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Objective: The traditional categorical division of surgical margins using a 5 mm cutoff in oral cavity squamous cell carcinoma (OCSCC) is controversial. The primary aim of this study was to investigate the presence of an optimal cutoff point or, alternatively, assess the potential improvement in predictive value by considering the surgical margins as a continuum. Methods: Retrospective analysis of OCSCC patients at a tertiary medical center in 1995–2020. Clinical, pathological, and surgical data were evaluated for effect on survivability by regression analyses. Results: The cohort included 266 patients (48.1% male, mean age 65.4 ± 17.7). Patient stratification by categorical margin status yielded no significant between‐group differences in survival (p = 0.54). Significance was achieved when margin distance was reevaluated as a continuous variable (p = 0.0018). Similar results were shown in local control (categorical p = 0.59 vs. continuous p = 0.06). Multivariate model excluded possible confounders. A predictive model was created to provide a more accurate prediction of survival. Conclusions: The continuum spectrum of margin distance better predicts survival outcomes and locoregional control in OCSCC. Level of Evidence: 3 Laryngoscope, 135:161–167, 2025 [ABSTRACT FROM AUTHOR]

In today's era, the ability to create and utilize digital games in the classroom is of great importance, for both teachers and students. Yet traditional teaching methods often lack the implementation of games in general, and of digital games in particular. This study presents a unique constructivist framework for creating and integrating digital‐game generators in the classroom, following four consecutive year‐long courses for preservice teachers at a college in Israel. Using design‐based research, year‐to‐year improvements (iterations) to the course were introduced, achieved through analysis of in‐class discussions, semi‐structured interviews, participants' reflective diaries and the generated games. The participants were required to apply the constructivist framework to a study unit in their field of expertise, during their practical school‐teaching experience. The findings in this study are based on the participants' teaching experience in secondary schools in three core subjects: English as a second language, mathematics and history. The developed consecutive framework comprises three core elements: the game, the pedagogical and didactic core, and the knowledge—all of which are important when integrating digital‐game generators into the classroom. The course and framework addressed in this study could be applied in additional teacher‐training programs, to increase digital‐game generation and related skills in classrooms. Practitioner notes What is already known about this topic Creating and implementing digital games in the classroom has gained momentum in recent years. Early exposure of preservice teachers to digital games during the teaching training phase may increase their use in the educational field. The developing and integration of digital games in the classroom, based on the constructivist approach, allows students to create games using existing game generators, while expressing their insights and knowledge in a personal and creative manner. What this paper adds Introduces an innovative framework integrating educational game generation into teacher training, addressing key pedagogical and content knowledge components. Demonstrates the successful application of this framework across multiple disciplines (English, mathematics and history) in secondary education. Presents a longitudinal study showcasing the iterative development and refinement of a game‐based learning approach in preservice teacher education. Provides evidence‐based insights into the effectiveness of incorporating digital game creation as a constructivist learning tool in teacher preparation programs. Implications for practice and/or policy The constructivist framework helps expose preservice teachers—and in early stages of their teacher training—to experimenting with different types of digital games and different methods for integrating them into their teaching. Such integration of digital games into their teaching may promote meaningful learning, with an emphasis on the development of important 21st‐century skills. In light of the proposed model, the study recommends promoting the topic of digital games in teacher training, for the benefit of the preservice teachers' future students. What is already known about this topic Creating and implementing digital games in the classroom has gained momentum in recent years. Early exposure of preservice teachers to digital games during the teaching training phase may increase their use in the educational field. The developing and integration of digital games in the classroom, based on the constructivist approach, allows students to create games using existing game generators, while expressing their insights and knowledge in a personal and creative manner. What this paper adds Introduces an innovative framework integrating educational game generation into teacher training, addressing key pedagogical and content knowledge components. Demonstrates the successful application of this framework across multiple disciplines (English, mathematics and history) in secondary education. Presents a longitudinal study showcasing the iterative development and refinement of a game‐based learning approach in preservice teacher education. Provides evidence‐based insights into the effectiveness of incorporating digital game creation as a constructivist learning tool in teacher preparation programs. Implications for practice and/or policy The constructivist framework helps expose preservice teachers—and in early stages of their teacher training—to experimenting with different types of digital games and different methods for integrating them into their teaching. Such integration of digital games into their teaching may promote meaningful learning, with an emphasis on the development of important 21st‐century skills. In light of the proposed model, the study recommends promoting the topic of digital games in teacher training, for the benefit of the preservice teachers' future students. [ABSTRACT FROM AUTHOR]

Objective: With inconsistencies regarding the possible effect of hyperemesis gravidarum on the course of pregnancy, this research aimed to study the association between hyperemesis gravidarum and pregnancy outcomes, while also addressing the trimester of diagnosis and severity. Methods: A retrospective cohort study was performed, including all singleton deliveries of mothers from the largest health maintenance organization in the country, in a single tertiary hospital between 1991 and 2021. The incidence of adverse pregnancy outcomes was compared between pregnancies with and without hyperemesis gravidarum diagnosis. Multivariable generalized estimation equation binary models were used to study the association between maternal hyperemesis gravidarum, trimester of diagnosis and hyperemesis gravidarum severity and the studied outcomes. Results: The study population included 232 476 pregnancies, of which 3227 (1.4%) were complicated with hyperemesis gravidarum. Women with hyperemesis gravidarum were more likely to deliver preterm (adj. OR = 1.33, 95% CI: 1.18–1.50), a newborn with low birthweight (adj. OR = 1.52, 95% CI: 1.16–1.98, only if diagnosed in the second trimester), and to have a cesarean delivery (adj. OR = 1.20, 95% CI: 1.09–1.32). They were less likely to deliver small gestational age newborn (adj. OR = 0.82, 95% CI: 0.69–0.99) and their offspring to experience perinatal mortality (adj. OR = 0.54, 95% CI: 0.31–0.93, among mild cases only). A dose–response association was observed between preterm birth and hyperemesis gravidarum (adj. OR = 1.26; 95% CI: 1.11–1.44, for mild cases and adj. OR = 2.04; 95% CI: 1.31–3.19, for severe cases). Conclusions: Hyperemesis gravidarum is associated with an increased risk for adverse pregnancy outcomes including mainly preterm delivery in a dose–response manner and when diagnosed during the second trimester. Synopsis: Hyperemesis gravidarum is associated with preterm birth in a dose–response manner, low birth weight, and cesarean delivery, especially when diagnosed in the second trimester. [ABSTRACT FROM AUTHOR]

Objective: To systematically evaluate which lesion‐based imaging features and methods allow for the best statistical prediction of poststroke deficits across independent datasets. Methods: We utilized imaging and clinical data from three independent datasets of patients experiencing acute stroke (N1 = 109, N2 = 638, N3 = 794) to statistically predict acute stroke severity (NIHSS) based on lesion volume, lesion location, and structural and functional disconnection with the lesion location using normative connectomes. Results: We found that prediction models trained on small single‐center datasets could perform well using within‐dataset cross‐validation, but results did not generalize to independent datasets (median R2N1 = 0.2%). Performance across independent datasets improved using large single‐center training data (R2N2 = 15.8%) and improved further using multicenter training data (R2N3 = 24.4%). These results were consistent across lesion attributes and prediction models. Including either structural or functional disconnection in the models outperformed prediction based on volume or location alone (P < 0.001, FDR‐corrected). Interpretation: We conclude that (1) prediction performance in independent datasets of patients with acute stroke cannot be inferred from cross‐validated results within a dataset, as performance results obtained via these two methods differed consistently, (2) prediction performance can be improved by training on large and, importantly, multicenter datasets, and (3) structural and functional disconnection allow for improved prediction of acute stroke severity. [ABSTRACT FROM AUTHOR]

Thick‐bedded halite sequences in the geological record are characterized by lateral variations, reflecting spatiotemporal variations in environmental forcing. Although temporal variations have been examined over seasonal scales or longer durations, there is a paucity of information regarding the dynamics of halite deposition at shorter durations of days and hours. Additionally, the influence of water discharges and surface salinity gradients remains poorly understood. Here, for the first time, in situ, hourly to weekly halite accumulation rates were measured on the Dead Sea floor (ca 20 m water depth), the only modern deep and hypersaline water body. Novel underwater photography methods were developed to directly observe halite precipitation at the lake floor, coeval with monitoring of the environmental drives, i.e. evaporation, meteorological and limnological conditions. Two fundamental environments were explored: a diluted plume environment arising from spring discharge; and a mixed hypersaline environment. The focus was on deposition during winter when the halite accumulation rate is highest, and the relationship between evaporation and halite accumulation is most straightforward since the water column is vertically uniform. Significant spatial variations in halite accumulation were found between the two environments, along with hourly variations in each environment. In the mixed hypersaline environment, over intra‐diurnal timescales, evaporation plays a more significant role in halite precipitation, whereas temperature has a greater impact on seasonal changes. In the diluted plume environment, the stability of the buoyant plume controls the rate of halite deposition; during windstorms, the plume is stirred, with higher surface water salinity and higher rate of halite accumulation. However, under calm winds, the plume is stable, with diluted surface water, and the rate of halite accumulation is a few times lower. Following these new findings, the implications for the interpretation of halite deposits are discussed. [ABSTRACT FROM AUTHOR]

A master equation containing a nonlinear term that gives rise to disentanglement has been recently explored. Here, a modified version, which is applicable for indistinguishable particles, is proposed, and studied for both the Bose–Hubbard and the Fermi–Hubbard models. It is found for both Bosons and Fermions that disentanglement can give rise to quantum phase transitions. [ABSTRACT FROM AUTHOR]

The article discusses the importance of considering differences between direct-acting oral anticoagulants (DOACs) in the treatment of patients with epilepsy who are also taking antiseizure medications (ASMs). It highlights the impact of CYP3A induction on exposure to P-glycoprotein substrates and provides recommendations for selecting the appropriate DOAC based on the patient's ASM regimen. The article emphasizes the need for a multidisciplinary approach involving epileptologists, hematologists, and clinical pharmacologists when making decisions about anticoagulation in patients with epilepsy. Additionally, it suggests monitoring DOAC activity and considering potential drug interactions, especially with cannabidiol, to ensure safe use of DOACs in patients with epilepsy. [Extracted from the article]

Summary: Large language models (LLMs) have significantly impacted various fields with their ability to understand and generate human‐like text. This study explores the potential benefits and limitations of integrating LLMs, such as ChatGPT, into haematology practices. Utilizing systematic review methodologies, we analysed studies published after 1 December 2022, from databases like PubMed, Web of Science and Scopus, and assessing each for bias with the QUADAS‐2 tool. We reviewed 10 studies that applied LLMs in various haematology contexts. These models demonstrated proficiency in specific tasks, such as achieving 76% diagnostic accuracy for haemoglobinopathies. However, the research highlighted inconsistencies in performance and reference accuracy, indicating variability in reliability across different uses. Additionally, the limited scope of these studies and constraints on datasets could potentially limit the generalizability of our findings. The findings suggest that, while LLMs provide notable advantages in enhancing diagnostic processes and educational resources within haematology, their integration into clinical practice requires careful consideration. Before implementing them in haematology, rigorous testing and specific adaptation are essential. This involves validating their accuracy and reliability across different scenarios. Given the field's complexity, it is also critical to continuously monitor these models and adapt them responsively. [ABSTRACT FROM AUTHOR]

Objectives: Laryngeal squamous cell carcinoma (SCC) is a predominantly male illness. Although the rate of female patients increased, a knowledge gap exists in the medical literature regarding gender‐based differences. Design: Retrospective cohort study. Setting: Adult patients treated for laryngeal SCC in a tertiary medical centre between 2006 and 2020. Data were collected on demographics, clinical presentation, treatment modalities, disease recurrence and survival status. Participants: Two hundred ninety‐one patients with laryngeal SCC, 50 (17.2%) females and 241 (82.8%) males. Main Outcome Measures: Disease‐specific survival (DSS), overall survival (OS) and disease‐free survival (DFS), as well as differences in disease characteristics and treatment modalities. Results: Tumour subsites differed significantly between females and males (36% vs. 19.5% supraglottic, 62% vs. 80.5% glottic and 2% vs. 0% subglottic, respectively; p = 0.006). Females were diagnosed at younger ages (61.7 ± 10.58 vs. 65.87 ± 11.11 years, p = 0.016) and advanced‐stage disease (58% vs. 39.4%, p = 0.018). Females were treated with combined modalities at higher rates (36% vs. 54.8% for single modality, p = 0.031). DSS rates did not differ between genders (log‐rank p = 0.12). Despite being diagnosed at more advanced disease stages, females demonstrated prolonged median OS compared to males (130.17 vs. 106.17 months, log‐rank p = 0.017). No significant differences in DFS were observed (log‐rank p = 0.32). In a multivariate Cox proportional hazards model, male gender remained an independent negative OS predictor (HR = 2.08; CI, 1.10–3.96; p = 0.025), along with increasing age (HR = 1.06; CI, 1.04–1.09; p < 0.001) and advanced disease stage (HR = 1.7; CI, 1.08–2.67; p = 0.023). Conclusions: Our findings suggest the importance of considering gender‐specific factors in the management of laryngeal SCC. [ABSTRACT FROM AUTHOR]

Insects flap their wings through a highly specialized musculoskeletal system that allows the wings to rotate about three degrees of freedom. Consequently, the wingtip trajectory is adjustable in 3D, and accompanied with appropriate wing feathering (wing pitch). Remarkably, the complex flapping motion is achieved by thoracic muscles acting on the wing hinge. The wings themselves do not possess muscles but adjust their shape and orientation by elastically deforming due to the loads applied on them during flapping. Previous attempts to develop insect‐inspired flapping drones have mostly focused on simplified linear flapping mechanisms, which do not utilize the interaction between the wing flexibility and flapping kinematics to its full potential. Here, the aim is to improve flapping drones' performance by introducing mechanisms that mimic insects' flight. The first is an elastic beam mechanism, allowing the wing root to swing during flapping, and the second is a passive wing pitch mechanism that allows the wing to rotate at stroke reversals. The two mechanisms are tested using high‐fidelity insect‐inspired 3D‐printed wings and show a sixfold improvement of aerodynamic performance compared to linear flapping kinetics of the same flexible wings. This underscores the necessity of bioinspired flapping mechanisms in future flapping drones. [ABSTRACT FROM AUTHOR]

This article discusses the challenges faced in recruiting participants for clinical trials and proposes the use of in silico screening tools to improve the selection of investigational antiseizure medications (ASMs). The authors present a novel drug structure-activity relationship exploration framework, the ASM MPO, which considers the unique physicochemical characteristics of ASMs. The ASM MPO tool is freely available for calculating the desirability of candidate molecules for drug development and repurposing. The authors suggest that the use of in silico screening tools can enhance the assessment of ASM candidates, reduce animal experimentation, improve the success rate of clinical trials, and minimize patient exposure to less efficacious compounds. [Extracted from the article]

ABSTRACT Objective Method Results Discussion Body checking is considered a behavioral expression of the core psychopathology of eating disorders (EDs), namely, overvaluation of body weight and shape. Compulsive checking is motivated by a desire to increase a sense of certainty regarding feared outcomes. Paradoxically, studies showed that repeated checking acts to reduce certainty, forming a vicious cycle. No previous study examined whether the same principle applies for body checking. This study filled this gap by examining the causal effect of repeated body checking on memory certainty regarding checked body parts.In a laboratory‐based study, 77 female participants without an ED checked the size and shape of six body parts. Their objective memory regarding which body part was last checked, and subjective certainty about this memory were assessed. Then, one group of participants continued to engage in repeated body checking, and another group repeatedly checked a neutral object. Finally, all participants completed the six body parts checking procedure again, and their objective memory and memory certainty were re‐assessed.In both checking groups, objective memory regarding the last body part checked was unaffected by the type of checking performed. Importantly, certainty about memory dropped considerably only among those in the repeated body‐checking group.The findings provide the first empirical evidence of a paradoxical effect demonstrating that repeated body checking reduces certainty about checked body parts. The study implies that repeated body checking reduces the quality of information obtained through checking and, as such, could potentially motivate further checking. [ABSTRACT FROM AUTHOR]

Rationale: Benzodiazepines (BZDs) construct a large group of psychoactive drugs acting as depressants of the central nervous system (CNS) and used in medicine as sedatives and anxiolytic and antiepileptic agents. The illicit use of these materials is a worldwide problem, and for many years, part of the benzodiazepines have been abused as rape drugs. For example, flunitrazepam (Rohypnol) is most commonly linked by media reports to drug‐facilitated sexual assaults, more commonly referred to as "date rape." Furthermore, there are growing concerns for other misuses of these drugs. Over the last few years, there was an increase in the number, type, and availability of new psychoactive substances (NPS) belonging to the benzodiazepine group, challenging standard forensic labs to fully identify the chemical structure of new, unknown benzodiazepines. Methods: This work demonstrates a new application of the automated tool for the detection and identification of benzodiazepine analogues using high‐resolution‐accurate‐mass LC‐MS analysis, followed by "Compound Discoverer" (CD) software data processing, to automatically detect various benzodiazepine analogues by picking peaks and compare them to in silico calculated modifications made on a predefined basic backbone. Subsequently, a complete structural elucidation for the proposed molecular formula is obtained by MS/MS data analysis of the suspected component. Results: This method was found to be useful for the automated detection and putative identification of a series of nine "unknown" benzodiazepine analogues, at concentrations in the low ng/mL range. Conclusions: We hereby present a general demonstration of this powerful tool for the forensic community in the detection and identification of hazardous unknown compounds. [ABSTRACT FROM AUTHOR]

Many bacteria possess proteasomes and a tagging system that is functionally analogous to the ubiquitin system. In this system, Pup, the tagging protein, marks protein targets for proteasomal degradation. Despite the analogy to the ubiquitin system, where the ubiquitin tag is recycled, it remained unclear whether Pup is similarly recycled, given how the bacterial proteasome does not include a depupylase. We previously showed in vitro that as Pup lacks effective proteasome degradation sites, it is released from the proteasome following target degradation, remaining conjugated to a degradation fragment that can be later depupylated. Here, we tested this model in Mycobacterium smegmatis, using a Pup mutant that is effectively degraded by the proteasome. Our findings indicate that Pup recycling not only occurs in vivo but is also essential to maintain normal pupylome levels and to support bacterial survival under starvation conditions. Accordingly, Pup recycling is an essential process in the mycobacterial Pup‐proteasome system. [ABSTRACT FROM AUTHOR]

Vast literature studies Independent Regulatory Agencies (IRAs). We contribute by studying the benefits of independence when the agent's work is relational and by studying developing and developed democracies worldwide and over many years. We do this by studying national Debt Management Offices (DMOs)—the state agencies that plan, issue, and manage national debt. DMOs define the benchmark assets on which capital markets and monetary policy depend—industry standards—and their decisions have allocative implications. We argue that formal independence of DMOs from political decision‐makers is a costly signal to large financial institutions on the government's potential to service and repay its debts. We introduce a new country‐year dataset of DMO legislation for 75 developing and developed democratic countries in the period 1950–2013. We find that DMO independence is likelier following debt defaults, war, high inflation, and high debts, and that DMO independence increases sovereign debt credibility. [ABSTRACT FROM AUTHOR]

Shwachman–Diamond syndrome (SDS) is an inherited bone marrow failure disorder that often presents at infancy. Progress has been made in revealing causal mutated genes (SBDS and others), ribosome defects, and hematopoietic aberrations in SDS. However, the mechanism underlying the hematopoietic failure remained unknown, and treatment options are limited. Herein, we investigated the onset of SDS embryonic hematopoietic impairments. We generated SDS and control human‐derived induced pluripotent stem cells (iPSCs). SDS iPSCs recapitulated the SDS hematological phenotype. Detailed stepwise evaluation of definitive hematopoiesis revealed defects that started at the early emerging hematopoietic progenitor (EHP) stage after mesoderm and hemogenic endothelium were normally induced. Hematopoietic potential of EHPs was markedly reduced, and the introduction of SBDS in SDS iPSCs improved colony formation. Transcriptome analysis revealed reduced expression of ribosome and oxidative phosphorylation‐related genes in undifferentiated and differentiated iPSCs. However, certain pathways (e.g., DNA replication) and genes (e.g., CHCHD2) were exclusively or more severely dysregulated in EHPs compared with earlier and later stages. To our knowledge, this study offers for the first time an insight into the embryonic onset of human hematopoietic defects in an inherited bone marrow failure syndrome and reveals cellular and molecular aberrations at critical stages of hematopoietic development toward EHPs. [ABSTRACT FROM AUTHOR]

Purpose Methods Results Conclusions Radiation‐induced angiosarcoma (RIAS) of the breast is a rare tumour with high rate of local recurrence. The aim of this study is to evaluate the outcome of radical resections.A retrospective analysis of all patients who underwent extended surgical resection for RIAS of the breast between 2013 and 2022. Included were patients who underwent radical resection, including complete resection of previously irradiated skin and underlying fascia of pectoralis major. Post‐operative and long‐term oncological outcomes were than analysed. A systematic review was performed using the MEDLINE database in the last 20 years.Twenty‐two (n = 22) patients met the inclusion criteria. The median length of the specimen was 220 mm (range, 120–377 mm). At a median follow‐up of 33.5 months (range, 7.9–102.4), 3 (13.6%) patients had both local and metastatic lung disease and 1 (4%) patient with only lung metastasis. The estimated 3‐ and 5‐year OS was 81.1% and 57.9%, respectively. The estimated 3‐ and 5‐year DSS was 91.7% and 65.5%, respectively. The estimated 3‐ and 5‐year DFS rate were both 75.2%. The systematic review identified 17 studies with a recurrence rate ranging from 33% to 100%.Treatment of RIAS of the breast with an up‐front locally extended approach is associated with a low rate of local recurrence compared with the reported literature. [ABSTRACT FROM AUTHOR]

The Tactual Span assesses tactile working memory (WM) using both hands while applying forward and backward conditions. The study objectives were to validate a one‐hand version of the Tactual Span and to evaluate WM laterality in the tactile modality. Of the 145 participants, 80 performed the Tactual Span with their right hand, and 65 performed it with their left hand. Moreover, all participants performed two span tasks in the visuo‐spatial and auditory modalities, each encompassing forward and backward conditions. Results revealed adequate Cronbach's alpha values for each hand in both conditions of the Tactual Span, along with a positive correlation between forward and backward conditions in each hand. However, overall performance on the Tactual Span was poorer compared to performance on the Auditory and Visuo‐spatial Spans. Furthermore, in the forward condition, there was a correlation between the Auditory Span and the Tactual Span, but only for the right hand. In the backward condition, the Auditory Span correlated with the Tactual Span in both hands. The findings indicate that there is no effect of hand laterality in tactile WM, showing the two hands are related to each other in their WM function. Additionally, the one‐hand version of the Tactual Span is deemed useful for evaluating tactile WM and can therefore be used in empirical and clinical settings for neuropsychological assessment purposes. [ABSTRACT FROM AUTHOR]

Lead chalcogenides are compelling materials for nanophotonics and optoelectronics due to their high refractive indices, extreme thermo‐optic coefficients, and high transparency in the mid‐infrared (MIR). In this study, PbTe hoppercubes (HC, face‐open box cubes) are synthesized and explored for their MIR resonant characteristics. Single‐particle microspectroscopy uncovered deep‐subwavelength light localization, with a spectral response dominated by both fundamental and multiple high‐order Mie‐resonant modes. Nanoimaging mapping using scattering‐type scanning near‐field optical microscopy (s‐SNOM) reveals that the scattering at the center of the HC is reduced by more than five times compared to the edges. 2D‐Hyperspectral scans conducted using a low‐power broadband MIR source and nanometer spatial resolutions provided information on the local amplitude and phase‐resolved near‐fields, including amplitude and phase mapping of higher order modes with measured Q‐factors of close to 100. Employing s‐SNOM to characterize complex resonant nanophotonic structures holds implications for quantum sensing, IR photodetection, non‐linear generation, and ultra‐compact high‐Q metaphotonics. [ABSTRACT FROM AUTHOR]

Dihydrolipoamide dehydrogenase (DLD) deficiency is an ultra‐rare autosomal‐recessive inborn error of metabolism, affecting no less than five mitochondrial multienzyme complexes. With approximately 30 patients reported to date, DLD deficiency was associated with three major clinical presentations: an early‐onset encephalopathic phenotype with metabolic acidosis, a predominantly hepatic presentation with liver failure, and a rare myopathic phenotype. To elucidate the demographic, phenotypic, and molecular characteristics of patients with DLD deficiency within the Israeli population, data were collected from metabolic disease specialists in four large tertiary medical centers in the center and south of Israel. Pediatric and adult patients with biallelic variants in DLD were included in the study. A total of 53 patients of 35 families were included in the cohort. Age at presentation ranged between birth and 10 years. Wide phenotypic variability was observed, from asymptomatic individuals in their sixth decade of life, to severe, neonatal‐onset disease with devastating neurological sequelae. Six DLD variants were noted, the most common of which was the c.685G>T (p.G229C) variant in homozygous form (24/53 patients, 45.3%; 13/35 families), observed mostly among patients of Ashkenazi‐Jewish descent, followed by the homozygous c.1436A>T (p.D479V) variant, found in 20 patients of Bedouin descent (37.7%; 16/35 families). Overall, patients did not necessarily present as one of the previously described distinct clinical phenotypes. DLD deficiency is a panethnic disorder, with significant phenotypic variability, and comprises a continuum, rather than three distinct clinical presentations. [ABSTRACT FROM AUTHOR]

Internet‐delivered cognitive‐behavioral therapy (ICBT) is an effective treatment for obsessive‐compulsive disorder (OCD). ICBT can be delivered in a self‐guided or clinician‐guided format. While a literature is emerging on the predictors of response to clinician‐guided ICBT, there is a lack of research examining the predictors of response to self‐guided ICBT. The aim of the present study was to examine predictors of outcome in a large sample of participants with OCD who commenced a self‐guided ICBT intervention. One hundred and fifty‐seven participants (Mage = 34.82; SD = 10.49; 78% female) were included in the study. Regression analyses were conducted to determine clinical and demographic predictors of (1) posttreatment symptom severity and (2) a clinically meaningful treatment response for both the intention‐to‐treat (ITT) and completer samples. The regression models significantly predicted posttreatment outcome for both the ITT (F(8, 148) = 15.844, p <.001) and completer sample (F(8, 101) = 5.929, p <.001), explaining 46% and 34% of the variance respectively. Higher baseline OCD severity, younger age, experiencing higher contamination or symmetry symptoms, and a history of past treatment were all found to be significantly associated with higher posttreatment severity in the ITT sample. In the completer sample only higher baseline OCD severity and severity of harm‐related obsessions and checking compulsions was significantly associated with higher posttreatment severity. When predicting treatment response the regression models for both the ITT and completer sample were nonsignificant. [ABSTRACT FROM AUTHOR]

Aggressive thoracic hemangiomas are rare, benign tumors that extend into the spinal canal and cause neurological symptoms. Delayed diagnosis and treatment, due to a paucity of literature on optimal treatment strategies, can increase morbidity. This case report describes a 19‐year‐old male patient with aggressive thoracic hemangioma who presented with upper back pain and progressive weakness of the lower extremities. The patient underwent preoperative embolization and sclerotherapy, followed by decompression, posterior instrumentation, and stabilization. The final diagnosis was confirmed by biopsy, and there was a significant improvement in neurology after the surgical intervention. The diagnosis of rare lesions, such as aggressive hemangiomas, requires a high level of clinical suspicion and the assistance of imaging modalities in patients with features of compressive myelopathy. A combination of endovascular and surgical approaches can lead to optimal outcomes. [ABSTRACT FROM AUTHOR]

Background: Diagnosis of Brugada syndrome (BrS) may be established by exposing a Type 1 Brugada pattern using a sodium channel blocker. Data on the outcomes of different patient populations with drug‐induced Type 1 Brugada pattern are limited. The present study reports on the characteristics and outcome of subjects with ajmaline induced Type 1 Brugada pattern. Methods: A multicenter retrospective study including all consecutive cases of ajmaline‐induced Type 1 Brugada pattern from seven centers. Results: A total of 260 patients (69.9% males, mean age 43.4 ± 13.5) were included. Additional characteristics included history of syncope (n = 56, 21.5%), family history of BrS (n = 58, 22.3%) or sudden cardiac death (n = 47, 18.1%) and ventricular fibrillation (n = 3, 1.2%). Patients were divided into those meeting current diagnostic criteria for drug‐induced BrS (DIBrS) and compared to the drug‐induced Brugada pattern (DIBrECG). Females were significantly overrepresented in the DIBrS group (n = 50, 40% vs. n = 29, 21.5%, p =.001). A significantly higher prevalence of type 2/3 Brugada ECG at baseline was found in the DIBrECG group (n = 108, 80.8% vs. n = 75, 60% in the DIBrS, p =.026). During a median follow up of three (IQR 1.50–5.32) years, a single event of significant arrhythmia occurred in the DIBrS group. Conclusion: Less than half of subjects with ajmaline‐induced Brugada pattern met current criteria for BrS. These individuals had very low rate of adverse outcomes during a follow up of 3 years, irrespective of the indication for the test or eligibility for the BrS diagnosis. [ABSTRACT FROM AUTHOR]

Background: The safety and impact of sodium glucose transporter 2 inhibitors (SGLT2‐I) in patients with left ventricular assist devices (LVAD) are unknown. Methods: A retrospective analysis of all consecutive patients who underwent LVAD Heart Mate 3 (HM3) implantation at a single medical center and received SGLT2‐I therapy following surgery was conducted. LVAD parameters, medical therapy, laboratory tests, echocardiography, and right heart catheterization (RHC) study results were recorded and compared before and after initiation of SGLT2‐I. Results: SGLT2‐I medications were initiated in 29 (21%) of 138 patients following HM3 implantation (23 (79%) received Empagliflozin and 6 (21%) Dapagliflozin). The mean age at the time of LVAD implantation was 62 ± 6.7 years, 25 (86%) were male, and 23 (79%) had diabetes mellitus. The median time from HM3 implantation to SGLT2‐I initiation was 108 days, IQR (26–477). Following SGLT2‐I therapy, the daily dose of furosemide decreased from 47 to 23.5 mg/day (mean difference = 23.5 mg/d, 95% CI 8.2–38.7, p = 0.004) and significant weight reduction was observed (mean difference 2.5 kg, 95% CI 0.7–4.3, p = 0.008). Moreover, a significant 5.6 mm Hg reduction in systolic pulmonary artery pressure (sPAP) was measured during RHC (95% CI 0.23–11, p = 0.042) in a subgroup of 11 (38%) patients. LVAD parameters were similar before and after SGLT2‐I initiation (p > 0.2 for all). No adverse events were recorded during median follow‐up of 354 days, IQR (206–786). Conclusion: SGLT2‐I treatment is safe in LVAD patients and might contribute to reduction in patients sPAP. [ABSTRACT FROM AUTHOR]

Objectives: Secretory Carcinoma is a malignant salivary gland tumor, initially described in 2010. This rare tumor is associated with the translocation t(12;15) (p13;q25), resulting in the fusion gene ETV6‐NTRK3. Since this tumor is quite rare, most publications describe only small cohorts of patients. We aimed to investigate the clinical, pathological, and prognostic features of this newly defined malignant entity. Data Sources: Pubmed, Google Scholar, and Web of Science databases. Review Methods: All published articles between 2010 and 2023 were reviewed. Search terms included the terms "Mammary Analogue Secretory Carcinoma" and "Secretory Carcinoma". All articles published in English reporting on Secretory Carcinoma of salivary glands were retrieved. Results: One‐hundred and 12 retrospective articles reporting a total of 674 patients were included, with 52% males and a mean age of 44.9 ± 18.9. The event rate for patients with advanced‐stage disease (Stage 3/4) at presentation was 24.1% (95% CI 17.6%–31.9%, I2 = 9.2%), 14.6% for regional metastases (95% CI 10.5%–20%, I2 = 12%), and the event rate of distant metastasis was 8.4% (95% CI 5.5%–12.7%, I2 = 4.2%). Adjuvant radiotherapy was administered for 30.3% of patients (95% CI 24.1%–37.2%, I2 = 21.5%). The recurrence rate was 19% (95% CI 15.1%–23.8%, I2 = 5%). Survival outcomes showed a 17.2% death of disease rate for Secretory Carcinoma patients (95% CI 13.5%–21.8%, I2 = 7.3%). Conclusions: Secretory Carcinoma is a rare and relatively newly defined entity arising in the parotid gland most commonly. Characterized as a low‐grade tumor, the majority of patients are diagnosed at an early stage, without regional or distant disease, and the prognosis is relatively good. Level of Evidence: NA Laryngoscope, 134:1716–1724, 2024 [ABSTRACT FROM AUTHOR]

Background: Patients with congenital absence of a lumbar pedicle and nerve root anomaly presenting with ipsilateral foraminal stenosis are extremely rare. Case Presentation: An 80‐year‐old man had low back and right thigh pain. Radiographs and computed tomography (CT) showed L3 vertebral body fracture and the absence of the right L3 lumbar pedicle. He was diagnosed with L2–L3 right foraminal stenosis caused by an L3 vertebral fracture and underwent lumbar fusion at L2–L3 and L3–L4. Intraoperatively, we confirmed that an anomalous nerve root was divided from the right L2 nerve root near the dorsal root ganglion (DRG). Conclusions: Patients with congenital absence of a lumbar pedicle are less prone to ipsilateral foraminal stenosis because they theoretically have a large space in the foramen. This rare case was caused because of additional instability due to vertebral fracture under the condition of a nerve root anomaly and lumbar degeneration. [ABSTRACT FROM AUTHOR]

Introduction: Accumulating research emphasizes the role of interpersonal coordination in arousal levels, which may manifest as cortisol synchrony, in interpersonal interactions. While the role of cortisol has been investigated in psychotherapy, cortisol synchrony and its characteristics and effect on treatment progress remain a relatively unexplored area. This study aims to explore the existence of distinct patterns of cortisol coordination throughout psychotherapy and test the associations of different coordination patterns with patients' pre‐treatment characteristics and treatment progress measures. Methods: Fifty patient–therapist dyads participated in 16 weeks of psychodynamic treatment for major depressive disorder. Salivary cortisol samples were collected before and after each session at four time points. Self‐report questionnaires and treatment session video‐coding were used to characterize and differentiate between patterns of cortisol coordination. Results: Three patterns of cortisol coordination were identified: synchronized, unsynchronized and stable‐therapist. These patterns differed in patient characteristics and treatment progress measures in that patients exhibiting a synchronized pattern tended to be more anxious and dominant in their relationships and were more prone to withdrawal ruptures. Conclusions: Results provide novel evidence regarding variability in patient–therapist cortisol patterns and its putative associations with treatment progress. [ABSTRACT FROM AUTHOR]

Introduction: Soft contact lenses may be a good alternative for early‐stage keratoconus (KC) patients who do not tolerate rigid gas permeable (RGP) lenses due to ocular discomfort or complications. This prospective study compared outcomes obtained after 2 weeks of wearing two types of soft silicone hydrogel contact lenses for keratoconus that varied in their diameter and central thickness (cc). Methods: Patients with Amsler–Krumeich grades I or II KC were fitted with small‐diameter (14.2 or 14.8 mm) SoftK (SD‐SoftK, cc = 0.48 mm) and large‐diameter (17 mm) SoftK (LD‐SoftK, cc = 0.60 mm) lenses, each worn for 2 weeks in a crossover design. Low (10%;10VA) and high (100%;100VA) contrast visual acuity, contrast sensitivity (CS, Pelli‐Robson), higher order aberrations (HOAs, Visionix Vx130), the number of trial lens modifications during fitting and the subjectively preferred lens were compared using Friedman tests with post‐hoc analysis. Results: Forty eyes (N = 20, 10 males, mean age: 39.0 ± 9.9 years, range: 23–55 years) were examined. Their habitual median (interquartile1, interquartile3) 10VA (LogMAR), 100VA (LogMAR) and CS (LogCS) were 0.52 (0.30, 0.50), 0.14 (0.10, 0.15) and 1.35 (1.35, 1.50), respectively. For the SD‐SoftK condition, the values were 0.23 (0.17, 0.30), 0.02 (0.00, 0.05) and 1.50 (1.50, 1.65), respectively. For the LD‐SoftK condition, the respective values were 0.36 (0.27, 0.44), 0.09 (0.05, 0.13) and 1.50 (1.50, 1.60). SD‐SoftK lenses significantly improved 10VA compared with habitual and LD‐SoftK. SD‐SoftK also significantly improved CS compared with habitual, but not LD‐SoftK. LD‐SoftK significantly improved spherical aberration compared with uncorrected (0.03 ± 0.10 μ vs. 0.07 ± 0.13 μ) but not SD‐SoftK (0.04 ± 0.07 μ). Both lenses required a mean of 1.5 modifications prior to final lens fitting. Fewer adverse events were seen with SD‐SoftK (N = 3) compared with LD‐SoftK (N = 8), and 75% of participants preferred SD‐SoftK lenses. Conclusion: SD‐SoftK lenses were preferred by 75% of subjects, were associated with fewer adverse events and significantly improved 10VA compared with LD‐SoftK lenses. SD‐SoftK lenses also significantly improved CS compared with the habitual correction, but this did not differ significantly from the LD‐SoftK lenses. [ABSTRACT FROM AUTHOR]

In 2018, 70 years after it was founded, the State of Israel accepted a new nationality law, one which reshaped the identity of the state. Supporters of this constitutional law argue that it is necessary since the Jewish‐national character of the state is under threat, and since liberal‐democratic principles and policies have acquired undesired dominance in public life. The nationality law, however, does much more than restore a lost or imagined collective identity: it is a significant setback to both the liberal and republican understandings of a democratic state, as well as to Jewish‐Arab relations. More broadly still, the law displays the growing distance between the ethical and political spheres in Israel; this distance is expressed in the law's remarkable modifications of the three Zionist revolutions pertaining to the material (land), the linguistic and the political‐communal dimensions of Jewish, national life. [ABSTRACT FROM AUTHOR]

Regulators who aim to reduce administrative burdens often promote trust‐based policy instruments, such as legal affidavits or honesty pledges, as substitutes to traditional bureaucratic procedures. However, little is known on how the general public view such instruments, and whether people would actually comply with them, and under what circumstances. Using a series of experimental vignettes, we examine public preferences toward these instruments under different conditions and contexts. We find that overall, people exhibit an aversion to using affidavits, even when they are inexpensive and can save a considerable amount of time compared to the traditional bureaucratic procedure. In contrast, honesty pledges are largely preferred over both the standard procedure and signing an affidavit. We discuss factors influencing the public choice of trust‐based instruments and offer recommendations to help policymakers promote public compliance using behaviorally informed policy instruments. [ABSTRACT FROM AUTHOR]

We explore and demonstrate the anticipated and actual emotions that are experienced by individuals who engage in dishonest behaviors that benefit others (altruistic dishonesty) versus the self (egoistic dishonesty), and primarily focus on the positive emotion of pride. Across three preregistered experiments (one scenario experiment and two incentivized behavioral ones), we found that engaging in altruistic dishonesty was not only more prevalent than egoistic dishonesty but also evoked more pride and less guilt and shame. Interestingly, the increase in pride and decrease in guilt and shame when cheating solely for the benefit of others were attenuated when participants cheated for the benefit of both others and themselves. These findings shed further light on the emotional processes involved in dishonesty and highlight the understudied role of pride. The positive association between engaging in altruistic dishonesty and pride may explain the relatively high rates of altruistic dishonesty observed in the current and previous studies, as it suggests that having an altruistic justification may not only enable cheaters to maintain a clear conscience but also even boost how they feel about themselves. [ABSTRACT FROM AUTHOR]

Objectives: Oral lichen planus (OLP) is a chronic inflammatory disorder involving epithelia with squamous differentiation. Although described as a potential malignant precursor, the characteristics of malignancies arising among these patients are not widely described. Our goal was to describe the patterns of disease recurrence of patients with oral cavity squamous cell carcinoma (OSCC) arising on the background of OLP. Methods: A retrospective analysis of all surgically treated patients with OSCC at a university‐affiliated tertiary care center between 2000 and 2020. Results: Two hundred seventy‐nine patients with OSCC treated surgically were included. Forty (14.3%) had OLP. The mean age of patients with OLP was 70.9 years compared with 64.3 years for non‐OLP patients (p = 0.03). OLP patients had a significantly higher rate of disease recurrence, persistence, or multiple primary disease (70% vs. 33.9%, p < 0.001). The mean number of sequential oncologic events for each patient with recurrence was also significantly higher among OLP patients (1.86 vs. 1.36, p = 0.03), a difference explained by a higher rate of multiple primary presentations (0.71 vs. 0.28, p = 0.008). A significant difference in disease‐free survival (DFS) was demonstrated between the groups as patients with OLP had a lower 5‐year DFS (34.7% vs. 61.3%, log‐rank p value <0.001). On multivariate analysis, OLP was significantly associated with multiple primary events (p < 0.001, Odds ratio = 7.42, 95% confidence interval 2.9–19). Conclusions: OSCC patients with OLP background demand close clinical follow‐up, as multiple primary disease is significantly more common and the DFS is significantly lower among these patients. A thorough clinical evaluation for all oral cavity subsites is mandatory. Level of Evidence: 3 Laryngoscope, 134:3146–3151, 2024 [ABSTRACT FROM AUTHOR]

Pyomyositis, accompanied by aseptic arthritis, has been previously documented in several publications. However, none of the authors in the mentioned case reports offered a pathophysiological explanation for this unusual phenomenon or proposed a treatment protocol. We present a case of a healthy, 70‐year‐old male who was presented to the emergency department 4 days after tripping over a pile of wooden planks and getting stabbed by a nail to his thigh. The right thigh was swollen. Unproportional pain was produced by a light touch to the thigh. A laboratory test and a CT scan were obtained. The working diagnosis was pyomyositis of the thigh and septic arthritis of the ipsilateral knee. The patient underwent urgent debridement and irrigation of his right thigh. An arthroscopic knee lavage was performed as well. Intraoperative cultures from the thigh revealed the growth of Streptococcus pyogenes and Staphylococcus aureus. Cultures from synovial fluid were sterile; thus, septic arthritis was very unlikely. The source of the knee effusion might have been an aseptic inflammatory response due to the proximity of the thigh infection. Anatomically, the quadriceps muscle inserts on the patella, and its tendon fuses with the knee capsule, creating a direct fascial track from the thigh to the knee. The inflammatory response surrounding the infection may have followed this track, creating a domino effect, affecting adjacent capillaries within the joint capsule, and causing plasma leakage into the synovial space, leading to joint effusion. Our suggested treatment is addressing the primary infection with antibiotics and considering adding anti‐inflammatory therapy, given our suspicion that this process has an inflammatory component. [ABSTRACT FROM AUTHOR]

Purpose: The association between birth order and adverse perinatal outcomes has been well studied in twin pregnancies. However, little is known about the differences in immediate perinatal outcomes as well as long‐term hospitalization of the offspring in triplet pregnancies according to their birth order. As such, we aimed to assess the differences in immediate perinatal outcomes and long‐term hospitalizations among triplets by their birth order. Methods: In a retrospective hospital‐based cohort study, immediate perinatal outcomes and long‐term hospitalizations were compared among triplet siblings according to their birth order. Deliveries occurred between the years 1991 and 2021 in a tertiary medical center. The study groups were followed until 18 years of age for cardiovascular, respiratory, neurological, and infection‐related hospitalizations. Generalized estimation equation (GEE) models were used to control for confounders. Kaplan–Meier survival curves were used to compare cumulative long‐term hospitalization incidences and Cox proportional hazards models were performed to control for confounders. Results: The study included 117 triplet deliveries. Rates of small for gestational age (SGA) infants increased linearly by birth order (6.0%, 7.7%, and 15.4% for the first, second, and third siblings, respectively; p‐value for trends = 0.035). Using a GEE model controlling for maternal age, being born third in a triplet pregnancy was independently associated with SGA (third vs. first sibling, adjusted OR 3.0, 95% CI 1.38–6.59, p = 0.005). No significant differences in cardiovascular, respiratory, neurological, and infection‐related hospitalizations were noted among the first, second, and third siblings. Likewise, using Kaplan–Meier survival analyses, no significant differences in the cumulative incidence of long‐term pediatric hospitalizations were noted between the siblings. In Cox proportional hazards models, controlling for weight and gender, birth order in a triplet pregnancy did not exhibit an association with long‐term hospitalizations of the offspring. Conclusion: Despite the association between birth order and SGA, birth order in triplets does not seem to have an impact on the risk for long‐term offspring hospitalization. [ABSTRACT FROM AUTHOR]

Objective: Mothers whose newborn experiences adversity may neglect their own health to care for their affected infant or following a perinatal death. Weight gain after pregnancy is one measure of maternal self‐care. We measured interpregnancy weight gain among women whose child had an adverse perinatal event. Methods: This population‐based observational study included 192 154 primigravid women with two consecutive singleton births in Ontario, Canada. Outcomes included net weight gain, and adjusted odds ratios (aOR) of moving to a higher body mass index (BMI) category between pregnancies, comparing women whose child did versus did not experience either a perinatal death, prematurity, severe neonatal morbidity, major congenital anomaly, or severe neurologic impairment. Results: Perinatal death was associated with a +3.5 kg (95% confidence interval [CI]: 2.1–4.9) net higher maternal weight gain in the subsequent pregnancy. Relative to term births, preterm birth <32 weeks (+3.2 kg, 95% CI: 1.9–4.6), 32–33 weeks (+1.8 kg, 95% CI: 0.7–2.8) and 34–36 weeks (+0.9 kg, 95% CI: 0.6–1.3) were associated with higher net weight gain. Having an infant with severe neonatal morbidity was associated with a +1.2 kg (95% CI: 0.3–2.1) weight gain. Likewise, the aOR of moving to a higher BMI category was 1.27 (95% CI, 1.14–1.42) following a perinatal death, 1.21 (95% CI: 1.04–1.41) after a preterm birth <32 weeks, and 1.11 (95% CI: 1.02–1.22) with severe neonatal morbidity. Conclusion: Greater interpregnancy weight gain, and movement to a higher BMI category, are each more likely in a woman whose first‐born was affected by certain major adverse perinatal events. Synopsis: Adverse perinatal events in the first pregnancy can lead to higher maternal interpregnancy weight gain and increased BMI in a subsequent pregnancy. [ABSTRACT FROM AUTHOR]

Several pieces of evidence suggest immune dysregulation could trigger the onset and modulate sequelae of new onset refractory status epilepticus (NORSE), including its subtype with prior fever known as febrile infection‐related epilepsy syndrome (FIRES). Consensus‐driven recommendations have been established to guide the initiation of first‐ and second‐line immunotherapies in these patients. Here, we review the literature to date on second‐line immunotherapy for NORSE/FIRES, presenting results from 28 case reports and series describing the use of anakinra, tocilizumab, or intrathecal dexamethasone in 75 patients with NORSE. Among them, 52 patients were managed with anakinra, 21 with tocilizumab, and eight with intrathecal dexamethasone. Most had elevated serum or cerebrospinal fluid cytokine levels at treatment initiation. Treatments were predominantly initiated during the acute phase of the disease (92%) and resulted, within the first 2 weeks, in seizure control for up to 73% of patients with anakinra, 70% with tocilizumab, and 50% with intrathecal dexamethasone. Cytokine levels decreased after treatment for most patients. Anakinra and intrathecal dexamethasone were mainly initiated in children with FIRES, whereas tocilizumab was more frequently prescribed for adults, with or without a prior febrile infection. There was no clear correlation between the response to treatment and the time to initiate the treatment. Most patients experienced long‐term disability and drug‐resistant post‐NORSE epilepsy. Initiation of second‐line immunotherapies during status epilepticus (SE) had no clear effect on the emergence of post‐NORSE epilepsy or long‐term functional outcomes. In a small number of cases, the initiation of anakinra or tocilizumab several years after SE onset resulted in a reduction of seizure frequency for 67% of patients. These data highlight the potential utility of anakinra, tocilizumab, and intrathecal dexamethasone in patients with NORSE. There continues to be interest in the utilization of early cytokine measurements to guide treatment selection and response. Prospective studies are necessary to understand the role of early immunomodulation and its associations with epilepsy and functional outcomes. [ABSTRACT FROM AUTHOR]

Estimates of primary productivity have traditionally disregarded dark inorganic carbon fixation by marine microorganisms. Currently, only limited data are available from different systems on this potentially ecologically important process. We present monthly dark inorganic carbon fixation and photosynthetic rates from the euphotic layer of the northern Gulf of Aqaba collected over a decade between 2010 and 2020. Averaged dark inorganic carbon fixation rates from surface to 100 m depth, ranged from 99 to 173 mg C m−2 d−1, which corresponds to ~ 43% of the annual primary productivity at this location. The lowest dark inorganic carbon fixation rates were found during winter, contributing ~ 7.5% of the integrated primary productivity. During the oligotrophic summer, dark inorganic carbon fixation comprised a larger fraction of the integrated primary productivity estimated as ~ 12%. In accordance, dark inorganic carbon fixation contributed ~ 6% to the particulate organic carbon flux during the winter and ~ 30% during summertime. Complimentary nutrient‐enrichment bioassays of seawater from 5 m show that dissolved organic nutrient enrichment (P and C based) significantly elevates dark inorganic carbon fixation, whereas addition of dissolved inorganic nutrients (PO43+, NO3−, or both) significantly increased photosynthesis but to a lesser extent dark inorganic carbon fixation. These results suggest that dark inorganic carbon fixation may be an important biochemical process throughout the euphotic zone of oligotrophic seas, and thus should be incorporated into oceanic carbon production estimates. [ABSTRACT FROM AUTHOR]

The problem of quantum measurement can be partially resolved by incorporating a process of spontaneous disentanglement into quantum dynamics. A modified master equation is proposed, which contains a nonlinear term giving rise to both spontaneous disentanglement and thermalization. It is found that the added nonlinear term enables limit cycle steady states, which are prohibited in standard quantum mechanics. This finding suggests that an experimental observation of such a limit cycle steady state can provide an important evidence supporting the spontaneous disentanglement hypothesis. [ABSTRACT FROM AUTHOR]

Background: Regional metastases are considered the most important prognostic factor in OSCC patients. We aimed to investigate the impact of regional disease among different age groups with OSCC. Methods: A retrospective comparison between patients 40 years old or younger, 41–69 years old, and 70 years or older treated for OSCC between 2000 and 2020 in a tertiary‐care center. Results: 279 patients were included. The mean age was 65 ± 17.7 and 133 were male (47.7%). Thirty‐six (12.9%) were 40 years old or younger, 101 (36.2%) were 41–69 years and 142 (50.9%) were 70 years or older. Five‐year overall survival and disease‐specific survival (DSS) were significantly better among patients younger than 40 compared to the mid‐age group and patients 70 years or older (76.7% vs. 69.4% vs.48.2%, Log‐rank p < 0.001, and 76.7% vs. 75.3% vs. 46.5%, Log‐rank p < 0.001, respectively). While an association between regional spread and overall survival and DSS was demonstrated among all age groups, the odds ratio (OR) for death of any cause and death of disease regarding cervical metastasis was much higher among patients younger than 40 compared with the 41–69 and 70+ age groups (death of any cause‐OR = 23, p‐value = 0.008, OR = 2.6, p‐value = 0.026, OR = 2.4, p‐value = 0.13, respectively. Death of disease‐OR = 23, p‐value = 0.008, OR = 2.3, p‐value = 0.082, OR = 4.1, p‐value = 0.001, respectively). In univariate analysis, regional metastasis was associated with disease‐free survival only among patients younger than 40 (p‐value = 0.04). Conclusions: Regional metastases correspond with worse prognosis in young patients compared to older patients. These patients may benefit from a comprehensive treatment approach with close post‐treatment follow‐up. Level of Evidence: 3 Laryngoscope, 134:2212–2220, 2024 [ABSTRACT FROM AUTHOR]

Ferroptosis and apoptosis are key cell‐death pathways implicated in several human diseases including cancer. Ferroptosis is driven by iron‐dependent lipid peroxidation and currently has no characteristic biomarkers or gene signatures. Here a continuous phenotypic gradient between ferroptosis and apoptosis coupled to transcriptomic and metabolomic landscapes is established. The gradual ferroptosis‐to‐apoptosis transcriptomic landscape is used to generate a unique, unbiased transcriptomic predictor, the Gradient Gene Set (GGS), which classified ferroptosis and apoptosis with high accuracy. Further GGS optimization using multiple ferroptotic and apoptotic datasets revealed highly specific ferroptosis biomarkers, which are robustly validated in vitro and in vivo. A subset of the GGS is associated with poor prognosis in breast cancer patients and PDXs and contains different ferroptosis repressors. Depletion of one representative, PDGFA‐assaociated protein 1(PDAP1), is found to suppress basal‐like breast tumor growth in a mouse model. Omics and mechanistic studies revealed that ferroptosis is associated with enhanced lysosomal function, glutaminolysis, and the tricarboxylic acid (TCA) cycle, while its transition into apoptosis is attributed to enhanced endoplasmic reticulum(ER)‐stress and phosphatidylethanolamine (PE)‐to‐phosphatidylcholine (PC) metabolic shift. Collectively, this study highlights molecular mechanisms underlying ferroptosis execution, identified a highly predictive ferroptosis gene signature with prognostic value, ferroptosis versus apoptosis biomarkers, and ferroptosis repressors for breast cancer therapy. [ABSTRACT FROM AUTHOR]

In plants, the contribution of the plasmotype (mitochondria and chloroplast) in controlling the circadian clock plasticity and possible consequences on cytonuclear genetic makeup have yet to be fully elucidated. A genome‐wide association study in the wild barley (Hordeum vulgare ssp. spontaneum) B1K collection identified overlap with our previously mapped DRIVERS OF CLOCKS (DOCs) loci in wild‐cultivated interspecific population. Moreover, we identified non‐random segregation and epistatic interactions between nuclear DOCs loci and the chloroplastic RpoC1 gene, indicating an adaptive value for specific cytonuclear gene combinations. Furthermore, we show that DOC1.1, which harbours the candidate SIGMA FACTOR‐B (SIG‐B) gene, is linked with the differential expression of SIG‐B and CCA1 genes and contributes to the circadian gating response to heat. High‐resolution temporal growth and photosynthesis measurements of B1K also link the DOCs loci to differential growth, Chl content and quantum yield. To validate the involvement of the Plastid encoded polymerase (PEP) complex, we over‐expressed the two barley chloroplastic RpoC1 alleles in Arabidopsis and identified significant differential plasticity under elevated temperatures. Finally, enhanced clock plasticity of de novo ENU (N‐Ethyl‐N‐nitrosourea) ‐induced barley rpoB1 mutant further implicates the PEP complex as a key player in regulating the circadian clock output. Overall, this study highlights the contribution of specific cytonuclear interaction between rpoC1 (PEP gene) and SIG‐B with distinct circadian timing regulation under heat, and their pleiotropic effects on growth implicate an adaptive value. [ABSTRACT FROM AUTHOR]

Material recovered from the Ma'agan Mikhael B shipwreck, off the coast of northern Israel, includes a significant assemblage of glass, which appears to represent waste workshop material (cullet) collected for recycling. Twenty‐three samples were selected for analysis for major and minor elements using SEM‐EDS, to provide insight into the activities and dating of the ship. The glass corresponds to known primary glass types, comprising a high‐ and a low‐lime subgroup of Levantine 1 (Apollonia type), and Egypt 1b. The assemblage is likely to date to the early part of the eighth century CE and, in conjunction with the radiocarbon dating of the ship, gives a possible date range for the wreck of 710–740 C.E. All groups contain glass‐working waste, glass chunks, and vessel fragments, and the majority are likely to have been collected from one or more workshops. It is unclear whether this cargo represents the byproducts of several campaigns of a single workshop which used different consignments of raw glass, or material from different workshops, collected at different ports of call. [ABSTRACT FROM AUTHOR]