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Abstract Obesity has a strong genetic component, with up to 20% of variance in body mass index (BMI) being accounted for by common polygenic variation. Most genetic polymorphisms associated with BMI are related to genes expressed in the central nervous system. At the same time, higher BMI is associated with neurocognitive changes. However, the direct link between genetics of obesity and neurobehavioral mechanisms related to weight gain is missing. Here, we use a large sample of participants (n > 4000) from the Adolescent Brain Cognitive Development cohort to investigate how genetic risk for obesity, expressed as polygenic risk score for BMI (BMI-PRS), is related to brain and behavioral measures in adolescents. In a series of analyses, we show that BMI-PRS is related to lower cortical volume and thickness in the frontal and temporal areas, relative to age-expected values. Relatedly, using structural equation modeling, we find that lower overall cortical volume is associated with higher impulsivity, which in turn is related to an increase in BMI 1 year later. In sum, our study shows that obesity might partially stem from genetic risk as expressed in brain changes in the frontal and temporal brain areas, and changes in impulsivity.

Background and Purpose Methods Results Conclusion Early and reliable prediction of hemorrhagic transformation (HT) in patients with acute ischemic stroke (AIS) is crucial for treatment decisions and early intervention. The purpose of this study was to conduct a systematic review and meta‐analysis on the performance of artificial intelligence (AI) and machine learning (ML) models that utilize neuroimaging to predict HT.A systematic search of PubMed, EMBASE, and Web of Science was conducted until February 19, 2024. Inclusion criteria were as follows: patients with AIS who received reperfusion therapy; AI/ML algorithm using imaging to predict HT; or presence of sufficient data on the predictive performance. Exclusion criteria were as follows: articles with less than 20 patients; articles lacking algorithms that operate solely on images; or articles not detailing the algorithm used. The quality of eligible studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies‐2 and Checklist for Artificial Intelligence in Medical Imaging. Pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were calculated using a random‐effects model, and a summary receiver operating characteristic curve was constructed using the Reitsma method.We identified six eligible studies, which included 1640 patients. Aside from an unclear risk of bias regarding flow and timing identified in two of the studies, all studies showed low risk of bias and applicability concerns in all categories. Pooled sensitivity, specificity, and DOR were .849, .878, and 45.598, respectively.AI/ML models can reliably predict the occurrence of HT in AIS patients. More prospective studies are needed for subgroup analyses and higher clinical certainty and usefulness. [ABSTRACT FROM AUTHOR]

While imaging studies have demonstrated volumetric differences in subcortical structures associated with dependence on various abused substances, findings to date have not been wholly consistent. Moreover, most studies have not compared brain morphology across those dependent on different substances of abuse to identify substance-specific and substance-general dependence effects. By pooling large multinational datasets from 33 imaging sites, this study examined subcortical surface morphology in 1628 nondependent controls and 2277 individuals with dependence on alcohol, nicotine, cocaine, methamphetamine, and/or cannabis. Subcortical structures were defined by FreeSurfer segmentation and converted to a mesh surface to extract two vertex-level metrics-the radial distance (RD) of the structure surface from a medial curve and the log of the Jacobian determinant (JD)-that, respectively, describe local thickness and surface area dilation/contraction. Mega-analyses were performed on measures of RD and JD to test for the main effect of substance dependence, controlling for age, sex, intracranial volume, and imaging site. Widespread differences between dependent users and nondependent controls were found across subcortical structures, driven primarily by users dependent on alcohol. Alcohol dependence was associated with localized lower RD and JD across most structures, with the strongest effects in the hippocampus, thalamus, putamen, and amygdala. Meanwhile, nicotine use was associated with greater RD and JD relative to nonsmokers in multiple regions, with the strongest effects in the bilateral hippocampus and right nucleus accumbens. By demonstrating subcortical morphological differences unique to alcohol and nicotine use, rather than dependence across all substances, results suggest substance-specific relationships with subcortical brain structures.

Background and purposeDeveloped using a rigorous mathematic framework, Maximum AmbiGuity distance for Phase Imaging (MAGPI) is a promising phase-imaging technique that provides optimal phase SNR and reduced susceptibility artifacts. We aimed to test the potential of MAGPI over routinely used SWI in the detection of traumatic cerebral microbleeds in athletes diagnosed with mild traumatic brain injury.Materials and methodsIn this prospective study, 10 athletes (18-22 years of age, 3 women/7 men) diagnosed with mild traumatic brain injury were enrolled. Brain MRIs were performed using 3T MR imaging at 2 days, 2 weeks, and 2 months after head trauma. The imaging protocol included whole-brain T1 MPRAGE, T2 FLAIR, conventional SWI, and the MAGPI multiecho sequence. Phase images from MAGPI were put through a previously described SWI process to generate MAGPI-SWI. Conventional and MAGPI-SWI were assessed independently by a board-certified neuroradiologist for the presence of contusions and cerebral microbleeds. All participants had routine neuropsychological assessment and Visuo-Motor Tests.ResultsAt initial assessment, 4 of the participants had visuo-motor performance indicative of mild traumatic brain injury, and 4 participants had a Post-Concussion Symptom Scale score of >21, a threshold that has been used to define moderate impairment. Cerebral microbleeds were identified in 6 participants on MAGPI-SWI, 4 of whom had evidence of concurrent contusions on FLAIR imaging. None of these cerebral microbleeds were identified confidently on conventional SWI due to substantial distortion and susceptibility artifacts.ConclusionsOptimal phase unwrapping with reduced susceptibility in MAGPI-SWI can clarify small microbleeds that can go undetected with routinely used conventional SWI.

This research investigates the intricacies of motivation and job satisfaction among military service members within the Lebanese Armed Forces (LAF) amidst various challenges. Employing an intrinsic–extrinsic framework, the study adopts a sequential mixed-method design. Interviews were conducted with 42 LAF service members, a Focus Group was convened with 12 LAF subject matter experts, and a survey was administered to 3880 LAF service members across the country. The findings underscore the significance of monetary rewards and praise as primary motivators. Notably, the expectation of rewards emerges as a crucial motivating factor closely linked to job satisfaction, while intrinsic factors exhibit comparatively lesser influence. Salary emerges as the foremost determinant of job satisfaction. Moreover, economic challenges, particularly the drastic decline in purchasing power, serve as a significant moderating factor, adversely impacting the relationship between motivation and job satisfaction. Health challenges, such as the scarcity and increased prices of medical supplies, also exert a negative moderating influence. Conversely, security challenges demonstrate no significant moderating impact. Insights gleaned from the Lebanese context emphasize the importance of offering competitive salaries and recognition programs, ensuring equitable compensation, designing reward systems aligned with performance expectations, regularly reviewing, and adjusting salary structures, providing comprehensive support for employees’ physical and mental well-being, and fostering a secure work environment.

Extensive research into mRNA vaccines for cancer therapy in preclinical and clinical trials has prepared the ground for the quick development of immune-specific mRNA vaccines during the COVID-19 pandemic. Therapeutic cancer vaccines based on mRNA are well tolerated, and are an attractive choice for future cancer immunotherapy. Ideal personalized tumor-dependent mRNA vaccines could stimulate both humoral and cellular immunity by overcoming cancer-induced immune suppression and tumor relapse. The stability, structure, and distribution strategies of mRNA-based vaccines have been improved by technological innovations, and patients with diverse tumor types are now being enrolled in numerous clinical trials investigating mRNA vaccine therapy. Despite the fact that therapeutic mRNA-based cancer vaccines have not yet received clinical approval, early clinical trials with mRNA vaccines as monotherapy and in conjunction with checkpoint inhibitors have shown promising results. In this review, we analyze the most recent clinical developments in mRNA-based cancer vaccines and discuss the optimal platforms for the creation of mRNA vaccines. We also discuss the development of the cancer vaccines’ clinical research, paying particular attention to their clinical use and therapeutic efficacy, which could facilitate the design of mRNA-based vaccines in the near future.

Background: Nirmatrelvir/Ritonavir has been shown to reduce the risk of COVID-19 progression by 88% compared to placebo, while Molnupiravir reduced it by 31%. However, these two agents have not been compared head-to-head. We therefore compared the safety and efficacy of both agents for the treatment of mild-to-moderate COVID-19 in immunocompromised cancer patients. Methods: We identified 240 cancer patients diagnosed with COVID-19 and treated with Molnupiravir or Nirmatrelvir/Ritonavir. Patients were matched using a 1:2 ratio based on age group (18–64 years vs. ≥65) and type of cancer. The collected data included demographics, comorbidities, and treatment outcome. Results: Both groups had comparable characteristics and presenting symptoms. However, dyspnea was more prevalent in the Molnupiravir group, while sore throat was more prevalent in the Nirmatrelvir/Ritonavir group. The rate of disease progression was comparable in both groups by univariate and multivariable analysis. Treatment with Molnupiravir versus Nirmatrelvir/Ritonavir revealed no significant difference in disease progression by multivariable analysis (adjusted OR = 1.31, 95% CI: 0.56–3.14, p = 0.70). Patients who received Nirmatrelvir/Ritonavir, however, were significantly more prone to having drug–drug interactions/adverse events (30% vs. 0%, p < 0.0001). Conclusions: In the treatment of mild-to-moderate COVID-19 in cancer patients, Molnupiravir was comparable to Nirmatrelvir/Ritonavir in preventing progression to severe disease/death and rebound events, and it had a superior safety profile.

A 40-year-old female patient presented to a secondary facility with dull lower abdominal pain and a persistent low-grade fever. Her laboratory results showed elevated inflammation markers. A CT scan revealed two abscesses in the lesser pelvic region in direct contact with the apex of the appendix, the posterior wall of the uterus, and the right-side appendages. The patient responded well to intravenous antibiotics, and an MRI scan revealed the cause to be an appendiceal rupture. The patient was scheduled for an appendectomy. The procedure started laparoscopically but had to be converted to an open one with a midline infra-umbilical incision in order to protect the right appendages. A standard appendectomy was conducted, and the histology report revealed rupture of the appendix with concomitant wall inversion in the context of fibrous adhesions as well as obstruction due to a fecalith. Patient recovery and follow-up were excellent. Acute appendicitis, while frequently encountered in surgical practice, can present a diagnostic conundrum when it manifests in an atypical manner. This unique form of inversion appeared to confer a protective role against peritonitis, primarily through the mechanism of obstruction occurring centrally to the rupture. We suggest that this case should be included in current classifications as a partial inversion of the appendix after rupture and inflammation.

Chronic liver diseases are a major global health concern. Aims: this study investigated the links between medical, clinical, anthropometric, and dietary factors with dysfunction-associated steatotic liver disease (MASLD) in the Lebanese population using a case-control approach to uncover factors influencing visceral obesity, sarcopenia, and sarcopenic obesity. Methods and Materials: a total of 120 participants (20–70 years old) were divided into case and control groups based on liver disease diagnosis. Patient information was gathered through a questionnaire encompassing demographics, medical history, and beverage consumption. Anthropometric and body composition data were collected in a clinical setting. Results: our findings indicated a clear association between the presence of MASLD and obesity, hypertension, and diabetes. The positive association with higher body mass index and all three conditions remained consistent even when data was stratified by case and control groups. A greater proportion of MASLD patients exhibited sarcopenic obesity. Furthermore, MASLD cases showed higher consumption of sugary beverages and a reduced intake of milk and water in their diets. Conclusions: this study shed light on the health attributes and diets of the Lebanese population with liver diseases and suggested more research in this area and in a more ethnically diverse population.

Machine foundations are subjected to significant dynamic impacts. These impacts could spread to the surrounding regions, affecting workers, sensitive equipment in the same institution, or nearby areas. This study analyzes the response of machine-supporting foundations to harmonic and explosive loads under operational conditions and provides closed-form solutions for predicting responses in terms of displacement, velocity, and acceleration time-histories to two common types of blast loads: a more accurate typical profile and simplified triangular profile. The soil-machine foundation system is regarded as a single-degree-of-freedom (SDOF) system that exhibits elastic–perfectly flexible resistance behavior. For the analysis of the SDOF system, two cases are considered: one assumes that the supporting soil keeps elastic during the explosion, and the peak displacement is less than the elastic one, while the other assumes that the blast occurs in an elastic state, and the peak displacement occurs in a plastic state. By using the closed-form analytical solutions, a detailed parametric analysis is carried out to evaluate the impacts of significant soil-foundation system characteristics such as mass, stiffness, and damping ratio on the response-time history of machine foundations. The findings are compared to those reported in the literature, and relevant conclusions are derived. Obtained results demonstrated that, despite its simplicity and usage of only positive phase to simulate blast loads, the simplified model’s response behavior differs significantly from the typical one. Furthermore, the derived solutions are utilized to design the foundations supporting vibrating machines for both harmonic and blast loads in a variety of conceivable scenarios depending on the blast magnitude.

Background: Guidelines recommend targeting decongestion in management of decompensated HF, with lower extremity edema often serving as the clinical target. LECW are seldom used in the acute setting, with a paucity of data on efficacy in HF, despite serving as a cornerstone of chronic lymphedema management. Primary objective: Study the efficacy and safety of LECW in acute decompensated HF. Methods: Open-label, randomized, parallel-group clinical trial. Primary outcomes: Days on intravenous (IV) diuretic therapy, total hospital length of stay (LOS), and 30-day all-cause readmission. Results: 32 patients were enrolled, with 29 patients completing the study. Enrollment was suspended due to the COVID-19 pandemic. Overall LOS was shorter in the intervention group (3.5 vs 6 days, p = 0.05), with no significant difference in total days on IV diuresis or 30-day readmission rate with use of LECW. Fewer patients required continuous diuretic infusion after treatment with LECW (0 vs 7 patients, p = 0.027). The intervention group scored significantly better on the MLWHF (55.5 vs 65, p = 0.021), including both the physical and emotional dimension scores. No adverse events were reported with use of LECW, including a significantly lower incidence of AKI (1 vs 13 patients, p = 0.005). Conclusion: The use of LECW resulted in reduced hospital LOS compared to standard therapy, with no difference in days of IV diuresis administration or 30-day readmission. Treatment with LECW also resulted in less continuous IV diuretic therapy, fewer incidence of AKI, and improved quality of life. Trends toward less escalation of diuresis, and greater reduction in edema were also observed.

Reward processing is essential for our mental-health and well-being. In the current study, we developed and validated a scalable, fMRI-informed EEG model for monitoring reward processing related to activation in the ventral-striatum (VS), a significant node in the brain's reward system. To develop this EEG-based model of VS-related activation, we collected simultaneous EEG/fMRI data from 17 healthy individuals while listening to individually-tailored pleasurable music – a highly rewarding stimulus known to engage the VS. Using these cross-modal data, we constructed a generic regression model for predicting the concurrently acquired Blood-Oxygen-Level-Dependent (BOLD) signal from the VS using spectro-temporal features from the EEG signal (termed hereby VS-related-Electrical Finger Print; VS-EFP). The performance of the extracted model was examined using a series of tests that were applied on the original dataset and, importantly, an external validation dataset collected from a different group of 14 healthy individuals who underwent the same EEG/FMRI procedure. Our results showed that the VS-EFP model, as measured by simultaneous EEG, predicted BOLD activation in the VS and additional functionally relevant regions to a greater extent than an EFP model derived from a different anatomical region. The developed VS-EFP was also modulated by musical pleasure and predictive of the VS-BOLD during a monetary reward task, further indicating its functional relevance. These findings provide compelling evidence for the feasibility of using EEG alone to model neural activation related to the VS, paving the way for future use of this scalable neural probing approach in neural monitoring and self-guided neuromodulation.

International medical graduates (IMGs) are medical graduates who have received their degree from international medical schools. IMGs must undertake a 3-step process to apply to the National Residency Matching Program match. First, they must obtain a valid standard certificate from the Educational Commission for Foreign Medical Graduates. Following certification, they must apply for and secure a position in a residency training program. Third, they must obtain a visa that would enable them to commence their training. In this article, we delve thoroughly into these stepladders to provide IMGs with a clear roadmap of the process as well as contacts to key agencies that may provide more comprehensive assistance.

AimTo examine individual variability between perceived physical features and hormones of pubertal maturation in 9-10-year-old children as a function of sociodemographic characteristics.MethodsCross-sectional metrics of puberty were utilized from the baseline assessment of the Adolescent Brain Cognitive Development (ABCD) Study-a multi-site sample of 9-10 year-olds (n = 11,875)-and included perceived physical features via the pubertal development scale (PDS) and child salivary hormone levels (dehydroepiandrosterone and testosterone in all, and estradiol in females). Multi-level models examined the relationships among sociodemographic measures, physical features, and hormone levels. A group factor analysis (GFA) was implemented to extract latent variables of pubertal maturation that integrated both measures of perceived physical features and hormone levels.ResultsPDS summary scores indicated more males (70%) than females (31%) were prepubertal. Perceived physical features and hormone levels were significantly associated with child's weight status and income, such that more mature scores were observed among children that were overweight/obese or from households with low-income. Results from the GFA identified two latent factors that described individual differences in pubertal maturation among both females and males, with factor 1 driven by higher hormone levels, and factor 2 driven by perceived physical maturation. The correspondence between latent factor 1 scores (hormones) and latent factor 2 scores (perceived physical maturation) revealed synchronous and asynchronous relationships between hormones and concomitant physical features in this large young adolescent sample.ConclusionsSociodemographic measures were associated with both objective hormone and self-report physical measures of pubertal maturation in a large, diverse sample of 9-10 year-olds. The latent variables of pubertal maturation described a complex interplay between perceived physical changes and hormone levels that hallmark sexual maturation, which future studies can examine in relation to trajectories of brain maturation, risk/resilience to substance use, and other mental health outcomes.

High serum concentrations of kidney-derived protein uromodulin [Tamm-Horsfall protein (THP)] have recently been shown to be independently associated with low mortality in both older adults and cardiac patients, but the underlying mechanism remains unclear. Here, we show that THP inhibits the generation of reactive oxygen species (ROS) both in the kidney and systemically. Consistent with this experimental data, the concentration of circulating THP in patients with surgery-induced acute kidney injury (AKI) correlated with systemic oxidative damage. THP in the serum dropped after AKI and was associated with an increase in systemic ROS. The increase in oxidant injury correlated with postsurgical mortality and need for dialysis. Mechanistically, THP inhibited the activation of the transient receptor potential cation channel, subfamily M, member 2 (TRPM2) channel. Furthermore, inhibition of TRPM2 in vivo in a mouse model mitigated the systemic increase in ROS during AKI and THP deficiency. Our results suggest that THP is a key regulator of systemic oxidative stress by suppressing TRPM2 activity, and our findings might help explain how circulating THP deficiency is linked with poor outcomes and increased mortality.

Solar heat gains contribute widely to the overheating in buildings, specifically in extreme climates. Climates which require large amounts of cooling energy during summer as well as heating energy during winter need to be carefully designed. Reducing solar transmittance through windows and improving building details/types can help minimize surface heat transfer. The use of shading to minimize solar transmission and heat gains through glazed and opaque surfaces is a strong method to reduce solar gains and can be an appropriate method to also improve thermal comfort in such extreme weathers. In the following paper, a method was followed in order to ensure thermal comfort without compromising the daylight factors inside. IESVE was used for the energy and daylighting analysis. Initially, a selected case study of a school building in Minneapolis was analyzed. Afterwards, a study was conducted using climate consultant to select the appropriate shading systems to be adopted. Next, selected classrooms were analyzed for the average daylight factor and solar heat gains pre and post applying the shading systems. The cooling hours were compared after the strategies were applied, a reduction up to 4% of cooling hours was seen post applying the shading devices. The correct study and application of shading devices can help reduce energy needs in summer, without increasing the heating loads in winter.

This work discusses the numerical investigation of dust deposition behaviour on solar PV panels. Moreover, installing vortex generators (VGs) as a passive cleaning method on the PV panels is introduced and analysed. Multiphase computational fluid dynamics (CFD) simulations are performed to predict the influence of VGs on both the air flow fields and the dust deposition on the basis of the environmental properties of Cairo, Egypt. The dust deposition reduction is predicted for different dust particle sizes and for different VGs sizes to find the optimum VG size that causes the highest reduction. It is found that installing VGs is effective for dust particles that are smaller than 50 µm. The results show that installing VGs will result in a deposition reduction of about 35%. It is concluded that installing VGs is effective in reducing the dust deposition when wind direction is from north, south, east, or west.

ABSTRACT Introduction: Most implantations of left ventricular assist devices (LVAD) are performed in low-volume centers. This study aimed to evaluate the procedural learning curve of HeartMate II (HM2) implantations by comparing outcomes between two time periods in a low-volume center. Methods: All 51 consecutive patients undergoing HM2 implantation between January 2009 and December 2017 were reviewed and allocated into 2 groups: early-era group (from 2009 to 2014; n=25) and late-era group (from 2015 to 2017; n=26). The primary outcome was the 90-day mortality rate, and the secondary outcome was a composite of mortality, neurological event, reoperation for bleeding, need for temporary right ventricular assist device, and pump thrombosis at 90 days. Median follow-up time was 51 months (0-136). A cumulative sum (CUSUM) control analysis was used to establish a threshold of implantations that optimizes outcomes. Results: Patients in the early era had a higher rate of diabetes, previous stroke, and inotrope support before HM2 implantation. The 90-day mortality rate was not significantly higher in the early era (24% vs. 15%, P=0.43), but the composite endpoint was significantly higher (76% vs. 42%, P=0.01). The CUSUM analysis found a threshold of 23 operations after which the composite endpoint was optimized. Conclusion: Patients undergoing HM2 implantation in a low-volume center have improving outcomes with number of cases and optimized results after a threshold of 23 cases. Significant changes in patient selection, surgical techniques, and patient management might lead to improved outcomes after LVAD implantation.