Significant Response Research Articles

An incomplete form of Kawasaki disease in a 2-month-old girl. How the diagnostic algorithm works in practice

BACKGROUND. Kawasaki disease is a rare, self-limiting inflammatory disease primarily affecting children under 5 years old. In 25 % of cases, it can lead to coronary artery aneurysms if not treated promptly with intravenous human immunoglobulin. A significant portion of Kawasaki disease patients present with an incomplete form, complicating diagnosis, while the risk of coronary artery aneurysms remains unchanged. Particularly vulnerable are infants under 6 months old, who may exhibit even more limited clinical symptoms, making them especially susceptible to severe cardiac complications. OBJECTIVE. To analyze a clinical case of an incomplete form of Kawasaki disease in a 2-month-old girl, raise awareness of Kawasaki disease, including its incomplete form, among healthcare workers in Ukraine, emphasize the critical importance of proper diagnostic evaluation of coronary arteries, and underscore the necessity of early administration of immunoglobulin when Kawasaki disease is suspected, even in the absence of pathological changes in the heart. MATERIALS AND METHODS. The study involved collecting medical history, physical examination data, laboratory and instrumental studies, and their analysis. The diagnosis of Kawasaki disease, including its incomplete form, was based on the 2017 recommendations of the American Heart Association. CLINICAL CASE. A 2-month-old girl presented with symptoms initially resembling a urinary tract infection, with no therapeutic response to multiple courses of antibacterial therapy. During the second week of illness, she developed swelling in her hands and feet, which, along with persistent fever, significant inflammatory response, and lack of improvement with antibiotics, led to the suspicion and diagnosis of Kawasaki disease based on the algorithm for incomplete Kawasaki disease. After administration of an immunomodulatory dose of intravenous human immunoglobulin at 2 g/kg on the 11th day of illness, there was a rapid regression of symptoms, normalization of inflammation markers, and overall improvement in the child's condition. By the second week of illness, small aneurysms of the right and left coronary arteries had formed but regressed within a few weeks from the onset of the disease. CONCLUSIONS. Kawasaki disease requires prompt therapeutic intervention and should be suspected in any child, especially those under one year of age, with a high fever lasting at least 5 days, unexplained by a preliminary diagnosis, and no response to antibiotic treatment in the presence of “bacterial” blood tests. Serial echocardiograms assessing coronary arteries, absolute dimensions, and Z-scores are mandatory.

Interplay between preclinical indices of obesity and neural signatures of fluid intelligence in youth.

Pediatric obesity rates have quadrupled in the United States, and deficits in higher-order cognition have been linked to obesity, though it remains poorly understood how deviations from normal body mass are related to the neural dynamics serving cognition in youth. Herein, we determine how age- and sex-adjusted measures of body mass index (zBMI) scale with neural activity in brain regions underlying fluid intelligence. Seventy-two youth aged 9-16 years underwent high-density magnetoencephalography while performing an abstract reasoning task. The resulting data were transformed into the time-frequency domain and significant oscillatory responses were imaged using a beamformer. Whole-brain correlations with zBMI were subsequently conducted to quantify relationships between zBMI and neural activity serving abstract reasoning. Our results reveal that participants with higher zBMI exhibit attenuated theta (4-8 Hz) responses in both the left dorsolateral prefrontal cortex and left temporoparietal junction, and that weaker temporoparietal responses scale with slower reaction times. These findings suggest that higher zBMI values are associated with weaker theta oscillations in key brain regions and altered performance during an abstract reasoning task. Thus, future investigations should evaluate neurobehavioral function during abstract reasoning in youth with more severe obesity to identify the potential impact.

Experimental and Modeling Analysis of the Tensile Properties of Heavy-Duty Coatings for Steel Structures

Coatings are essential for protecting steel structures from corrosion and mechanical stresses, especially under challenging environmental conditions. To this end, this study systematically examines the effects of temperature (20 °C to 50 °C), strain rate (6.67 × 10−4 s−1 to 1.67 × 10−2 s−1), and intermediate coat thickness (140 μm to 700 μm, the layer between the primer and topcoat) on the uniaxial tensile properties of heavy-duty coatings for steel structures. Experimental and theoretical analyses were conducted to quantitatively assess the influence of these factors on the mechanical properties of the coatings. A multifactor constitutive model was developed based on the Sherwood–Frost model by integrating material characteristics and fitting experimental data, incorporating response functions for temperature, strain rate, and intermediate coat thickness. The results reveal that increased temperature causes temperature-induced softening, while higher strain rates lead to strain rate-dependent strengthening of the coatings. In contrast, the effect of layer thickness on mechanical properties follows a non-monotonic trend, influenced by the structural and material characteristics of the coatings, with the most significant mechanical response occurring at 560 μm thickness. These findings suggest that optimal coating design must consider multiple factors to enhance mechanical performance. Additionally, the correlation coefficients (r) between the model predictions and experimental results are 0.97 or higher, indicating the model’s effectiveness in predicting and optimizing the mechanical performance of heavy-duty coatings under complex conditions.

MDMA-assisted psychotherapy for the treatment of PTSD: A systematic review and meta-analysis of randomized controlled trials (RCTs).

Post-traumatic stress disorder (PTSD) is a mental health disorder resulting from exposure to traumatic events, manifesting in various debilitating symptoms. Despite available treatments, many individuals experience inadequate response or significant side effects. Previous reviews suggest promising outcomes with MDMA-assisted psychotherapy (MDMA-AT), but limitations prompt the need for a comprehensive evaluation. We searched various online databases and registries such as MEDLINE (via PubMed), Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to retrieve RCTs that fit our inclusion criteria. We performed meta-analyses using Review Manager by applying a random-effects model. Dichotomous and continuous outcomes were pooled as risk ratios (RR) and standard mean difference (SMD), respectively. Nine studies with a total of 297 participants with PTSD were included in our meta-analysis. The control group consisted of inactive doses of MDMA (25-40 mg) or placebo. Our meta-analysis showed that MDMA-AT led to a significant reduction in the Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) severity scores as compared to the control group (SMD -1.10, 95% CI: -1.62 to -0.59). More patients in the MDMA-AT group exhibited significant response (RR 1.59, 95% CI: 1.22, 2.08) and remission (RR 2.32, 95% CI: 1.47 to 3.66) as compared to patients in the control group. There was no significant difference regarding the incidence of ≥1 treatment-emergent adverse events (TEAE), ≥1 severe TEAE, and suicidal ideation between the two groups. MDMA-AT demonstrates significant efficacy in improving PTSD symptoms, enhancing both response and remission rates in individuals with chronic, treatment-resistant PTSD, while maintaining a favorable safety profile.

Serological responses to target Streptococcus pyogenes vaccine antigens in patients with proven invasive beta-haemolytic streptococcal infections.

Rising incidence of invasive beta-haemolytic streptococcal (iBHS) infections has prompted consideration of vaccination as a preventative strategy for at-risk populations. The benefits of a vaccine targeting Lancefield group A (Streptococcus pyogenes; Strep A) would increase if cross-species immunity against Lancefield groups C/G (Streptococcus dysgalactiae subspecies equisimilis; SDSE) and B (Streptococcus agalactiae; GBS) was demonstrated. A prospective, observational study of adult patients with iBHS infections due to Strep A, SDSE or GBS. Antibody responses to six Strep A candidate antigens were assayed on acute and convalescent sera. A serological response was defined as an increase of >0.2log10 arbitrary units/mL (AU/mL). Sixty-seven participants were enrolled. Thirty-three participants were included in the final analysis (12, 11 and 10 with Strep A, SDSE and GBS, respectively). The median serological response for participants with Strep A was significant for all tested antigens (median >0.2log10 difference between acute and convalescent samples; P<0.05 for all). Those with SDSE had comparable and significant median (IQR) responses to streptolysin-O (0.65 [0.36-1.67], P=0.004), S. pyogenes adhesion and division protein (0.68 [0.36-1.63], P=0.005) and C5a peptidase (ScpA; 0.30 [0.23-1.06]), P=0.004). GBS responses were limited to ScpA only (0.34 [0.08-0.52], P=0.05). Patients with invasive Strep A infection mount robust antibody responses to six non-M protein vaccine candidate antigens. Similar significant responses to C5a peptidase in those with invasive SDSE and GBS infection highlight the importance of further research into cross-species protection and immunological correlates of vaccine efficacy.

Novel Colorimetric and Near-Infrared Ratiometric Fluorescent Probe for Sensing Cysteine in Food Samples, Plants, and Living Cells.

Cysteine (Cys) is a crucial biothiol that acts a significant function in food samples and biological systems, including plant roots and living cells. Hence, we developed a novel colorimetric and near-infrared ratiometric fluorescent probe (CT), composed of coumarin and tetrahydroacridine-conjugated indole salt, for the detection of Cys. Upon reaction with Cys, the probe undergoes a specific N-substitution reaction, resulting in a notable colorimetric change and a significant ratiometric fluorescent response in both visible and near-infrared emission channels. These dual-channel ratiometric fluorescence changes are completely independent, enabling the probe to obtain great selectivity, sensitivity, and exceptional detection accuracy. Leveraging these attributes, the probe was employed to provide accurate quantitative analysis of Cys in food samples. Furthermore, confocal imaging demonstrated that the probe could monitor both exogenous and endogenous Cys levels in living cells and track Cys changes in plant roots under heavy metal stress. This work presents a dependable and accurate imaging solution for tracking and identifying Cys of real food, plants, and living cells.

Anlotinib treatment for rapidly progressing pediatric embryonal rhabdomyosarcoma in the maxillary gingiva: a case report

BackgroundEmbryonal rhabdomyosarcoma (ERMS) is a highly aggressive form of soft-tissue sarcoma that predominantly affects children. Due to limited benefits and resistance to therapy, there is an unmet need to explore alternative therapeutic strategies.Case presentationIn this report, we present a rare case of pediatric ERMS located on the right side of the maxillary gingiva. A composite reference guide integrating clinical, radiographic, and histopathologic findings was used for a definitive diagnosis. Targeted next-generation sequencing of tumor biopsy was performed to identify genetic alterations. A 12-year-old female was admitted to the Pediatric Intensive Care Unit (PICU) and underwent a tracheotomy to relieve asphyxiation caused by a 5.5 cm diameter mass compressing the tongue root and pharyngeal cavity. Hematoxylin and eosin staining revealed a hybrid morphology characterized by clusters of round and spindle cells. Further immunohistochemistry assays indicated positive immunoreactivity for desmin, myogenin, and MyoD1. Various genetic alterations were identified, including mutations in GNAS, HRAS, LRP1B, amplification of MDM2 and IGF1R, and two novel IGF1R fusions. Negative PAX-FOXO1 fusion status supported the clinical diagnosis of ERMS. Initial treatment involved standard chemotherapy; however, the tumor persisted in its growth, reaching a maximum volume of 12 cm × 6 cm × 4 cm by the completion of treatment. Subsequent oral administration of anlotinib yielded a significant antitumor response, characterized by substantial tumor necrosis and size reduction. Following the ligation of the tumor pedicle and its removal, the patient developed a stabilized condition and was successfully discharged from PICU.ConclusionsOur study highlights the importance of accurate diagnosis established on multifaceted assessment for the effective treatment of ERMS. We present compelling evidence supporting the clinical use of anlotinib as a promising treatment strategy for pediatric ERMS patients, especially for those resistant to conventional chemotherapy.

Researching The Dynamic Response Law of High and Steep Subgrade Slopes Using ABAQUS

The study aimed to investigate the dynamic response of vehicles traveling on expressways across high and steep subgrade slopes under vehicle loads. This was done by creating a finite element model of high and steep subgrade slopes through ABAQUS software and its secondary program development. Specific engineering examples were used to analyze the dynamic response states and laws of high and steep subgrade slopes under varying vehicle speeds and load conditions. The study's results indicate that: (1) When the vehicle is travelling at 100 km/h, its vibration frequency is close to the natural frequency of the subgrade in the section, leading to strong dynamic responses. (2) As the number of axles increases, the pressure on the contact surface between the wheel and the roadbed rises, and dynamic responses become stronger. The four-axle vehicle shows the most significant dynamic response. (3) The maximum vertical stress fluctuates around an intermediate value over time. (4) The highest maximum vertical displacement value is observed in the penultimate analysis step, with a noticeable peak value. At this point, the vehicle load has the most prominent impact on the roadbed slope.

Wholesale Central Banks Digital Currencies and New Opportunities for Interbank Settlements with the Prospect of Entering International Transactions

A new generation of digital technologies that make it possible to speed up settlements and reduce their cost was born from crypto-currency projects, but the prospects of their economically effective and socially responsible application associate with central bank digital currency. The article discusses the issues of digitalization of central bank money in relation to interbank settlements, including for servicing cross-border payment turnover. So far, this topic has not found a significant response in Russian scientific journals. This publication aims to popularize it by summarizing and analyzing examples extracted from foreign experiments. The advantages of digitalization are compared with the capabilities of conventional payment systems. Descriptions and comparisons of the architectures of the new generation payment system are given, in the range of which it is possible to choose compromises between benefits, risks and costs in the search for the optimal solution. In conclusion, the prospects for the transition to an experiment with digitalization of wholesale payments in Russia are assessed following the upcoming introduction of the “retail” digital ruble

All (economic) politics is local: Voting responses to localized price shocks during the great recession

AbstractThe connection between individual and macroeconomic conditions and voting behavior is well‐established. We contribute to the less resolved “spatial gap” in the literature that centers on how the localized economic conditions of where voters live influence their likelihood to vote. We test how space mediates the tension between voter mobilization and withdrawal in the face of economic shocks. We consider a scenario, the Great Recession, where economic shocks were quite localized and sudden, and compile an extensive dataset of all registered voters in the four‐county Tampa metropolitan area between 2006 and 2015. Using sales prices and property characteristics from the tax assessor rolls, we estimate a neighborhood‐level shock to housing values induced by the Great Recession. Results show that when we do not account for local neighborhood variation, the Great Recession is associated with a significant decrease in voter turnout. However, when we account for localized economic shocks, we find that residents in neighborhoods with negative price shocks were more likely to vote after the Recession, especially in non‐local elections. In addition, the propensity to vote increases with the size of the negative price shock. There is some evidence that variation at the neighborhood level matters more than voter‐level heterogeneity. The positive voting response is most profound in predominantly Black neighborhoods, and, to a lesser extent, in predominantly Hispanic and the lowest income neighborhoods. Increases in the propensity to vote are robust to models controlling for baseline economic vulnerabilities, such as localized unemployment, the weakness of the local housing market and exposure to sectors hit hardest by the Recession. The results indicate that dramatic and sudden changes in localized economic conditions can drive voting behavior, and in ways that are distinct from macroeconomic drivers. In addition, the housing asset channel appears to be a powerful one, which can induce significant voting responses at the national level apart from other localized economic drivers, especially among homeowners.

7213 Severe IGF-2 Mediated Hypoglycemia In A Patient With Adrenocortical Carcinoma: A Case Report

Abstract Disclosure: M. Camelo Pereira: None. P. Itersky: None. S. Sternlieb: None. N. Manuel: None. J. Dendy: None. Background: Hypoglycemia has been rarely described as a complication of adrenocortical carcinoma (ACC). Tumor cells produce insulin-like growth factor II, causing a paraneoplastic syndrome with severe refractory hypoglycemia. We report the unusual case of a patient with known ACC presented with seizures and severe IGF-2 mediated hypoglycemia. Clinical case: A 21-year-old man presented to a regional hospital due to new onset seizures in September 2023. He had been diagnosed with ACC in July 2022, when he presented to the hospital with frank Cushing’s syndrome. CT scan of his chest and abdomen at that time revealed a large left suprarenal mass and multiple lung and liver masses; a biopsy from the liver lesion confirmed the diagnosis of ACC and he was started on treatment with mitotane, levoketoconazole and hydrocortisone. Oncology attempted treatment with 3 cycles of cisplatin and etoposide, with no significant response; subsequently, treatment with Keytruda initially decreased tumor size, but ultimately his CT scan showed progression of disease and mitotane was stopped in August 2023. When brought to the hospital in September 2023 due to seizures and altered mental status, the patient’s blood glucose (BG) was 25 mg/dL (70-110 mg/dL) on point of care testing, so he was started on IV 10% dextrose with improvement in BG and mental status. He underwent endotracheal intubation and was taken to the intensive care unit, showed improvement and was eventually transferred to the general medical floor, where the dextrose infusion was discontinued. However, the following day, he had another hypoglycemic episode complicated with a seizure and had to be reintubated, returning to intensive care. The patient was subsequently transferred to a large tertiary hospital. Evaluation showed undetectable point-of-care BG (&amp;lt; 5 mg/dL) as well as hypokalemia. Fasting labs showed undetectable BHB, undetectable insulin, C-peptide of 0.32 ng/mL (0.78 - 5.19 ng/mL), and negative insulin antibodies. IGF-2/IGF-1 ratio was elevated at 15.6, suggesting IGF-2 mediated hypoglycemia. He was started on IV glucose 20% and glucagon infusions. Mitotane was restarted aiming to decrease tumor burden and consequently IGF-2 levels. Given his hypokalemia, his levoketoconazole dose had to be increased; he was also treated with stress dose steroids. His BG levels improved, and he had partial neurologic recovery, however ultimately curative treatment was not possible given the extent of his disease, so he was transitioned to comfort-focused care. Conclusion: This case illustrates the importance of appropriate workup of IGF-2 mediated hypoglycemia, allowing for the best possible therapeutic approach. In our case, reducing tumor burden was not feasible since the patient had widely metastatic disease, leading to a poor outcome. Presentation: 6/3/2024

12459 Exceptional Response To A Single Dose Of Pembrolizumab As Salvage Therapy In A Patient With Metastatic Adrenocortical Carcinoma (ACC)

Abstract Disclosure: L. Branchaud-Croisetière: None. J. Castilloux: None. E. Turcotte: None. A. Bégin: None. M. St-Jean: Advisory Board Member; Self; GlaxoSmithKline, HRA Pharmaceuticals. Research Investigator; Self; AstraZeneca, Novo Nordisk, Spruce Biosciences. Speaker; Self; GlaxoSmithKline, Recordati Rare Diseases. In advanced ACC, limited effective treatment options are available beyond mitotane and cytotoxic chemotherapy. PD-L1 blockade has shown promising results in small numbers of advanced ACC. In ACC, the reported partial response rate to pembrolizumab is around 25%.[1] Only one case of a significant partial response to a single dose of Pembrolizumab as salvage therapy for metastatic ACC was previously published.[1] In April 2023, a 19-year-old woman presented with severe hypertension, hypokalemia and clinical signs of Cushing syndrome (CS). Thoraco-abdominal scan revealed a left-sided cluster of confluent adrenal masses (7.3 x 14.4 x 11.4 cm), a left cortical renal lesion (2.8x2x2.1cm), a right ovarian teratoma (7.9 x 7.8x7.9 cm) and at least 25 pulmonary micronodules. FDG-PET SCAN revealed a significant hypermetabolism of the left adrenal lesions (SUV 18.6), ovarian teratoma (SUV 5.5) and pulmonary micronodules (SUV 1.1-2). Cortisol and androgens secretion was confirmed biochemically. Initially, she was not candidate for a debulking surgery because the tumor was surrounding the aorta, and mesenteric arteries. Hypertension and hypokalemia were treated with spironolactone, amlodipine, amiloride and irbesartan. Cushing syndrome was treated with metyrapone. In April 2023, Etoposide-Doxorubicine-Cisplatin (EDP) was administered in combination with Mitotane (max: 8g/day). After 6 cycles of EDP-M the disease regressed slightly but was considered stable based on RECIST criteria. After 8 cycles, the follow-up imaging showed a progression of the adrenal lesion (9.2x18.2cm) but stable pulmonary micronodules. A biopsy of the adrenal lesion, for therapeutic purpose, revealed microsatellite stability (MSS). The patient refused germinal genetic testing. It was decided in multidisciplinary tumor board to try Pembrolizumab. In December 2023, she received one cycle of Pembrolizumab (140mg), but the treatment was complicated by grade 4 immune-mediated hepatitis. A few weeks following Pembrolizumab she completely normalized her blood pressure and hypokalemia despite cessation of all her anti-hypertensive drugs. Pembrolizumab and Mitotane were stopped and hepatitis completely resolved after two months of Mycophenolate Mofetil and ongoing decreasing dose of prednisone. In March 2024, CT scan showed a 60% regression of the adrenal mass (4.1 x 7.2 cm), stability of the renal lesion and ovarian teratoma and complete resolution of the pulmonary micronodules. We suspect an ongoing effect of immunotherapy and Mitotane, since Mitotane levels were still in the therapeutic range (15.1 mg/L) six weeks following cessation. Mitotane was resumed in March 2024. The patient will potentially have a resection of the left adrenal lesion in the next month. This is second published case of a significant response to Pembrolizumab as second-line therapy for advanced ACC. [1] Raj Net al. J Clin Oncol. 2020 Presentation: 6/1/2024

6414 Refractory Hyperthyroidism Following COVID-19 Infection

Abstract Disclosure: A.T. Wahba: None. A.A. Shibli-Rahhal: None. A 40-year-old man presented with 2 weeks of palpitations, weight loss, decreased appetite and malaise. The symptoms were preceded by neck pain for 1-2 weeks that improved spontaneously. He was in atrial fibrillation at 126 bpm, but otherwise clinically stable. He had a mildly tender enlarged thyroid with no palpable nodules, and the rest of his exam was negative. A chest CT with IV contrast ruled out pulmonary embolism. His TSH was &amp;lt; 0.01 µIU/mL (N:0.27-4.20), free T4 &amp;gt; 7.77 ng/dL (N: 0.80-1.80) and free T3 of 29.7 (N: 2.6-4.4 pg/ml), obtained prior to contrast administration. TSI antibody was negative and thyroid ultrasound showed diffuse enlargement with heterogeneous echotexture and reduced vascularity on doppler images. Thyroid uptake and scan could not be obtained due to iodinated contrast exposure. The patient’s medical history was notable for nonischemic cardiomyopathy (EF 50%), cardiac arrest with implantable cardiac defibrillator, and paroxysmal atrial fibrillation. He was previously treated with amiodarone for 2 years, and it was stopped 2 months before presentation. Other relevant medical problems included subclinical hypothyroidism diagnosed within the previous year and an uncomplicated acute COVID-19 infection 1 month prior to presentation.Given his cardiac history and high Burch-Wartofsky score, he received PTU 200 mg Q4h, hydrocortisone 100mg Q8h and propranolol for 3 days. As his FT3 level declined to 9.8 pg/ml, he was transitioned to methimazole 40 mg daily, propranolol and prednisone 40 mg daily and discharged with outpatient follow up. The atrial fibrillation worsened again 1 week later, and his FT3 increased to 20.2 with a FT4 &amp;gt; 7.77. He was put back on PTU 200 mg TID, prednisone and propranolol were continued and cholestyramine 2g BID was added. 1 week later, his FT4 and FT3 were unchanged. The tests were performed using a different assay and the results were consistent. Two sessions of plasma exchange (PLEX) did not yield a significant response, so thyroidectomy was eventually performed. Pathology showed morphologic findings consistent with type 2 amiodarone-induced thyrotoxicosis. While pathology showed amiodarone-induced changes, the patient’s hyperthyroidism occurred after a COVID-19 infection and was associated with neck pain, pointing to severe viral thyroiditis. De novo thyroid hormone production has been reported following COVID-19 infection, but the minimal improvement in thyroid hormone levels with thionamide therapy suggests that de novo secretion had little contribution to this patient’s hyperthyroidism. Presentation: 6/3/2024

Intranasal delivery of a recombinant adenovirus vaccine encoding the PEDV COE elicits potent mucosal and systemic antibody responses in mice.

Porcine epidemic diarrhea virus (PEDV) is an enteropathogenic coronavirus that causes substantial economic loss to the global pig industry. The emergence of PEDV variants has increased the need for new vaccines, as commercial vaccines confer inferior protection against currently circulating strains. It is well established that the induction of mucosal immunity is crucial for PEDV vaccines to provide better protection against PEDV infection. In this study, we constructed a recombinant adenovirus expressing the core neutralization epitope (COE) of G2b PEDV based on human adenovirus serotype 5 (Ad5). We evaluated the effects of different administration routes and doses of vaccine immunogenicity in Balb/c mice. Both intramuscular (IM) and intranasal (IN) administration elicited significant humoral responses, including COE-specific IgG in serum and mucosal secretions, along with serum-neutralizing antibodies. Moreover, IN delivery was more potent than IM in stimulating IgA in serum and mucosal samples and in dampening the immune response to the Ad5 vector. The immune response was stronger after high versus low dose IM injection, whereas no significant difference was observed between high and low IN doses. In summary, our findings provide important insights for developing novel PEDV vaccines.IMPORTANCEPorcine epidemic diarrhea (PED) is a highly contagious disease that has severe economic implications for the pork industry. Developing an effective vaccine against PEDV remains a necessity. Here, we generated a recombinant adenovirus vaccine based on Ad5 to express the COE protein of PEDV (rAd5-PEDV-COE) and systematically evaluated the immunogenicity of the adenovirus-vectored vaccine using different administration routes (intramuscular and intranasal) and doses in a mouse model. Our results show that rAd5-PEDV-COE induced potent systemic humoral response regardless of the dose or immunization route. Notably, intranasal delivery was superior to induce peripheral and mucosal IgA antibodies compared with intramuscular injection. Our data provide valuable insights into designing novel PEDV vaccines.

Identification and field verification of the aggregation pheromone components produced by male Holotrichia parallela Motschulsky (Coleoptera: Scarabaeidae).

The chafer beetle, Holotrichia parallela, causes damage to numerous economically significant crops worldwide. Adult beetles exhibit aggregation behavior likely mediated by a male-produced pheromone. Advancements in biological research technology have facilitated the identification of insect aggregation pheromones and promoted their applications as bait for trapping and monitoring pests. Currently, only a few active components of aggregation pheromones from Holotrichia species have been identified. However, the specific components of aggregation pheromones produced by H. parallela remain unknown. In this study, we initially observed from Y-tube olfactometer assays that both male and female H. parallela were significantly attracted to volatiles emitted by males, but not to those from females. We then collected hindgut crude extracts of male adults and carried out gas chromatography-mass spectrometry analysis to identify potential aggregation pheromone components. Pentadecyl acetate, cis-13-docosenol, and behenic acid were identified as male-specific compounds in comparison to female extracts, serving as components of the aggregation pheromone in H. parallela. We further evaluated their attractiveness to H. parallea in both laboratory and field experiments. In laboratory settings, pentadecyl acetate, cis-13-docosenol, and behenic acid evoked significant responses to both males and females at specific concentrations, as evidenced by both electroantennography tests and behavioral bioassays. Under field conditions, traps baited with these three compounds captured significantly more H. parallela adults compared to control traps. In this study, we found that pentadecyl acetate, cis-13-docosenol, and behenic acid are specifically present in male H. parallela, serving as aggregation pheromones. Both laboratory and field-trapping experiments suggest their potential as monitoring and controlling tools against H. parallela adults. © 2024 Society of Chemical Industry.

Association between bike-sharing systems and the blood pressure of local citizens: a cross-sectional study in China

IntroductionGlobally, hypertension stands as the foremost preventable risk factor for cardiovascular disease and premature death. However, scalable approach to lowering blood pressure (BP) at the population level remains lacking. We...

Bright Light Therapy for Nonseasonal Depressive Disorders

Seasonal humor disorders are prone to have a link with daylight exposure. However, the effect of external light on nonseasonal disorders remains unclear. Evidence is lacking for the validity of bright light therapy (BLT) as an adjunctive treatment for these patients. To assess BLT effectiveness as an adjunctive treatment for nonseasonal depressive disorders. In March 2024, a comprehensive search was performed of publications in the MEDLINE, Embase, and Cochrane databases for randomized clinical trials (RCTs) evaluating BLT effects in patients with nonseasonal depression. RCTs published since 2000 were eligible. Comparisons between BLT and dim red light or antidepressant monotherapy alone were considered for inclusion. Using the systematic review approach on RCTs published from January 1, 2000, through March 25, 2024, differences between patients treated with and without BLT were estimated using the Mantel-Haenszel method; heterogeneity was assessed using I2 statistics. Remission of symptoms, response to treatment rates, and depression scales were assessed. In this systematic review and meta-analysis of 11 unique trials with data from 858 patients (649 female [75.6%]), statistically significant better remission and response rates were found in the BLT group (remission: 40.7% vs 23.5%; odds ratio [OR], 2.42; 95% CI, 1.50-3.91; P <.001; I2 = 21%; response: 60.4% vs 38.6%; OR, 2.34; 95% CI, 1.46-3.75; P <.001; I2 = 41%). With BLT, subgroup analysis based on follow-up times also showed better remission (<4 weeks: 27.4% vs 9.2%; OR, 3.59; 95% CI, 1.45-8.88; P = .005; I2 = 0% and >4 weeks: 46.6% vs 29.1%; OR, 2.18; 95% CI, 1.19-4.00; P = .01; I2 = 47%) and response (<4 weeks: 55.6% vs 27.4%; OR, 3.65; 95% CI, 1.81-7.33; P <.001; I2 = 35% and >4 weeks: 63.0% vs 44.9%; OR, 1.79; 95% CI, 1.01-3.17; P = .04; I2 = 32%) rates. Results of this systematic review and meta-analysis reveal that BLT was an effective adjunctive treatment for nonseasonal depressive disorders. Additionally, results suggest that BLT may improve the response time to the initial treatment.

TR3-56 and Treg Regulatory T Cell Subsets as Potential Indicators of Graft Tolerance Control in Kidney Transplant Recipients.

Identification of early signatures of immune rejection represents a key challenge in the clinical management of kidney transplant. To address such an issue, we enrolled 53 kidney transplant recipients without signs of graft rejection, no infectious episodes and no change in the immunosuppressive regimen in the last 6 months. An extensive immune profile revealed increased activation of the T cells, a decreased amount and growth ability of the Treg and a higher level of the TR3-56 regulatory T cell subset, described by us as involved in the preferential control of cytotoxic T lymphocytes. In renal transplant recipients, the high level of the TR3-56 cells associates with a reduction in both the amount and the growth ability of the Treg. Moreover, when the transplanted subjects were categorised according to their stable or unstable disease status, as defined by changes in serum creatinine ≥0.2 mg/dL in two consecutive detections, a higher TR3-56 level and defective Treg growth ability were observed to characterise patients with unstable graft control. Further studies are required to substantiate the hypothesis that immune profiling, including TR3-56 evaluation, might represent a valuable diagnostic tool to identify patients at risk of developing significant anti-donor allo-immune responses.

Belowground diversity drives multifunctionality in grazing pastures on the eastern Tibetan Plateau

Livestock grazing can alter ecosystem structure, functions, and services across diverse biomes, with grazing intensity being a key factor affecting grassland function. Although the effects of grazing on plant and soil properties have been extensively studied, the effects of grazing intensity on biodiversity and ecosystem multifunctionality (EMF) remain largely unexplored. Therefore, this study addresses this gap using 28 indicator variables from a well-controlled yak grazing intensity experiment in alpine meadows on the eastern Tibetan Plateau. The results showed that aboveground diversity (calculated using plant species richness and insect diversity) exhibited a hump-shaped and significant response to increasing grazing intensity, multidiversity (whole-ecosystem biodiversity) and belowground diversity (calculated using nematode richness and microbial diversity) showed no significant response, and EMF significantly declined. Grazing decreased carbon and nitrogen cycling indices (calculated by carbon and nitrogen in plants and soils), but did not affect phosphorus cycling. Structural equation modelling indicated that EMF was directly affected by grazing intensity and belowground diversity (i.e., nematode and fungal diversity), rather than by multidiversity, aboveground diversity, and plant pathogens. Grazing-induced decreases in plant pathogens showed no direct or indirect effects on EMF but increased multidiversity and aboveground diversity. Overall, our results highlight the critical role of conserving belowground diversity in promoting and maintaining multifunctionality in grazing pastures on the Tibetan Plateau.

A case of neoadjuvant targeted therapy with pralsetinib for locally advanced lung adenocarcinoma with RET fusion mutation

This case report details the successful treatment of a 68-year-old male patient with locally advanced RET-rearranged lung adenocarcinoma using neoadjuvant pralsetinib. The patient initially presented with a suspicious right upper lobe nodule, which was later diagnosed as lung adenocarcinoma following genetic testing that revealed a RET exon 12 fusion. After 2 months of neoadjuvant treatment with pralsetinib, a significant radiological response was observed, with a reduction in tumor size and metabolic activity. Subsequently, the patient underwent video-assisted thoracoscopic right upper lobectomy and mediastinal lymph node dissection. Postoperative pathological analysis revealed a major pathological response, with only 5% residual tumor cells in the primary lesion and no viable tumor cells in the lymph nodes. Postoperative pathological staging of TNM was ypT1aN0M0, stage IA1(AJCC, 8th edition). The patient recovered well after surgery, demonstrating the potential efficacy of neoadjuvant pralsetinib in locally advanced RET-rearranged lung adenocarcinoma. However, further clinical validation is required to establish the role of neoadjuvant targeted therapy and postoperative adjuvant therapy in this patient population.