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Abstract In vitro fertilization is typically associated with high failure rates per transfer, leading to an acute need for the identification of embryos with high developmental potential. Current methods are tailored to specific times after fertilization, often require expert inspection, and have low predictive power. Automatic methods are challenged by ambiguous labels, clinical heterogeneity, and the inability to utilize multiple developmental points. In this work, we propose a novel method that trains a classifier conditioned on the time since fertilization. This classifier is then integrated over time and its output is used to assign soft labels to pairs of samples. The classifier obtained by training on these soft labels presents a significant improvement in accuracy, even as early as 30 h post-fertilization. By integrating the classification scores, the predictive power is further improved. Our results are superior to previously reported methods, including the commercial KIDScore-D3 system, and a group of eight senior professionals, in classifying multiple groups of favorable embryos into groups defined as less favorable based on implantation outcomes, expert decisions based on developmental trajectories, and/or genetic tests.

Abstract Background It has been shown – mostly in animal models - that circadian clock genes are expressed in granulosa cells and in corpora luteum and might be essential for the ovulatory process and steroidogenesis. Objective We sought to investigate which circadian clock genes exist in human granulosa cells and whether their expression and activity decrease during aging of the ovary. Study design Human luteinized granulosa cells were isolated from young (age 18–33) and older (age 39–45) patients who underwent in-vitro fertilization treatment. Levels of clock genes expression were measured in these cells 36 h after human chorionic gonadotropin stimulation. Methods Human luteinized granulosa cells were isolated from follicular fluid during oocyte retrieval. The mRNA expression levels of the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2 were analyzed by quantitative polymerase chain reaction. Results We found that the circadian genes CRY1, CRY2, PER1, PER2, CLOCK, ARNTL, ARNTL2, and NPAS2, are expressed in cultured human luteinized granulosa cells. Among these genes, there was a general trend of decreased expression in cells from older women but it reached statistical significance only for PER1 and CLOCK genes (fold change of 0.27 ± 0.14; p = 0.03 and 0.29 ± 0.16; p = 0.05, respectively). Conclusions This preliminary report indicates that molecular circadian clock genes exist in human luteinized granulosa cells. There is a decreased expression of some of these genes in older women. This decline may partially explain the decreased fertility and steroidogenesis of reproductive aging.

School bullying and cyberbullying are serious public health problems that negatively affect the lives of school-aged children. We examined the correlation between risk behaviors and lack of resiliency factors with bullying and cyberbullying across seven Mediterranean countries. The sample consisted of 33,399 adolescents (51.1% girls) aged 11, 13, and 15 years who participated in the Health Behavior in School-aged Children (HBSC) survey in 2018 in Greece, Israel, Italy, Macedonia, Malta, Portugal, and Spain. Bivariate logistic regressions were conducted to test the relationship between risk behaviors, resilience, and bullying. All risk behaviors and lack of resiliency factors examined were related to involvement in bullying as a victim, perpetrator, or bully-victim, both in school and cyberbullying. Moreover, the odds of involvement in school bullying and cyberbullying increased as the number of risk behaviors and the lack of resiliency factors grew. Our results may contribute to the development and implementation of anti-bullying programs.

Volunteering can serve as a protective factor against substance abuse. Yet, it is unclear whether volunteering in specific community organizations, such as emergency services, promotes or protects against substance use. We aimed to (1) describe community volunteering characteristics among adolescents; (2) investigate differences in the prevalence of substance use according to community volunteering type; and (3) determine whether volunteering type was a predictor of substance use. We analyzed data from the 2018-2019 Health Behavior in School-aged Children survey among Israeli adolescents aged 11-17 years (N = 3972). Most participants (N = 2452; 61.7%) did not volunteer at all, 27.1% (N = 1077) volunteered in youth movements/councils, and 11.2% (N = 443) volunteered in community emergency services. In comparison to the emergency services group, there was a higher volunteering frequency among the youth movements/councils group. Of the three groups (nonvolunteering, volunteering in youth movements/councils, and volunteering in community emergency services), those in the community emergency services group reported a significantly higher prevalence of weekly alcohol use, lifetime cannabis use, and new psychoactive drug use, while no significant between-group differences were observed in smoking tobacco prevalence. Volunteering in the community emergency services has been linked to substance use, requiring the development of intervention programs by the school staff, before their active volunteering (e.g., guidance on emotional stress and substance abuse). Also, teachers can act as a protective factor for students, and identify emotional distress and anxiety in their students to prevent substance abuse. Furthermore, emergency services workers and instructors should also be aware of the higher risk of substance use among volunteering youth and should be given tools to better collaborate with parents and teachers in dealing with it.

BackgroundOvarian cancer is the leading cause of mortality among gynecological malignancies. Carboplatin and poly (ADP-ribose) polymerase inhibitors (PARPi) are often implemented in the treatment of ovarian cancer. Homologous recombination deficient (HRD) tumors demonstrate increased sensitivity to these treatments; however, many ovarian cancer patients are homologous recombination proficient (HRP). TTFields are non-invasive electric fields that induce an HRD-like phenotype in various cancer types. The current study aimed to investigate the impact of TTFields applied together with carboplatin or PARPi (olaparib or niraparib) in preclinical ovarian cancer models.MethodsA2780 (HRP), OVCAR3 (HRD), and A2780cis (platinum-resistant) human ovarian cancer cells were treated in vitro with TTFields (1 V/cm RMS, 200 kHz, 72 h), alone or with various drug concentrations. Treated cells were measured for cell count, colony formation, apoptosis, DNA damage, expression of DNA repair proteins, and cell cycle. In vivo, ID8-fLuc (HRP) ovarian cancer cells were inoculated intraperitoneally to C57BL/6 mice, which were then treated with either sham, TTFields (200 kHz), olaparib (50 mg/kg), or TTFields plus olaparib; over a period of four weeks. Tumor growth was analyzed using bioluminescent imaging at treatment cessation; and survival analysis was performed.ResultsThe nature of TTFields-drug interaction was dependent on the drug’s underlying mechanism of action and on the genetic background of the cells, with synergistic interactions between TTFields and carboplatin or PARPi seen in HRP and resistant cells. Treated cells demonstrated elevated levels of DNA damage, accompanied by G2/M arrest, and induction of an HRD-like phenotype. In the tumor-bearing mice, TTFields and olaparib co-treatment resulted in reduced tumor volume and a survival benefit relative to olaparib monotherapy and to control.ConclusionBy inducing an HRD-like phenotype, TTFields sensitize HRP and resistant ovarian cancer cells to treatment with carboplatin or PARPi, potentially mitigating a-priori and de novo drug resistance, a major limitation in ovarian cancer treatment.

Abstract Blastocyst selection is primarily based on morphological scoring systems and morphokinetic data. These methods involve subjective grading and time-consuming techniques. Artificial intelligence allows for objective and quick blastocyst selection. In this study, 608 blastocysts were selected for transfer using morphokinetics and Gardner criteria. Retrospectively, morphometric parameters of blastocyst size, inner cell mass (ICM) size, ICM-to-blastocyst size ratio, and ICM shape were automatically measured by a semantic segmentation neural network model. The model was trained on 1506 videos with 102 videos for validation with no overlap between the ICM and trophectoderm models. Univariable logistic analysis found blastocyst size and ICM-to-blastocyst size ratio to be significantly associated with implantation potential. Multivariable regression analysis, adjusted for woman age, found blastocyst size to be significantly associated with implantation potential. The odds of implantation increased by 1.74 for embryos with a blastocyst size greater than the mean (147 ± 19.1 μm). The performance of the algorithm was represented by an area under the curve of 0.70 (p

Fiber Bragg gratings (FBGs) inscribed by UV light and different femtosecond laser techniques (phase mask, point-by-point, and plane-by-plane) were exposed—in several irradiation cycles—to accumulated high doses of gamma rays (up to 124 MGy) and neutron fluence (8.7 × 1018/cm2) in a research-grade nuclear reactor. The FBG peak wavelengths were measured continuously in order to monitor radiation-induced shifts. Gratings inscribed on pure silica core fibers using near-IR femtosecond pulses through a phase mask showed the smallest shifts (<30 pm), indicating that these FBGs are suitable for temperature measurement even under extreme ionizing radiation. In contrast, the pointwise inscribed femtosecond gratings and a UV-inscribed grating showed maximal shifts of around 100 pm and 400 pm, respectively. Radiation-induced red shifts are believed to arise from gamma radiation damage, which may partially recover after irradiation is stopped. At the highest neutron exposures, grating peak blue shifts started to appear, apparently due to fiber compaction. [ABSTRACT FROM AUTHOR]

Objectives: The demand for ED services, both in terms of patient numbers and complexity has risen over the past decades. According to reports, there has been an increase in the ED patient presentation rate from 330 per 1000 to 334 per 1000 between 2018–2019 and 2022–2023. Consequently, new care models have been introduced to address this surge in demand, mitigate associated risks and improve overall safety. Among these models is the concept of 'front loading' clinical care, involving the initiation of interventions at the point of arrival. The present study evaluates the impact of introducing phlebotomists at triage. Methods: We conducted a cross‐sectional survey using purposive sampling at a single quaternary metropolitan ED with an annual census of greater than 90 000, encompassing all clinical staff in the ED. The survey data were analysed quantitatively and complemented by a thematic analysis. Results: The response rate for the questionnaire was 61% (n = 207), with good representation from all ED craft groups. Nearly all the staff (99.5%) reported being aware of the presence of phlebotomists in the ED, whereas only 57% of the staff reported working in triage (P = 0.05, 0.00 to 0.04). 'Valuable/vital resource' featured as a common response. Early decision‐making, patient safety, staff and patient satisfaction emerged as consistent themes. Conclusions: Staff expressed satisfaction that patient care now begins in the waiting room, especially after extended waiting periods prior to cubicle allocation. They assert that this improvement significantly enhances timely treatment and disposition decisions, as well as overall patient satisfaction. [ABSTRACT FROM AUTHOR]

Automated live embryo imaging has transformed in vitro fertilization (IVF) into a data‐intensive field. Unlike clinicians who rank embryos from the same IVF cycle cohort based on the embryos visual quality and determine how many embryos to transfer based on clinical factors, machine learning solutions usually combine these steps by optimizing for implantation prediction and using the same model for ranking the embryos within a cohort. Herein, it is established that this strategy can lead to suboptimal selection of embryos. It is revealed that despite enhancing implantation prediction, inclusion of clinical properties hampers ranking. Moreover, it is found that ambiguous labels of failed implantations, due to either low‐quality embryos or poor clinical factors, confound both the optimal ranking and even implantation prediction. To overcome these limitations, conceptual and practical steps are proposed to enhance machine learning‐driven IVF solutions. These consist of separating the optimizing of implantation from ranking by focusing on visual properties for ranking and reducing label ambiguity. [ABSTRACT FROM AUTHOR]

Objectives: Evaluating the effectiveness and safety of repeated high‐dose intradetrusor abobotulinumtoxin A (Dysport®) injections for the treatment of pediatric neurogenic bladders refractory to medications. Design: Retrospective interventional study. Participants: The cohort included 37 children (22 boys and 15 girls) of median age 9.2 years. Inclusion criteria were diagnosis of neurogenic bladder and failure to respond to medical treatment. Exclusion criteria were augmented bladder, insufficient data, and interval of > 11 months between video‐urodynamic study and Dysport injection. Interventions: All participants were treated with an intra‐detrusor injection of Dysport 30 IU/kg (up to 1000 IU) under general anesthesia. Repeated (second and third) injections were scheduled (6–12 months) in patients who demonstrated an improvement in cystometric parameters. All participants underwent video urodynamic testing before onset of treatment and 4–5 months after subsequent injection. Main Outcome Measures: Success of treatment was defined as a decrease in end filling pressure (EFP) to < 40 cm H2O and/or a 20% increase in maximal cystometric capacity (MCC). These parameters along with initial bladder features were evaluated for ability to predict treatment success. Results: No side effects of Dysport were observed or reported. The overall success rate was 62%. MCC increased by a median of 30% (IQR 200–300, p < 0.001), 37% (IQR 197–310, p = 0.001) and 45% (IQR 245–300, p = 0.025) after the first, second and third injections, respectively. Median EFP decreased from 45 cm H2O to 34 cm H2O (IQR 20–45, p = 0.029), 23 cm H2O (IQR 20–37, p = 0.004), and 20 cm H2O (IQR 12–32, p = 0.049) after the first, second, and third injections, respectively. No predicting factor of success of treatment were found; However, three of five cases of "end stage" bladder showed improvement. Conclusions: High‐dose Dysport injection is safe and effective for the treatment of neurogenic bladder. Studies with larger cohort and a control group would further elucidate which bladders would benefit most. At present, we recommend treating also bladders with "end stage" features with botulinum toxin before considering augmentation. [ABSTRACT FROM AUTHOR]