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Miltefosine, an orally administered drug, is an important component of the therapeutic arsenal against visceral and mucosal forms of leishmaniasis. However, data regarding the safety and tolerability of miltefosine treatment for cutaneous leishmaniasis (CL) are relatively limited. The aim of this study was to evaluate the tolerability, safety, and adverse events (AEs) of miltefosine treatment in patients with CL. In this cohort study, we reviewed the medical records of all miltefosine-treated patients between 1 January 2016 and 31 December 2022, at Israel Defense Forces military dermatology clinics and the dermatology and Tropical Medicine Clinics at Chaim Sheba Medical Center, Ramat-Gan, Israel. A total of 68 patients (54 males, 79%) with a median age of 30.3 ± 15.6 years (range: 18–88) were included in this study. Leishmania species were identified as L. major (n = 37, 54.4%), L. tropica (n = 12, 17.6%), L. braziliensis (n = 18, 26.5%), and L. infantum (n = 1, 1.5%) using polymerase chain reaction (PCR). Miltefosine tablets were administered orally at a dose of 50 mg, three times daily, for 28 days. Overall, 44 patients (65%) completed the 28-day treatment, and the remaining patients required dose reduction or early discontinuation of treatment. AEs (of any degree) were common, reported in 91% of patients. Both previously reported and previously unreported AEs were documented. Gastrointestinal symptoms (66.1%) and malaise (23.5%) typically occurred during the first two weeks of treatment and tended to subside. Other AEs, including acute renal failure (20.6%), sudden and severe pleuritic chest pain (7.6%), acne exacerbation (11.8%), suppuration of CL lesions (17.8%), and AEs related to the male genitourinary system (39.6% of males), typically occurred towards the end of treatment. The latter included testicular pain, epididymitis, diminution or complete absence of ejaculate, inability to orgasm, and impotence. Severe AEs necessitated treatment discontinuation (29.4%) or hospitalization (10.3%). URTI-like symptoms, arthritis, cutaneous eruption, pruritus, and laboratory abnormalities were also observed. Overall, the cure rate (for all patients combined) evaluated 3 months after the completion of treatment was 60%. The tolerability of miltefosine treatment for CL is low. Close clinical and laboratory monitoring is required during treatment, as severe AEs are not uncommon. As new insights regarding its toxicities emerge, further studies are required to define the role of miltefosine in the treatment of CL. Full article

The goal of teaching quantum physics (QP) in high school is a problematic and highly turbulent area of divergent views, curricula studies, and claims. The innovative curricular approach of discipline-culture (DC) suggests a way of overcoming its significant difficulties. It suggests presenting QP as a fundamental theory structured in terms of the nucleus, body, and periphery. Applying this perspective in our study, we interviewed nine experts with respect to their view of how the nucleus of QP should be presented to high-school students. With the different viewpoints of the core essentials in hand, we compiled the nucleus of the QP. We also examined this subject using nine introductory university textbooks that might suit high school students and considered their coherence and suitability with regard to the specified nucleus. We found some confusion regarding the status of theoretical items: some fundamental principles, as perceived in the eyes of the experts, are presented as phenomena. Not only does this mismatch represent a special barrier for both the teachers and students to understand QP, it promotes an inadequate image of QP as well as a distorted view of the nature of science. Finally, we offer a framework for a DC-based QP curriculum free of the noted deficiencies. Full article

High-grade serous ovarian carcinoma (HGSOC) is the most common type of epithelial ovarian cancer. The majority of cases are diagnosed at advanced stages, when intraperitoneal (IP) spread has already occurred. Despite significant surgical and chemotherapeutic advances in HGSOC treatment over the past decades, survival rates with HGSOC have only modestly improved. Chimeric antigen receptor (CAR)-T cells enable T cells to directly bind to tumor-associated antigens in a major histocompatibility complex-independent manner, thereby inducing tumor rejection. While CAR-T cell therapy shows great promise in hematological malignancies, its use in solid tumors is limited. Therefore, innovative approaches are needed to increase the specificity of CAR-modified T cells against solid tumors. The aim of this study was to assess the efficacy and safety of intraperitoneal (IP) versus intravenous (IV) CAR-T cell therapy in the treatment of HGSOC. We constructed a CAR that targets the ErbB2/HER2 protein (ErbB2CAR), which is overexpressed in HGSOC, and evaluated the functionality of ErbB2CAR on ovarian cancer cell lines (OVCAR8, SKOV3, and NAR). Our findings show that an IP injection of ErbB2CAR-T cells to tumor-bearing mice led to disease remission and increased survival compared to the IV route. Moreover, we found that IP-injected ErbB2CART cells circulate to a lesser extent, making them safer for non-tumor tissues than IV-injected cells. Further supporting our findings, we show that the effect of ErbB2CAR-T cells on primary HGSOC tumors is correlated with ErbB2 expression. Together, these data demonstrate the advantages of an IP administration of CAR-T cells over IV administration, offering not only a safer strategy but also the potential for counteracting the effect of ErbB2CAR in HGSOC. Significance: IP-injected ErbB2CAR-T cells led to disease remission and increased survival compared to the IV route. These findings demonstrate the advantages of IP administration, offering a safe treatment strategy with the potential for counteracting the effect of ErbB2CAR in HGSOC. Full article

Quantum computation by the adiabatic theorem requires a slowly-varying Hamiltonian with respect to the spectral gap. We show that the Landau–Zener–Stückelberg oscillation phenomenon, which naturally occurs in quantum two-level systems under non-adiabatic periodic drive, can be exploited to find the ground state of an N-dimensional Grover Hamiltonian. The total runtime of this method is $O(\sqrt{2^n})$ , which is equal to the computational time of the Grover algorithm in the quantum circuit model. An additional periodic drive can suppress a large subset of Hamiltonian control errors by using coherent destruction of tunneling, thus outperforming previous algorithms. Full article

In 2017, there were nearly 80,000 asylum seekers and undocumented migrant workers in Israel, most of whom did not have health insurance. We evaluated trends in medical visits of asylum seekers and undocumented migrant workers who presented to Terem Refugee Clinic (TRC), a large clinic in Tel Aviv available only to uninsured residents of Israel. Data were collected from electronic medical records at TRC from 2013–2017. Diagnoses were grouped into categories using ICD-10-equivalent diagnosis codes. We used a chi-squared test for trends to test the significance of trends 2013 to 2017. There were 99,569 medical visits from 2013 to 2017 at TRC. Visits were lowest in 2013 (11,112), and relatively stable from 2014–2017 (range: 19,712–23,172). Most visits were among adults aged 18–35 (41.2%) and children <2 years old (23.7%). Only 3% of visits were from patients aged >50. The percentage of infectious disease diagnoses decreased over the study period, from 9.4% of all diagnoses in adults in 2014 to 5.2% in 2017, and from 32.0% of all diagnoses in children in 2013 to 19.4% in 2017. The annual percentage of respiratory diagnoses in children and adults 18–35 years of age, musculoskeletal in all adults, and digestive in adults except women ≥35 years old increased. Over time, asylum seekers and undocumented migrant workers visited TRC with fewer infectious diseases diagnoses overall but more respiratory diseases, including acute respiratory infections and more musculoskeletal diseases. Full article