeconomic class (SEC; low/intermediate/high), hemoglobin testing (yes/no), and hemoglobin level (if tested). Excluded were infants with documented or suspected hemoglobinopathy. Results At study initiation, the rate of performance of hemoglobin testing was 54.7%, and the IA prevalence rate was 7.8%. The performance rate was lower in the Jewish than the non-Jewish subpopulation. The low-SEC subpopulation had a similar hemoglobin testing rate to the high-SEC subpopulation but double the IA prevalence rate. Overall, by the end of the intervention (2014), the performance rate increased to 87.5%, and the AI prevalence rate decreased to 3.4%. In 2019, there was little change in the performance rate from the end of the intervention (88%) and the IA prevalence was further reduced to 2.7%. The non-Jewish and low-SEC subpopulations showed the most improvement which was maintained and even bettered 5 years after the intervention ended. Conclusions The 10-year IA intervention program introduced by CHS in 2005 led to a reduction in IA prevalence rate to about 3.5% in all sub-populations evaluated. By program end, the results in the weaker subpopulations, which had the highest prevalence of IA at baseline, were not inferior to those in the stronger subpopulations. We recommended to the Israel Ministry of Health to adopt the intervention countrywide, and we challenge other countries to consider similar interventions.

BackgroundThe outcome of COVID-19 in allogeneic hematopoietic stem cell transplantation (HSCT) recipients is almost uniformely considered poor. The aim of present study was to retrospectively analyse the outcome and risk factors for mortality in a large series of patients who developed COVID-19 infection after an allogeneic HSCT.MethodsThis multicenter retrospective study promoted by the European Hematology Association – Infections in Hematology Study Working Group, included 326 adult HSCT patients who had COVID-19 between January 2020 and March 2022.ResultsThe median time from HSCT to the diagnosis of COVID-19 was 268 days (IQR 86-713; range 0-185 days). COVID-19 severity was mild in 21% of the patients, severe in 39% and critical in 16% of the patients. In multivariable analysis factors associated with a higher risk of mortality were, age above 50 years, presence of 3 or more comorbidities, active hematologic disease at time of COVID-19 infection, development of COVID-19 within 12 months of HSCT, and severe/critical infections. Overall mortality rate was 21% (n=68): COVID-19 was the main or secondary cause of death in 16% of the patients (n=53).ConclusionsMortality in HSCT recipients who develop COVID-19 is high and largely dependent on age, comorbidities, active hematologic disease, timing from transplant and severity of the infection.

Adherence to prescription medications is critical for both remission from schizophrenia and control of physical comorbidities. While schizophrenia with comorbid hypothyroidism is common, there is little research on adherence to hypothyroidism treatment in this population. The current study used a retrospective, matched case-control design. The cohort included 1,252 patients diagnosed with schizophrenia according to ICD-10 and 3,756 controls matched for gender, age, socioeconomic status and ethnicity without diagnosis of schizophrenia. All data were retrieved from the electronic medical database of a large health maintenance organization. Retrieved data included demographics, thyroid functionality test results and prescribed medications. Measures of adherence to therapy were used for analyses as were data from follow-ups of patients with hypothyroidism. A diagnosis of hypothyroidism was found in 299 patients, 115 of whom were also diagnosed with schizophrenia. The 184 without schizophrenia constituted the control group. No statistically significant differences were found between the two groups regarding prescriptions for L-thyroxin and TSH levels and number of TSH tests. Adherence of patients with schizophrenia to hypothyroidism treatment was found to be as good as that of individuals without a schizophrenia diagnosis.

The presence of sugar in the gut causes induction of SGLT1, the sodium/glucose cotransporter in intestinal epithelial cells (enterocytes), and this is accompanied by stimulation of sugar absorption. Sugar sensing was suggested to involve a G-protein coupled receptor and cAMP - protein kinase A signalling, but the sugar receptor has remained unknown. We show strong expression and co-localization with SGLT1 of the β2-adrenergic receptor (β2-AR) at the enterocyte apical membrane and reveal its role in stimulating glucose uptake from the gut by the sodium/glucose-linked transporter, SGLT1. Upon heterologous expression in different reporter systems, the β2-AR responds to multiple sugars in the mM range, consistent with estimated gut sugar levels after a meal. Most adrenergic receptor antagonists inhibit sugar signaling, while some differentially inhibit epinephrine and sugar responses. However, sugars did not inhibit binding of I125-cyanopindolol, a β2-AR antagonist, to the ligand-binding site in cell-free membrane preparations. This suggests different but interdependent binding sites. Glucose uptake into everted sacs from rat intestine was stimulated by epinephrine and sugars in a β2-AR-dependent manner. STD-NMR confirmed direct physical binding of glucose to the β2-AR. Oral administration of glucose with a non-bioavailable β2-AR antagonist lowered the subsequent increase in blood glucose levels, confirming a role for enterocyte apical β2-ARs in stimulating gut glucose uptake, and suggesting enterocyte β2-AR as novel drug target in diabetic and obese patients. Future work will have to reveal how glucose sensing by enterocytes and neuroendocrine cells is connected, and whether β2-ARs mediate glucose sensing also in other tissues.