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Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder of motor neurons. Although most cases of ALS are sporadic (sALS) and of unknown etiology, there are also inherited familial ALS (fALS) cases that share a phenotype similar to sALS pathological and clinical phenotype. In this study, we have identified two new potential genetic ALS biomarkers in human bone marrow mesenchymal stem cells (hMSC) obtained from sALS patients, namely the TDP-43 (TAR DNA-binding protein 43) and SLPI (secretory leukocyte protease inhibitor). Together with the previously discovered ones-CyFIP2 and RbBP9, we investigated whether these four potential ALS biomarkers may be differentially expressed in tissues obtained from mutant SOD1(G93A) transgenic mice, a model that is relevant for at least 20% of the fALS cases. Quantitative real-time PCR analysis of brain, spinal cord and muscle tissues of the mSOD1(G93A) and controls at various time points during the progression of the neurological disease showed differential expression of the four identified biomarkers in correlation with (i) the tissue type, (ii) the stage of the disease and (iii) the gender of the animals, creating thus a novel spatiotemporal molecular signature of ALS. The biomarkers detected in the fALS animal model were homologous to those that were identified in hMSC of our sALS cases. These results support the possibility of a molecular link between sALS and fALS and may indicate common pathogenetic mechanisms involved in both types of ALS. Moreover, these results may pave the path for using the mSOD1(G93A) mouse model and these biomarkers as molecular beacons to evaluate the effects of novel drugs/treatments in ALS.

Abstract Mechanical engineering (ME) departments in research universities face the challenge of educating mechanical engineers who will graduate with a balanced knowledge in engineering science and mechanical design. The source of this challenge is the inherent difference between teaching analytical thinking, which is required for most engineering-science courses, and design thinking, which is required for project-based design courses. The purpose of this paper is first to propose a new approach that can potentially bridge the educational gap between analytical and design thinking, which we refer to as integrated thinking. Second, we show how it can be applied to various ME undergraduate courses, which we refer to as integrated courses. Our approach reforms science engineering courses by (a) stressing the physical interpretation of mathematical derivations; (b) requiring students to analyze, design, and sketch simple mechanical devices based on the learned theoretical material; and (c) modifying project-based design courses to emphasize the importance of analysis as part of the creative design process. A pilot course focusing on dynamics and vibration, which we called Integrated Design and Analysis, was offered in the ME department at the Technion, where it was well-attended by senior ME students. The positive feedback of the students who took the course suggests that integrated thinking might be successfully applied in many areas of ME education, such as fluid mechanics and heat transfer, control, and mechatronics, and that our approach may contribute to changing the current divided pattern in ME education.

This paper describes a novel approach to systematically improve information interactions based solely on its wording. Following an interdisciplinary literature review, we recognized three key attributes of words that drive user engagement: (1) Novelty (2) Familiarity (3) Emotionality. Based on these attributes, we developed a model to systematically improve a given content using computational linguistics, natural language processing (NLP) and text analysis (word frequency, sentiment analysis and lexical substitution). We conducted a pilot study (n=216) in which the model was used to formalize evaluation and optimization of academic titles. A between-group design (A/B testing) was used to compare responses to the original and modified (treatment) titles. Data was collected for selection and evaluation (User Engagement Scale). The pilot results suggest that user engagement with digital information is fostered by, and perhaps dependent upon, the wording being used. They also provide empirical support that engaging content can be systematically evaluated and produced. The preliminary results show that the modified (treatment) titles had significantly higher scores for information use and user engagement (selection and evaluation). We propose that computational linguistics is a useful approach for optimizing information interactions. The empirically based insights can inform the development of digital content strategies, thereby improving the success of information interactions.elop more sophisticated interaction measures. Comment: Dvir, N., & Gafni, R. (2019). Systematic improvement of user engagement with academic titles using computational linguistics. Proceedings of the Informing Science and Information Technology Education Conference, Jerusalem, Israel, pp. 501-512 Santa Rosa, CA: Informing Science Institute. https://doi.org/10.28945/4338

A comprehensive physical model of adiabatic three-wave mixing is developed for the fully nonlinear regime, i.e., without making the undepleted pump approximation. The conditions for adiabatic evolution are rigorously derived, together with an estimate of the bandwidth of the process. Furthermore, these processes are shown to be robust and efficient. Finally, numerical simulations demonstrate adiabatic frequency conversion in a wide variety of physically attainable configurations.

Managing in the community without accommodation requires that persons be able to walk an adequate distance. However, little information is available regarding how walking distance changes over the course of inpatient rehabilitation.To describe, for inpatients participating in subacute rehabilitation, the distances walked without stopping at admission and discharge and to document the reliability and responsiveness of the measure.Observational longitudinal study.Subacute rehabilitation.Male and female inpatients of multiple diagnostic groups who were at least 60 years old (n = 130).Participants were asked to walk at a self-selected speed as far as they could without stopping. They walked on a 15.2-m out-and-back course for a maximum of 2 minutes upon admission, the next day, and at discharge.The mean distances walked upon admission, the next day, and at discharge were 35.6, 39.9, and 77.0 m, respectively. Good test-retest reliability was demonstrated for the distances walked upon admission and the next day (intraclass correlation coefficient = 0.948). The distance walked increased significantly between admission and discharge (t = 22.22, P.001). The effect size and standardized response mean for these distances were large-2.36 and 1.95, respectively. The minimum detectable change was 11.1 m. The minimal clinically important difference determined by receiver operator characteristic curve analysis ranged from 28.8 m to 43.6 m depending on the anchor used. The associated areas under the curve ranged from 0.700-0.897.Based on our findings, we conclude that distance walked without stopping is an informative, reliable, and responsive measure of gait performance for patients undergoing subacute rehabilitation. We therefore encourage the systematic documentation of distance walked among inpatients undergoing subacute rehabilitation.

Distal rectal cancer resection is an ongoing challenge for the colorectal surgeon. In recent years new technical approaches, especially with implementation of transanal platforms were developed to help in the visualization and resection of these tumors. Nevertheless, the use of these platforms is demanding with significant complications during the onset phase.Patients with very low rectal cancer were operated on in a single tertiary center with a combined abdominal and transanal endoscopic microsurgery (TEM) approach. Demographic, pathological, and surgical data were collected retrospectively with an emphasis on distal margin involvement.Nineteen patients were operated on during the study period. All patients had negative distal resection margins with a low complication rate. The distant metastasis and local recurrence rates were low with a mean follow-up of 2 years.TEM provides an appealing and viable option for the resection of low rectal cancer in a combined transabdominal and transanal approach in patients with a good response after neoadjuvant treatment. This is one of the available platforms a colorectal surgeon might benefit from having in his armamentarium. It has a very low complication rate with maintenance of oncological principles, enabling a clear visualization of the distal rectum, and thus ensures free distal resection margins.

Background In a double-blind placebo-controlled randomized trial with parallel groups, the efficacy of individually prescribed homeopathic medicines was evaluated in women with premenstrual syndrome (PMS). Methods In an outpatient department of a university clinic in Jerusalem, Israel (1996–1999), women with PMS, aged 18 to 50 years, entered a 2-month screening phase with prospective daily recording of premenstrual symptoms by the Menstrual Distress Questionnaire (MDQ). They were included after being diagnosed with PMS. A reproducible treatment protocol was used: women received a homeopathic prescription based on symptom clusters identified in a questionnaire. The symptoms were verified during a complementary, structured, interview. Only women whose symptoms matched the symptom profile of one of 14 pre-selected homeopathic medicines were included. Each participant was administered active medicine or placebo via random allocation. Primary outcome measures were differences in changes in mean daily premenstrual symptom (PM) scores by the MDQ. Analysis was by intention-to-treat. Results A total of 105 women were included: 49 were randomized to active medicine and 56 to placebo. Forty-three women in the active medicine group and 53 in the placebo group received the allocated intervention with at least one follow-up measurement and their data were analyzed. Significantly greater improvement of mean PM scores was measured in the active medicine group (0.443 [standard deviation, SD, 0.32] to 0.287 [SD, 0.20]) compared to placebo (0.426 [SD, 0.34] to 0.340 [SD, 0.39]); p = 0.043. Conclusions Individually prescribed homeopathic medicines were associated with significantly greater improvement of PM scores in women with PMS, compared to placebo. Replication, with larger sample size and other refinements, is recommended to confirm the efficacy of this treatment in other settings.

Objective Isotretinoin is among the most notorious human teratogens, documented originally as causing up to 30% of malformations. This systematic review and meta-analysis aimed to evaluate the rates of major malformation (MM) among isotretinoin-exposed pregnant women over the years through a systematic review and meta-analysis.Methods Eligible studies were searched and identified using various databases. Single-arm meta-analysis and meta-analysis of odd ratios among controlled studies were performed using Review Manager version 5.3.Results Ten eligible studies that combined 2,783 isotretinoin-exposed women were included in our study. The rate of MM weighted for the sample size was 15%. Three studies that included an unexposed comparison group were eligible for the meta-analysis. The pooled odds ratio of MM for isotretinoin-exposed women was 3.76. After 2006, the pooled odds ratio of MM for isotretinoin exposure was significantly lower at 1.04.Conclusion The current rate of MM in isotretinoin-exposed women was substantially lower after 2006.