BACKGROUND: The revolutionary technology of smartphone-based retinal imaging has been consistently improving over the years. Smartphone-based retinal image acquisition devices are designed to be portable, easy to use, and cost-efficient, which enables eye care to be more widely accessible especially in geographically remote areas. This enables early disease detection for those who are in low- and middle- income population or just in general has very limited access to eye care. This study investigates the limitation of smartphone compatibility of existing smartphone-based retinal image acquisition devices. Additionally, this study aims to propose a universal adapter design that is usable with an existing smartphone-based retinal image acquisition device known as the PanOptic ophthalmoscope. This study also aims to simulate the reliability, validity, and performance overall of the developed prototype.
METHODS: A literature review has been conducted that identifies the limitation of smartphone compatibility among existing smartphone-based retinal image acquisition devices. Designing and modeling of proposed adapter were performed using the software AutoCAD 3D. For the proposed performance evaluation, finite element analysis (FEA) in the software Autodesk Inventor and 5-point scale method were demonstrated.
RESULTS: Published studies demonstrate that most of the existing smartphone-based retinal imaging devices have compatibility limited to specific older smartphone models. This highlights the benefit of a universal adapter in broadening the usability of existing smartphone-based retinal image acquisition devices. A functional universal adapter design has been developed that demonstrates its compatibility with a variety of smartphones regardless of the smartphone dimension or the position of the smartphone\'s camera lens. The proposed performance evaluation method generates an efficient stress analysis of the proposed adapter design. The end-user survey results show a positive overall performance of the developed universal adapter. However, a significant difference between the expert\'s views on the developed adapter and the quality of images is observed.
CONCLUSIONS: The compatibility of existing smartphone-based retinal imaging devices is still mostly limited to specific smartphone models. Besides this, the concept of a universal and suitable adapter for retinal imaging using the PanOptic ophthalmoscope was presented and validated in this paper. This work provides a platform for future development of smartphone-based ophthalmoscope that is universal.

Generation Z is expected to officially surpass the Baby Boomers in the labor market by 2024 and to represent 30% of the global workforce by 2030. In the work environment, they are referred to oxymoronically as competitively ambivalent. Therefore, it is necessary to investigate the reasons for this behavior and to identify initiatives that would facilitate understanding between Generation Z and other generations. The aim of the present study was to find out whether Generation Z in the Czech Republic and Slovakia, which lives in conditions of deepening polarization of society and differentiated opportunities (e.g., in access to education, consumption of goods and services, work and entertainment), exhibits compatible value orientation or whether significant antagonisms exist in the value system. The study utilized the referential Schwartz\'s theory of values, which handles universal values dynamically. This theoretical framework was extended to include the dimension of instrumental values that were contextualized in the labor market environment. The results show that the representatives of Generation Z in the Czech Republic and Slovakia prefer collective values (Benevolence and Universalism) in the first two places. However, they subsequently lean toward two individual values (Hedonism and Self-Direction). The comparison of the results in the European context showed the same values being shared by the representatives of Generation Z with preference nuances. The comparison of Generation Z representatives with members of other generations in the European context showed consistency of sharing collective values (Benevolence and Universalism). Discussion: Intergenerational value congruence, as well as knowledge of the difference in preferred values across generations (the collectivism value of Tradition shared by Baby Boomers and Generation X, and Hedonism as an individualism value shared by Generation Y and Generation Z) can help the successful integration of Generation Z representatives in the labor market. A way toward intergenerational synergy can be the recommended strategies for managing Generation Z in the context of career paths: Flexibility of development; Gamification; Mentoring.

OBJECTIVE: The NCCN guidelines recommend genetic testing in those patients at increased risk of breast cancer in order to identify candidates for increased frequency of screening or prophylactic mastectomy. However, genetic testing may now identify patients who may benefit from recently developed targeted breast cancer therapy. In order to more widely identify these patients, we implemented genetic counseling for all patients diagnosed with breast cancer.
METHODS: In 2021, all patients evaluated within a Midwestern community hospital system diagnosed with breast cancer were offered genetic counseling. This group of patients was compared to a cohort of patients in 2021 who were offered genetic counseling based on NCCN guidelines. With Pearson\'s chi square, Fisher\'s Exact test, Mann-Whitney U, and multivariate regression as appropriate, individual demographic data and genetic testing completion between 2019 and 2021 were evaluated.
RESULTS: A total of 973 patients were reviewed. 439 were diagnosed with breast cancer in 2019 and 534 in 2021. Demographics and stage at diagnosis (p = 0.194) were similar between years. Completion of genetic testing increased from 204 (46.5%) in 2019 to 338 (63.3%) in 2021 (p < 0.01) with the universal counseling protocol. Specifically, genetic testing completion increased significantly in older patients (p = 0.041) and patients receiving Medicare benefits (p = 0.005). The overall pathogenic variants found increased from 32 to 39 with the most common including BRCA2 (n = 11), CFTR (n = 9), CHEK2 (n = 8), BRCA1 (n = 6).
CONCLUSIONS: Universal genetic counseling was related to a significant increase in genetic testing completion and an increase in pathogenic variants found among breast cancer patients, specifically in subpopulations which may have been previously excluded by traditional NCCN genetic testing screening guidelines.

Nematodes play a vital ecological role in soil and marine ecosystems, but there is limited information about their dietary diversity and feeding habits. Due to methodological challenges, the available information is based on inference rather than confirmed observations. The lack of correct dietary requirements also hampers rearing experiments. To achieve insight into the prey of mononchid nematodes, this study employed high-throughput Illumina paired-end sequencing using universal eukaryotic species 18S primers on 10 pooled mononchid nematode species, namely Mylonchulus brachyuris, M. brevicaudatus, Mylonchulus sp., Clarkus parvus, Prionchulus sp. M. hawaiiensis, M. sigmaturellus, M. vulvapapillatus, Anatonchus sp. and Miconchus sp. The results indicate that mononchids are associated with a remarkable diversity of eukaryotes, including fungi, algae, and protists. While the metabarcoding approach, first introduced here for mononchids, proved to be a simple and rapid method, it has several limitations and crucial methodological challenges that should be addressed in future studies. Ultimately, such methods should be able to evaluate the dietary complexity of nematodes and provide a valuable avenue for unraveling the dietary requirements of previously unculturable nematodes. This can contribute to the methodology of understanding their feeding habits and contributions to ecosystem dynamics.

Homozygous familial hypercholesterolemia (HoFH) is an ultra-rare inherited condition that affects approximately one in 300,000 people. The disorder is characterized by extremely high, life-threatening levels of low-density lipoprotein (LDL) cholesterol from birth, leading to significant premature cardiovascular morbidity and mortality, if left untreated. Homozygous familial hypercholesterolemia is severely underdiagnosed and undertreated in the United States (US), despite guidelines recommendations for universal pediatric lipid screening in children aged 9-11. Early diagnosis and adequate treatment are critical in averting premature cardiovascular disease in individuals affected by HoFH. Yet, an unacceptably high number of people living with HoFH remain undiagnosed, misdiagnosed, and/or receive a late diagnosis, often after a major cardiovascular event. The emergence of novel lipid-lowering therapies, along with the realization that diagnosis is too often delayed, have highlighted an urgency to implement policies that ensure timely detection of HoFH in the US. Evidence from around the world suggests that a combination of universal pediatric screening and cascade screening strategies constitutes an effective approach to identifying heterozygous familial hypercholesterolemia (HeFH). Nevertheless, HoFH and its complications manifest much earlier in life compared to HeFH. To date, little focus has been placed on the detection of HoFH in very young children and/or infants. The 2023 Updated European Atherosclerosis Society Consensus Statement on HoFH has recommended, for the first time, broadening pediatric guidelines to include lipid screening of newborn infants. Some unique aspects of HoFH need to be considered before implementing newborn screening. As such, insights from pilot studies conducted in Europe may provide some preliminary guidance. Our paper proposes a set of actionable measures that states can implement to reduce the burden of HoFH. It also outlines key research and policy gaps that need to be addressed in order to pave the way for universal newborn screening of HoFH in the US.

Broadly neutralizing antibodies (bnAbs) targeting the hemagglutinin (HA) stem of influenza A viruses (IAVs) tend to be effective against either group 1 or group 2 viral diversity. In rarer cases, intergroup protective bnAbs can be generated by human antibody paratopes that accommodate the conserved glycan differences between the group 1 and group 2 stems. We applied germline-engaging nanoparticle immunogens to elicit a class of cross-group bnAbs from physiological precursor frequency within a humanized mouse model. Cross-group protection depended on the presence of the human bnAb precursors within the B cell repertoire, and the vaccine-expanded antibodies enriched for an N55T substitution in the CDRH2 loop, a hallmark of the bnAb class. Structurally, this single mutation introduced a flexible fulcrum to accommodate glycosylation differences and could alone enable cross-group protection. Thus, broad IAV immunity can be expanded from the germline repertoire via minimal antigenic input and an exceptionally simple antibody development pathway.

Background: Recent research suggests a concerning trend of non-suicidal self-injury (NSSI) and suicidal behaviors emerging at younger ages (as early as age 12). Early onset of NSSI is linked to more severe outcomes. While universal school-based prevention programs have shown promise in addressing suicidal behaviors, there is limited research on their effectiveness in preventing NSSI onset among adolescents. This study aims to evaluate the efficacy of a universal prevention program in schools for NSSI and mental complaints while enhancing resilience and mental health in 11-14-year-old adolescents. Methods: In total, 329 Flemish secondary school students (55.6% female), aged 11 to 14 years, participated in a 4 h classroom universal prevention, with a focus on emotion regulation, mental health, and specific strategies to prevent NSSI and reduce stigma. For both the intervention and control group (N = 124), a pre-, post-, and one-month follow-up questionnaire was administered, containing reliable and valid measures for NSSI and suicidality, emotion regulation, help-seeking behaviors, well-being, and psychological distress. Results: The prevention program effectively reduced NSSI and psychological distress, particularly for adolescents with a history of NSSI. Conclusions: These findings support previous research on the effectiveness of school-based programs in reducing mental complaints and suggest promising outcomes for NSSI prevention.

The effectiveness of universal preventive approaches in reducing the incidence of affective/psychotic disorders is unclear. We therefore aimed to synthesise the available evidence from randomised controlled trials. For studies reporting change in prevalence, we simulated all possible scenarios for the proportion of individuals with the disorder at baseline and at follow-up to exclude them. We then combined these data with studies directly measuring incidence and conducted random effects meta-analysis with relative risk (RR) to estimate the incidence in the intervention group compared to the control group. Eighteen studies (k=21 samples) were included investigating the universal prevention of depression in 66,625 individuals. No studies were available investigating universal prevention on the incidence of bipolar/psychotic disorders. 63 % of simulated scenarios showed a significant preventive effect on reducing the incidence of depression (k=9 - 19, RR=0.75-0.94, 95 %CIs=0.55-0.87,0.93-1.15, p=0.007-0.246) but did not survive sensitivity analyses. There is some limited evidence for the effectiveness of universal interventions for reducing the incidence of depression but not for bipolar/psychotic disorders.

Kinetoplastids are unicellular eukaryotic flagellated parasites found in a wide range of hosts within the animal and plant kingdoms. They are known to be responsible in humans for African sleeping sickness (Trypanosoma brucei), Chagas disease (Trypanosoma cruzi), and various forms of leishmaniasis (Leishmania spp.), as well as several animal diseases with important economic impact (African trypanosomes, including Trypanosoma congolense). Understanding the biology of these parasites necessarily implies the ability to manipulate their genomes. In this study, we demonstrate that transfection of a ribonucleoprotein complex, composed of recombinant Streptococcus pyogenes Cas9 (SpCas9) and an in vitro-synthesized guide RNA, results in rapid and efficient genetic modifications of trypanosomatids, in marker-free conditions. This approach was successfully developed to inactivate, delete, and mutate candidate genes in various stages of the life cycle of T. brucei and T. congolense, and Leishmania promastigotes. The functionality of SpCas9 in these parasites now provides, to the research community working on these parasites, a rapid and efficient method of genome editing, without requiring plasmid construction and selection by antibiotics but requires only cloning and PCR screening of the clones. Importantly, this approach is adaptable to any wild-type parasite.

UNASSIGNED: With efforts underway to develop a universal coronavirus vaccine, otherwise known as a pan-coronavirus vaccine, this is the time to offer potential funders, researchers, and manufacturers guidance on the potential value of such a vaccine and how this value may change with differing vaccine and vaccination characteristics.
UNASSIGNED: Using a computational model representing the United States (U.S.) population, the spread of SARS-CoV-2 and the various clinical and economic outcomes of COVID-19 such as hospitalisations, deaths, quality-adjusted life years (QALYs) lost, productivity losses, direct medical costs, and total societal costs, we explored the impact of a universal vaccine under different circumstances. We developed and populated this model using data reported by the CDC as well as observational studies conducted during the COVID-19 pandemic.
UNASSIGNED: A pan-coronavirus vaccine would be cost saving in the U.S. as a standalone intervention as long as its vaccine efficacy is ≥10% and vaccination coverage is ≥10%. Every 1% increase in efficacy between 10% and 50% could avert an additional 395,000 infections and save $1.0 billion in total societal costs ($45.3 million in productivity losses, $1.1 billion in direct medical costs). It would remain cost saving even when a strain-specific coronavirus vaccine would be subsequently available, as long as it takes at least 2-3 months to develop, test, and bring that more specific vaccine to the market.
UNASSIGNED: Our results provide support for the development and stockpiling of a pan-coronavirus vaccine and help delineate the vaccine characteristics to aim for in development of such a vaccine.
UNASSIGNED: The National Science Foundation, the Agency for Healthcare Research and Quality, the National Institute of General Medical Sciences, the National Center for Advancing Translational Sciences, and the City University of New York.