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The interaction of helminth infections with type 2 diabetes (T2D) has been a major area of research in the past few years. This paper, therefore, focuses on the systematic review of the effects of helminthic infections on metabolism and immune regulation related to T2D, with mechanisms through which both direct and indirect effects are mediated. Specifically, the possible therapeutic role of helminths in T2D management, probably mediated through the modulation of host metabolic pathways and immune responses, is of special interest. This paper discusses the current possibilities for translating helminth therapy from basic laboratory research to clinical application, as well as existing and future challenges. Although preliminary studies suggest the potential for helminth therapy for T2D patients, their safety and efficacy still need to be confirmed by larger-scale clinical studies.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
Background: Nipocalimab (a fully human, effectorless anti-neonatal Fc receptor (FcRn) monoclonal antibody) may ameliorate gMG disease manifestations by selectively targeting FcRn IgG recycling and lowering IgG, including pathogenic autoantibodies in generalized myasthenia gravis (gMG). The objective was to evaluate the effectiveness and safety of intravenous nipocalimab added to background standard-of-care therapy in adolescents with gMG. Methods: Seropositive patients (12-<18 years) with gMG (MGFA Class II-IV) on stable therapy but inadequately controlled, were enrolled in a 24-week open label study. Nipocalimab was administered as a 30 mg/kg IV loading dose followed by 15 mg/kg IV every 2 Weeks. Results: Seven adolescents were enrolled; 5 completed 24-weeks of dosing. The mean(SD) age was 14.1(1.86) years; seven were anti-AChR+, six were female. Mean(SD) baseline MG-ADL/QMG scores were 4.29(2.430)/12.50(3.708). Nipocalimab showed a significant reduction in total serum IgG at week-24; the mean(SD) change from baseline to week-24 for total serum IgG was -68.98%(7.561). The mean(SD) change in MG-ADL/QMG scores at week-24 was -2.40(0.418)/-3.80(2.683); 4 of 5 patients achieved minimum symptom expression (MG-ADL score 0-1) by week-24. Nipocalimab was well-tolerated; there were no serious adverse events. There were no clinically meaningful laboratory changes. Conclusions: Nipocalimab demonstrated efficacy and safety in this 6-month trial in seropositive adolescents with gMG.
Patients with cancer frequently experience insomnia that significantly impacts their quality of life, worsens existing symptoms, and potentially hinders treatment outcomes and recovery. Here, we report on 3 cancer patients whose insomnia was improved with low-dose olanzapine.
Methods
A retrospective review of medical records was conducted for 3 cancer patients experiencing insomnia treated with olanzapine at Johns Hopkins Hospital. The data collection included the type of cancer diagnosis, the level of insomnia severity experienced by individuals, and treatment results and outcome.
Results
Olanzapine improved sleep in all 3 patients and decreased nausea/vomiting and anxiety in patients 2 and 3.
Significance of results
A low dose of olanzapine has potential to treat insomnia in cancer patients. The ideal dosing regimens and potential risks are unclear, especially for long-term use. More research and clinical trials are needed to evaluate off-label use of olanzapine for insomnia, including its efficacy and risks, and to optimize the dosage to reduce its side effects in cancer patients. Oncology providers should consider olanzapine as a potential treatment for insomnia, especially given its off-label uses and potential benefits.
This study explored mental workload recognition methods for carrier-based aircraft pilots utilising multiple sensor physiological signal fusion and portable devices. A simulation carrier-based aircraft flight experiment was designed, and subjective mental workload scores and electroencephalogram (EEG) and photoplethysmogram (PPG) signals from six pilot cadets were collected using NASA Task Load Index (NASA-TLX) and portable devices. The subjective scores of the pilots in three flight phases were used to label the data into three mental workload levels. Features from the physiological signals were extracted, and the interrelations between mental workload and physiological indicators were evaluated. Machine learning and deep learning algorithms were used to classify the pilots’ mental workload. The performances of the single-modal method and multimodal fusion methods were investigated. The results showed that the multimodal fusion methods outperformed the single-modal methods, achieving higher accuracy, precision, recall and F1 score. Among all the classifiers, the random forest classifier with feature-level fusion obtained the best results, with an accuracy of 97.69%, precision of 98.08%, recall of 96.98% and F1 score of 97.44%. The findings of this study demonstrate the effectiveness and feasibility of the proposed method, offering insights into mental workload management and the enhancement of flight safety for carrier-based aircraft pilots.
The impinging–freezing of supercooled water droplets (SLDs) is the root cause of aircraft icing. This work presented an experimental investigation of a millimeter-sized supercooled droplet (−10 $^\circ {\rm{C}}$) impact onto cold surfaces. For the majority of the current research on freezing behaviour, the quantitative analysis of impingement contributions was neglected. The present study established prediction models for the frozen area ratio, initial freezing height and solidification time by changing Weber number and Stefan number. The results showed that with the decrease in surface temperatures, the maximum spreading factor and the peak height factor were unchanged; however, the receding velocity of the liquid film reduced. Besides, regardless of the three freezing modes (quasi-static, instantaneous and delayed), the frozen area ratio consistently increased with decreasing Weber number. For the Stefan number exceeded 0.12, the frozen area ratio increased with decreasing surface temperature; otherwise, it was independent of the surface temperature. In addition, the initial height of asymmetrical frozen droplets was characterised using the ‘two-ellipse’ method, revealing an inverse proportionality to the square root of the frozen area ratio. Furthermore, the solidification time of the hemisphere and pancake frozen droplets shortened with the decrease in the initial height and surface temperature. This fundamental study provides valuable insights for understanding aircraft icing and optimising anti-icing systems.
This paper presents an improved signal-processing method based on the Hilbert-Huang transform (HHT), which is applied to the fault feature extraction of the aerospace generator rotating rectifier (AGRR). Initially, the excitation current of the alternating-current (AC) exciter is utilised as measurable information for data collection. Subsequently, the HHT is processed with variational mode decomposition (VMD), followed by the improvement of the variational Hilbert-Huang transform (VHHT) using particle swarm optimisation (PSO) to determine the modal decomposition number and the secondary penalty factor. Finally, the proposed PSO-VHHT method is compared with several other signal processing-based feature extraction methods through both simulated and practical experiment data, and an analysis of the diagnostic performance of these methods is also conducted.
Objectives/Goals: Mathematical models of airborne virus transmission lack supporting field and clinical data such as viral aerosol emission rates and airborne infectious doses. Here, we aim to measure inhalation exposure to influenza aerosols in a room shared with persons with community-acquired influenza and estimate the infectious dose via inhalation. Methods/Study Population: We recruited healthy volunteer recipients and influenza donors with polymerase chain reaction (PCR)-confirmed community-acquired infection. On admission to a hotel quarantine, recipients provided sera to determine baseline immunity to influenza virus, and donor infections were confirmed by quantitative real-time polymerase chain reaction. Donors and recipients were housed in separate rooms and interacted in an “event room” with controlled ventilation (0.2 – 0.5 air changes/hour) and relative humidity (20–40%). We collected ambient bioaerosol exposure samples using NIOSH BC-251 samplers. Donors provided exhaled breath samples collected by a Gesundheit-II (G-II). We analyzed aerosol samples using dPCR and fluorescent focus assays for influenza A and sera by hemagglutinin inhibition assay (HAI) against donor viruses and vaccine strains. Results/Anticipated Results: Among two cohorts (24b and 24c), we exposed 11 recipients (mean age: 36; 55% female) to 5 donors (mean age: 21; 80% female) infected with influenza A H1N1 or H3N2. Eight G-II and two NIOSH bioaerosol samples (1–4 µm and ≥4 µm) were PCR positive. We cultured virus from one G-II sample. Based on previous literature, we hypothesized that ~50% of immunologically naïve people (HAI Discussion/Significance of Impact: We demonstrated that it is feasible to recruit donors with community-acquired influenza and expose recipients to measurable virus quantities under controlled conditions. However, baseline immunity was high among volunteers. Our work sets the stage for designing studies with increased sample sizes comprising immunologically naïve volunteers.
Objectives/Goals: We describe the prevalence of individuals with household exposure to SARS-CoV-2, who subsequently report symptoms consistent with COVID-19, while having PCR results persistently negative for SARS-CoV-2 (S[+]/P[-]). We assess whether paired serology can assist in identifying the true infection status of such individuals. Methods/Study Population: In a multicenter household transmission study, index patients with SARS-CoV-2 were identified and enrolled together with their household contacts within 1 week of index’s illness onset. For 10 consecutive days, enrolled individuals provided daily symptom diaries and nasal specimens for polymerase chain reaction (PCR). Contacts were categorized into 4 groups based on presence of symptoms (S[+/-]) and PCR positivity (P[+/-]). Acute and convalescent blood specimens from these individuals (30 days apart) were subjected to quantitative serologic analysis for SARS-CoV-2 anti-nucleocapsid, spike, and receptor-binding domain antibodies. The antibody change in S[+]/P[-] individuals was assessed by thresholds derived from receiver operating characteristic (ROC) analysis of S[+]/P[+] (infected) versusS[-]/P[-] (uninfected). Results/Anticipated Results: Among 1,433 contacts, 67% had ≥1 SARS-CoV-2 PCR[+] result, while 33% remained PCR[-]. Among the latter, 55% (n = 263) reported symptoms for at least 1 day, most commonly congestion (63%), fatigue (63%), headache (62%), cough (59%), and sore throat (50%). A history of both previous infection and vaccination was present in 37% of S[+]/P[-] individuals, 38% of S[-]/P[-], and 21% of S[+]/P[+] (P<0.05). Vaccination alone was present in 37%, 41%, and 52%, respectively. ROC analyses of paired serologic testing of S[+]/P[+] (n = 354) vs. S[-]/P[-] (n = 103) individuals found anti-nucleocapsid data had the highest area under the curve (0.87). Based on the 30-day antibody change, 6.9% of S[+]/P[-] individuals demonstrated an increased convalescent antibody signal, although a similar seroresponse in 7.8% of the S[-]/P[-] group was observed. Discussion/Significance of Impact: Reporting respiratory symptoms was common among household contacts with persistent PCR[-] results. Paired serology analyses found similar seroresponses between S[+]/P[-] and S[-]/P[-] individuals. The symptomatic-but-PCR-negative phenomenon, while frequent, is unlikely attributable to true SARS-CoV-2 infections that go missed by PCR.
The Weill Cornell Heart to Heart Community Outreach Campaign (H2H) is a free outreach program that provides mobile health screenings. The program brings medical and nursing faculty and students to the underserved, uninsured communities of New York City. Participants are screened for diabetes and heart disease risk factors through onsite exams, including point of care blood tests. If an abnormality is found, they receive a medical consultation to offer personalized advice and referrals to free/low-cost clinics when needed. The goal is to help underserved individuals understand their cardiometabolic health and to promote early intervention. This article describes the development of the program, including factors that were essential to the collaboration, challenges faced, barriers to implementation, and its evolution throughout the first 12 years. The program has benefited from strong foundational program leadership, effective inter-institutional collaboration, and maintaining community trust.
We use the 529 college savings plan setting to investigate whether and why households make suboptimal choices to invest in local assets. We estimate that 67% of open accounts between 2010 and 2020 were located suboptimally due to the plans’ tax inefficiencies and high expenses. Over the accounts’ projected lifetimes, such investments yielded expected losses of 8% on average or $15.6 billion in 2020 alone. We then investigate why suboptimal investment is so prevalent. Consistent with households’ lack of understanding of state-level tax benefits, we find that a meaningful proportion of households does not account for the potential tax benefits and costs of local versus nonlocal 529 investment. Household financial literacy and plan disclosure complexity appear to explain suboptimal investment patterns, which further supports the role of information-processing frictions. Our study presents novel evidence on individuals’ preferences for local assets and how information-processing frictions shape their investment decisions, reducing their financial well-being.
During the investigation of parasitic pathogens of Mytilus coruscus, infection of a Perkinsus-like protozoan parasite was detected by alternative Ray's Fluid Thioglycolate Medium (ARFTM). The diameter of hypnospores or prezoosporangia was 8–27 (15.6 ± 4.0, n = 111) μm. The prevalence of the Perkinsus-like species in M. coruscus was 25 and 12.5% using ARFTM and PCR, respectively. The ITS1-5.8S-ITS2 fragments amplified by PCR assay had 100% homology to that of P. beihaiensis, suggesting that the protozoan parasite was P. beihaisensis and M. coruscus was its new host in East China Sea (ECS). Histological analysis showed the presence of trophozoites of P. beihaiensis in gill, mantle and visceral mass, and the schizonts only found in visceral mass. Perkinsus beihaiensis infection led to inflammatory reaction of hemocyte and the destruction of digestive tubules in visceral mass, which had negative effect on health of the farmed M. coruscus and it deserves more attention.
Future events can spring to mind unbidden in the form of involuntary mental images also known as ‘flashforwards’, which are deemed important for understanding and treating emotional distress. However, there has been little exploration of this form of imagery in youth, and even less so in those with high psychopathology vulnerabilities (e.g. due to developmental differences associated with neurodiversity or maltreatment).
Aims:
We aimed to test whether flashforwards are heightened (e.g. more frequent and emotional) in autistic and maltreatment-exposed adolescents relative to typically developing adolescents. We also explored their associations with anxiety/depression symptoms.
Method:
A survey including measures of flashforward imagery and mental health was completed by a group of adolescents (n=87) aged 10–16 (and one of their caregivers) who met one of the following criteria: (i) had a diagnosis of autism spectrum disorder; (ii) a history of maltreatment; or (ii) no autism/maltreatment.
Results:
Flashforwards (i) were often of positive events and related to career, education and/or learning; with phenomenological properties (e.g. frequency and emotionality) that were (ii) not significantly different between groups; but nevertheless (iii) associated with symptoms of anxiety across groups (particularly for imagery emotionality), even after accounting for general trait (non-future) imagery vividness.
Conclusions:
As a modifiable cognitive risk factor, flashforward imagery warrants further consideration for understanding and improving mental health in young people. This implication may extend to range of developmental backgrounds, including autism and maltreatment.
The 10-item Montgomery–Åsberg Depression Rating Scale (MADRS) measures different dimensions of depression symptomatology. Digital traits may generate deeper understanding of the MADRS subscales and provide insights about depression symptomatology.
Objectives
To identify digital traits that predict specific MADRS subscales and ascertain which digital traits are important for which MADRS subscales.
Methods
During a Phase II decentralised clinical trial in major depressive disorder (MDD), patients completed the MADRS and used AiCure (LLC, New York, NY, USA), a smartphone application, to complete image description tasks at baseline. Digital measurements identified from the literature as relevant to MDD symptomatology were conducted using audio and video data derived from the image description tasks. Digital measurements included speech (rate, sentiment and first-person singular pronouns), vocal acoustics (intensity, pause fraction and fundamental frequency), facial expressivity (regional facial movement) and head pose (Euclidean and angular head movement). Digital traits analysis involved data pre-processing followed by machine learning (ML) using Elastic Net, Decision Tree, and Random Forest models; model performance was evaluated using 5-fold cross-validation and mean absolute error (MAE). Important digital traits were calculated by percentage change in MAE after permuting a specific variable. Important digital traits for the MADRS Apparent Sadness subscale score were mapped to defined, interpretable domains.
Results
The ML model predictions varied for different MADRS subscales (Table). Overall, Elastic Net and Random Forest models outperformed Decision Tree across all subscales scores other than suicidal thoughts. Half of the literature-based digital traits contributed to the prediction of ≥1 MADRS sadness sub-scale score. The important digital traits for the Apparent Sadness subscale score could be mapped to 4 domains (Figure); this aligned with findings from the literature.
Image:
Image 2:
Conclusions
Digital traits collected from patients with MDD were able to predict certain MADRS subscales better than others.
Funding
Boehringer Ingelheim.
Disclosure of Interest
Z. Zhu Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., Y. Wu Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., J. Seidel Employee of: Boehringer Ingelheim International GmbH, D. Roy Employee of: Boehringer Ingelheim Pharmaceuticals, Inc., E. Salzmann Employee of: Boehringer Ingelheim International GmbH
Adolescence is a period marked by highest vulnerability to the onset of depression, with profound implications for adult health. Neuroimaging studies have revealed considerable atrophy in brain structure in these patients with depression. Of particular importance are regions responsible for cognitive control, reward, and self-referential processing. However, the causal structural networks underpinning brain region atrophies in adolescents with depression remain unclear.
Objectives
This study aimed to investigate the temporal course and causal relationships of gray matter atrophy within the brains of adolescents with depression.
Methods
We analyzed T1-weighted structural images using voxel-based morphometry in first-episode adolescent patients with depression (n=80, 22 males; age = 15.57±1.78) and age, gender matched healthy controls (n=82, 25 males; age = 16.11±2.76) to identify the disease stage-specific gray matter abnormalities. Then, with granger causality analysis, we arranged the patients’ illness duration chronologically to construct the causal structural covariance networks that investigated the causal relationships of those atypical structures.
Results
Compared to controls, smaller volumes in ventral medial prefrontal cortex (vmPFC), dorsal anterior cingulate cortex (dACC), middle cingulate cortex (MCC) and insula areas were identified in patients with less than 1 year illness duration, and further progressed to the subgenual ACC, regions of default, frontoparietal networks in longer duration. Causal network results revealed that dACC, vmPFC, MCC and insula were prominent nodes projecting exerted positive causal effects to regions of the default mode and frontoparietal networks. The dACC, vmPFC and insula also had positive projections to the reward network, which included mainly the thalamus, caudate and putamen, while MCC also exerted a positive causal effect on the insula and thalamus.
Conclusions
These findings revealed the progression of structural atrophy in adolescent patients with depression and demonstrated the causal relationships between regions involving cognitive control, reward and self-referential processes.
Depression is a common mental health disorder that often starts during adolescence, with potentially important future consequences including ‘Not in Education, Employment or Training’ (NEET) status.
Methods
We took a structured life course modeling approach to examine how depressive symptoms during adolescence might be associated with later NEET status, using a high-quality longitudinal data resource. We considered four plausible life course models: (1) an early adolescent sensitive period model where depressive symptoms in early adolescence are more associated with later NEET status relative to exposure at other stages; (2) a mid adolescent sensitive period model where depressive symptoms during the transition from compulsory education to adult life might be more deleterious regarding NEET status; (3) a late adolescent sensitive period model, meaning that depressive symptoms around the time when most adults have completed their education and started their careers are the most strongly associated with NEET status; and (4) an accumulation of risk model which highlights the importance of chronicity of symptoms.
Results
Our analysis sample included participants with full information on NEET status (N = 3951), and the results supported the accumulation of risk model, showing that the odds of NEET increase by 1.015 (95% CI 1.012–1.019) for an increase of 1 unit in depression at any age between 11 and 24 years.
Conclusions
Given the adverse implications of NEET status, our results emphasize the importance of supporting mental health during adolescence and early adulthood, as well as considering specific needs of young people with re-occurring depressed mood.
In underserved communities across New York City, uninsured adults encounter a greater risk of cardiovascular disease (CVD) and diabetes. The Heart-to-Heart Community Outreach Program (H2H) addresses these disparities by screening for CVD risk factors, identifying healthcare access barriers, and fostering community engagement in translational research at the Weill Cornell Medicine Clinical and Translational Science Award (CTSA) hub. Screening events are hosted in partnership with faith-based institutions. Participants provide a medical history, complete a survey, and receive counseling by clinicians with referrals for follow-up care. This study aims to quantify H2H screening participant health status; identify socioeconomic, health access, and health-related barriers disproportionately promoting the onset of CVD and diabetes; and develop long-term community partnerships to enable underserved communities to influence activities across the translational research spectrum at our CTSA hub. The population served is disproportionately non-white, and uninsured, with many low-income and underserved individuals. The program was developed in partnership with our Community Advisory Board to empower this cohort to make beneficial lifestyle changes. Leveraging partnerships with faith-based institutions and community centers in at-risk New York City neighborhoods, H2H addresses the increasing burden of diabetes and CVD risk factors in vulnerable individuals while promoting community involvement in CTSA activities, serving as a model for similar initiatives.
While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the GC gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS25OHD, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the GC gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.
As an important component of prehistoric subsistence, an understanding of bone-working is essential for interpreting the evolution of early complex societies, yet worked bones are rarely systematically collected in China. Here, the authors apply multiple analytical methods to worked bones from the Longshan site of Pingliangtai, in central China, showing that Neolithic bone-working in this area, with cervid as the main raw material, was mature but localised, household-based and self-sufficient. The introduction of cattle in the Late Neolithic precipitated a shift in bone-working traditions but it was only later, in the Bronze Age, that cattle bones were utilised in a specialised fashion and dedicated bone-working industries emerged in urban centres.
The effect of treatment with praziquantel (PZQ) on the tegument of adult Schistosoma mansoni worms and on liver egg-granulomas has been examined in mice infected with PZQ-resistant and -susceptible parasite isolates. Two PZQ-resistant S. mansoni isolates, one selected by passage in the laboratory under drug pressure and one from Senegal established from eggs excreted by an uncured patient, were compared with PZQ-susceptible control isolates. Scanning electron microscopic observations on the tegument of Schistosoma adult worms treated in vivo with PZQ showed that more severe damage was inflicted by PZQ on susceptible worms than on drug-resistant worms. Observations on the pathology of Schistosoma egg-granulomas in the liver of infected mice after treatment with PZQ indicated that eggs from susceptible control isolates were more sensitive to PZQ than those from drug-resistant isolates.