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Household food security and income play central roles in sustainable development at the global, national, and local levels. Smallholder vegetable farming systems are widely regarded as crucial contributors to enhancing household food security and income in the developing world. Comprehensive whole-farm analysis of smallholder vegetable farming systems points out greater diversity and heterogeneity driven by interactions of socioeconomic and biophysical factors such as land profiles, land use, farm assets, enterprise income, off/non-farm activities, and household structure and expenditure. However, three distinct farm typologies exist (Resource and Livelihood Constrained Off-farm Dependent/Supplemented–RLCOD farmers, Resource and Livelihood Abundant and Commercial Oriented–RLACO farmers, and Medium Resources and Livelihoods Constrained Market Oriented–MRLCMO farmers), exhibiting significant differences and variability in structural and functional factors. The production of maize, groundnuts, soybean, and bean crops remains the primary source of livelihood for all farm typologies. Similarly, vegetable production is vital for farmers’ livelihoods in all farm types, yielding more income than food needs. However, both crop and vegetable productivity and production are still low and below the national and potential target across farm typologies. Small-scale irrigation offers one alternative solution in the context of increasing climate change. Small livestock (chickens, goats, and pigs) play a significant role in the livelihood of vegetable farmers despite their low productivity. Disparities exist across farm typologies in available arable and irrigable land, available household labor, capacity to hire additional labor, farm assets, and inputs, as well as participation in off-farm and non-labor-farm activities. While vegetable production and its proportion sold and earned income emerge as critical factors affecting household food accessibility and acquisition, additional factors such as crop production, proportion of crops sold, daily food expenditure, livestock income, and TLU significantly influence household access for different farm typologies, requiring consideration to achieve food security in vegetable farming systems.

In 2017 the Uganda Police Force (UPF) issued a Strategy for Community Policing (COP). The aim of the strategy is to provide a framework for the operationalisation of COP in the country. COP in Uganda is viewed both as a philosophy and an organisational strategy aiming at promoting new partnerships between the police and the community. This research examines how the UPF applies the COP strategy in Gulu Uganda to create new partnerships between the police and the community as part of the preparation for transforming Gulu into a city in Uganda. Anchored in qualitative research conducted in 2018–2019 in Gulu municipality, we examined COP in theory and practice. We fleshed out the different COP interventions installed by the police, observed how these applications of COP are perceived by the community and local leadership, and evaluated the extent to which these applications and perceptions contribute to creating new partnerships between the police and the public, as well as how these constitute an operationalisation of the UPF strategy for COP. There are several interventions labelled as COP in Gulu, including joint patrols, Mayumba Kumi, sensitisation activities, and partnerships with NGOs. Most of these applications are ‘old wine in new bottles’ and do not qualify as attempts to create new partnerships between the police and the public. In linkage to the mode of governance exercised by the Government of Uganda, the data collected indicates that the public at large still views the police as a corrupt, unpredictable, and a violent force that serves the interests of elites rather than a public service. As long as the police is viewed in such a way, it is difficult to create meaningful partnerships between the police and the public, and subsequently it becomes difficult to successfully apply the UPF COP strategy.

This paper analyses the origin and evolution of the Aguu, a group of street youth/children labelled as a criminal gang operating in the streets of Gulu, Uganda. Based on a series of interviews, focus group discussions, participant observations, archival work and literature review, the paper traces the origin of the Aguu to the conflict in Northern Uganda, and describes the transformation of the Aguu from street youth/children linked to war and displacement to their present day labelling as ‘criminal gang’. Anchored in an analysis based on Assemblage Theory, this paper demonstrates the complexity, multiplicity and fluidity of the Aguu identity as a group whose inception and evolution, both internal and external, occurs through a process of relationship between social, political, economic and infrastructural changes linked to war, culture, aid and politics, affecting present day security discourses in Gulu, Uganda.

Introduction: The cumulative burden of coronavirus disease 2019 (COVID-19) on the United States’ healthcare system is substantial. To help mitigate this burden, novel solutions including telehealth and dedicated screening facilities have been used. However, there is limited data on the efficacy of such models and none assessing patient comfort levels with these changes in healthcare delivery. The aim of our study was to evaluate patients’ perceptions of a drive-through medical treatment system in the setting of the COVID-19 pandemic. Method: Patients presenting to a drive-through COVID-19 medical treatment facility were surveyed about their experience following their visit. An anonymous questionnaire consisting of five questions, using a five-point Likert scale was distributed via electronic tablet. Results: We obtained 827 responses over two months. Three quarters of respondents believed care received was similar to that in a traditional emergency department (ED). Overall positive impression of the drive-through was 86.6%, and 95% believed that it was more convenient. Conclusion: Overall, the drive-through medical system was perceived as more convenient than the ED and was viewed as a positive experience. While representing a dramatic change in the delivery model of medical care, if such systems can provide comparable levels of care, they may be a viable option for sustained and surge healthcare delivery.

Food security in sub-Saharan Africa is one of the major issues confronting the continent. Innovative use of fresh water, the world’s scarcest food production resource, is vital for family-run small-holder agricultural systems, which supply up to 80% of the world’s food. Agriculture employs 70% of Tanzania’s rural population and supplies 95% of the country’s food. The goal was to measure the impact of smart drip irrigation kits on smallholder farmers’ resilience and rural poverty in Tanzania. A household survey was conducted using an exploratory sequential design in four districts (Babati, Hai, Kasulu, and Kilosa) in Tanzania. A total of 383 respondents (Micro-investing (MI) farmers, n = 195; control, n = 187) were randomly selected from a pool of 3444 farmers. Partial budgeting and enterprise economic analysis were used for the calculation of gross margins, and multivariate analysis was used for poverty analysis. Gross margin analysis showed that communities using drip-irrigated vegetable farming are more profitable. Partial budgeting analysis showed that micro-irrigation increased the revenue generation for most vegetable varieties. However, multivariate analysis was unable to confirm that household poverty was markedly reduced through the adoption of this technology. Half of the MI farmers could afford an education for their children due to the extra income generated from MI. This investment strategy has the potential to improve smallholder livelihoods and resilience to climate change.

Using proprietary data from AngelList Talent, we study how startup job seekers' search and application behavior changed during the COVID-19 downturn. We find that workers shifted their searches and applications away from less-established startups and toward more-established ones, even within the same individual over time. At the firm level, this shift was not offset by an influx of new job seekers. Less-established startups experienced a relative decline in the quantity and quality of applications, ultimately affecting their hiring. Our findings uncover a flight-to-safety channel in the labor market that may amplify the procyclical nature of entrepreneurial activities. [ABSTRACT FROM AUTHOR]

Background: Anesthesiologists provide crucial anesthesiology services in the operating room and non-operating room locations. Combined with an aging and growing Israeli population, there is an increasing demand for anesthesiology services. A previous study performed in 2005 showed that most anesthesiologists are immigrant physicians with few Israeli medical school graduates. Since then, physician immigration decreased, many have retired and demand for anesthesia services has increased while insufficient numbers of new anesthesiologists were trained, leading to a shortage, limiting surgeries and other procedures in many hospitals. The present study examined the composition of the Israeli anesthesiology workforce in 2021and compared it to the 2005 workforce. Methods: A cross-sectional survey of demographic and professional information about each Israeli hospital anesthesiologists was solicited from 34 anesthesiology department chairs responsible for 36 Israeli acute care hospitals. Results: There are 1313 anesthesiologists in the 36 hospitals, resulting in a ratio of 14.2 anesthesiologists per 100,000 population. 22.6% of anesthesiologists will reach retirement age over the next ten years. The proportion of female anesthesiologists was 28.7%. While Israeli medical school graduates increased to 18.1% from 12.2% in 2005, non-Israeli citizens and non-permanent residents comprised 8.5% of the workforce. Conclusions: Despite growth in the ratio of anesthesiologists per population, a workforce shortage is expected to worsen over the next ten years due to retirements, shortened call hours, and the Yatziv reform which bans graduates of certain overseas medical schools from obtaining Israeli Medical Licenses. The current workforce has compensated for the existing shortage of anesthesiologists by enlisting non-Israeli trainees from overseas. Yet, it is crucial to maintain and enlarge the local Israeli workforce to forestall a worsening shortage. [ABSTRACT FROM AUTHOR]

ABSTRACTIn the 1990s, a new literary genre appeared – the chick lit – dealing with the stories of women in their 20s and 30s in the big city, including accessible and humoristic poetics. This article maps the characteristics of the genre as well as its origins: diary, journalistic writing, romance, glamor novel and Bildungsroman. Comparison between the Anglo-Saxon chick lit and the Israeli chick lit novel The Song of the Siren reveals that the genre is less successful in conservative societies than in liberal Western ones. However, its subversiveness is deeper and it promotes anti-stereotype themes regarding women’s singlehood (which becomes legitimate), in choosing a partner who enables the female character to be dominant and find her place and career in the public sphere.

Abstract From interpersonal interactions to international arms races, game theorists and social scientists have long studied decision-making in zero-sum situations. Yet, what happens when people can freely choose whether to enter zero-sum situations in the first place? Thirteen studies (including five pre-registered) consistently document evidence for zero-sum aversion—the desire to avoid situations that are (or are believed to be) zero-sum. Across different contexts (economic games, market entry decisions, performance reviews, negotiations, job applications), samples (online participant pool, MBA students, community sample), and designs (within- and between-participant, real and hypothetical decisions), people avoid zero-sum situations that inversely link their and others’ outcomes as well as refrain from putting others in such situations. Because people fear that zero-sum situations will be rife with conflict, they exhibit zero-sum aversion even when doing so is costly. Finally, we find that people require zero-sum situations to provide substantially higher payoffs (e.g., compensation) to overcome their zero-sum aversion. We conclude with a discussion of the implications for interpersonal and intergroup conflict.

Abstract Main In recent years, substantial advances in social neuroscience have been realized, including the generation of numerous rodent models of autism spectrum disorder. Still, it can be argued that those methods currently being used to analyze animal social behavior create a bottleneck that significantly slows down progress in this field. Indeed, the bulk of research still relies on a small number of simple behavioral paradigms, the results of which are assessed without considering behavioral dynamics. Moreover, only few variables are examined in each paradigm, thus overlooking a significant portion of the complexity that characterizes social interaction between two conspecifics, subsequently hindering our understanding of the neural mechanisms governing different aspects of social behavior. We further demonstrate these constraints by discussing the most commonly used paradigm for assessing rodent social behavior, the three-chamber test. We also point to the fact that although emotions greatly influence human social behavior, we lack reliable means for assessing the emotional state of animals during social tasks. As such, we also discuss current evidence supporting the existence of pro-social emotions and emotional cognition in animal models. We further suggest that adequate social behavior analysis requires a novel multimodal approach that employs automated and simultaneous measurements of multiple behavioral and physiological variables at high temporal resolution in socially interacting animals. We accordingly describe several computerized systems and computational tools for acquiring and analyzing such measurements. Finally, we address several behavioral and physiological variables that can be used to assess socio-emotional states in animal models and thus elucidate intricacies of social behavior so as to attain deeper insight into the brain mechanisms that mediate such behaviors. Conclusions In summary, we suggest that combining automated multimodal measurements with machine-learning algorithms will help define socio-emotional states and determine their dynamics during various types of social tasks, thus enabling a more thorough understanding of the complexity of social behavior.

Abstract Background Mediterranean (MED) diet is a rich source of polyphenols, which benefit adiposity by several mechanisms. We explored the effect of the green-MED diet, twice fortified in dietary polyphenols and lower in red/processed meat, on visceral adipose tissue (VAT). Methods In the 18-month Dietary Intervention Randomized Controlled Trial PoLyphenols UnproceSsed (DIRECT-PLUS) weight-loss trial, 294 participants were randomized to (A) healthy dietary guidelines (HDG), (B) MED, or (C) green-MED diets, all combined with physical activity. Both isocaloric MED groups consumed 28 g/day of walnuts (+ 440 mg/day polyphenols). The green-MED group further consumed green tea (3–4 cups/day) and Wolffia globosa (duckweed strain) plant green shake (100 g frozen cubes/day) (+ 800mg/day polyphenols) and reduced red meat intake. We used magnetic resonance imaging (MRI) to quantify the abdominal adipose tissues. Results Participants (age = 51 years; 88% men; body mass index = 31.2 kg/m2; 29% VAT) had an 89.8% retention rate and 79.3% completed eligible MRIs. While both MED diets reached similar moderate weight (MED: − 2.7%, green-MED: − 3.9%) and waist circumference (MED: − 4.7%, green-MED: − 5.7%) loss, the green-MED dieters doubled the VAT loss (HDG: − 4.2%, MED: − 6.0%, green-MED: − 14.1%; p < 0.05, independent of age, sex, waist circumference, or weight loss). Higher dietary consumption of green tea, walnuts, and Wolffia globosa; lower red meat intake; higher total plasma polyphenols (mainly hippuric acid), and elevated urine urolithin A polyphenol were significantly related to greater VAT loss (p < 0.05, multivariate models). Conclusions A green-MED diet, enriched with plant-based polyphenols and lower in red/processed meat, may be a potent intervention to promote visceral adiposity regression. Trial registration ClinicalTrials.gov , NCT03020186

Visualisation of spermathecal secretory cell (SSC) secretion in Drosophila reveals that the SSC produces extracellular vesicles to modulate and coordinate reproductive tract activity.

Abstract The overexpression of Epidermal Growth Factor Receptor (EGFR) and dysregulation of its downstream effector pathways are important molecular hallmarks of oral cancers. Present study investigates the chemopreventive potential of polymeric black tea polyphenols (PBPs)/thearubigins (TRs) in the hamster model of oral carcinogenesis as well as determine the effect of PBPs on EGFR and the molecular players in the EGFR pathway. In dose-dependent manner, pre and concurrent treatment with PBPs (1.5%, 5%, 10%) decreased the number and volume of macroscopic tumors as well as the number and area of microscopic lesions. Interestingly, at 10% dose of PBPs, no macroscopic or microscopic tumors were observed. We observed PBPs mediated dose-dependent decrease in oxidative DNA damage (8OHdG); inflammation (COX-2); proliferation (PCNA, Cyclin D1); expression of EGFR, and its downstream signaling kinases (pAkt, Akt, and mTOR); hypoxia (HIF1α) and angiogenesis (VEGF). There was also a PBPs mediated dose-dependent increase in apoptosis (Bax). Thus, our data clearly indicate that the observed chemopreventive potential of PBPs was due to modulation in the EGFR pathway associated with cell proliferation, hypoxia, and angiogenesis. Taken together, our results demonstrate preclinical chemopreventive efficacy of PBPs and give an insight into its mechanistic role in the chemoprevention of experimental oral cancer.

Abstract Post-COVID-19 condition refers to a range of persisting physical, neurocognitive, and neuropsychological symptoms after SARS-CoV-2 infection. The mechanism can be related to brain tissue pathology caused by virus invasion or indirectly by neuroinflammation and hypercoagulability. This randomized, sham-control, double blind trial evaluated the effect of hyperbaric oxygen therapy (HBOT or HBO2 therapy) on post-COVID-19 patients with ongoing symptoms for at least 3 months after confirmed infection. Seventy-three patients were randomized to receive daily 40 session of HBOT (n = 37) or sham (n = 36). Follow-up assessments were performed at baseline and 1–3 weeks after the last treatment session. Following HBOT, there was a significant group-by-time interaction in global cognitive function, attention and executive function (d = 0.495, p = 0.038; d = 0.477, p = 0.04 and d = 0.463, p = 0.05 respectively). Significant improvement was also demonstrated in the energy domain (d = 0.522, p = 0.029), sleep (d = − 0.48, p = 0.042), psychiatric symptoms (d = 0.636, p = 0.008), and pain interference (d = 0.737, p = 0.001). Clinical outcomes were associated with significant improvement in brain MRI perfusion and microstructural changes in the supramarginal gyrus, left supplementary motor area, right insula, left frontal precentral gyrus, right middle frontal gyrus, and superior corona radiate. These results indicate that HBOT can induce neuroplasticity and improve cognitive, psychiatric, fatigue, sleep and pain symptoms of patients suffering from post-COVID-19 condition. HBOT’s beneficial effect may be attributed to increased brain perfusion and neuroplasticity in regions associated with cognitive and emotional roles.

Abstract Background Various mammalian species emit ultrasonic vocalizations (USVs), which reflect their emotional state and mediate social interactions. USVs are usually analyzed by manual or semi-automated methodologies that categorize discrete USVs according to their structure in the frequency-time domains. This laborious analysis hinders the effective use of USVs as a readout for high-throughput analysis of behavioral changes in animals. Results Here we present a novel automated open-source tool that utilizes a different approach towards USV analysis, termed TrackUSF. To validate TrackUSF, we analyzed calls from different animal species, namely mice, rats, and bats, recorded in various settings and compared the results with a manual analysis by a trained observer. We found that TrackUSF detected the majority of USVs, with less than 1% of false-positive detections. We then employed TrackUSF to analyze social vocalizations in Shank3-deficient rats, a rat model of autism, and revealed that these vocalizations exhibit a spectrum of deviations from appetitive calls towards aversive calls. Conclusions TrackUSF is a simple and easy-to-use system that may be used for a high-throughput comparison of ultrasonic vocalizations between groups of animals of any kind in any setting, with no prior assumptions.

Abstract COVID-19, which is caused by the SARS-CoV-2, has ravaged the world for the past 2 years. Here, we review the current state of research into the disease with focus on its history, human genetics and genomics and the transition from the pandemic to the endemic phase. We are particularly concerned by the lack of solid information from the initial phases of the pandemic that highlighted the necessity for better preparation to face similar future threats. On the other hand, we are gratified by the progress into human genetic susceptibility investigations and we believe now is the time to explore the transition from the pandemic to the endemic phase. The latter will require worldwide vigilance and cooperation, especially in emerging countries. In the transition to the endemic phase, vaccination rates have lagged and developed countries should assist, as warranted, in bolstering vaccination rates worldwide. We also discuss the current status of vaccines and the outlook for COVID-19.

Background Total knee arthroplasty (TKA) is associated with severe postoperative pain. Multimodal analgesia, including peripheral nerve block, is recommended for post-operative pain relief. Administration of some pain medications prior to surgery has shown to be more effective than after the operation. This is a prospective, randomized controlled trial designed to compare the analgesic efficacy of the adductor canal block (ACB) performed immediately before or immediately after primary total knee arthroplasty (TKA). We hypothesized that ACB before the surgery will reduce postoperative pain and improve knee function. Methods A total of 50 patients were enrolled and randomized into 2 groups, with 26 patients receiving a preoperative ACB and 24 receiving a postoperative ACB. Results Treatment groups were similar in terms of gender ( p = .83), age ( p = 0.61) weight ( p = .39) and ASA score. Average visual analogue scale (VAS) on arrival to the post-anesthesia care unit (PACU) were 4.9 ± 3.2 in the preoperative ACB versus 3.4 ± 2.8 for the postoperative ACB ( p = .075). VAS scores at different time points as well as the mean, minimal and maximal reported VAS scores were not significantly different between the two groups. The cumulative quantities of Fentanyl administered by the anesthesia team was comparable between the groups. Similarly, the dosage of Morphine, Tramadol, Acetaminophen and Dipyrone showed only small variations. The Quality of Recovery Score, Knee Society Scores and knee range of motion did not differ between the groups. Conclusions Our findings demonstrate no significant differences in patient total narcotics consumption, pain scores and functional scores, between preoperative and postoperative ACB in patients undergoing TKA. Trial Registration The trial was registered at www.clinicaltrials.gov and was assigned the registration number NCT02908711 Level of Evidence level I randomized controlled trial.

Abstract Background Evidence on the impact of COVID-19 and lockdown remains at an early stage. There is limited research about the impact of hard lockdown restrictions on families, specifically how these restrictions impact on women and children’s experiences of domestic violence, including intimate partner violence (IPV) and child abuse in South Africa. We conducted research among men and women in Gauteng province, South Africa to understand their experiences of the COVID-19 national lockdown and its impact and link to women and children’s experiences of domestic violence. Methods We conducted a qualitative study, using social media to recruit men and women who were 18 years and older, living with a spouse and/or children in Gauteng province, South Africa during the lockdown. To collect the data, we conducted telephone interviews, and analyzed data using the thematic approach. Results The lockdown had unprecedented negative economic impacts on families, and exacerbated some of the risk factors for violence against women and children in the home in South Africa. Some women reported experiences of emotional violence. Experiences of physical violence were mostly amongst children. The risk factors for women and children’s experiences of violence in the home differed by socio-economic class. Job losses and reduction in earnings resulted to food insecurity which was a key driver of violence in most low socio-economic status (SES) families. Confinement in the home with spouses was an unfamiliar and difficult experience, associated with conflict and perpetration of violence by men in high SES families. Participants across socio-economic groups reported high levels of stress with limited psychosocial support available during the lockdown. Conclusions Our finding showing a link between low-socio-economic status and increased risk for domestic violence during the lockdown in South Africa suggests the need for socio-economic interventions to mitigate these risks. Structural and social relief measures need to be strengthened to reduce the loss of jobs and income and to address food insecurity during pandemics. Psychosocial support should be provided to men and women to mitigate the mental health impacts of the pandemics and lockdown.

Abstract Background Injury remains a major concern to public health in the European region. Previous iterations of the Global Burden of Disease (GBD) study showed wide variation in injury death and disability adjusted life year (DALY) rates across Europe, indicating injury inequality gaps between sub-regions and countries. The objectives of this study were to: 1) compare GBD 2019 estimates on injury mortality and DALYs across European sub-regions and countries by cause-of-injury category and sex; 2) examine changes in injury DALY rates over a 20 year-period by cause-of-injury category, sub-region and country; and 3) assess inequalities in injury mortality and DALY rates across the countries. Methods We performed a secondary database descriptive study using the GBD 2019 results on injuries in 44 European countries from 2000 to 2019. Inequality in DALY rates between these countries was assessed by calculating the DALY rate ratio between the highest-ranking country and lowest-ranking country in each year. Results In 2019, in Eastern Europe 80 [95% uncertainty interval (UI): 71 to 89] people per 100,000 died from injuries; twice as high compared to Central Europe (38 injury deaths per 100,000; 95% UI 34 to 42) and three times as high compared to Western Europe (27 injury deaths per 100,000; 95%UI 25 to 28). The injury DALY rates showed less pronounced differences between Eastern (5129 DALYs per 100,000; 95% UI: 4547 to 5864), Central (2940 DALYs per 100,000; 95% UI: 2452 to 3546) and Western Europe (1782 DALYs per 100,000; 95% UI: 1523 to 2115). Injury DALY rate was lowest in Italy (1489 DALYs per 100,000) and highest in Ukraine (5553 DALYs per 100,000). The difference in injury DALY rates by country was larger for males compared to females. The DALY rate ratio was highest in 2005, with DALY rate in the lowest-ranking country (Russian Federation) 6.0 times higher compared to the highest-ranking country (Malta). After 2005, the DALY rate ratio between the lowest- and the highest-ranking country gradually decreased to 3.7 in 2019. Conclusions Injury mortality and DALY rates were highest in Eastern Europe and lowest in Western Europe, although differences in injury DALY rates declined rapidly, particularly in the past decade. The injury DALY rate ratio of highest- and lowest-ranking country declined from 2005 onwards, indicating declining inequalities in injuries between European countries.

Abstract Background Previous studies have linked the Mediterranean diet (MED) with improved cardiometabolic health, showing preliminary evidence for a mediating role of the gut microbiome. We recently suggested the Green-Mediterranean (Green-MED) diet as an improved version of the healthy MED diet, with increased consumption of plant-based foods and reduced meat intake. Here, we investigated the effects of MED interventions on the gut microbiota and cardiometabolic markers, and the interplay between the two, during the initial weight loss phase of the DIRECT-PLUS trial. Methods In the DIRECT-PLUS study, 294 participants with abdominal obesity/dyslipidemia were prospectively randomized to one of three intervention groups: healthy dietary guidelines (standard science-based nutritional counseling), MED, and Green-MED. Both isocaloric MED and Green-MED groups were supplemented with 28g/day walnuts. The Green-MED group was further provided with daily polyphenol-rich green tea and Mankai aquatic plant (new plant introduced to a western population). Gut microbiota was profiled by 16S rRNA for all stool samples and shotgun sequencing for a select subset of samples. Results Both MED diets induced substantial changes in the community structure of the gut microbiome, with the Green-MED diet leading to more prominent compositional changes, largely driven by the low abundant, “non-core,” microorganisms. The Green-MED diet was associated with specific microbial changes, including enrichments in the genus Prevotella and enzymatic functions involved in branched-chain amino acid degradation, and reductions in the genus Bifidobacterium and enzymatic functions responsible for branched-chain amino acid biosynthesis. The MED and Green-MED diets were also associated with stepwise beneficial changes in body weight and cardiometabolic biomarkers, concomitantly with the increased plant intake and reduced meat intake. Furthermore, while the level of adherence to the Green-MED diet and its specific green dietary components was associated with the magnitude of changes in microbiome composition, changes in gut microbial features appeared to mediate the association between adherence to the Green-MED and body weight and cardiometabolic risk reduction. Conclusions Our findings support a mediating role of the gut microbiome in the beneficial effects of the Green-MED diet enriched with Mankai and green tea on cardiometabolic risk factors. Trial registration The study was registered on ClinicalTrial.gov ( NCT03020186 ) on January 13, 2017.

Abstract Background Site-directed mutagenesis (SDM) is a key method in molecular biology; allowing to modify DNA sequences at single base pair resolution. Although many SDM methods have been developed, methods that increase efficiency and versatility of this process remain highly desired. Method We present a versatile and simple method to efficiently introduce a variety of mutation schemes using Gibson-assembly but without the need to design uniquely designated Gibson primers. Instead, we explore the re-use of standard SDM primers (completely overlapping in sequence) in combination with regular primers (~ 25 bps long) for amplification of fragments flanking the site of mutagenesis. We further introduce a rapid amplification step of the Gibson-assembled product for analysis and quality control, as well as for ligation, or re-ligation at instances the process fails (avoiding expenditure of added Gibson reaction mixtures). Results We first demonstrate that standard SDM primers can be used with the Gibson assembly method and, despite the need for extensive digestion of the DNA past the entire primer sequence, the reaction is attainable within as short as 15 min. We also find that the amount of the assembled Gibson product is too low to be visualized on standard agarose gel. Our added amplification step (by use of the same short primers initially employed) remedies this limitation and allows to resolve whether the desired Gibson-assembled product has been obtained on agarose gel or by sequencing of amplicons. It also provides large amounts of amplicons for subsequent ligations, bypassing the need to re-employ Gibson mixtures. Lastly, we find that our method can easily accommodate SDM primers with degenerate sequences. Conclusion We employ our alternative approach to delete, replace, insert, and degenerate sequences within target DNA sequences, specifically DNA sequences that proved very resistant to mutagenesis by multiple other SDM methods (standard and commercial). Importantly, our approach involves the re-use of SDM primers from our primer-inventory. Our scheme thereby reduces the need (and time and money) to design and order new custom Gibson-primers. Together, we provide a simple and versatile protocol that spans only 4 days (including the added amplification step), requires minimal primer sets and provides very high yields and success rates (> 98%).

Abstract Data on epidemiology and prognosticators of persistent post-concussion syndrome (PPCS) after mild traumatic brain injury (mTBI) in the pediatric population is scarce. The aim of this study was to evaluate the prevalence of PPCS in children after mTBI and to identify clinical variables in children who are at high risk for developing PPCS. A multicenter, retrospective matched cohort in which PPCS symptoms were evaluated in children 8–15-year-old, 6–60 months after being admitted to the emergency department because of mTBI. The control group included children admitted to the emergency department because of uncomplicated distal radius fractures. The children's guardians were interviewed for the presence of PPCS symptoms using the "Rivermead Post-Concussion Questionnaire". A multivariable logistic regression model was used to identify predictors of PPCS. Two-hundred and five children were included in the mTBI group and 205 in the control. The median time from the injury was 33.5 months in the mTBI group and 33.8 in the control. The prevalence of PPCS in the mTBI group was 25.3% and PPCS like symptoms in the control was 2.4%, p

Abstract Introduction Aging is the biggest cancer risk, and immune checkpoint (IC) inhibition (ICI) is a revolutionary cancer immunotherapy approach. Nonetheless, there are limited preclinical/clinical data regarding aging effects on ICI outcomes or age effects on IC expression in different organs or tumors. Methods Flow cytometry assessed IC on immune and non‐immune cells in various organs in young and aged BL6 mice. Comparisons: aged versus young naïve WT versus interferon‐γKO mice and WT challenged with B16F10 melanoma and treated with αPD‐1 or αPD‐L1 ICI. We co‐cultured young and aged T cells and myeloid cells in vitro and used OMIQ analyses to test cell–cell interactions. Results αPD‐1 ICI treated melanoma in young and aged hosts, whereas αPD‐L1 ICI was only effective in young. We found considerable, previously undescribed age effects on expression of various IC molecules participating in the ICI treatment, including PD‐1, PD‐L1, PD‐L2, and CD80, in distinct organs and in the tumor. These data help explain differential ICI efficacy in young and aged hosts. Host interferon‐γ influenced age effects on IC expression in both directions depending on specific IC molecule and tissue. IC expression was further affected by tumor challenge on immune, non‐immune, and tumor cells in tumor and other organs. In in vitro co‐culture, αPD‐1 versus αPD‐L1 distinctly influenced polyclonal T cells in young versus aged, suggesting mechanisms for distinct age‐related ICI outcomes. Conclusion Age affects IC expression on specific immune cells in an organ‐ and tissue‐specific manner. ICs were generally higher on aged immune cells. High immune‐cell PD‐1 could help explain αPD‐1 efficacy in aged. High co‐expression of CD80 with PD‐L1 on dendritic cells could help explain lack of αPD‐L1 efficacy in aged hosts. Factors other than myeloid cells and interferon‐γ also affect age‐related IC expression and T cell function, meriting additional studies.

Abstract The Late Quaternary witnessed a dramatic wave of large mammal extinctions, that are usually attributed to either human hunting or climatic change. We hypothesized that the large mammals that survived the extinctions might have been endowed with larger brain sizes than their relatives, which could have conferred enhanced behavioral plasticity and the ability to cope with the rapidly changing Late Quaternary environmental conditions. We assembled data on brain sizes of 291 extant mammal species plus 50 more that went extinct during the Late Quaternary. Using logistic, and mixed effect models, and controlling for phylogeny and body mass, we found that large brains were associated with higher probability to survive the Late Quaternary extinctions, and that extant species have brains that are, on average, 53% larger when accounting for order as a random effect, and 83% when fitting a single regression line. Moreover, we found that models that used brain size in addition to body size predicted extinction status better than models that used only body size. We propose that possessing a large brain was an important, yet so far neglected characteristic of surviving megafauna species.

Primary (non-motile) cilia represent structurally and functionally diverse organelles whose roles as specialized cellular antenna are central to animal cell signaling pathways, sensory physiology and development. An ever-growing number of ciliary proteins, including those found in vertebrate photoreceptors, have been uncovered and linked to human disorders termed ciliopathies. Here, we demonstrate that an evolutionarily-conserved PPEF-family serine-threonine phosphatase, not functionally linked to cilia in any organism but associated with rhabdomeric (non-ciliary) photoreceptor degeneration in the Drosophila rdgC (retinal degeneration C) mutant, is a bona fide ciliary protein in C. elegans. The nematode protein, PEF-1, depends on transition zone proteins, which make up a 'ciliary gate' in the proximal-most region of the cilium, for its compartmentalization within cilia. Animals lacking PEF-1 protein function display structural defects to several types of cilia, including potential degeneration of microtubules. They also exhibit anomalies to cilium-dependent behaviors, including impaired responses to chemical, temperature, light, and noxious CO2 stimuli. Lastly, we demonstrate that PEF-1 function depends on conserved myristoylation and palmitoylation signals. Collectively, our findings broaden the role of PPEF proteins to include cilia, and suggest that the poorly-characterized mammalian PPEF1 and PPEF2 orthologs may also have ciliary functions and thus represent ciliopathy candidates. [ABSTRACT FROM AUTHOR]

Background: Many patients hospitalized for COVID-19 experience long-term health problems, but comprehensive longitudinal data up to 2 years remain limited. We aimed to (1) assess 2-year trajectories of health outcomes, including comparison between intensive care unit (ICU) treated and non-ICU-treated patients, and (2) identify risk factors for prominent health problems post-hospitalization for COVID-19. Methods: The CO-FLOW multicenter prospective cohort study followed adults hospitalized for COVID-19 at 3, 6, 12, and 24 months post-discharge. Measurements included patient-reported outcomes (a.o., recovery, symptoms, fatigue, mental health, sleep quality, return to work, health-related quality of life [HRQoL]), and objective cognitive and physical tests. Additionally, routine follow-up data were collected. Results: 650 patients (median age 60.0 [IQR 53.0–67.0] years; 449/650 [69%] male) surviving hospitalization for COVID-19 were included, of whom 273/650 (42%) received ICU treatment. Overall, outcomes improved over time. Nonetheless, 73% (322/443) of patients had not completely recovered from COVID-19, with memory problems (274/443; 55%), concentration problems (259/443; 52%), and dyspnea (251/493; 51%) among most frequently reported symptoms at 2 years. Moreover, 61% (259/427) had poor sleep quality, 51% (222/433) fatigue, 23% (102/438) cognitive failures, and 30% (65/216) did not fully return to work. Objective outcome measures showed generally good physical recovery. Most outcomes were comparable between ICU- and non-ICU-treated patients at 2 years. However, ICU-treated patients tended to show slower recovery in neurocognitive symptoms, mental health outcomes, and resuming work than non-ICU-treated patients, while showing more improvements in physical outcomes. Particularly, female sex and/or pre-existing pulmonary disease were major risk factors for poorer outcomes. Conclusions: 73% (322/443) of patients had not completely recovered from COVID-19 by 2 years. Despite good physical recovery, long-term neurocognitive complaints, dyspnea, fatigue, and impaired sleep quality persisted. ICU-treated patients showed slower recovery in neurocognitive and mental health outcomes and resumption of work. Tailoring long-term COVID-19 aftercare to individual residual needs is essential. Follow-up is required to monitor further recovery. Trial registration: NL8710, registration date 12-06-2020. [ABSTRACT FROM AUTHOR]

In winter, many reptiles have a period of inactivity ("brumation"). During brumation there is no energetic intake, therefore there would be an advantage to reducing energetic expenditure. The size of energetically costly organs, a major determinant of metabolic rate, is known to be flexible in many tetrapods. Seasonal plasticity of organ size could serve as both an energy‐saving mechanism and a source of nutrients for brumating reptiles. We studied a population of an invasive gecko, Tarentola annularis, to test for seasonal changes in activity, metabolic rate, and mass of various organs. The observed period of inactivity was December–February. Standard metabolic rates during the activity season were 1.85 times higher than in brumating individuals. This may be attributed to decreased organ mass during winter: heart mass decreased by 37%, stomach mass by 25%, and liver mass by 69%. Interestingly, testes mass increased by 100% during winter, likely in preparation for the breeding season, suggesting that males prioritize breeding over other functions upon return to activity. The size of the kidneys and lungs remained constant. Organ atrophy occurred only after geckos reduced their activity, so we hypothesize that organ mass changes in response to (rather than in anticipation of) cold winter temperatures and the associated fasting. Degradation of visceral organs can maintain energy demands in times of low supply, and catabolism of the protein from these organs can serve as a source of both energy and water during brumation. These findings bring us closer to a mechanistic understanding of reptiles' physiological adaptations to environmental changes. [ABSTRACT FROM AUTHOR]

Background: Over the last few decades, the efficacy of biological therapies for COPD has been evaluated by different randomized controlled trials (RCTs). Still, the evaluation of real-world data and patient-reported outcome measures (PROMs) have not been performed in this field before. In the current work, we present a systematic literature review of the real-world data and PROMs of biological treatments for COPD. Methods: Three large databases (MEDLINE/PubMed, Scopus, and ScienceDirect) were utilized for the systematic literature review. Clinical studies (RCT, cohorts, case series/reports) assessing patients with COPD treated by any biological therapy were included. Results: The review resulted in twelve eligible studies (nine randomized controlled trials and three "real-world" case series/reports). The evaluation of PROMs in the included studies was mainly limited to the severity and burden of respiratory symptoms. Most biological therapies were associated with improved PROMs compared to the baseline, although not for the placebo. Dupilumab was the only biologic therapy with proven efficacy in RCT for both objective and subjective measures. One prior study reported patients' self-perceived drug effects, and none evaluated patients' perceived disease status. Only 25 patients were assessed in a real-world setting for all biologic therapies combined. Real-world data were retrospective in the form of case reports or series. Conclusions: There are limited data on patients' experience with biological therapies for COPD. While real-world data and PROMs are missing, biases such as a placebo effect must be considered, requiring their incorporation with objective outcomes from prospective controlled trials. [ABSTRACT FROM AUTHOR]

Acute myeloid leukemia (AML) is a complex hematological malignancy characterized by diverse genetic alterations, each with distinct clinical implications. Chromosome 3 inversion (inv(3)) is a rare genetic anomaly found in approximately 1.4–1.6% of AML cases, which profoundly affects prognosis. This review explores the pathophysiology of inv(3) AML, focusing on fusion genes like GATA2::EVI1 or GATA2::MECOM. These genetic rearrangements disrupt critical cellular processes and lead to leukemia development. Current treatment modalities, including intensive chemotherapy (IC), hypomethylating agents (HMAs) combined with venetoclax, and allogeneic stem cell transplantation are discussed, highlighting outcomes achieved and their limitations. The review also addresses subgroups of inv(3) AML, describing additional mutations and their impact on treatment response. The poor prognosis associated with inv(3) AML underscores the urgent need to develop more potent therapies for this AML subtype. This comprehensive overview aims to contribute to a deeper understanding of inv(3) AML and guide future research and treatment strategies. [ABSTRACT FROM AUTHOR]

Background Muscles affected by postparetic synkinesis have imbalanced tonicity that limit perioral mimetic movement and inhibit the ability to smile. The depressor anguli oris (DAO) muscle has been a common myectomy target for the treatment of perioral synkinesis. While addition of buccinator myectomies to DAO myectomies has risen, no studies have analyzed the effects of buccinator myectomies. The goal of this study was to evaluate and compare the effects of a DAO myectomy with and without concomitant buccinator myectomy through objective facial metrics and subjective patient-reported outcomes. Methods This study is a retrospective review of patients with postparetic synkinesis who underwent DAO myectomy (DAO myectomy group) or DAO myectomy with buccinator myectomy (DAO + Buccinator myectomies group). Outcomes included postoperative differences in objective smile measures (smile angle, excursion, and dental show) using validated software and patient-reported outcomes using the Facial Disability Index (FDI) questionnaire and a myectomy-specific questionnaire. Results After chart review, 18 patients were included in the DAO myectomy group and 19 in the DAO + Buccinator myectomies group. There were no significant postoperative differences between the groups in (1) smile excursion, angle, or dental show at resting, closed smile, or open smile (p > 0.05), (2) FDI physical and social scores, p = 0.198 and 0.932, respectively, or (3) myectomy-specific questionnaire responses (p > 0.05). Conclusion The addition of a buccinator myectomy to a DAO myectomy does not provide significant clinical benefit when compared with an isolated DAO myectomy, based on objective measures and subjective patient-reported outcomes. [ABSTRACT FROM AUTHOR]

Aim: In continuous environments, niche limits of species often determine their distribution limits. However, when these limits spatially coincide with a perceived dispersal barrier, the determinants of species' ranges may be confounded. We investigate the distribution pattern of the Brown Hornbill (Aves: Bucerotidae), which spans significant riverine barriers, but stops south of the Brahmaputra River. Considering its preference for low‐elevation evergreen forests, we posit that the lack of sufficient habitats north of the Brahmaputra prevents dispersal of the Brown Hornbill, and not the river itself. Location: The Brahmaputra valley and the Indo‐Burma hotspot. Taxa: Anorrhinus austeni, Aceros nipalensis. Methods: We analysed citizen‐science occurrence data on hornbill presence against a suite of climatic, canopy‐specific and topographical predictors to model the environmental niche of the Brown Hornbill. We used presence‐only maximum entropy modelling in an information theoretic framework, in conjunction with constructing binary logistic regression models using presence and pseudoabsence data. We compared niche models of the Brown Hornbill and the Rufous‐necked hornbill, a close relative with a similar distribution, but which has spanned the Brahmaputra River. Results: Despite the presence of suitable wet‐evergreen forests north of the Brahmaputra River, the hilly terrains in the region act as a biogeographic barrier for the Brown Hornbill, which prefers lowland evergreen forests. Further, highly suitable regions for the Brown and the Rufous‐necked Hornbills precisely delineate low and high‐elevation evergreen forests respectively, indicating that these birds are separated along an elevational axis. Main Conclusions: The Brahmaputra River lies at the cusp of two subtly different environmental regimes. It may therefore serve as the niche limit for certain organisms and not as a physical obstacle to their dispersal. Our study implicitly predicts how widespread deforestation prevalent in the lowland evergreen forests of this region adversely impacts the distributions of organisms that depend on them, such as the Brown Hornbill. Further, our study proffers an approach to ascertain determinants of species distributions in a hypothesis testing framework. [ABSTRACT FROM AUTHOR]

We studied levels of awareness of impending death in older patients and their family caregivers. Using a mixed methods approach, we interviewed 70 family caregivers in Israel. Of the caregivers, 64% reported having been aware of the impending death, 33% were unaware, and 3% uncertain. Caregivers reported their perception that 36% of patients were aware, 27% unaware, and for 37% they were uncertain about the patient's awareness. Mechanisms that increased caregivers' awareness were specific diagnosis, significant deterioration in health, preparation by a health professional, or patient preparations for death. This study clarifies processes which aid awareness, and the relationship between awareness and actual preparation for dying. [ABSTRACT FROM AUTHOR]

Asparaginase (ASP)-containing regimens for acute lymphoblastic leukemia (ALL) are associated with venous thromboembolism (VTE). We evaluated the prevalence, risk factors, role of prophylaxis and clinical impact of VTE among adolescents and young adult (AYA) patients (15–50 years) treated on Dana-Farber Cancer Institute (DFCI) ALL protocols. The 1- and 2-year cumulative incidence of VTE were 31.9% (95% CI: 27.0%, 36.9%) and 33.5% (95% CI: 28.5%, 38.5%) respectively, with most events occurring during ASP-based consolidation phase (68.6%). VTE was more frequent in patients with overweight/obese vs. normal BMI (39.2% vs. 29.0%, p = 0.048). In a 1-year landmark analysis, the 4-year overall survival was 91.5%, without difference between patients with vs. without VTE (93.8% vs. 90.0%, p = 0.93). Relapse and non-relapse mortality rates were also similar. Among patients treated at Dana-Farber/Harvard Cancer Center, cerebral sinus vein thrombosis occurred in 3.6% of patients (8.5% of VTE events) in comparison to pulmonary embolism (32.9%) and deep vein thromboses (58.6%, 24.4% line-associated). In a Cox regression model for VTE free-time, elevated BMI was associated with shorter VTE free-time (HR 1.94 [95% CI 1.13-3.35], p = 0.018), while low molecular weight heparin (LMWH) prophylaxis as time-varying covariate was not. In conclusion, we found that VTE was frequent in AYAs treated on DFCI ALL protocols but did not impact survival outcomes. Overweight/obese BMI increased risk for VTE. [ABSTRACT FROM AUTHOR]

This study constitutes one of the first investigations aiming to examine the association between traumatic experiences within religious settings and symptoms of post-traumatic stress among religious lesbians, gays, and bisexuals. Furthermore, the study tested whether the anticipated positive link between those traumatic experiences and post-traumtic stress is influenced by a positive perception of God’s image. The sample consisted of 146 Israeli Jewish lesbians, gays, and bisexuals who professed a belief in God or demonstrated religious inclinations either presently or in the past. They completed self-report measures via an online questionnaire, assessing traumatic experiences within religious settings, post-traumtic stress symptoms, and positive perceptions of God’s image. The findings revealed a significant and robust positive connection between traumatic experiences within religious settings and post-traumtic stress. A positive perception of God’s image exhibited a negative correlation with post-traumtic stress but did not moderate the relationship traumatic experiences within religious settings and symptoms of post-traumatic stress. These findings highlight the significance of traumatic experiences within religious settings as a distinct potential risk factor of post-traumtic stress among lesbians, gays, and bisexuals and underscore the necessity of enhancing awareness among mental health professionals, religious leaders, and legal entities regarding the detrimental effects of those expereinces. [ABSTRACT FROM AUTHOR]

Background Objectives Methods Results and Conclusions The rising importance of digital technologies in everyday communication has played a key role in processes of political polarization and rising mistrust and intolerance. We suggest this crisis could be productively conceptualized as a crisis in perspective‐taking—the tendency and competency to actively consider others' mental and emotional states.This conceptual paper sets out to propose a theoretical framework that identifies the key affordances of digital platforms for promoting perspective‐taking in formal educational settings (K‐12 and higher education): (1) connecting diverse individuals, (2) simulating interactions with other perspectives and (3) supporting the articulation and sharing of perspectives.Rather than summarizing the state of existing research, this paper aims to offer a novel conceptualization that allows unpacking the interplay between research on perspective‐taking and work on the affordances and constraints of digital media. We identify the three key affordances outlined above, exemplifying them by focusing on one type of digital tool and comparing them along two axes: (i) the depth vs. diversity of interactions it supports and (ii) its cultivation of intergroup perspective‐taking vs. interpersonal perspective‐taking.This framework, we argue, articulates the advantages and limitations of digital tools towards engagement in perspective‐taking, while providing a conceptual roadmap, and practical considerations, for researchers and practitioners interested in cultivating digitally mediated perspective‐taking in educational settings. [ABSTRACT FROM AUTHOR]

Hyperbaric oxygen therapy (HBOT) has recently emerged as a promising neuromodulatory modality for treating several neurological and psychological disorders. Various studies indicate that HBOT can promote brain recovery and neuroplasticity through the modulation of key cellular and molecular mechanisms. HBOT affects multiple primary pathways and cellular functions including mitochondrial biogenesis and function (increased Bcl-2, reduced Bax, and enhanced ATP production), neurogenesis (upregulation of Wnt-3 and VEGF/ERK signaling), synaptogenesis (elevated GAP43 and synaptophysin expression), and anti-inflammatory responses (reduced TNF-a and IL-6). These mechanisms contribute to significant clinical benefits, such as enhanced cognitive function, improved recovery from traumatic brain injury and post-concussion syndrome, and symptom reduction in conditions like post-traumatic stress disorder and fibromyalgia. By influencing these molecular targets, HBOT offers a novel approach to neuromodulation that warrants further exploration. This review discusses the representative mechanisms of action of HBOT and highlights its therapeutic neuromodulatory effects and potential clinical applications across various neurological and psychiatric conditions. [ABSTRACT FROM AUTHOR]

Background: Dysregulated pathways in cancer may be hub addicted. Identifying these dysregulated networks for targeting might lead to novel therapeutic options. Objective: Considering the hypothesis that central hubs are associated with increased lethality, identifying key hub targets within central networks could lead to the development of novel drugs with improved efficacy in advanced metastatic solid tumors. Design: Exploring transcriptomic data (22,000 gene products) from the WINTHER trial (N = 101 patients with various metastatic cancers), in which both tumor and normal organ-matched tissue were available. Methods: A retrospective in silico analysis of all genes in the transcriptome was conducted to identify genes different in expression between tumor and normal tissues (paired t -test) and to determine their association with survival outcomes using survival analysis (Cox proportional hazard regression algorithm). Based on the biological relevance of the identified genes, hub targets of interest within central networks were then pinpointed. Patients were grouped based on the expression level of these genes (K -mean clustering), and the association of these groups with survival was examined (Cox proportional hazard regression algorithm, Forest plot, and Kaplan–Meier plot). Results: We identified four key central hub genes— PLOD3, ARHGAP11A, RNF216, and CDCA8, for which high expression in tumor tissue compared to analogous normal tissue had the most significant correlation with worse outcomes. The correlation was independent of tumor or treatment type. The combination of the four genes showed the highest significance and correlation with the poorer outcome: overall survival (hazard ratio (95% confidence interval (CI)) = 10.5 (3.43–31.9) p = 9.12E−07 log-rank test in a Cox proportional hazard regression model). Findings were validated in independent cohorts. Conclusion: The expression of PLOD3, ARHGAP11A, RNF216, and CDCA8 constitute, when combined, a prognostic tool, agnostic of tumor type and previous treatments. These genes represent potential targets for intercepting central hub networks in various cancers, offering avenues for novel therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background: Selective Immunoglobulin A Deficiency (SIgAD) is one of the most prevalent immunodeficiencies, characterized by an increased risk of mucosal infections. Attention deficit hyperactivity disorder (ADHD) is among the most common neurodevelopmental disorders and is associated with significantly higher rates of various infectious diseases, white blood cell abnormalities, and considerable morbidity. This study aimed to evaluate the prevalence of ADHD among patients with SIgAD. Methods: We conducted a retrospective, observational, population-based case–control study, within Leumit Health Services, by comparing individuals diagnosed with SIgAD to a matched control group. Data were extracted from electronic health records. Results: Of the >700,000 registered individuals, 772 aged ≥4 years with SIgAD were identified (mean age 22.0 ± 17.5 years; male/female ratio 1:1). The 5:1 matched control group consisted of 3860 subjects without SIgAD, with no significant differences between the groups regarding age, gender, ethnicity, and socioeconomic status. ADHD prevalence was significantly higher in the SIgAD group (16.2%) than in the control group (12.9%), with an odds ratio of 1.30 (95% confidence interval 1.05–1.61, p = 0.017), as was the use of methylphenidate (6.6% vs. 4%). Additionally, respiratory and intestinal infections were significantly more common in the SIgAD group (p < 0.001). Conclusion: A significantly higher prevalence of ADHD was observed in patients with SIgAD compared to strictly matched controls without SIgAD. These findings enhance our understanding of the pathophysiology of ADHD and its associated health complications. [ABSTRACT FROM AUTHOR]

Simple Summary: Chronic graft vs. host disease (cGVHD) is a major complication that appears after allogeneic hematopoietic cell transplantation. As result, this has a significant and detrimental impact on both the quality of life and survival of patients after transplantation. In recent years, three novel therapies have been approved by the FDA for the management of cGVHD. To date, previous studies have not analyzed the effect of these novel drugs on other health-associated conditions such as metabolic syndrome, bone health, return to employment, mental health, and other para-medical outcomes. In this study, during three different time periods, we aimed to assess and highlight the association between novel advanced treatments for cGVHD and their impact on the quality of life of patients after allogeneic transplantation. Objectives—chronic graft vs. host disease (cGVHD) is associated with substantial morbidity and mortality. We aimed to analyze advances in treatment strategy and outcomes during the last decade due to the incorporation of novel immunosuppressive therapy (IST) drugs in the armamentarium. Methods—we retrospectively analyzed all patients > 18 years with cGVHD after their first hematopoietic cell transplantation (HCT) between 2012 and 2020 (n = 91), divided into three treatment periods: 2012–2014, 2015–2017, and 2018–2020 (groups 1, 2, and 3, respectively). Results—mean cumulative steroid dose and dose/total cGVHD-treatment days was lower in groups 2–3 compared to 1 (p = 0.008 and p = 0.042, respectively). The median IST-free survival was 79 (95%CI54–94) months, with more patients in group 3 (47% (95%CI 25–54%) discontinuing IST at 3 years, p = 0.1). Groups 2–3 compared to 1 had better glycemic control (p < 0.01), higher bone density (p = 0.06), and fewer cardiovascular events. The number of admissions/patient dropped from 0.7/year in group 1 to 0.24/year and 0.36/year in groups 2–3, respectively (p = 0.36). Employment reintegration was higher in groups 2–3 compared with 1 (p = 0.05) and so was earlier return to work (p = 0.01). There were no differences in survival outcomes. Conclusions—the incorporation of novel agents appears to be associated with reduced overall steroid burden, improved cGVHD control, and fewer long-term side effects. [ABSTRACT FROM AUTHOR]

This mixed‐methods study evaluates the efficacy of artificial intelligence (AI)‐assisted reviewer selection in academic publishing across diverse disciplines. Twenty journal editors assessed AI‐generated reviewer recommendations for a manuscript. The AI system achieved a 42% overlap with editors' selections and demonstrated a significant improvement in time efficiency, reducing selection time by 73%. Editors found that 37% of AI‐suggested reviewers who were not part of their initial selection were indeed suitable. The system's performance varied across disciplines, with higher accuracy in STEM fields (Cohen's d = 0.68). Qualitative feedback revealed an appreciation for the AI's ability to identify lesser‐known experts but concerns about its grasp of interdisciplinary work. Ethical considerations, including potential algorithmic bias and privacy issues, were highlighted. The study concludes that while AI shows promise in enhancing reviewer selection efficiency and broadening the reviewer pool, it requires human oversight to address limitations in understanding nuanced disciplinary contexts. Future research should focus on larger‐scale longitudinal studies and developing ethical frameworks for AI integration in peer‐review processes. [ABSTRACT FROM AUTHOR]

Dorsal neural tube-derived retinoic acid promotes the end of neural crest production and transition into a definitive roof plate. Here, we analyze how this impacts the segregation of central and peripheral lineages, a process essential for tissue patterning and function. Localized in ovo inhibition in quail embryos of retinoic acid activity followed by single-cell transcriptomics unraveled a comprehensive list of differentially expressed genes relevant to these processes. Importantly, progenitors co-expressed neural crest, roof plate and dI1 interneuron markers, indicating a failure in proper lineage segregation. Furthermore, separation between roof plate and dI1 interneurons is mediated by Notch activity downstream of retinoic acid, highlighting their crucial role in establishing the roof plate-dI1 boundary. Within the peripheral branch, where absence of retinoic acid resulted in neural crest production and emigration extending into the roof plate stage, sensory progenitors failed to separate from melanocytes, leading to formation of a common glia-melanocyte cell with aberrant migratory patterns. In summary, the implementation of single-cell RNA sequencing facilitated the discovery and characterization of a molecular mechanism responsible for the segregation of dorsal neural fates during development. [ABSTRACT FROM AUTHOR]

This paper focuses on the Zionist challenges regarding "Jewish labor" through the micro-history of the Salonikian longshoremen on the eve of their emigration from Greece (early 1930s), and during the first period of integration in the Haifa Port (1933–1936). To date, the hegemonic perspective on Salonikian longshoremen has emphasized the immigrants' crucial role in overcoming the Arab-dominated port labor market. However, while tending to paint a romantic picture of national fervor, this Zionist view obscured the economic, ethnic, and cultural confrontation involved in realizing "Jewish labor". These multiple forms of confrontation occurred not only between ethnic groups (Jewish-Arab struggle) but also within the local Jewish labor community. Re-visiting the Zionist agenda from the vantage point of both the Salonikian longshoremen and the Zionist establishment enables to present largely neglected aspects of the complex relations between the Sephardic Salonikians and the Ashkenazi/Eastern European-dominated Jewish labor establishment. Due to heavy doubts about the Salonikian commitment to the uphill battle for "Jewish labor," the Haifa Labor Council excluded the latter from the labor community. Consequently, the cultural marginality of the Salonikians weakened the Zionist vision of uniting all Jewish wage earners into a cohesive working class in the middle of the 1930s. [ABSTRACT FROM AUTHOR]

Research on children's literature focuses on preschool children's books (children aged 3–6) and on juvenile fiction, yet is lacking in studies on toddler books (ages 0–3). In this paper, I present a definition of the genre of toddler books (often referred to as boardbooks, despite it including non-boardbooks), while focusing on the illustrational aspects, that are at least as dominant as the written texts, if not more so. I also examine the plots and themes that are presented in toddlers' books, distinguishing between concept books (lexical books with no narrative), ritual books (which engage in instilling certain habits), and narrative books (toddlers' books that depict a complex narrative and serve as preparation for prereader books). The findings of the study indicate that toddlers' books are often infants' first encounter with both narrative thought and visual art, hence their significant place in their development. [ABSTRACT FROM AUTHOR]

Education policies are typically anchored in official texts that provide a foundation for their enactment in schools. What are the implications of an invisible policy not anchored in any official text due to political motives? This study explores the enactment of an invisible education policy that regulates religious enclave schools. These schools' curricula are the source of frequent conflict between states and religious enclave communities. The study draws on the case of the National Haredi Education (NHE) reform in Israel that enabled ultra-Orthodox (Haredi) private schools in Israel to affiliate with a new stream of public schools whose regulations were not anchored in any official text. The data comprised interviews with principals, teachers, and supervisors, as well as document analysis. The findings showed that the enactment of the NHE policy was primarily manifested in invisible changes, such as teacher professionalisation and pupil assessment. Curricular changes visible to the wider school community were enacted differently in different schools. Our findings also characterised the implications of the NHE policy's invisibility. The lack of institutional recognition hindered the reform, but the autonomy of the implementing agents enabled them to promote changes within their purview and become policy entrepreneurs. [ABSTRACT FROM AUTHOR]

Summary: We studied the association between non-osteoporotic fractures and future major osteoporotic fractures, using UK health records. Non-osteoporotic fractures were found to increase the risk of major osteoporotic fractures, although to a lesser extent than osteoporotic fractures. This highlights the importance of considering all previous fractures in assessing future fracture risk. Purpose: Previous studies demonstrated that osteoporotic fractures—minor and major—increase the risk for future major osteoporotic fractures; we test whether non-osteoporotic fractures are also associated with such increased risk. Methods: The study is a retrospective cohort study using UK primary care electronic health records. Exposure groups were defined according to fracture location prior to the year 2011 (index date): major, minor, and non-osteoporotic. The outcome of incident major osteoporotic fractures following the index date was compared between the exposure groups and the general population. Results: The general study population included 1,951,388 patients. The exposure groups included 39,931 patients with a prior major osteoporotic fracture, 19,397 with a prior minor osteoporotic fracture, and 50,115 patients with a prior non-osteoporotic fracture. The standardized Incidence Rate Ratio for future major osteoporotic fractures was 2.73 (95% confidence interval: 2.64–2.82), 2.43 (2.32–2.54), and 1.83 (1.74–1.92), respectively. Conclusion: Non-osteoporotic fractures are significantly associated with increased risk for future major osteoporotic fractures relative to the general population, yet to a lesser extent compared to major and minor osteoporotic fractures. [ABSTRACT FROM AUTHOR]

Background—Gastroesophageal reflux disease (GERD) is commonly diagnosed in patients with severe obesity. The outcomes of patients with preoperative GERD after sleeve gastrectomy (SG) are unclear, and some surgeons consider GERD a contraindication for SG. Methods—A retrospective analysis of a tertiary university hospital database was conducted. All patients with preoperative GERD undergoing SG between January 2012 and January 2020 and having at least two years of follow-up were included in the analysis. A validated GERD-associated quality of life questionnaire (GERD-HRQL) was completed by all patients. Results—During the study period, 116/1985 patients (5.8%) were diagnosed with GERD before SG. In total, 55 patients were available for a two-year follow-up and were included in the analysis. Median follow-up was 40 months (range 24–156 months). Mean total weight loss (TWL) was 24.0% ± 12.0%. On follow-up, 43 patients (78.1%) reported having GERD symptoms. In patients who underwent postoperative endoscopy, less than a third had esophagitis. The mean GERD-HRQL score was 25.2 ± 10.9. On univariable analysis, patients with poor GERD-HRQL had lower BMI at baseline (41.5 ± 12.4 vs. 44.9 ± 10.0 kg/m2, p = 0.03), were less commonly smokers at baseline (8.1% vs. 33.3%, p = 0.02), and had lower TWL at the end of the follow-up (22.2% ± 10.4% vs. 28.9% ± 13.7%, p = 0.05). On multivariable analysis, smoking status at baseline and TWL at last follow-up were independent predictors of better GERD-HRQL. Conclusions—In conclusion, most GERD patients after SG have a relatively high GERD-HRQL score, most patients still have GERD symptoms during the follow-up, and approximately a third of patients have endoscopic signs of esophagitis. There was an association between patients with higher TWL and smoking at baseline and better GERD-HRQL outcomes. The latter is potentially due to smoking cessation. [ABSTRACT FROM AUTHOR]

Aim: To explore the effect of Mankai, a cultivated aquatic duckweed green plant, on postprandial glucose (PG) excursions in type 2 diabetes (T2D). Methods: In a 4‐week, randomized crossover‐controlled trial, we enrolled 45 adults with T2D (HbA1c range: 6.5%‐8.5%) from two sites in Israel. Participants were randomized to drink Mankai (200 mL of raw‐fresh‐aquatic plant + 100 mL of water, 40 kcal, ~10 g of dry matter equivalent) or water (300 mL) following dinner, for 2 weeks each, with a 4‐day washout interval, without dietary, physical activity or pharmacotherapy alterations. We used continuous glucose monitoring (CGM) devices. Results: Forty patients (adherence rate = 88.5%; 743 person‐intervention‐days, 68.9% men, age = 64 years, HbA1c = 6.8%) completed the study with a consistent diet and complete CGM reads. Only two‐thirds of the individuals responded beneficially to Mankai. Overall, Mankai significantly lowered the PG peak by 19.3% (∆peak = 24.3 ± 16.8 vs. 30.1 ± 18.5 mg/dL; P <.001) and delayed the time‐to‐peak by 20.0% (112.5 [interquartile range: 75‐135] vs. 90 [60‐105] min; P <.001) compared with water. The PG incline and decline slopes were shallower following postdinner Mankai (incline slope: 16.8 vs. water: 29.9 mg/[dL h]; P <.001; decline slope: −6.1 vs. water: −7.9 mg/[dL h]; P <.01). Mean postprandial net incremental area‐under‐the‐glucose‐curve was lowered by 20.1% with Mankai compared with water (P =.03). Results were consistent across several sensitivity and subgroup analyses, including across antidiabetic pharmacotherapy treatment groups. Within 2 weeks, the triglycerides/high‐density lipoprotein cholesterol ratio in the Mankai group (−0.5 ± 1.3) decreased versus water (+0.3 ± 1.5, P =.05). Conclusions: Mankai consumption may mitigate the PG response in people with T2D with an ~20% improvement in glycaemic values. These findings provide case‐study evidence for plant‐based treatments in T2D to complement a healthy lifestyle and pharmacotherapy. [ABSTRACT FROM AUTHOR]

Marine sponges are well-known for hosting rich microbial communities. Sponges are the most prolific source of marine bioactive compounds, which are frequently synthesized by their associated microbiota. Calyx nicaeensis is an endemic Mediterranean sponge with scarce information regarding its (bioactive) secondary metabolites. East Mediterranean specimens of mesophotic C. nicaeensis have never been studied. Moreover, no research has inspected its associated bacteria. Thus, we studied the sponge's bacterial diversity and examined bacterial interspecific interactions in search of a promising antibacterial candidate. Such novel antimicrobial agents are needed since extensive antibiotic use leads to bacterial drug resistance. Bacteria cultivation yielded 90 operational taxonomic units (OTUs). A competition assay enabled the testing of interspecific interactions between the cultured OTUs. The highest-ranked antagonistic bacterium, identified as Paenisporosarcina indica (previously never found in marine or cold habitats), was mass cultured, extracted, and separated using size exclusion and reversed-phase chromatographic methods, guided by antibacterial activity. A pure compound was isolated and identified as 3-oxy-anteiso-C15-fatty acid-lichenysin. Five additional active compounds await final cleaning; however, they are lichenysins and surfactins. These are the first antibacterial compounds identified from either the C. nicaeensis sponge or P. indica bacterium. It also revealed that the genus Bacillus is not an exclusive producer of lichenysin and surfactin. [ABSTRACT FROM AUTHOR]