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Abstract The vibration and acoustic noise of a permanent‐magnet synchronous motor are analysed and evaluated. Acoustic noise sound levels, their prominent frequencies, and the noisiest motor speed range are predicted. According to many resources, the radial vibration of the stator system due to the magnetic attraction between rotor permanent magnets and stator iron teeth is the main reason for the acoustic noise propagation of the PMSMs. The dominant orders of the spatial circumferential harmonics of the radial magnetic forces (RMFs) have been investigated and compared. The complete and complicated mechanical components, materials, and harmonics of the magnetic forces of the motor and their interaction are simplified and equalised to a vibration model, which consists of the interaction between the stator system and the dominant harmonic orders of the RMFs. Based on this approach, the simplest and most adequate semi‐analytical‐FEM model for noise prediction in PMSMs is proposed. This model, in addition to simplification, clarifies the role of the main mechanical and electromagnetic origins of noise generation. The acoustic noise prediction, using the proposed method has been compared with the experimental results. There is a proper agreement between the analytical, the FEM, and measurement results.

Abstract Nowadays, the use of hybrid systems has become very common all over the world. In this study, the aim is to minimize the use of grid energy to provide heating and cooling energy with the help of a hybrid heat pump equipped with a flat solar collector, phase change material (PCM), and photovoltaic (PV) panels. To achieve the best results, a numerical dynamic model consisting of different solar PV panels in three models, batteries, inverters, and hybrid heat pump along with collector and PCM has been modeled by solving Engineering Equation Solver (EES) and TRNSYS software. According to the proposed scenarios, multi‐objective optimization has been done to simultaneously improve the study answers in several sections by multi‐objective particle swarm optimization algorithm with MATLAB software. Also, economic and environmental optimization is also presented separately for comparing and reviewing solutions. The results of multi‐objective optimization show that the amount of lifecycle cost (LCC) when using polycrystalline panel is 21.26% lower than monocrystalline panel and 38.71% higher than thin film panel. As a result, according to the specific conditions and attitude, you can choose the desired system. Also, in the economic optimization, it was found that the best system is related to the polycrystalline panel, the volume of PCM used in the system is equal to 1 m 3, the number of panels used is 18, and the minimum amount of LCC is $3929.08.

Abstract This article investigated the charge and discharge management structure of electric vehicles (EVs) in intelligent parking lots (IPLs). It seems that with the expansion of renewable energy sources (RESs) as clean energy and investigation of the effects of EVs on the operation and planning of future distribution networks around the way EVs exchange energy with each other and the upstream network operator, RESs such as solar and wind sources, along with hydrogen storage are essential. Therefore, a new stochastic multi‐scenario approach for charge/discharge management of EVs parked in IPL was proposed, in which a newly developed model for the IPL with a hydrogen storage system (HSS) consisting of a fuel cell, an electrolyzer, and a hydrogen storage tank was presented. In the proposed model, the constraints of upstream network and power balance constraints, with the operating constraints related to the IPL, including EVs, renewable energy sources, and the hydrogen storage system, were formulated as the most important objectives of the optimization problem. The optimization algorithm, Competitive Swarm Optimizer (CSO), was formulated for implementation, and its results were compared with those of the PSO and GWO algorithms. The CSO must handle a variety of practical, large‐scale optimization problems. Based on the obtained results, the excess energy purchased from the upstream network or renewable sources was used as hydrogen storage for consumption during peak hours. As expected, the technical constraints and financial goals of the system were met, and the proposed system was evaluated on a 33‐bus network. As the expected benefits will be the most beneficial with the presence of renewable sources, the final profit will be reduced by taking into account uncertainty for charge/discharge management in EVs such as the uncertainty of electric load, market price, wind turbine, and photovoltaic cell sources. Nonetheless, the profit obtained from renewable resources is preferable to losses resulting from the uncertainty of the system, and according to expectation, the performance of the system for managing the optimal charging and discharging of EVs in the IPL will be acceptable with the maximum profit for the grid.

ABSTRACT Vertical axis wind turbine (VAWT) has a rotating axis perpendicular to the wind direction. This type of wind turbine that is suitable for urban environments has low wind direction dependency and noise. In this research, a novel surrogated approach for optimizing a VAWT is proposed, used, tested, and verified, which is not reported in literature. The proposed method consisted of 3D computational fluid dynamics (CFD) analysis of wind flow through the wind turbine with FLUENT software by solving the unsteady turbulent equations. However, 3D CFD analysis was time and cost consuming to obtain the output result (power coefficient) from input values (airfoil chord length, pitch angle, and tip speed ratio as turbine design variables). Thus, artificial neural network (ANN) was applied to obtain weight functions to correlate FLUENT software inputs and outputs after learning process. Finally, genetic algorithm was used for maximizing the turbine power coefficient considering three defined design variables. The optimum value of power coefficient was improved to 0.244, and the optimum values of design variables for blade chord length, blade pitch angle, and blade tip speed ratio were 0.218, −0.453, and 1.24, respectively. This novel surrogated method reduced the computational time and cost of VAWT optimizing considerably.

ABSTRACT Worldwide, humans have strongly altered river networks. Key changes resulted in modified hydromorphology, poor habitat quality and availability, migration barriers, and pollution. Restoration measures aim at mitigating anthropogenic stressors and at restoring connectivity, but the biological success of these measures is not guaranteed. Analyzing genetic diversity and metapopulation structure of target species in the river network with genetic markers can help to understand recolonization processes and to identify persisting gene flow barriers. Here, we studied the population genetic structure of the two pollution‐tolerant detritivorous isopod species, Asellus aquaticus and Proasellus coxalis, in the former heavily degraded and polluted, but now mostly restored Emscher catchment in Germany. For both species, we analyzed mitochondrial cytochrome c oxidase I (COI) gene sequences and nuclear genome‐wide single nucleotide polymorphism (SNP) data. Surprisingly, we found a strong metapopulation structure for both species with several isolated populations on a small‐scale of few kilometers, but a still high genetic diversity, especially in the COI gene. For both taxa, potentially cryptic species are known, but our SNP data showed that the mitochondrial lineages represent only one species, each, in the study area. This highlights the importance of integrating high‐resolution nuclear markers into species identification because species diversity may otherwise be overestimated. While we could identify some migration barriers and find indications for passive dispersal by birds or humans, these factors could not fully explain the local metapopulation structure, suggesting that also other drivers, such as isolation by adaptation, priority effects, or biotic interactions, play a role in shaping the population genetic structure.

Abstract Recent findings of NO near Gale Crater on Mars have been explained by two pathways: formation of nitric acid (HNO3) in a warm climate or formation of peroxynitric acid (HO2NO2) in a cool climate. Here, we put forth two hitherto unexplored pathways: (a) deposition of nitric/peroxynitric acid onto ice particles in a cold atmosphere, which settle quickly onto Mars' surface and (b) solar energetic particle‐induced production of nitric/peroxynitric acid. The deposition rates are enhanced and NO production is more efficient under the higher atmospheric pressures typical of Mars' ancient atmosphere. Depending on the unknown rate at which nitric/peroxynitric acid is lost from the surface, the new pathways could result in larger NO‐levels than those detected by the Mars Science Laboratory. We predict a 2:1 ratio of nitrite:nitrate would have deposited in cool surface climates with an icy atmosphere, whereas orders of magnitude more nitrate than nitrite is expected from warm surface climates.

Abstract In the mid‐latitudes extreme precipitation events are strongly associated with cold fronts. By exploring drivers across different scales and relating them to precipitation, we aim to improve our understanding of processes influencing cold frontal extremes. Using hourly ERA5 data over Europe and the North Atlantic, cold fronts are detected and the associated conditions are identified. Quantile regression models are employed to find drivers of frontal precipitation and to quantify these relations. Additionally, we use composites to study the synoptic conditions and meso‐scale structure of extreme events. We find that humidity close to the detected fronts, convergence and the low level jet speed contribute most to the formation of extreme precipitation. Synoptic conditions favoring the formation of extreme events are also identified. These results improve our understanding of cold frontal processes leading to precipitation. Additionally, they provide the foundation for a process‐based evaluation of frontal dynamics in climate models.

Background Prior analyses of the relationship between insurance status and receipt of tests and procedures have yielded conflicting findings and have focused on outpatient care. We sought to characterize the relationship between primary payer and diagnostic and procedural intensity, comparing rates of cardiac tests and procedures in matched hospitalized Medicaid and commercially insured patients. Methods and Results We created a propensity score–matched sample of Medicaid and commercially insured adults hospitalized at all acute care hospitals in Kentucky, Maryland, New Jersey, and North Carolina from 2016 to 2018. The main outcome was receipt of a cardiac test or procedure: echocardiogram, stress test, cardiac catheterization (elective, in acute coronary syndrome, in ST‐segment–elevation myocardial infarction), and pacemaker and subcutaneous cardiac rhythm monitor implantation. Generalized linear models with a hospital‐specific indicator variable were estimated to calculate the adjusted odds of a commercially insured patient receiving a given test or procedure relative to a Medicaid patient. Models controlled for race, ethnicity, and zip code income quartile. Commercially insured patients were more likely to receive each cardiac test or procedure, with adjusted odds ratios ranging from 1.16 (95% CI, 1.00–1.34) for cardiac catheterization in ST‐segment–elevation myocardial infarction to 1.40 (95% CI, 1.27–1.54) for pacemaker implantation. Conclusions Hospitalized commercially insured patients were more likely to undergo a range of cardiac tests and procedures, some of which may represent low‐value care. This may be driven by a combination of physician and patient preference, financial incentives, and social determinants of health. Our findings support the need for hospital payment models focused on increasing value and reducing inequities.

Abstract Objective Mental health complaints are prevalent among people with epilepsy, yet there are major barriers that prevent access to psychological care, including high out‐of‐pocket costs and a lack of accessible specialized services. The purpose of the current study is to examine the comparative efficacy, acceptability, cost‐effectiveness, and long‐term outcomes of a digital psychological intervention when delivered under two models of care (i.e., guided vs. unguided) in supporting the mental health and functioning of adults with epilepsy. Method Approximately 375 participants across Australia will be enrolled. Eligible participants will have a confirmed diagnosis of epilepsy, experience difficulties with their emotional health, be at least 18 years of age, and live in Australia. Participants will be randomized (2:2:1) to receive the Wellbeing Neuro Course, a 10‐week internet‐delivered program, with (i.e., guided) or without guidance by a mental health clinician (i.e., unguided), or be allocated to a treatment‐as‐usual waiting‐list control group. Participants will complete online questionnaires at pre‐, post‐treatment, and 3‐ and 12‐month follow‐up and consent to have their data linked to their medical records to capture healthcare system resource use and costs. Analysis Primary outcome measures will be symptoms of depression and anxiety. A cost‐utility analysis will be undertaken using the Australian healthcare system perspective and according to current economic evaluation guidelines. Resource use and costs to the healthcare system during the study period will be captured via data linkage to relevant administrative datasets in Australia. Significance The results of this trial will provide important data concerning the relative outcomes of these different models of care and will inform the integration of digital psychological interventions translation into healthcare services. Ethics and Dissemination The Human Research Ethics Committee of Macquarie University approved the proposed study (Reference No: 520231325151475). The results will be disseminated through peer‐reviewed publication(s). ANZCTR Trial Registration Number ACTRN12623001327673. Plain Language Summary This study seeks to find out if a 10‐week online psychological treatment can improve the mental health and well‐being of Australian adults with epilepsy. Around 375 participants will be randomly assigned to different groups: one will receive treatment with guidance from mental health clinician (guided group), one without guidance (unguided group), and one starting later (waiting control group). All participants will fill out the same outcome measures online. The main goal of this research is to compare these groups and assess how well the treatment works in improving mental health outcomes.

Abstract Coronavirus disease 2019 (COVID‐19) often leads to a spectrum of pulmonary complications, including interstitial lung disease (ILD) with the potential for fibrotic sequelae. Assessing the presence of ongoing active inflammation versus established residual fibrosis as a result of lung parenchymal injury and repair in these patients is a clinical challenge. Better understanding of the disease process is crucial for guiding appropriate therapeutic strategies. We aim to investigate the use of positron emission tomography / computer tomography (PET/CT) scans and their role in diagnosing interstitial pneumonitis (IP) post COVID infections.

Key Clinical Message Homozygous variants of Calcium Voltage‐Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation were previously identified as causes of periodic paralysis and congenital early‐onset myopathy, while it could be manifested as a late‐onset congenital core myopathy. Abstract Calcium Voltage‐Gated Channel Subunit Alpha1 S (CACNA1S) gene mutation has been linked to various neuromuscular conditions in recent years. Congenital myopathy with core‐like features is one of the cardinal associations reported previously, causing severe respiratory insufficiency and death in neonates. Informed consent was received from the patients. Subsequently, peripheral blood leukocytes were utilized to extract genomic DNA. Moreover, exome enrichment was implemented through the Twist Human Core Exome Kit (Twist Bioscience) and exome sequenced using Illumina NovaSeq 6000 platform (Illumina, San Diego, CA, USA). Sanger sequencing using BIG Dye Terminators confirmed the presence of the final variant. Finally, the candidate variants were classified based on the American College of Medical Genetics and Genomics (ACMG) guidelines. In this report, we describe two siblings, who presented with childhood and late‐onset progressive muscle weakness, and had a homozygous variant in exon 2 of the CACNA1S gene defined as c.188C > A (p.Ala63Asp) (NM_000069.3). The SIFT, Polyphen2, CADD PHRED, and Mutation Taster analysis tools classified the variant as pathogenic/damaging. The muscle biopsy of the younger brother revealed intermyofibrillar network pattern disruption as cytoplasmic core‐like lesions. The muscle magnetic resonance imaging (MRI) reported grade IIa and IIb fatty changes. Finally, the electromyography (EMG) findings suggested a myopathic change pattern. This report illustrates the clinical variability in CACNA1S‐related myopathy by reviewing prior reports and adding newly found aspects, additionally expanding the gene defects associated with core myopathy.

Abstract Deciphering nature's remarkable way of encoding functions in its biominerals holds the potential to enable the rational development of nature‐inspired materials with tailored properties. However, the complex processes that convert solution‐state precursors into solid biomaterials remain largely unknown. In this study, an unconventional approach is presented to characterize these precursors for the diatom‐derived peptides R5 and synthetic Silaffin‐1A1 (synSil‐1A1). These molecules can form defined supramolecular assemblies in solution, which act as templates for solid silica structures. Using a tailored structural biology toolbox, the structure‐function relationships of these self‐assemblies are unveiled. NMR‐derived constraints are employed to enable a recently developed fractal‐cluster formalism and then reveal the architecture of the peptide assemblies in atomistic detail. Finally, by monitoring the self‐assembly activities during silica formation at simultaneous high temporal and residue resolution using real‐time spectroscopy, the mechanism is elucidated underlying template‐driven silica formation. Thus, it is demonstrated how to exercise morphology control over bioinorganic solids by manipulating the template architectures. It is found that the morphology of the templates is translated into the shape of bioinorganic particles via a mechanism that includes silica nucleation on the solution‐state complexes’ surfaces followed by complete surface coating and particle precipitation.

Abstract Introduction Death due to covid‐19 is one of the biggest health challenges in the world. There are many models that can predict death due to COVID‐19. This study aimed to fit and compare Decision Tree (DT), Support Vector Machine (SVM), and AdaBoost models to predict death due to COVID‐19. Methods To describe the variables, mean (SD) and frequency (%) were reported. To determine the relationship between the variables and the death caused by COVID‐19, chi‐square test was performed with a significance level of 0.05. To compare DT, SVM and AdaBoost models for predicting death due to COVID‐19 from sensitivity, specificity, accuracy and the area under the rock curve under R software using psych, caTools, random over‐sampling examples, rpart, rpartplot packages was done. Results Out of the total of 23,054 patients studied, 10,935 cases (46.5%) were women, and 12,569 cases (53.5%) were men. Additionally, the mean age of the patients was 54.9 ± 21.0 years. There is a statistically significant relationship between gender, fever, cough, muscle pain, smell and taste, abdominal pain, nausea and vomiting, diarrhea, anorexia, dizziness, chest pain, intubation, cancer, diabetes, chronic blood disease, Violation of immunity, pregnancy, Dialysis, chronic lung disease with the death of covid‐19 patients showed (p

Abstract Background and Aims Cardiovascular diseases (CVDs) are one of the major diseases in developing and developed countries and have high prevalence and mortality rates. Pharmacological interventions, especially the use of combination medications, can have preventive effects in patients with CVDs. Recently, in the PolyIran trial, a combination of atorvastatin, hydrochlorothiazide, aspirin, and valsartan or enalapril (Polypill) was shown to be effective in providing survival benefits as a primary prevention strategy. In the present study, we examine the cost‐effectiveness of the use of polypill compared to its individual components (named as medication monotherapy) in the prevention of CVDs in Iran. Methods This was an economic evaluation study conducted to compare the cost‐utility of polypill with that of medication monotherapy for 10,000 hypothetical cohorts of people over 35 years of age using the Markov model and with a lifetime horizon. The study perspective was patient perspective and direct medical costs, quality‐adjusted life‐years (QALYs), and incremental cost‐effectiveness ratio were estimated. To deal with uncertaintysensitivity analyses were used. Results The results showed that polypill, with the lowest costs (871 USD) and highest QALYs (14.55), had the most cost‐utility than medication monotherapy. Also, the results showed that the highest sensitivities were related to the utilities of angina and stroke states. At the 21,768 USD threshold, polypill had a 92% probability of being cost‐effective versus other medications. Conclusion Considering that polypill had the most cost‐utility, it is suggested that health system policymakers pay special attention to polypill in designing clinical guidelines. Also, through covering this medication by health insurance organizations, it is possible to complete the country's medicine pharmacopeia in preventing CVDs.

Key Clinical Message Hydatid cyst is a sly disease that can manifest with a spectrum of symptoms in almost every part of the human body, so it is crucial to be familiar with different scenarios that a patient may present. Abstract The echinococcus granulosus parasite causes hydatid disease and is common in areas with animal husbandry and agriculture. Here, we report a middle age woman who presented with abdominal pain that further investigation revealed a cyst in subdiaphragmatic area.

ABSTRACT Objectives Gingiva is one of the supporting tissues around the teeth that can be affected by various neoplastic or nonneoplastic lesions. Previous studies have examined several types of gingival lesions, but the lack of a standardized classification system has hindered meaningful comparisons. Additionally, many studies focused primarily on reactive lesions. Our study aims to contribute to the understanding of gingival lesions by investigating their prevalence across age groups, genders, sites, and by their clinical presentation. This research could lead to improved diagnostic accuracy and treatment strategies. Materials and Methods This retrospective study explores the prevalence of gingival lesions based on biopsies during a 22‐year span. The patient's demographic details, including age, gender, and lesion's clinical presentation were systematically collected. These lesions were categorized into six groups. Descriptive statistics, χ2 test of independence, and one‐way ANOVA were used for data analysis. Results Among the 7668 biopsied lesions, 684 (8.9%) lesions were located in the gingiva, with a greater occurrence in women (63.5%). Soft tissue tumors represented the most prevalent group in the gingival lesions (72.1%), and peripheral giant cell granuloma (PGCG) was the most frequent lesion (21.2%), followed by, pyogenic granuloma (19.3%), peripheral ossifying fibroma (17.8%) and focal fibrous hyperplasia (7.6%); all of which predominantly affected women, with mean ages falling in the fourth decade of life. Squamous cell carcinoma was recognized as the most common malignancy. Conclusion In this study, PGCG was found to be the most common lesion in the gingiva in Iranian population. Further analysis using a unanimous categorization is required to confirm these results.

Abstract Background Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive genetic disorder with approximately 1000 known cases worldwide, in which calcium phosphate microliths deposit in the alveolar air spaces. As of writing this report, no definitive conventional therapy exists, and many PAM cases may progress to severe respiratory failure and potential death. Bilateral lung transplantation (BLx) seems to be the most optimal solution; however, this procedure is challenging along with limited reports regarding the outcome in PAM. We report a case of PAM successfully treated with BLx for the first time in Iran. Method We present the case of a 42‐year‐old female with a longstanding history of cough, not responding to conventional antitussive medication, who was diagnosed as a case of PAM following a hospitalization due to coughing, dyspnea on exertion, and hemoptysis. Despite treatment with corticosteroid and medical treatment, no improvement was achieved and she subsequently developed respiratory and right ventricular failure, with oxygen ventilation dependence. Eventually, she was scheduled for BLx. The operation was successful and during her 2‐year follow‐up, no recurrence or significant postoperative complications has been reported. Conclusion This case presentation and literature review confirm the effectiveness of BLx as a promising treatment for PAM‐diagnosed patients, improving both life expectancy and quality of life.

Abstract Objective In patients undergoing hypoglossal nerve stimulation (HGNS), we examined the Insomnia Severity Index (ISI) to understand how baseline sleep onset insomnia (SOI), sleep maintenance insomnia (SMI), and early morning awakening (EMA) affected postsurgical outcomes. Study Design Observational. Setting Multicenter registry. Methods We included patients from the Adherence and Outcomes of Upper Airway Stimulation for Obstructive Sleep Apnea International Registry (ADHERE) with a baseline ISI from 2020 to 2023. Regression analysis examined the association of ISI question scores for SOI, SMI, and EMA and outcomes: Apnea‐Hypopnea Index (AHI) reduction, device usage, changes in the Epworth Sleepiness Scale (ESS) and overall ISI score, final visit (FV) completion, and satisfaction. Results No relationship was noted between insomnia subtypes and AHI reduction or FV completion. In the subgroup of patients with baseline moderate/severe insomnia, patients with major impairment for SOI used their device 64 min/day longer than those with minimal impairment. Among all patients, those with baseline major impairment for SOI had a 2.3 points greater improvement in ISI from baseline to FV compared to patients with minimal impairment, while patients with baseline major impairment for SMI had a 2.0 and 3.5 points greater improvement in the ESS and ISI than those with minimal impairment. Patients with EMA and moderate/severe baseline insomnia had decreased odds of being satisfied after surgery. Conclusion In ADHERE, nocturnal symptoms of insomnia did not limit HGNS efficacy or therapy use. Conversely, those with worse insomnia subtype impairments at baseline had improved outcomes related to adherence, sleepiness, and insomnia at the FV.

Abstract Background and Aims The incidence of thyroid cancer has witnessed a significant global increase and stands as one of the most prevalent cancers in Iran. This surge is primarily attributed to the escalating incidence of papillary thyroid cancer (PTC), with overdiagnosis emerging as an equally noteworthy factor. Consequently, this study aims to ascertain the incidence of thyroid cancer, along with its clinical presentation, demographic characteristics, and surgical features in patients undergoing thyroid surgery. Methods This cross‐sectional study involved the evaluation of patient files from referral centers in Shiraz spanning the years 2015−2020. Demographic and clinical information pertaining to thyroid cancer was extracted and subsequently analyzed using SPSS software. Results A total of 533 documented cases of thyroid cancer undergoing surgery revealed an annual rate of 89 cases in our location. The average age of the patients was 43.9 ± 13.4 years (ranging from 13 to 92), with females constituting 429 (83.5%) of the cases, and 278 (54.1%) being malignant. Conventional PTC emerged as the most prevalent pathology, accounting for 239 (45.0%) of the cases. Patients with thyromegaly exhibited significantly higher incidences of nonmalignant tumors (p = 0.01), while those with malignant tumors were notably younger than those with nonmalignant tumors (p = 0.001). Conclusion Our study revealed a progressive rise in the number of patients undergoing thyroidectomy over the years, with PTC constituting the majority of cases. Malignant cases were more frequently observed in younger patients, and in smaller lesion sizes, highlighting the importance of early screening and optimizing detection methods, especially in high‐risk populations.

Abstract Objectives Our study aims to determine the incidence and potential risk factors for cerebral radiation necrosis (CRN) following treatment of sinonasal malignancies. Methods One hundred thirty‐two patients diagnosed with sinonasal malignancies over an 18‐year period were identified at two institutions. Forty‐six patients meeting inclusion criteria and treated with radiation therapy were included for analysis. Demographic and clinical‐pathologic characteristics were collected and reviewed. Post‐treatment magnetic resonance imaging (MRI) at least 1 year following treatment was reviewed to determine presence or absence of CRN. Results CRN was identified on MRI in 8 of 46 patients (17.4%) following radiation treatment. Patients with a history of reirradiation were more likely to develop CRN (50% vs. 10.5%, p .05). CRN patients had a higher proportion of tumors with skull base involvement than non‐CRN patients (100% vs. 57.9%, p = .037). Demographics, comorbidities, pathology, primary tumor subsite, chemotherapy use, and stage of disease demonstrated no significant increase in risk of CRN. Conclusions Reirradiation and tumor skull base involvement were significant risk factors associated with CRN. Higher average total prescribed and BEDs of radiation were seen in the CRN groups, but these differences were not statistically significant. Gender, comorbidities, tumor subsite, tumor location, and treatment type were not significantly different between groups. Level of evidence Level 3.

Background We aimed to correlate alterations in the rat sarcoma virus (RAS)/mitogen‐activated protein kinase pathway in vascular anomalies to the clinical phenotype for improved patient and treatment stratification. Methods and Results This retrospective multicenter cohort study included 29 patients with extracranial vascular anomalies containing mosaic pathogenic variants (PVs) in genes of the RAS/mitogen‐activated protein kinase pathway. Tissue samples were collected during invasive treatment or clinically indicated biopsies. PVs were detected by the targeted sequencing of panels of genes known to be associated with vascular anomalies, performed using DNA from affected tissue. Subgroup analyses were performed according to the affected genes with regard to phenotypic characteristics in a descriptive manner. Twenty‐five vascular malformations, 3 vascular tumors, and 1 patient with both a vascular malformation and vascular tumor presented the following distribution of PVs in genes: Kirsten rat sarcoma viral oncogene (n=10), neuroblastoma ras viral oncogene homolog (n=1), Harvey rat sarcoma viral oncogene homolog (n=5), V‐Raf murine sarcoma viral oncogene homolog B (n=8), and mitogen‐activated protein kinase kinase 1 (n=5). Patients with RAS PVs had advanced disease stages according to the Schobinger classification (stage 3–4: RAS, 9/13 versus non‐RAS, 3/11) and more frequent progression after treatment (RAS, 10/13 versus non‐RAS, 2/11). Lesions with Kirsten rat sarcoma viral oncogene PVs infiltrated more tissue layers compared with the other PVs including other RAS PVs (multiple tissue layers: Kirsten rat sarcoma viral oncogene, 8/10 versus other PVs, 6/19). Conclusions This comparison of patients with various PVs in genes of the RAS/MAPK pathway provides potential associations with certain morphological and clinical phenotypes. RAS variants were associated with more aggressive phenotypes, generating preliminary data and hypothesis for future larger studies.

Abstract Aim To explore predictors of care burden among the caregivers of patients with COVID‐19. Design The findings of this cross‐sectional study were presented in accordance with the guidelines outlined in the Strengthening the Reporting of Observational Studies in Epidemiology statement. Methods The samples included 172 caregivers in Imam Reza and Farabi Hospitals, located in Kermanshah, Iran, who were enrolled in the study using convenience sampling. A demographic information form and the Caregiver Burden Inventory were administered. The data were collected between 13 May 202 and 20 August 2021. Results Of the caregivers, 62.8% (n = 108) were male and 71.5% (n = 123) were over 40 years old. Furthermore, 66.3% (n = 114) of caregivers had severe and very severe care burden, with a mean care burden of 78.9 ± 20.4 out of 120. A statistically significant difference was found between care burden and the variables of monthly income, health status, number of patients under care and residence status (p

Abstract Background High concentrations of low‐density lipoprotein cholesterol (LDL‐C) have been a known risk factor for cardiovascular diseases. Also, the role of oxidized LDL (ox‐LDL) in forming atherosclerosis plaque has been proven. However, it has not yet been proven that atherogenic LDL‐C by‐products like ox‐LDL will decrease by keeping the LDL levels at the desired level. This study aimed to examine the relationship between LDL‐C and ox‐LDL in different LDL‐C values in patients with type 2 diabetes (T2D). Methods In this cross‐sectional study, 347 patients with T2D who received statins were enrolled. LDL‐C values were defined into four groups as LDL‐C 100 mg/dL in patients with T2D. However, the revealed association of ox‐LDL with TG level and TG/HDL ratio may be considered in the clinic.

Abstract Objective Circadian and multidien cycles of seizure occurrence are increasingly discussed as to their biological underpinnings and in the context of seizure forecasting. This study analyzes if patient reported seizures provide valid data on such cyclical occurrence. Methods We retrospectively studied if circadian cycles derived from patient‐based reporting reflect the objective seizure documentation in 2003 patients undergoing in‐patient video‐EEG monitoring. Results Only 24.1% of more than 29000 seizures documented were accompanied by patient notifications. There was cyclical underreporting of seizures with a maximum during nighttime, leading to significant deviations in the circadian distribution of seizures. Significant cyclical deviations were found for focal epilepsies originating from both, frontal and temporal lobes, and for different seizure types (in particular, focal unaware and focal to bilateral tonic–clonic seizures). Interpretation Patient seizure diaries may reflect a cyclical reporting bias rather than the true circadian seizure distributions. Cyclical underreporting of seizures derived from patient‐based reports alone may lead to suboptimal treatment schemes, to an underestimation of seizure‐associated risks, and may pose problems for valid seizure forecasting. This finding strongly supports the use of objective measures to monitor cyclical distributions of seizures and for studies and treatment decisions based thereon.

Glioblastoma (GBM) is the most common and aggressive malignant primary brain tumor in adults. The standard treatment achieves a median overall survival for GBM patients of only 15 months. Hence, novel therapies based on an increased understanding of the mechanistic underpinnings of GBM are desperately needed. In this study, we show that elevated expression of 28S rRNA (cytosine‐C(5))‐methyltransferase NSUN5, which methylates cytosine 3782 of 28S rRNA in GBM cells, is strongly associated with the poor survival of GBM patients. Moreover, we demonstrate that overexpression of NSUN5 increases protein synthesis in GBM cells. NSUN5 knockdown decreased protein synthesis, cell proliferation, sphere formation, migration, and resistance to temozolomide in GBM cell lines. NSUN5 knockdown also decreased the number and size of GBM neurospheres in vitro. As a corollary, mice harboring U251 tumors wherein NSUN5 was knocked down survived longer than mice harboring control tumors. Taken together, our results suggest that NSUN5 plays a protumorigenic role in GBM by enabling the enhanced protein synthesis requisite for tumor progression. Accordingly, NSUN5 may be a hitherto unappreciated target for the treatment of GBM.

Abstract Many symbionts are sexually transmitted and impact their host's development, ecology, and evolution. While the significance of symbionts that cause sexually transmitted diseases (STDs) is relatively well understood, the prevalence and potential significance of the sexual transmission of mutualists remain elusive. Here, we study the effects of sexually transmitted mutualist nematodes on their dung beetle hosts. Symbiotic Diplogastrellus monhysteroides nematodes are present on the genitalia of male and female Onthophagus beetles and are horizontally transmitted during mating and vertically passed on to offspring during oviposition. A previous study indicates that the presence of nematodes benefits larval development and life history in a single host species, Onthophagus taurus. However, Diplogastrellus nematodes can be found in association with a variety of beetle species. Here, we replicate these previous experiments, assess whether the beneficial effects extend to other host species, and test whether nematode‐mediated effects differ between male and female host beetles. Rearing three relatively distantly related dung beetle species with and without nematodes, we find that the presence of nematodes benefits body size, but not development time or survival across all three species. Likewise, we found no difference in the benefit of nematodes to male compared to female beetles. These findings highlight the role of sexually transmitted mutualists in the evolution and ecology of dung beetles.

Abstract Heterogeneous chemical cycles of pyrogenic nitrogen and halides influence tropospheric ozone and affect the stratosphere during extreme Pyrocumulonimbus (PyroCB) events. We report field‐derived N2O5 uptake coefficients, γ(N2O5), and ClNO2 yields, φ(ClNO2), from two aircraft campaigns observing fresh smoke in the lower and mid troposphere and processed/aged smoke in the upper troposphere and lower stratosphere (UTLS). Derived φ(ClNO2) varied across the full 0–1 range but was typically

Abstract Structural variations (SVs) are a major source of domestication and improvement traits. We present the first duck pan‐genome constructed using five genome assemblies capturing ∼40.98 Mb new sequences. This pan‐genome together with high‐depth sequencing data (∼46.5×) identified 101,041 SVs, of which substantial proportions were derived from transposable element (TE) activity. Many TE‐derived SVs anchoring in a gene body or regulatory region are linked to duck's domestication and improvement. By combining quantitative genetics with molecular experiments, we, for the first time, unraveled a 6945 bp Gypsy insertion as a functional mutation of the major gene IGF2BP1 associated with duck bodyweight. This Gypsy insertion, to our knowledge, explains the largest effect on bodyweight among avian species (27.61% of phenotypic variation). In addition, we also examined another 6634 bp Gypsy insertion in MITF intron, which triggers a novel transcript of MITF, thereby contributing to the development of white plumage. Our findings highlight the importance of using a pan‐genome as a reference in genomics studies and illuminate the impact of transposons in trait formation and livestock breeding.

Abstract Multiple parasites and pathogens cause disease in aquatic wildlife and in aquaculture species, generating a need for monitoring and management. Conventional disease monitoring methods involve laborious, costly, and invasive capture and examination of host species, and require specialized expertise for every host and pathogen of interest. Environmental DNA could provide simultaneous occurrence data for multiple pathogens across different host taxa, valuable for using parasite diversity as, for example, a bioindicator of ecosystem disturbance. Here, we tested the potential for simultaneous detection of four wildlife pathogens in water samples from 280, mainly riverine, sites across Switzerland. We targeted the crayfish pathogen Aphanomyces astaci, the amphibian pathogen Batrachochytrium dendrobatidis, and the fish pathogens Saprolegnia parasitica and Tetracapsuloides bryosalmonae. The eDNA detection showed a widespread distribution of A. astaci, S. parasitica, and T. bryosalmonae, although A. astaci and T. bryosalmonae were not detected in some alpine river catchments. B. dendrobatidis was detected only rarely, which was expected since the sampling did not target amphibian breeding sites. Co‐detection rates were higher in rivers than in lakes, likely reflecting the habitat preferences and distributions of the host species. We discuss the advantages and limitations of eDNA‐based pathogen monitoring and list a set of recommendations for managers. Our study illustrates how eDNA‐based techniques can monitor several pathogen species concurrently, thus facilitating more comprehensive disease monitoring schemes. Combined with metabarcoding approaches in the future, eDNA‐based sampling and detection can facilitate the incorporation of parasite and pathogen occurrence and diversity as an indicator for aquatic ecosystem health, and for revealing the hidden biodiversity and structure of parasite communities.

Key Clinical Message Children are more likely to develop Langerhans cell histiocytosis (LCH), a rare disorder with an unknown cause. LCH often invades skeletal systems, while it has occasionally been seen in the sternum or ribs. The best course of treatment for single‐site, skeletal LCH is yet unknown. We present an instance of sternal LCH with adult onset. By fusing and reconstructing chest computed tomography, it was possible to determine the extent of surrounding soft tissue invasion. Because LCH is so uncommon, it could be challenging to recall when we see a sternal lesion. Adult Patients who arrive with anterior chest discomfort and an osteolytic sternal lesion should include LCH on their differential diagnosis list.

Abstract Cardiovascular rhythms representing functional states of the autonomic nervous system (ANS) are insufficiently reflected by the current physiological model based on low and high frequency bands (LF, HF, resp.). An intermediate (IM) frequency band generated by a brainstem pacemaker was included in systemic physiological ANS analyses of forehead skin perfusion (SP), ECG, and respiration. Data of 38 healthy participants at T0 and T1 (+1 week) before, during, and following osteopathic cranial vault hold (CVH) stimulation were analyzed including momentary frequencies of highest amplitude, amplitudes in low (0.05–0.12 Hz), IM (0.12–0.18 Hz), and high (0.18–0.4 Hz) frequency bands, and established heart rate variability (HRV) metrics. During CVH, LF interval durations increased, whereas IM/HF band durations decreased significantly. Amplitudes increased significantly in all frequency bands. A cluster analysis found one response pattern dominated by IM activity (47% of participants) with highly stable 0.08 Hz oscillation to CVH, and one dominated by LF activity (0.10 Hz) at T0, increasing to IM activity at T1. Showing frequency ratios at ≈3:1, respiration was not responsible for oscillations in PPG during CVH. HRV revealed no significant responses. Rhythmic patterns in SP and respiration matched previous findings on a reticular “0.15 Hz rhythm”. Involvement of baroreflex pathways is discussed as alternative explanation.

Abstract Aim To determine the prevalence of self‐medication and reasons for self‐medication (SM) for the prevention/treatment of COVID‐19 among the adult population. Design Cross‐sectional study. Methods This study was performed on 147 adults in Kermanshah, Iran. Data were collected by a researcher‐made questionnaire and analysed by SPSS‐18 software using descriptive and inferential statistics. Results The prevalence of SM in the participants was 69.4%. Vitamin D and vitamin B complex were the most commonly used drugs. The most common symptoms leading to SM were fatigue and rhinitis. Strengthening the immune system and prevention of COVID‐19 (48%) were the main reasons for SM. Factors related to SM included marital status [OR = 8.04, 95% CI = (3.62, 17.83)], education [OR = 0.16, 95%CI = (0.08, 0.35)] and monthly income [OR = 0.09, 95%CI = (0.03, 0.26)]. Patient or Public Contribution Yes

Abstract Aim The aim of this study was to identify the defining characteristics of spiritual distress (00066). Design This study was conducted by integrated review method using Broom method. Methods PubMed, ProQuest, Web of Science, Embase, Scopus, and Cochran Library, and Persian scientific databases were searched from January 2010 to December 2020. Results Twenty‐one article and 74 defining characteristics were identified. 33 of these defining characteristics was mentioned in NANDA. The criteria with the highest frequency and repetition in articles were lack of peace, lack of hope, change in anger behaviour, lack of meaning in life, change in fear and crying behaviour, Concern about belief and values system and/or God. Conclusion Some of the spiritual distress defining characteristics overlap with other nursing diagnoses, including anxiety and hopelessness. Clinical and content validation studies need to be conducted and the main criteria for diagnosing spiritual distress in different cultures and religions need to be identified.

Key Clinical Message Osseous choristoma is a rare entity, mainly found on the posterior tongue. It is described as a nodular or exophytic lesion with firm to hard consistency. Clinicians should consider osseous choristoma when confronting lesions with the same features. Abstract Osseous choristoma is an unusual growth of ectopic bone in the soft tissue. This lesion is extremely rare, with a few cases reported in the literature, and they typically appear in the head and neck region, particularly the posterior tongue. The current report presents a case of osseous choristoma in the palate of a 51‐year‐old female. The patient had slight discomfort, which was resolved after surgical excision of the lesion, and no recurrence was observed. This research presents an instance of osseous choristoma in a less common location and concurrently acts as a review of this rare condition.

Abstract Many organisms actively manipulate the environment in ways that feed back on their own development, a process referred to as developmental niche construction. Yet, the role that constructed biotic and abiotic environments play in shaping phenotypic variation and its evolution is insufficiently understood. Here, we assess whether environmental modifications made by developing dung beetles impact the environment‐sensitive expression of secondary sexual traits. Gazelle dung beetles both physically modify their ontogenetic environment and structure their biotic interactions through the vertical inheritance of microbial symbionts. By experimentally eliminating (i) physical environmental modifications and (ii) the vertical inheritance of microbes, we assess the degree to which (sym)biotic and physical environmental modifications shape the exaggeration of several traits varying in their degree and direction of sexual dimorphism. We expected the experimental reduction of a larva's ability to shape its environment to affect trait size and scaling, especially for traits that are sexually dimorphic and environmentally plastic. We find that compromised developmental niche construction indeed shapes sexual dimorphism in overall body size and the absolute sizes of male‐limited exaggerated head horns, the strongly sexually dimorphic fore tibia length and width, as well as the weakly dimorphic elytron length and width. This suggests that environmental modifications affect sex‐specific phenotypic variation in functional traits. However, most of these effects can be attributed to nutrition‐dependent plasticity in size and non‐isometric trait scaling rather than body‐size‐independent effects on the developmental regulation of trait size. Our findings suggest that the reciprocal relationship between developing organisms, their symbionts, and their environment can have considerable impacts on sexual dimorphism and functional morphology.

Abstract Sigmoid volvulus accounts for 20%–50% of colonic obstructions in Eastern countries. This occurs mostly in patients with a lack of mobility and a history of chronic constipation. There are some very known complications of a undescended intra‐abdominal testicle such as cancer, ischemia, and infertility; But the rotation of the colon around the spermatic cord of one UDT is a very rare phenomenon that there is no similar report. A 67‐year‐old man came to the emergency department with a complaint of abdominal pain and obstipation. On examination, patient was febrile (T: 38.5) and had mild general tenderness. According to the appearance of coffee beans in the X‐ray, the diagnosis of sigmoid volvulus was made. In the requested tests, leukocytosis was observed. Rectosigmoidoscopy was unsuccessful. The patient underwent laparotomy. After manual untwisting, a tubular structure at the base of the meso‐sigmoid was noticed. With further exploration, the testis was observed intra‐abdominally. Orchidectomy and sigmoidectomy were performed by Hartmann's method. Sigmoid volvulus is one of the common cases that surgeons frequently encounter. The case scenarios are often the same, and from experience, most cases result from a long meso and an elongated sigmoid secondary to prolonged constipation. Therefore, it is clear that a scrotal examination would not be part of the routine examination of a patient with sigmoid volvulus. In this article, by reporting a very rare etiology for a very common pathology, we tried to point out the importance of head‐to‐toe examination in all patients.

Abstract Water scarcity threatens human life and it is likely to be a main concern in the next century. In this work, a novel multigeneration system (MGS) is introduced and assessed with energy, exergy, and economic analyses. This MGS includes a gas cycle, multieffect distillation, an absorption refrigeration cycle, a heat recovery steam generator, and electrodialysis. Electrodialysis is integrated into this configuration to produce sodium hydroxide and hydrogen chloride from brine to prevent its release to the environment with harmful impacts. The other products are electricity, cooling, and demineralized water. For the evaluation of the proposed system, one computer code is provided in engineering equation solver software. For physical properties calculation, the library of this software is used. The MGS produces 614.7 GWh of electrical energy, 87.44 GWh of cooling, 12.47 million m3 of demineralized water, and 0.092 and 0.084 billion kg of sodium hydroxide and hydrogen chloride over a year. Energy and exergy evaluations demonstrate that the MGS energy and exergy efficiencies are 31.3% and 18.7%, respectively. The highest and lowest value of exergy destruction rate is associated with the combustion chamber and pump, respectively. The economic evaluation indicates that the net present value of this proposed system is 3.8 billion US$, while the internal rate of return and payback period, respectively, are 0.49 and 2.1 years.

Abstract Background Colorectal cancer incidence increases with patient age. The aim of this study was to assess, at the nationwide level, in‐hospital mortality, and failure to rescue in geriatric patients (≥ 80 years old) with colorectal cancer arising from postoperative complications. Methods All patients receiving surgery for colorectal cancer in Germany between 2012 and 2018 were identified in a nationwide database. Association between age and in‐hospital mortality following surgery and failure to rescue, defined as death after complication, were determined in univariate and multivariate analyses. Results Three lakh twenty‐eight thousands two hundred and ninety patients with colorectal cancer were included of whom 77,287 were 80 years or older. With increasing age, a significant relative increase in right hemicolectomy was observed. In general, these patients had more comorbid conditions and higher frailty. In‐hospital mortality following colorectal cancer surgery was 4.9% but geriatric patients displayed a significantly higher postoperative in‐hospital mortality of 10.6%. The overall postoperative complication rate as well as failure to rescue increased with age. In contrast, surgical site infection (SSI) and anastomotic leakage (AL) did not increase in geriatric patients, whereas the associated mortality increased disproportionately (13.3% for SSI and 29.9% mortality for patients with AI, both p

Abstract Aims The aetiology of peripartum cardiomyopathy (PPCM) is still not clear, and it is unknown who would recover from PPCM. In this meta‐analysis, for the first time, we aimed to explore the prognostic value of potential baseline factors that may help predict recovery in patients with PPCM. Methods A systematic approach following the Meta‐analysis of Observational Studies in Epidemiology guideline was taken by using appropriate keywords in PubMed, Scopus, and Embase databases. Studies that had compared different clinical and paraclinical markers at the time of diagnosis related to cardiovascular function between recovered and non‐recovered patients with PPCM were included. To find potential predictors of recovery, the odds ratio (OR) was calculated for different parameters using the random‐effects model. Results Eighteen cohort studies including 1047 patients with PPCM were enrolled. Six markers out of the 11 potentially eligible markers were associated with PPCM recovery. Baseline echocardiographic parameters [left ventricular ejection fraction (LVEF) (OR = 4.84 [2.53; 9.26]), left ventricular end‐diastolic diameter (OR = 3.67 [2.58; 5.23]), left ventricular end‐systolic diameter (OR = 3.99 [2.27; 7.02]), and fractional shortening (OR = 6.14 [1.81; 20.85])] were strong predictors of PPCM recovery. Systolic blood pressure (OR = 2.16 [1.38; 3.38]) and diastolic blood pressure (OR = 2.06 [1.07; 3.96]) at diagnosis were also associated with recovery. Conclusions Patients with PPCM who have a higher baseline LVEF, lower left ventricular diameters, and higher blood pressure levels have a greater chance to recover from PPCM.

Abstract One of the objectives of oncology phase I dose‐escalation studies has been to determine the maximum tolerated dose (MTD). Although MTD is no longer set as the dose for further development in contemporary oncology drug development, MTD determination is still important for informing the therapeutic index. Bayesian adaptive model‐based designs are becoming mainstream in oncology first‐in‐human trials. Herein, we illustrate via simulations the use of systemic exposure in Bayesian adaptive dose–toxicity models to estimate MTD. We extend traditional dose–toxicity models to incorporate pharmacokinetic exposure, which provides information on exposure–toxicity relationships. We pursue dose escalation until the maximum tolerated exposure (corresponding to the MTD) is reached. By leveraging pharmacokinetics, dose escalation considers exposure and interindividual variability on a continuous rather than discrete domain, offering additional information for dose‐escalation decisions. To demonstrate this, we generated 1000 simulations (starting dose of 1/25th the reference dose and six dose levels) for several different scenarios. Both rule‐based and model‐based designs were compared using metrics of potential safety, accuracy, and reliability. The mean results over simulations and different toxicity scenarios showed that model‐based designs were better than rule‐based methods and that exposure–toxicity model‐based methods have the potential to valuably complement dose–toxicity model‐based methods. Exposure–toxicity model‐based methods had decreased underdose risk accompanied by a relatively smaller increase in overdose risk, resulting in improved net reliability. MTD estimation accuracy was compromised when exposure variability was large, emphasizing the importance of appropriate control of pharmacokinetic variability in phase I dose‐escalation studies.

Abstract Greenland rainfall has come into focus as a climate change indicator and from a variety of emerging cryospheric impacts. This study first evaluates rainfall in five state‐of‐the‐art numerical prediction systems (NPSs) (CARRA, ERA5, NHM‐SMAP, RACMO, MAR) using in situ rainfall data from two regions spanning from land onto the ice sheet. The new EU Copernicus Climate Change Service (C3S) Arctic Regional ReAnalysis (CARRA), with a relatively fine (2.5 km) horizontal grid spacing and extensive within‐model‐domain observational initialization, has the lowest average bias and highest explained variance relative to the field data. ERA5 inland wet bias versus CARRA is consistent with the field data and other research and is presumably due to more ERA5 topographic smoothing. A CARRA climatology 1991–2021 has rainfall increasing by more than one‐third for the ice sheet and its peripheral ice masses. CARRA and in situ data illuminate extreme (above 300 mm per day) local rainfall episodes. A detailed examination CARRA data reveals the interplay of mass conservation that splits flow around southern Greenland and condensational buoyancy generation that maintains along‐flow updraft ‘rapids’ 2 km above sea level, which produce rain bands within an atmospheric river interacting with Greenland. CARRA resolves gravity wave oscillations that initiate as a result of buoyancy offshore, which then amplify from terrain‐forced uplift. In a detailed case study, CARRA resolves orographic intensification of rainfall by up to a factor of four, which is consistent with the field data.

Abstract A 17‐gene stemness (LSC17) score determines risk in acute myeloid leukaemia patients treated with standard chemotherapy regimens. The present study further analysed the impact of the LSC17 score at diagnosis on outcomes following allogeneic haematopoietic cell transplantation (HCT). Out of 452 patients with available LSC17 score, 123 patients received allogeneic HCT. Transplant outcomes, including overall (OS), leukaemia‐free survival (LFS), relapse incidence (RI) and non‐relapse mortality (NRM), were compared according to the LSC17 scored group. The patients with a low LSC17 score had higher OS (56.2%) and LFS (54.4%) at 2 years compared to patients with high LSC17 score (47.2%, p = 0.0237 for OS and 46.0%, p = 0.0181 for LFS). The low LSC17 score group also had a lower relapse rate at 2 years (12.7%) compared to 25.3% in the high LSC17 score group (p = 0.017), but no difference in NRM (p = 0.674). Worse outcomes in the high LSC17 score group for OS, LFS and relapse were consistently observed across all stratified sub‐groups. The use of more intensive conditioning did not improve outcomes for either group. In contrast, chronic graft‐versus‐host‐disease was associated with more favourable outcomes in both groups. The 17‐gene stemness score is highly prognostic for survival and relapse risk following allogeneic HCT.

Ribosomal biogenesis and protein synthesis are deregulated in most cancers, suggesting that interfering with translation machinery may hold significant therapeutic potential. Here, we show that loss of the tumor suppressor adenomatous polyposis coli (APC), which constitutes the initiating event in the adenoma carcinoma sequence for colorectal cancer (CRC), induces the expression of RNA polymerase I (RNAPOL1) transcription machinery, and subsequently upregulates ribosomal DNA (rDNA) transcription. Targeting RNAPOL1 with a specific inhibitor, CX5461, disrupts nucleolar integrity, and induces a disbalance of ribosomal proteins. Surprisingly, CX5461‐induced growth arrest is irreversible and exhibits features of senescence and terminal differentiation. Mechanistically, CX5461 promotes differentiation in an MYC‐interacting zinc‐finger protein 1 (MIZ1)‐ and retinoblastoma protein (Rb)‐dependent manner. In addition, the inhibition of RNAPOL1 renders CRC cells vulnerable towards senolytic agents. We validated this therapeutic effect of CX5461 in murine‐ and patient‐derived organoids, and in a xenograft mouse model. These results show that targeting ribosomal biogenesis together with targeting the consecutive, senescent phenotype using approved drugs is a new therapeutic approach, which can rapidly be transferred from bench to bedside.

Abstract Background The presence of autoantibodies in the serum of cancer patients has been associated with immune‐checkpoint inhibitor (ICI) therapy response and immune‐related adverse events (irAEs). A prospective evaluation of different autoantibodies in different cancer entities is missing. Materials and Methods In this prospective cohort study, we included a pan‐cancer cohort of patients undergoing ICI treatment and measured a comprehensive panel of autoantibodies at treatment start and at the time point of first response evaluation. The presence and induction of autoantibodies (ANA, ENA, myositis, hepatopathy, rheumatoid arthritis) in different cancer entities were assessed and the association between autoantibodies and disease control rate (DCR), objective response rate (ORR), and progression‐free survival (PFS), as well as the development of grade 3 or higher irAEs were evaluated by logistic regression models, cox proportional hazard models, and Kaplan–Meier estimators. Results Of 44 patients with various cancer entities, neither the presence of any positive autoantibody measurement nor the presence of positive antinuclear antibodies (ANA) [≥1:80] at baseline was associated with the examined clinical endpoints (DCR, ORR, PFS) in univariable and multivariable analyses. After 8–12 weeks of ICI treatment, DCR, ORR, and PFS did not significantly differ between patients with and without any positive autoantibody measurement or positive ANA titers. The frequency of irAEs did not differ depending on autoantibody status of the patients. Conclusion Autoantibodies at treatment initiation or induction after 8–12 weeks of ICI treatment are not associated with treatment efficacy as indicated by DCR, ORR, and PFS or higher grade irAEs.

Abstract Nowadays, the development of various technologies for improving the quality of life in human societies and, consequently, increased global warming have prioritized environmental factors to reduce major industrial pollutants including carbon dioxide (CO2). Designing efficient integrated processes improves the performance of the whole system. In this study, a novel integrated structure is designed to capture CO2 from power plants' flue gases and liquefy it. For this purpose, a monoethanolamine‐based CO2 capture cycle, an ejector refrigeration system, a Kalina power unit, and a organic Rankine power plant are utilized. High‐ and low‐temperature heat of the system is provided by the heat pump cycle and geothermal energy, respectively. Then, 2.641 kg/s of liquid CO2 is generated as the final product of the system. In the proposed system, 20,562 kW heat duty and 657.3 kW power are supplied geothermal energy and the photovoltaic (PV) system, respectively. The coefficient of performance of the heat pump cycle and thermal efficiency of the organic Rankine unit is calculated at 3.661% and 12.64%, respectively. Results of the exergy investigation indicate that the highest exergy destruction belonged to PV cells, which independently accounted for 39.81% of the total reversibility. The exergy efficiency and total reversibility of the structure are computed at 24.2% and 6555 kW. Sensitivity analysis was performed on several of the most important parameters of the combined structure. The outcomes indicate that the ratio of liquid CO2 rate to total power consumption and net power consumption increase up to 4.096 kg/s LCO2/MW and 1669 kW, respectively, when the CO2 concentration in the flue gas increases from 1 to 9 mol%.