mTORC1 regulates cell survival under glucose starvation through 4EBP1/2-mediated translational reprogramming of fatty acid metabolism.

Energetic stress compels cells to evolve adaptive mechanisms to adjust their metabolism. Inhibition of mTOR kinase complex 1 (mTORC1) is essential for cell survival during glucose starvation. How mTORC1 controls cell viability during glucose starvation is not well understood. Here we show that the mTORC1 effectors eukaryotic initiation factor 4E binding proteins 1/2 (4EBP1/2) confer protection to mammalian cells and budding yeast under glucose starvation. Mechanistically, 4EBP1/2 promote NADPH homeostasis by preventing NADPH-consuming fatty acid synthesis via translational repression of Acetyl-CoA Carboxylase 1 (ACC1), thereby mitigating oxidative stress. This has important relevance for cancer, as oncogene-transformed cells and glioma cells exploit the 4EBP1/2 regulation of ACC1 expression and redox balance to combat energetic stress, thereby supporting transformation and tumorigenicity in vitro and in vivo. Clinically, high EIF4EBP1 expression is associated with poor outcomes in several cancer types. Our data reveal that the mTORC1-4EBP1/2 axis provokes a metabolic switch essential for survival during glucose starvation which is exploited by transformed and tumor cells.

Monitoring jellyfish outbreaks along Israel's Mediterranean coast using digital footprints.

With mounting global concerns about jellyfish outbreaks, monitoring their occurrence remains challenging. Tapping into the wealth of digital data that internet users share online, which includes reports of jellyfish sightings, may provide an alternative or complement to more conventional expert-based or citizen science monitoring. Here, we explore digital footprints as a data source to monitor jellyfish outbreaks along the Israeli Mediterranean coast. We compiled jellyfish sighting data for the period 2011-2022 from multiple platforms, including leading social media platforms, searches in the Google search engine, and Wikipedia page views. Employing time series analysis, cross-correlation, and various evaluation metrics for presence/absence data, we compared weekly data from three sources: digital footprints, citizen science, and traditional expert-based field monitoring. Consistent seasonal patterns emerge across datasets, with notable correlations, particularly in jellyfish abundance. The cross-correlation between digital footprint and citizen science data exceeds >0.7, with Twitter and Instagram showing the highest correlation. Citizen science data often precedes digital footprints by up to one week. Correlation with traditional, expert-based field monitoring is limited as a result of limited data availability. Digital footprints demonstrate substantial agreement with the other data sources regarding jellyfish presence/absence and major outbreaks, especially for data from Wikipedia, Twitter, and Instagram. Overall, we highlight digital footprint data as a reliable, cost-effective tool for passive monitoring of jellyfish outbreaks, which can aid characterization in data-scarce coastal regions, including retrospective assessment. Transferring and scaling up the proposed approach should consider data accessibility as well as platform relative popularity and usage in the regions under investigation.

The Effect of Short-Term Acute Residential Treatment on Psychiatric Rehospitalization.

ABSTRACT: Short-Term Acute Residential Treatment (START) homes, located in the community and operating in noninstitutional atmospheres, seek to reduce rehospitalization. This report investigates whether these homes reduced rates and duration of subsequent inpatient stays in psychiatric hospitals. For 107 patients treated in START homes after psychiatric hospitalization, we compared the number and duration of psychiatric hospitalizations before and after their START stay. We found that, compared with the year before the START stay, in the year after the START stay, patients had fewer episodes of rehospitalization (1.60 [SD = 1.23] vs. 0.63 [SD = 1.05], t[106] = 7.097, p < 0.001) and a briefer accumulative duration of inpatient stays (41.60 days [SD = 49.4] vs. 26.60 days [SD = 53.25], t[106] = -2.32, p < 0.03). This suggests that START homes can reduce rehospitalization rates and should be considered a valid alternative to psychiatric hospitalization.

COVID-19 and severe mental illness in Israel: testing, infection, hospitalization, mortality and vaccination rates in a countrywide study.

Previous studies on psychiatric patients infected with COVID-19 have reported a more severe course of disease and higher rates of mortality compared with the general population. This cohort study linked Israeli national databases including all individuals ever hospitalized for a psychiatric disorder (cases), and COVID-19 testing, infection, hospitalization, mortality, and vaccinations, between March 1st 2020 and March 31st 2021. Cases were 125,273 individuals aged 18 and above ever hospitalized in a psychiatric facility (ICD-10 F10-F69 or F90-F99), compared to the total population, n = 6,143,802. Compared with the total population, cases were less likely to be tested for COVID-19, 51.2% (95% CI: 50.8-51.7) vs 62.3% (95% CI 62.2-62.4) and had lower rates of confirmed COVID infection, 5.9% (95% CI: 5.8-6.1) vs 8.9% (95% CI: 8.9-8.9). Among those infected, risks for COVID-19 hospitalization, COVID-19 attributed mortality and all-cause mortality were higher for cases than the total population, adjusted odds ratios were 2.10; (95% CI: 1.96-2.25), 1.76; (95% CI: 1.54-2.01) and 2.02; (95% CI: 1.80-2.28), respectively. These risks were even higher for cases with non-affective psychotic disorders and bipolar disorder. Age adjusted rates of vaccination were lower in cases, 60.4% (95% CI: 59.9-60.8) vs 74.9% (95% CI: 74.8-75.0) in the total population, and particularly low for cases with non-affective psychotic disorders, 56.9% (95% CI: 56.3-57.6). This study highlights the need to increase testing for COVID-19 in individuals ever hospitalized for a psychiatric disorder, closely monitor those found positive, and to reach out to encourage vaccination.

The assessment of a growing mobile anesthesia practice from 2016 to 2019: A retrospective observational cohort study of 89,999 cases comparing ambulatory surgery (ASC) and office-based surgery (OBS) centers using a high-fidelity, anesthesia-specific electronic medical record (EMR).

Office-based surgery (OBS) has emerged as a significant subspecialty of ambulatory surgery. There are few clinical trials and limited published data on patient characteristics, anesthesia, or outcomes distinguishing OBS from ambulatory surgery centers (ASCs). We examined retrospective data from a large mobile anesthesia practice for 89,999 procedures from 2016 to 2019. Data was abstracted from billing and an anesthesia-specific electronic medical record, segregating procedures performed in ASCs versus OBS. The number and breadth of procedures increased substantially. Compared to ASCs, OBS patients were more likely male (52% vs. 48%), older (61 years vs. 55 years), and to have a higher American Society of Anesthesiologists (ASAs) status (33% vs. 20% ASA 3 or higher). The procedure mix varied substantially between the two settings. The major complication rate was 0.07% for the ASCs and 0.24% for OBS (p = 0.2, confidence interval [CI] -0.15 to 0.04). Minor complications were 11.2% in OBS versus 17.3% the ASCs (p < 0.0001, 95% CI 5.2-7). The practice demonstrates a low rate of complications, and despite the limitations of this study, the organization and structure of this large mobile anesthesia practice serves as a template for effective risk mitigation and patient safety.

Machine Learning Improves Trace Explosive Selectivity: Application to Nitrate-Based Explosives.

Ion mobility spectrometry (IMS) is the method of choice to detect trace amounts of explosives in most airports and border crossing settings. For most explosives, the IMS detection limits are suitably low enough to meet security requirements. However, for some explosive families, the selectivity is not sufficient. One such family is nitrate-based explosives, where discrimination between various nitrate threats and ambient nitrates is challenging. Using a small database, machine learning methods were utilized to examine the extent of improvement in IMS selectivity for detection of nitrate-based explosives. Five classes were considered in this preliminary study: ammonium nitrate (AN), an ∼95:5 mixture of AN and fuel oil (ANFO), urea nitrate (UN), nitrate due to environmental pollution, and samples that did not contain any explosive (blanks). The preliminary results clearly show that the incorporation of machine learning methods can lead to a significant improvement in IMS selectivity.

Comparison of deep learning models for natural language processing-based classification of non-English head CT reports.

PURPOSE: Natural language processing (NLP) can be used for automatic flagging of radiology reports. We assessed deep learning models for classifying non-English head CT reports. METHODS: We retrospectively collected head CT reports (2011-2018). Reports were signed in Hebrew. Emergency department (ED) reports of adult patients from January to February for each year (2013-2018) were manually labeled. All other reports were used to pre-train an embedding layer. We explored two use cases: (1) general labeling use case, in which reports were labeled as normal vs. pathological; (2) specific labeling use case, in which reports were labeled as with and without intra-cranial hemorrhage. We tested long short-term memory (LSTM) and LSTM-attention (LSTM-ATN) networks for classifying reports. We also evaluated the improvement of adding Word2Vec word embedding. Deep learning models were compared with a bag-of-words (BOW) model. RESULTS: We retrieved 176,988 head CT reports for pre-training. We manually labeled 7784 reports as normal (46.3%) or pathological (53.7%), and 7.1% with intra-cranial hemorrhage. For the general labeling, LSTM-ATN-Word2Vec showed the best results (AUC = 0.967 ± 0.006, accuracy 90.8% ± 0.01). For the specific labeling, all methods showed similar accuracies between 95.0 and 95.9%. Both LSTM-ATN-Word2Vec and BOW had the highest AUC (0.970). CONCLUSION: For a general use case, word embedding using a large cohort of non-English head CT reports and ATN improves NLP performance. For a more specific task, BOW and deep learning showed similar results. Models should be explored and tailored to the NLP task.

The long noncoding RNA TP73-AS1 promotes tumorigenicity of medulloblastoma cells.

Medulloblastoma is the most common malignant brain cancer in children. Since previous studies have mainly focused on alterations in the coding genome, our understanding of the contribution of long noncoding RNAs (lncRNAs) to medulloblastoma biology is just emerging. Using patient-derived data, we show that the promoter of lncRNA TP73-AS1 is hypomethylated and that the transcript is highly expressed in the SHH subgroup. Furthermore, high expression of TP73-AS1 is correlated with poor outcome in patients with TP53 wild-type SHH tumors. Silencing TP73-AS1 in medulloblastoma tumor cells induced apoptosis, while proliferation and migration were inhibited in culture. In vivo, silencing TP73-AS1 in medulloblastoma tumor cells resulted in reduced tumor growth, reduced proliferation of tumor cells, increased apoptosis and led to prolonged survival of tumor-bearing mice. Together, our study suggests that the lncRNA TP73-AS1 is a prognostic marker and therapeutic target in medulloblastoma tumors and serves as a proof of concept that lncRNAs are important factors in the disease.

Next generation of dentists moving to amalgam-free dentistry: Survey of posterior restorations teaching in North America.

OBJECTIVES: The dental field is gradually reducing the use of amalgam and moving towards adhesive restoration. This change is in accordance with the advancement and improvement of composite resin materials and adhesion systems. Consequently, posterior cavity preparations teaching should be re-examined to determine whether dental schools are adapting their curriculum to fit the current trends in dentistry and what rationale supports their decisions. METHODS: An online questionnaire was constructed to assess the time dedicated to teaching composite materials and amalgam, in addition to the principles of posterior preparations, for composite restorations in North American dental schools. RESULTS: A total 33 schools responded to the questionnaire. A large variation was found in teaching methods and techniques of posterior restorations. The reasoning for teaching amalgam restorations was diverse as were the principles of composite resin preparation taught. CONCLUSION: No agreed principles of cavity preparation for resin composite restorations were found, as opposed to explicit agreement on amalgam cavity preparations. The results demonstrate a lack of clear guidelines for cavity preparation of resin composite restorations. Dental schools may benefit when a consensus on this topic is achieved.

Psychiatrists' Media Involvement: A Survey of Attitudes.

BACKGROUND: Psychiatrists may face challenging core medical ethics questions since the media encourages their assistance and participation at various levels. This paper examines attitudes of psychiatrists regarding their involvement with the media and their view of their professional association in such incidents. METHODS: A survey was completed by a convenience sample of 81 Israeli psychiatrists. The specially designed questionnaire was compiled by the research team focusing on potential involvement of the psychiatrist regarding reality shows; discussing criminality and responsibility in the media; media involvement of the national psychiatric association and appearing in the media in matters of public education and mental health literacy. RESULTS: Psychiatrists are largely reluctant to engage with the mass media. At the same time, they support a strong media presence by their professional psychiatric association. CONCLUSION: Professional psychiatry associations should consider deliberating the issue of media involvement further and contemplate further development of ethical recommendations on the issue.

Severe Mental Illness and Acute Stress: A Study of Service Utilization in a Conflict Zone.

Patients suffering from severe mental illness (SMI) are considered especially vulnerable to stress. In this study, their use of acute stress services in a military context affecting civilian populations was assessed, using naturally occurring data. The proportion of patients with a previously known SMI, defined as any chronic psychotic disorder or bipolar disorder, among all civilians examined at a center for treatment of stress during a military conflict versus at the ER in usual times, was compared, using the Chi square statistical test. Among 354 subjects examined at the center for treatment of stress, 12 had a SMI diagnosis. Among 404 subjects examined at the ER in usual times, 16 had a SMI diagnosis. Patients with SMI were under-represented, but not in a statistically significant manner, at the center for treatment of stress (χ2 = 0.31, p = ns). Although these results may imply that patients with SMI are not more vulnerable to external stress than the general population, we believe that they may have difficulties in seeking immediate help in such traumatogenic contexts. In order to reduce the occurrence of PTSD and gain efficacy in the treatment of the primary disorder, psychiatric services should perhaps make a reaching out effort to identify and examine these patients in the community. .

Specific Ethical Codes for Mental Health Care Professionals: Do We Need to Annotate?

BACKGROUND: In Israel a general code of ethics exists for physicians, drafted by the Israel Medical Association. The question arises whether psychiatrists require a separate set of ethical guidelines. OBJECTIVES: To examine the positions of Israeli psychiatrists with regard to ethics in general and professional ethics in particular, and to explore opinions regarding a code of ethics or ethical guidelines for psychiatry.  Methods: A specially designed questionnaire was compiled and completed by psychiatrists recruited for the study. METHODS: A specially designed questionnaire was compiled and completed by psychiatrists recruited for the study. RESULTS: Most participants reported low levels of perceived knowledge regarding ethics, professional ethics, and the general code of ethics. Older and more experienced professionals reported a higher level of knowledge. Most psychiatrists agreed or strongly agreed with the need for a distinct code of ethics/ethical guidelines for psychiatrists. This support was significantly higher among both psychiatrists under 50 years and residents. CONCLUSIONS: Our findings suggest that the existing code of ethics and position papers may not be sufficient, indicating a potential need to develop and implement a process to create the ethical code itself. In addition, the findings highlight the importance of ethics education, suggesting that the need for a code of ethics is more urgent in the early stages of professional training, as younger professionals may be more exposed to advanced media technology. While some may fear that a distinct code of ethics will distance psychiatry from modern medicine, others assert that the profession combines aspects from the humanities and social sciences that require a unique sort of management and thus this profession requires a distinct code of ethics.

The evolution of the emergency mental health system in Israel - from the 1980's until today.

Emergency and disaster situations such as war or terrorism can leave a devastating impact on the mental well-being of victimized populations. In Israel, the civilian aspects of trauma-related mental distress were first extensively tackled during the 1980s, and mainly within the terror-stricken Jerusalem and the localities along the northern border. Since then, a systematic process of trial and error has led to the evolution of emergency mental health services in the country. Over the course of about forty years, it has grown to be an exemplary one. It is a system deeply rooted in the ground, resulting from both a change of discourse and a naturalistic process of lesson learning, that is, drawing conclusions from actual fieldwork. This process and its implications on the mental well-being of Israelis are thoroughly discussed in this research.

Classical mapping for Hubbard operators: application to the double-Anderson model.

A classical Cartesian mapping for Hubbard operators is developed to describe the nonequilibrium transport of an open quantum system with many electrons. The mapping of the Hubbard operators representing the many-body Hamiltonian is derived by using analogies from classical mappings of boson creation and annihilation operators vis-à-vis a coherent state representation. The approach provides qualitative results for a double quantum dot array (double Anderson impurity model) coupled to fermionic leads for a range of bias voltages, Coulomb couplings, and hopping terms. While the width and height of the conduction peaks show deviations from the master equation approach considered to be accurate in the limit of weak system-leads couplings and high temperatures, the Hubbard mapping captures all transport channels involving transition between many electron states, some of which are not captured by approximate nonequilibrium Green function closures.

Testamentary capacity of the schizophrenic patient.

Testamentary capacity refers to an individual's capability to write his or her own will. Psychiatrists are required occasionally to give expert opinions regarding the testamentary capacity of individuals with a medical history or suspected diagnosis of a mental illness. This may stem from the patient/lawyer/ family initiative to explore the current capacity to testate in anticipation of a possible challenge, or may be sought when testamentary capacity of a deceased has been challenged. In this article we examine the medico-legal construct of testamentary capacity of the schizophrenic patient, and discuss the various clinical situations specific to schizophrenic patients, highlighting their impact on the medical opinion regarding testamentary capacity through examining the rulings of Israel's Supreme Court in a specific case where the testamentary capacity of a mentally ill individual who was challenged postmortem, and provide a workable framework for the physician to evaluate the capacity of a schizophrenic patient to write a will..

Enhancing the use of institutional ethics committees in mental health care in Israel.

Institutional ethics committees were established and functioned in Israel prior to the application of the Patients Rights Act of 1996. These committees were voluntary and comprised of multidisciplinary teams in order to obtain numerous viewpoints stemming from various different fields. This intent was based on an understanding that the issue of ethics and the process of making ethical decisions inherently address moral and social considerations which are beyond the realm of medical practice. In contrast to the voluntary institutional ethics committees, the Patients Rights Act of 1996 instituted statutory ethics committees. These committees were mandated to investigate defined areas and, in contrast to the former committees that were considered to be valuable as advisory and enlightening entities, their decisions are binding. However, it appears that the utilization of these ethics committees within the domain of mental health facilities is limited in scope and their use varies greatly between institutions. The employment of these committees in mental health institutions focuses mainly around issues that relate to information management and mentally ill patients' refusal of medical treatment. Several explanations exist for this phenomenon. Suggestions as to how the situation may be remedied are addressed as well as the complementary role that these ethics committees may play in modern day clinical practice.

Steady state conductance in a double quantum dot array: the nonequilibrium equation-of-motion Green function approach.

We study steady state transport through a double quantum dot array using the equation-of-motion approach to the nonequilibrium Green functions formalism. This popular technique relies on uncontrolled approximations to obtain a closure for a hierarchy of equations; however, its accuracy is questioned. We focus on 4 different closures, 2 of which were previously proposed in the context of the single quantum dot system (Anderson impurity model) and were extended to the double quantum dot array, and develop 2 new closures. Results for the differential conductance are compared to those attained by a master equation approach known to be accurate for weak system-leads couplings and high temperatures. While all 4 closures provide an accurate description of the Coulomb blockade and other transport properties in the single quantum dot case, they differ in the case of the double quantum dot array, where only one of the developed closures provides satisfactory results. This is rationalized by comparing the poles of the Green functions to the exact many-particle energy differences for the isolate system. Our analysis provides means to extend the equation-of-motion technique to more elaborate models of large bridge systems with strong electronic interactions.

A Cartesian quasi-classical model to nonequilibrium quantum transport: the Anderson impurity model.

We apply the recently proposed quasi-classical approach for a second quantized many-electron Hamiltonian in Cartesian coordinates [B. Li and W. H. Miller, J. Chem. Phys. 137, 154107 (2012)] to correlated nonequilibrium quantum transport. The approach provides accurate results for the resonant level model for a wide range of temperatures, bias, and gate voltages, correcting the flaws of our recently proposed mapping using action-angle variables. When electron-electron interactions are included, a Gaussian function scheme is required to map the two-electron integrals, leading to quantitative results for the Anderson impurity model. In particular, we show that the current mapping is capable of capturing quantitatively the Coulomb blockade effect and the temperature dependence of the current below and above the blockade.