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In this Correspondence, F. Mari and colleagues report a second two-generation family with distal arthrogryposis caused by a mutation in MET tyrosine kinase.

Abstract Vaccine diplomacy is a subset of global health diplomacy and refers to the use and delivery of vaccines to achieve a country’s global health goals and foreign policy objectives. Countries have used vaccine diplomacy to increase their soft power during the COVID-19 pandemic. China, an emerging world power, was no exception in this trend. By December 2022, China had dispatched 1.65 billion vaccines worldwide; approximately one-third of the Chinese vaccines were sent to the Association of Southeast Asian Nations (ASEAN) countries. China attempted to increase its soft power via vaccine diplomacy to appeal to its neighbours with which it has long-standing territorial disputes in the South China Sea (SCS). Focusing on two key claimants in the SCS, our study has the following research question: How effective was Chinese COVID-19 vaccine diplomacy in the Philippines and Vietnam from a soft power perspective? Through a qualitative multiple case study research design, we determined the effectiveness of Chinese vaccine diplomacy in the Philippines and Vietnam by using four indicators of soft power: public opinion, foreign policy, attractiveness, and business and trade. Data collection consisted of a literature search of academic literature and newspaper articles that were published between 26 May and 13 June 2022. A thematic analysis was conducted to analyse the data. Analysing the effectiveness of Chinese vaccine diplomacy based on the four indicators of soft power, our results show that only the indicators of attractiveness in Vietnam and business and trade in the Philippines have somewhat improved. In contrast, the indicators of public opinion and foreign policy showed neutral or negative results for China. This study concludes that Chinese vaccine diplomacy in the Philippines and Vietnam during the COVID-19 pandemic was unsuccessful from a soft power perspective. One reason is that China undermined its soft power approach by simultaneously using hard power tactics in Southeast Asia. Using vaccine diplomacy to increase soft power is not always desirable from a global health perspective. Instead, countries should focus on equitable vaccine access and address asymmetrical power relations.

Abstract Since the handover of the sovereignty of Hong Kong from Britain to China in 1997, convergence between Mainland China and Hong Kong has gradually emerged. During this process, young people have engaged in demonstrations to express their dissatisfaction with government policies and limited socio-economic progression. However, the underlying reasons for their dissatisfaction have not been fully investigated. This study investigates their perceived challenges and opportunities during the convergence, with the objective of identifying the factors affecting the Mainland China–Hong Kong convergence and examining young people’s perceived challenges and opportunities during the convergence. Mixed research methods of focus groups and a survey were adopted. Ten focus groups with 83 participants were conducted to collect qualitative data on the factors relating to convergence. Based on the qualitative data, a questionnaire was constructed to investigate young people’s perceived challenges and opportunities during the convergence, using a sample of 1253 young people. Ordinary least-squares regression was applied to analyse the relationships among identified factors. The study found that Hong Kong’s youth tended to regard the Mainland China–Hong Kong convergence as an opportunity for socio-economic progression, and they identified three challenges during the convergence. It also revealed that young people’s higher education, perceived housing challenges, and perceived socio-economic challenges are negatively related to the convergence, whereas their perceived challenges associated with entrepreneurship and innovation are positively related to the convergence. The development of more well-balanced and mutually beneficial policies that satisfy the needs of young people will lead to a higher acceptance of the convergence. As such, young people will be more willing to embrace the opportunities and face the challenges brought about by the convergence, resulting in a more harmonious society and socio-economic progression.

Abstract Cancers represent complex autonomous systems, displaying self‐sufficiency in growth signaling. Autonomous growth is fueled by a cancer cell's ability to “secrete‐and‐sense” growth factors (GFs): a poorly understood phenomenon. Using an integrated computational and experimental approach, here we dissect the impact of a feedback‐coupled GTPase circuit within the secretory pathway that imparts secretion‐coupled autonomy. The circuit is assembled when the Ras‐superfamily monomeric GTPase Arf1, and the heterotrimeric GTPase Giαβγ and their corresponding GAPs and GEFs are coupled by GIV/Girdin, a protein that is known to fuel aggressive traits in diverse cancers. One forward and two key negative feedback loops within the circuit create closed‐loop control, allow the two GTPases to coregulate each other, and convert the expected switch‐like behavior of Arf1‐dependent secretion into an unexpected dose–response alignment behavior of sensing and secretion. Such behavior translates into cell survival that is self‐sustained by stimulus‐proportionate secretion. Proteomic studies and protein–protein interaction network analyses pinpoint GFs (e.g., the epidermal GF) as key stimuli for such self‐sustenance. Findings highlight how the enhanced coupling of two biological switches in cancer cells is critical for multiscale feedback control to achieve secretion‐coupled autonomy of growth factors.

Multidrug resistant (MDR) bacteria are recognized to be one of the most important problems in public health. The outer membrane permeability is a critical intrinsic mechanism of bacterial resistance. In addition, bacteria produce a small number of dormant persister cells causing multidrug tolerance that reduces antimicrobial efficacy. This study aimed to evaluate the inhibitory effects of the combination of aromatic isothiocyanates (ITCs) with membrane-active agents on bacterial persisters and MDR Gram-negative bacteria. Our study demonstrated that membrane-active agents, particularly ethylenediaminetetraacetic acid (EDTA) synergistically enhanced the inhibitory activity of aromatic benzyl ITC and phenethyl ITC against most Gram-negative bacteria strains with fractional inhibitory concentration index values ranging from 0.18 to 0.5 and 0.16 to 0.5, respectively, and contributed to an 8- to 64-fold minimal inhibitory concentration reduction compared with those of aromatic ITCs alone. The EDTA-aromatic ITCs combination effectively reduced the survival rates of tested bacteria and significantly eradicated bacterial persisters (p = 0.033 and 0.037, respectively). The growth kinetics analysis also supported the enhanced inhibitory effect of EDTA-aromatic ITCs combination against tested bacteria. Our results suggested an alternate treatment strategy against Gram-negative bacteria, promoting the entry of aromatic ITCs into bacterial cytoplasm to facilitate bacterial clearance and thus preventing the development of bacterial resistance. [ABSTRACT FROM AUTHOR]

Abstract The genetic changes sustaining the development of cancers of unknown primary (CUP) remain elusive. The whole‐exome genomic profiling of 14 rigorously selected CUP samples did not reveal specific recurring mutation in known driver genes. However, by comparing the mutational landscape of CUPs with that of most other human tumor types, it emerged a consistent enrichment of changes in genes belonging to the axon guidance KEGG pathway. In particular, G842C mutation of PlexinB2 (PlxnB2) was predicted to be activating. Indeed, knocking down the mutated, but not the wild‐type, PlxnB2 in CUP stem cells resulted in the impairment of self‐renewal and proliferation in culture, as well as tumorigenic capacity in mice. Conversely, the genetic transfer of G842C‐PlxnB2 was sufficient to promote CUP stem cell proliferation and tumorigenesis in mice. Notably, G842C‐PlxnB2 expression in CUP cells was associated with basal EGFR phosphorylation, and EGFR blockade impaired the viability of CUP cells reliant on the mutated receptor. Moreover, the mutated PlxnB2 elicited CUP cell invasiveness, blocked by EGFR inhibitor treatment. In sum, we found that a novel activating mutation of the axon guidance gene PLXNB2 sustains proliferative autonomy and confers invasive properties to stem cells isolated from cancers of unknown primary, in EGFR‐dependent manner.

Abstract Fn14 is a cell surface receptor with key functions in tissue homeostasis and injury but is also linked to chronic diseases. Despite its physiological and medical importance, the regulation of Fn14 signaling and turnover is only partly understood. Here, we demonstrate that Fn14 is cleaved within its transmembrane domain by the protease γ‐secretase, resulting in secretion of the soluble Fn14 ectodomain (sFn14). Inhibition of γ‐secretase in tumor cells reduced sFn14 secretion, increased full‐length Fn14 at the cell surface, and enhanced TWEAK ligand‐stimulated Fn14 signaling through the NFκB pathway, which led to enhanced release of the cytokine tumor necrosis factor. γ‐Secretase‐dependent sFn14 release was also detected ex vivo in primary tumor cells from glioblastoma patients, in mouse and human plasma and was strongly reduced in blood from human cancer patients dosed with a γ‐secretase inhibitor prior to chimeric antigen receptor (CAR)‐T‐cell treatment. Taken together, our study demonstrates a novel function for γ‐secretase in attenuating TWEAK/Fn14 signaling and suggests the use of sFn14 as an easily measurable pharmacodynamic biomarker to monitor γ‐secretase activity in vivo.

Purpose: Heterozygous STAT1 Gain-of-Function (GOF) mutations are the most common cause of chronic mucocutaneous candidiasis (CMC) among Inborn Errors of Immunity. Clinically, these mutations manifest as a broad spectrum of immune dysregulation, including autoimmune diseases, vascular disorders, and malignancies. The pathogenic mechanisms of immune dysregulation and its impact on immune cells are not yet fully understood. In treatment, JAK inhibitors have shown therapeutic effectiveness in some patients. Methods: We analyzed clinical presentations, cellular phenotypes, and functional impacts in five Taiwanese patients with STAT1 GOF. Results: We identified two novel GOF mutations in 5 patients from 2 Taiwanese families, presenting with symptoms of CMC, late-onset rosacea, and autoimmunity. The enhanced phosphorylation and delayed dephosphorylation were displayed by the patients' cells. There are alterations in both innate and adaptive immune cells, including expansion of CD38+HLADR +CD8+ T cells, a skewed activated Tfh cells toward Th1, reduction of memory, marginal zone and anergic B cells, all main functional dendritic cell lineages, and a reduction in classical monocyte. Baricitinib showed therapeutic effectiveness without side effects. Conclusion: Our study provides the first comprehensive clinical and molecular characteristics in STAT1 GOF patient in Taiwan and highlights the dysregulated T and B cells subsets which may hinge the autoimmunity in STAT1 GOF patients. It also demonstrated the therapeutic safety and efficacy of baricitinib in pediatric patient. Further research is needed to delineate how the aberrant STAT1 signaling lead to the changes in cellular populations as well as to better link to the clinical manifestations of the disease. [ABSTRACT FROM AUTHOR]

Purpose: Anti-granulocyte-macrophage colony-stimulating factor autoantibodies (anti-GM-CSF Abs) are implicated in the pathogenesis of Cryptococcus gattii (C. gattii) infection and pulmonary alveolar proteinosis (PAP). Their presence has also been noted in nocardiosis cases, particularly those with disseminated disease. This study delineates a case series characterizing clinical features and specificity of anti-GM-CSF Abs in nocardiosis patients. Methods: In this study, eight patients were recruited to determine the presence or absence of anti-GM-CSF Abs. In addition to the detailed description of the clinical course, we thoroughly investigated the autoantibodies regarding the characteristics, isotypes, subclasses, titers, and neutralizing capacities by utilizing the plasma samples from patients. Results: Of eight patients, five tested positive for anti-GM-CSF Abs, all with central nervous system (CNS) involvement; patients negative for these antibodies did not develop CNS nocardiosis. Distinct from previously documented cases, none of our patients with anti-GM-CSF Abs exhibited PAP symptoms. The titer and neutralizing activity of anti-GM-CSF Abs in our cohort did not significantly deviate from those found in C. gattii cryptococcosis and PAP patients. Uniquely, one individual (Patient 3) showed a minimal titer and neutralizing action of anti-GM-CSF Abs, with no relation to disease severity. Moreover, IgM autoantibodies were notably present in all CNS nocardiosis cases investigated. Conclusion: The presence of anti-GM-CSF Abs suggests an intrinsic immunodeficiency predisposing individuals toward CNS nocardiosis. The presence of anti-GM-CSF Abs helps to elucidate vulnerability to CNS nocardiosis, even with low titer of autoantibodies. Consequently, systematic screening for anti-GM-CSF Abs should be considered a crucial diagnostic step for nocardiosis patients. [ABSTRACT FROM AUTHOR]

Abstract The aim of the research is the bibliometric analysis of research on COVID-19 and tourism in order to detect research lines and gaps, the main authors, the countries with the highest number of publications, the most analysed study areas, the journals with the most number of publications and the articles with the highest number of citations. The Web of Science (WOS) database was used to extract the publications and the VOSviewer software was used to represent the data analysed. The keywords used resulted in 1792 publications that were subjected to a filtering process to avoid introducing articles that did not meet the inclusion criteria. Finally, the analysis was composed by 921 publications. The analysis locates a new line of research that visualizes the crisis as an opportunity to propel a new, more sustainable tourism. Tourist perception and the risk of transmission, together with the analysis of measures and policies are other of the most researched topics. China is the country with the most articles on COVID-19 and tourism according to the author’s main affiliation, as well as being the most analysed area of study. To the best of our knowledge, this is the first article to carry out a bibliometric analysis of COVID-19 and tourism publications.

Abstract Vaccination against an airborne pathogen is very effective if it induces also the development of mucosal antibodies that can protect against infection. The mRNA‐based vaccine‐encoding SARS‐CoV‐2 full‐length spike protein (BNT162b2, Pfizer/BioNTech) protects also against infection despite being administered systemically. Here, we show that upon vaccination, cognate IgG molecules are also found in the saliva and are more abundant in SARS‐CoV‐2 previously exposed subjects, paralleling the development of plasma IgG. The antibodies titer declines at 3 months from vaccination. We identified a concentration of specific IgG in the plasma above which the relevant IgG can be detected in the saliva. Regarding IgA antibodies, we found only protease‐susceptible IgA1 antibodies in plasma while they were present at very low levels in the saliva over the course of vaccination of SARS‐CoV‐2‐naïve subjects. Thus, in response to BNT162b2 vaccine, plasma IgG can permeate into mucosal sites and participate in viral protection. It is not clear why IgA1 are detected in low amount, they may be proteolytically cleaved.

The development of composite materials with fewer interface problems always helps to obtaining good properties. Two types of insulating biopolymers (7% w/w) were incorporated into a conductive matrix (polyaniline) during polymerization. The synthesis method, inspired by the synthesis of polyaniline and the coating of chitosan for the development of flexible electrodes, produces thermosets that are more thermally stable than the matrix until 350 °C. While one (gum) reduces the electrical conductivity, the other (lignin) increases the basic value of the raw material (~ 0.72 S Cm–1) by a factor of 10. The physicochemical and morphological analyses show the formation of the polymer on the surface of the biopolymer with the appearance of new chemical bonds by interactions between hydroxyls of the biopolymer and the nitrogen of amine function from the polyaniline. [ABSTRACT FROM AUTHOR]

Background: Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). Methods: In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. Results: Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). Conclusions: Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer. [ABSTRACT FROM AUTHOR]

Playing music is a complex task that relies on the combination of musicians' technical and expressive skills. While the literature has investigated the effects of musical expressivity on the listeners, the way how technical difficulty and emotional expressivity affect musicians during playing has surprisingly received no attention. In an attempt to fill this gap in the literature, we collected behavioral and physiological data from twelve violinists playing 29 pieces that included both technical exercises and excerpts from classical repertoire for violin. After playing each stimulus, participants rated it for emotional expressivity and technical difficulty. During the entire session, cardiac parameters and electrodermal activity were collected, together with the kinematic parameters of the bowing gesture. A set of Linear Mixed-Effect (LME) models suggested that emotional expressivity attributed to music affected the fluidity of bowing (i.e., smoothness), with the excerpts rated as more expressive being performed in a less smooth way. In contrast, LME models revealed no effects of expressivity and technical difficulty on any of the physiological parameters of violinists. Our results offer novel insights into the psychophysiological dynamics that link motor parameters with musical expressivity. These findings could influence educational practices in music and deepen our understanding of aesthetic emotions. [ABSTRACT FROM AUTHOR]

This paper presents the detailed design configuration and investigation of a small-scale dual-band metamaterial absorber (MTMA) for solid and liquid sensing applications. The overall dimension of the MTMA unit cell is 10 × 10 × 1.57 mm3 and constitutes an affordable FR-4 substrate. The absorber exhibits dual absorption peaks at 3.470 GHz for the S-band and 7.219 GHz for the C-band, respectively. Both absorption characteristics have been validated through comprehensive simulation and experimental procedures. The dual-band absorption rate exceeded 99% during simulations, and experimental validation showed an absorption rate above 98%. For sensing applications, various solid materials, including different Rogers substrates (RT 5880, RT 5870, RT 4003 and RT 4835) and liquids such as sunflower and crown oil, were utilized. Our findings indicate that the proposed MTMA achieves a maximum Q-factor of 191 and a sensitivity of up to 2.5 for both solid and liquid sensing applications compared to previous studies. The simulation and experimental validation of the result indicate that suggested MTMA can be effectively used in different sensing applications such as the medical and communications industry. [ABSTRACT FROM AUTHOR]

The maintenance of intestinal homeostasis is a fundamental process critical for organismal integrity. Sitting at the interface of the gut microbiome and mucosal immunity, adaptive and innate lymphoid populations regulate the balance between commensal micro-organisms and pathogens. Checkpoint inhibitors, particularly those targeting the CTLA-4 pathway, disrupt this fine balance and can lead to inflammatory bowel disease and immune checkpoint colitis. Here, we show that CTLA-4 is expressed by innate lymphoid cells and that its expression is regulated by ILC subset-specific cytokine cues in a microbiota-dependent manner. Genetic deletion or antibody blockade of CTLA-4 in multiple in vivo models of colitis demonstrates that this pathway plays a key role in intestinal homeostasis. Lastly, we have found that this observation is conserved in human IBD. We propose that this population of CTLA-4-positive ILC may serve as an important target for the treatment of idiopathic and iatrogenic intestinal inflammation. At the mucosal interface of the gut and microbiome immune cells play pivotal roles to regulate between commensalism, colonisation and pathogenic invasion. Here, Lo et al. show CTLA-4 expression in innate lymphoid cells is linked to mucosal homeostasis in a microbiome dependent manner. [ABSTRACT FROM AUTHOR]

Background: Epidermoid cysts are benign, slow growing extra-axial lesions most commonly found in the cerebellopontine angle that have a characteristic imaging pattern of restricted diffusion on diffusion-weighted imaging (DWI). Methods: A 10-year-old male with a history of asthma and diabetes was found to have a lesion within the fourth ventricle on a magnetic resonance imaging (MRI) brain study. MRI showed a well-circumscribed vermian lesion without contrast enhancement or restricted diffusion with mild hydrocephalus. He was referred to the neurosurgical service once he acutely developed symptoms of dizziness. He underwent a gross-total resection of the lesion on which histopathology confirmed an epidermoid cyst. Results: Here, we report a case of an atypical epidermoid cysts found in the midline of the fourth ventricle without restricted diffusion on MRI. Conclusion: Avid restricted-diffusion on DWI is usually pathognomonic for an epidermoid cyst when evaluating an extra-axial lesion, yet we report the second case in the literature of an epidermoid cyst without this classical imaging characteristic. [ABSTRACT FROM AUTHOR]

While it has been recognized that science, technology, engineering, and mathematics (STEM) education requires an interdisciplinary approach, integrating multiple subjects in a meaningful way remains challenging for teachers. This study aimed to design a STEM curriculum, emphasizing explicit and continuous scaffolding of students' reflection on scientific and engineering knowledge. The primary goal was to foster knowledge integration in their engineering designs and enhance their attitudes toward STEM. The study involved fifty tenth-grade students who were guided to discuss and reflect on relevant scientific and engineering knowledge and to apply mathematics for data collection and analysis during the design of their technology products. The research instruments included an assessment of the progression of knowledge integration in students' engineering designs through student journals and pre- and post-test surveys on attitudes toward science, technology, engineering, and the learning environment. The results reveal that the introduction and explicit scaffolding students' reflection on scientific and engineering knowledge led to a gradual improvement in knowledge integration within their engineering designs. Students also significantly enhanced their attitudes toward STEM and the learning environment compared to the general school curriculum. This study contributes to interdisciplinary learning that promotes the integration of scientific and engineering knowledge in students' engineering design processes, and to interdisciplinary assessment that evaluates students' knowledge integration across learning progressions and outcomes. [ABSTRACT FROM AUTHOR]

Objective: Cranial computed tomography (CT) scan is the most widely used tool to rule out intracranial lesions after pediatric traumatic brain injury (TBI). However, in pediatric population, the radiation exposure can lead to an increased risk of hematological and brain neoplasm. Defined in 2019 National Institute for Health and Care Excellence (NICE) guidelines as "troponins for the brain", serum biomarkers measurements, particularly S100B, have progressively emerged as a supplementary tool in the management of TBI thanks to their capacity to predict intracranial post-traumatic lesions. Methods: This systematic review was conducted following the PRISMA protocol (preferred reporting items for systematic reviews and meta-analyses). No chronological limits of study publications were included. Studies reporting data from children with TBI undergoing serum S100B measurement and computed tomography (CT) scans were included. Results: Of 380 articles screened, 10 studies met the inclusion criteria. Patients admitted with mild-TBI in the Emergency Department (ED) were 1325 (80.25%). The overall pooled sensitivity and specificity were 98% (95% CI, 92–99%) and 45% (95% CI, 29–63%), respectively. The meta-analysis revealed a high negative predictive value (NVP) (99%; 95% CI, 94–100%) and a low positive predictive value (PPV) (41%; 95% CI, 16–79%). Area under the curve (AUC) was 76% (95% CI, 65–85%). The overall pooled negative predictive value (NPV) was 99% (95% CI, 99–100%). Conclusions: The measurement of serum S100B in the diagnostic workflow of mTBI could help informed decision-making in the ED setting, potentially safely reducing the use of CT scan in the pediatric population. The high sensitivity and excellent negative predictive values look promising and seem to be close to the values found in adults. Despite this, it must be pointed out the high heterogeneity (> 90%) found among studies. In order for S100B to be regularly introduced in the pediatric workflow for TBI, it is important to conduct further studies to obtain cut-off levels based on pediatric reference intervals. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the rate of hyperechoic liver lesions that are clinically actionable and evaluate imaging and clinical factors associated with these to determine the need for follow-up. Materials and methods: This retrospective study included 228 hyperechoic hepatic lesions on ultrasound in 228 patients. Reference standards included either dynamic contrast enhanced MRI (n = 130) or CT (n = 46), follow-up ultrasound performed at least 2 years from baseline (n = 50), or histopathology (n = 2). Three radiologists independently assessed imaging features including lesion orientation, degree of hyper-echogenicity, lesion heterogeneity, and background liver echotexture. Univariable and multivariable logistic regression was used to determine features associated with an actionable hyperechoic lesion. Results: Of the 228 hyperechoic lesions, 14 (6.1%) lesions were clinically actionable (or requiring follow-up), and 214 (93.9%) were clinically insignificant. Features that differed between patients with clinically insignificant vs. actionable lesions included: age (52.9 ± 15.1 vs. 63.9 ± 15.8 years, p = 0.004), male sex (43.9% vs 71.4%, p = 0.045), history of cirrhosis (6.5% vs 50%, p < 0.001), lesion size (1.9 ± 1.4 cm vs. 3.5 ± 2.8 cm, p = 0.003), heterogeneous lesion echogenicity (16.4% vs. 50%, p = 0.006), and cirrhotic/coarsened background liver (7.5% vs. 35.7%, p = 0.005). Stepwise logistic regression and multivariable analysis identified age, presence of cirrhosis, and lesion size as features most predictive of an actionable lesion (OR 1.04, 24.3, 1.77 respectively). Reader agreement for imaging features was fair to moderate (k = 0.29–0.53). 100%(168/168) of hyperechoic liver lesions measuring ≤ 3 cm in patients without a history of malignancy or underlying liver disease were clinically insignificant. Conclusion: Our study findings support the overall favorable diagnoses of hyperechoic liver lesions ≤ 3 cm in patients without underlying risk factors. [ABSTRACT FROM AUTHOR]

Aims/hypothesis: Although the benefits of sodium–glucose cotransporter 2 inhibitor (SGLT2i) use in chronic kidney disease (CKD) are well established, the effects of these therapeutic agents in patients with advanced CKD are less certain. We hypothesised that the continued use of these drugs, even when renal function deteriorates to stage 4 CKD or worse, is safe and associated with improved cardiorenal survival. Methods: This is a retrospective cohort study utilising data from medical records from two institutions. All patients with type 2 diabetes mellitus who were prescribed an SGLT2i between 1 January 2016 and 31 December 2021, who subsequently had eGFR <30 ml/min per 1.73 m2 recorded on two occasions at least 90 days apart, were identified. The date on which the eGFR first reached any level less than 30 ml/min per 1.73 m2 was defined as the index date. Individuals were then categorised into the SGLT2i continuation group or the discontinuation group according to the use of SGLT2i after the index date. Inverse probability of treatment weighting (IPTW) was performed to minimise confounding. Outcomes of interest included heart failure outcomes, cardiovascular outcomes, renal outcomes and safety outcomes. Results: According to the eligibility criteria, 337 patients in the continuation group and 358 in the discontinuation group were identified. After IPTW, continuation of SGLT2i use was associated with significantly lower risks of the composite of major adverse cardiovascular events compared with discontinuation of SGLT2i use (HR 0.65 [95% CI 0.43, 0.99]), largely driven by reduced risk of myocardial infarction during follow-up (subdistribution HR [SHR] 0.43 [95% CI 0.21, 0.89]). The incidences of an eGFR decline of 50% or more (SHR 0.58 [95% CI 0.42, 0.81]) and all-cause hospital admission (SHR 0.77 [95% CI 0.64, 0.94]) were also significantly lower in the continuation group. None of the studied safety outcomes were significantly different when comparing the two groups. Blood haemoglobin levels were significantly higher in the continuation group at the end of follow-up (114.6 g/l vs 110.4 g/l, with a difference of 4.12 g/l; p=0.047). Conclusions/interpretation: In patients with CKD who were treated with an SGLT2i, continuation of SGLT2i use after eGFR declined to 30 ml/min per 1.73 m2 or less was associated with lower risks of cardiovascular and renal events compared with discontinuation of SGLT2i use. Continued use of SGLT2i throughout the course of CKD should be considered to optimise patient outcomes. [ABSTRACT FROM AUTHOR]

Zirconium-89 radiolabeled immuno-positron emission tomography (89Zr-iPET) has become a critical tool for patient stratification before and after immunotherapies for therapeutic evaluation. In this study, random and site-specific radiolabeling of 89Zr-iPET tracers were investigated. Traditional lysine-based conjugation and enzyme-based GlyCLICK® kit method were used to prepare DFO-anti-PD-L1-mAb conjugates with a chelator-to-antibody ratio (CAR) of 0–7 and 2.0, respectively. Then, conjugates with different CAR levels were radiolabeled with 89Zr to obtain randomly or site-specifically radiolabeled 89Zr-iPET tracer. [ABSTRACT FROM AUTHOR]

This research examines the effects of information disclosure ratings (IDR) on firm-specific stock price crash risk. We present evidence that there is a statistically significant negative relationship between stock price crash risk and IDR. Specifically, effective information disclosure attracts greater investor attention and leads to more liquidity, which mitigates the stock price crash risk. Our findings remain robust after controlling for relevant variables and addressing the issue of endogeneity. This research proves that high IDR mitigates the stock price crash risk by eliciting market reaction, which not only introduces a novel perspective for investors in their analysis of corporate risks but also offers valuable directions for policy formulation to guide the market. [ABSTRACT FROM AUTHOR]

Summary: While US Asian and Pacific Islander adults have lower 25-hydroxyvitamin D (25(OH)D) levels than White adults, ethnic subgroup data remain limited. In a large California population, the adjusted prevalence of 25(OH)D < 20 ng/mL (50 nmol/L) was 1.5- to 2.7-fold higher for Asian/Pacific Islander compared to White adults, with substantial variation by ethnicity. Purpose: US Asian and Pacific Islander (PI) adults generally have lower 25-hydroxyvitamin D [25(OH)D] levels than non-Hispanic White (NHW) adults, but subgroup data remain limited. We compared sex- and ethnicity-specific prevalence of low 25(OH)D among older Asian/PI and NHW adults. Methods: Data from 102,556 Asian/PI and 381,724 NHW adults aged 50–89 years with measured 25(OH)D in 2012–2019 and body mass index (BMI, within ± 1 year) were examined in a California healthcare system. Low 25(OH)D < 20 ng/mL (50 nmol/L) was examined by race and ethnicity. Covariates included age, smoking, BMI, and season of measurement. Modified Poisson regression was used to estimate prevalence ratios (aPR), adjusting for covariates. Results: Among 31,287 Asian/PI men and 71,269 Asian/PI women, the prevalence of low 25(OH)D was 22.6% and 14.7%, respectively, significantly higher than observed for 122,162 NHW men (12.3%) and 259,562 NHW women (9.9%). Within Asian/PI subgroups, low 25(OH)D prevalence ranged from 17 to 18% (Korean, Japanese, Filipino), 22 to 24% (Chinese, Vietnamese), 28% (South Asian), and 35% (Native Hawaiian/PI) among men and 11 to 14% (Japanese, Filipina, Chinese, Korean), 17 to 18% (South Asian, Vietnamese), and 26% (Native Hawaiian/PI) among women. The corresponding aPRs (NHW reference) for men and women were as follows: Native Hawaiian/PI, 2.70 and 2.34; South Asian, 2.56 and 2.07; Vietnamese, 2.17 and 2.31; Chinese, 2.04 and 1.89; Korean, 1.60 and 1.85; Filipino, 1.58 and 1.52; and Japanese, 1.58 and 1.49 (p < 0.001). Conclusion: In a large US healthcare population of older Asian/PI adults, low 25(OH)D prevalence was 1.5- to 2.7-fold higher for Asian/PI compared to NHW adults, with substantial variation by sex and ethnicity. [ABSTRACT FROM AUTHOR]

Aim: The aim was to assess the characteristics of patients who required imaging studies during admission to an acute supportive palliative care unit (ASPCU). Methods: A consecutive number of patients who performed imaging studies during ASPCU admission in a month period were assessed. Epidemiological data, ongoing anticancer treatment, cancer diagnosis, reasons for admission, referral, and type of imaging study were recorded. Indications, findings, consequent actions for treatment, prognosis, and discharge were also collected. Results: Twenty-one of 56 patients admitted to ASPCU in the period taken into consideration were assessed. Pain and deterioration of the general condition were the most frequent indications for admission. Computed tomography (CT) was the most frequent imaging study performed. Indications for performing imaging studies depended on individual clinical needs. Findings suggested different clinical decisions, after a comprehensive oncological and palliative care assessment and family conference, the most frequent of which was to withdraw oncological treatments. The majority of patients underwent transition to palliative care and were discharged home or to hospice. Conclusion: Imaging studies were of paramount importance for clinical treatment and decision-making process in an intensive ASPCU. There is the need to explore the need and the possible outcomes of imaging studies, as well cost-effectiveness in any ASPCU. [ABSTRACT FROM AUTHOR]

The biosynthesis of nanoparticles is an important research area focused on developing innovative, cost-effective, efficient, and environmentally friendly synthesis techniques with a wide range of applications. This study employs a straightforward and practical method to produce TiO2 nanoparticles (NPs) for use in photocatalysis, antibacterial, antifungal, and antidiabetic applications. It utilizes extract-assisted biosynthesis with Moringa oleifera. To enhance the material and evaluate the impact of bioinspiration on various parameters, the resulting TiO2 NPs undergo calcination at 500 °C. Structural confirmation, bandgap analysis, and functional group studies of MO/TiO2 (Moringa oleifera/TiO2) nanoparticles are conducted using XRD, UV-DRS, FT-IR, and PL analysis. To examine the surface morphological characteristics of the anatase TiO2 nanoparticles, SEM and TEM-EDS electron microscopy analyses were accomplished. The produced TiO2 nanoparticles are also assessed for their photocatalytic and antidiabetic properties. Photocatalytic activity is determined by decolorizing methylene blue dye in the presence of sunlight, revealing that optimal conditions for complete color removal involve using 0.3 g of TiO2 and a concentration of 4 × 10− 5 M at pH 7. A total decolorization efficiency is achieved after 180 min in the presence of MO/TiO2. The biosynthesized Moringa oleifera leaf extracted TiO2 (MO/TiO2) was used for photocatalytic and biomedical applications. MO/TiO2 exhibited the best photocatalytic activity and showed maximum inhibitoin in invitro antidiabetic activity. Invivo antidiabetic activity showed the Moringa oleifera leaf-extracted TiO2 catalyst significantly reduced blood glucose levels. [ABSTRACT FROM AUTHOR]

Multisystem inflammatory syndrome is a severe complication of SARS-CoV-2 infection in children (MIS-C). To date, data on long-term sequelae mainly concern cardiac outcomes. All ≤ 18 year olds consecutively admitted to the Buzzi Children's Hospital with a diagnosis of MIS-C between October 1, 2020, and May 31, 2022, were followed up for up to 12 months by a dedicated multidisciplinary team. They underwent laboratory tests, multi-organ clinical and instrumental assessments, and psychosocial evaluation. 56/62 patients, 40 M, mean age 8.7 years (95% CI 7.7, 9.7), completed the follow-up. Cardiological, gastroenterological, pneumological, and neurological evaluations, including IQ and EEG, were normal. Alterations of HOMA-IR index and/or TyG index, observed in almost all patients during hospitalisation, persisted in about a third of the population at 12 months. At 6 and 12 months respectively, impairment of adaptive functions was observed in 38/56 patients (67.9%) and 25/56 (44.6%), emotional and behavioural problems in 10/56 (17.9%) and 9/56 (16.1%), and decline in QoL in 14/56 (25.0%) and 9/56 (16.1%). Psychosocial well-being impairment was significantly more frequent in the subgroup with persistent glycometabolic dysfunction at 12 months (75% vs. 40.9% p < 0.001). Conlusion: The mechanisms that might explain the long-term persistence of both metabolic alterations and neuro-behavioural outcomes and their possible relationship are far from being clarified. Our study points out to the potential long-term effects of pandemics and to the importance of a multidisciplinary follow-up to detect potential negative sequelae in different areas of health, both physical and psychosocial. What is known: • Multisystem inflammatory syndrome in children (MIS-C) is a severe complication of SARS-CoV-2 infection. • Few data exist on the medium- and long-term outcomes of MIS-C, mostly focused on cardiac involvement. Emerging evidence shows neurological and psychological sequelae at mid- and long-term follow-up. What is new: • This study reveals that MIS-C may lead to long-term glycometabolic dysfunctions joined to impairment in the realm of general well-being and decline in quality of life, in a subgroup of children. • This study highlights the importance of a long-term multidisciplinary follow-up of children hospitalised with MIS-C, in order to detect the potential long-term sequelae in different areas of health, both physical and psychosocial well-being. [ABSTRACT FROM AUTHOR]

Clinical manifestations of congenital syphilis (CS) include liver disease with/without impaired liver function, identified as syphilitic hepatitis. Hepatic involvement may be dramatic; therefore, early diagnosis is crucial to provide treatment and prevent fatal outcomes. A new resurgence of CS cases has been described in recent years worldwide. We reported our experience with a case series of infants hospitalized for liver disease with a final diagnosis of CS, highlighting the wide spectrum of liver involvement, the rapid progression in cases with late diagnosis, and the pitfalls of the management of this forgotten but reemerging disease. A retrospective analysis of CS patients with hepatic presentation in the period 2008–2023 was conducted. We collected five cases (three female) with a median age of 13.8 days (range 1–84 days). In three cases, mothers were not screened for syphilis during pregnancy, and in two cases, they were seronegative in the first trimester screening. None practiced specific therapy during pregnancy. Hepatic involvement was characterized by hepatosplenomegaly, in four cases associated with cholestatic jaundice and in three cases with liver failure. Rapid plasma reagin (RPR) and Treponema pallidum hemagglutination assay (TPHA) were positive in all cases in mothers and infants. CS presented with multiorgan involvement and was fatal in one case. Conclusions: It is important to consider CS in infants with cholestasis and acute liver failure, but also in sick infants with isolated hepatomegaly. Early recognition of infants with CS is critical to identify missed cases during pregnancy and to start early treatment. What is known: • In recent years, it has been seen an increase of congenital syphilis cases in both low- and middle-income countries. • In most cases, infants born to mothers untreated for syphilis appear normal without signs of infection at birth but may develop manifestations of the disease after months or years if left untreated. • What is new: • Congenital syphilis is an emerging problem that may result in multiorgan involvement with liver disease predominant at onset. • It is important to consider congenital syphilis in infants with cholestasis and liver failure, but also in sick infants with isolated hepatomegaly. [ABSTRACT FROM AUTHOR]

Background: While monoclonal antibodies (mAbs) targeting the CGRP pathway have revolutionized migraine management due to their improved tolerance and adherence, concerns remain about their potential impact on blood pressure (BP), especially in older patients, due to CGRP-mediated vasodilation blockade. Given the growing use of these therapies in older populations, assessing their cardiovascular (CV) safety is of paramount importance. Methods: This multicentric observational prospective study focused on migraine sufferers aged ≥ 60 who began erenumab, galcanezumab, or fremanezumab for prevention. Baseline, three-month, and twelve-month BP measurements were collected. Changes in antihypertensive medication and "Newly or Worsened Hypertensive" patients (NWHP) were assessed. Results: Among 155 patients receiving anti-CGRP mAbs (40 Erenumab, 47 Galcanezumab, 68 Fremanezumab), 42.5% had hypertension history and 39% were on antihypertensive treatment. No significant systolic or diastolic BP changes occurred at any time point compared to baseline (all p > 0.05), with no differences between the three groups. After one year, 20/155 (12.9%) patients were considered NWHP; 11/20 had prior hypertension, and 5/11 adjusted antihypertensive therapy. Among 9/20 newly hypertensive patients, 5/9 had a single measurement above the normal threshold with no requirement for new pharmacological therapy. A higher baseline BP value was associated with increased BP (p = 0.002). Conclusions: The study concludes that treatment with anti-CGRP mAbs over one year does not significantly affect BP in patients aged ≥ 60, nor does it increase the incidence of hypertension compared to general population trends. Nonetheless, continuous monitoring and further long-term studies are necessary to fullya scertain the cardiovascular safety of these medications in the elderly. [ABSTRACT FROM AUTHOR]

Purpose: Amniotic fluid stem cell extracellular vesicles (AFSC-EVs) hold regenerative potential to treat hypoplastic lungs secondary to congenital diaphragmatic hernia (CDH). This study aims to investigate sex-specific differences in pulmonary hypoplasia severity and responses to AFSC-EV administration in an experimental CDH mouse model. Methods: C57BL/6J dams were fed with nitrofen + bisdiamine (left-sided CDH) or olive oil only (control) at embryonic day (E) 8.5. Lungs were dissected (E18.5), grown ex vivo and treated with medium ± AFSC-EVs that were collected via ultracentrifugation and characterized (nanoparticle tracking analysis, electron microscopy, Western blotting). Pulmonary hypoplasia was assessed via mean linear intercept (MLI). Gene and protein expression changes (Cd31, Enos, Il1b, TNFa) were measured via RT-qPCR and immunofluorescence. Pups were genotyped for Sry. Results: Experimental CDH showed a male predominance without sex differences for pulmonary hypoplasia severity, fetal lung vascularization, and inflammation. AFSC-EV administration led to improved lung growth (decreased MLI), improved fetal lung vascularization (increased Cd31 and Enos), and decreased fetal lung inflammation (Il1b, TNFa). There was no sex-specific response to AFSC-EV administration. Conclusion: This study shows sex-independent impaired lung growth, vascularization and fetal lung inflammation in a CDH mouse model. Antenatal administration of AFSC-EVs reverses aspects of pulmonary hypoplasia secondary to CDH independent of the biological sex. [ABSTRACT FROM AUTHOR]

A fundamental understanding of the active sites in working catalysts can guide the rational design of new catalysts with improved performances. In this work, we have followed the evolution of homogeneous and heterogeneous Pd catalysts under the reaction conditions for aerobic oxidative coupling of toluene for the production of 4,4′-bitolyl. We have found that subnanometer Pd clusters made with a few Pd atoms are the working active sites in both homogeneous and heterogeneous catalytic systems. Moreover, water can promote the activity of Pd clusters by nearly one-order magnitude for oxidative coupling reaction by facilitating the activation of O2. These new insights lead to the preparation of a catalyst made with Pd clusters supported on a two-dimensional zeolite, which expands the scope of the oxidative coupling of aromatics to larger substrates. A fundamental understanding of the active sites in working catalysts can guide the rational design of new catalysts with improved performances. Here, regioselective oxidative coupling of toluene to 4,4'-bitolyl is achieved with zeolite-encapsulated Pd catalysts under acid-free conditions, and the active sites are identified to be the subnanometer Pd clusters confined in the channels of Beta zeolite. [ABSTRACT FROM AUTHOR]

In the post-pandemic world, open educational resources (OER) have the potential to ensure educational equity by providing all students with access to learning materials and by supporting teachers' instructional practices through readily available, adaptable resources. However, the quality of OER continues to be a concern. Therefore, this study explored the use of (1) GeoGebra and scaffolding strategies to develop OER for secondary school mathematics teaching and (2) formative evaluation techniques to enhance the quality of the OER. A GeoGebra expert and a total of 40 frontline teachers participated in three review cycles of the OER development in the project. The feedback from each cycle informed the application of scaffolding strategies in the development of OER for the subsequent cycles. In Cycles 2 and 3, teachers rated the OER and provided feedback through surveys for further improvement. The results indicated that teacher ratings were significantly higher in Cycle 3 (n = 40, Mdn = 5) than in the previous cycle (n = 21, Mdn = 4) regarding the appropriateness of the OER for students with different learning preferences, z = − 2.87, p < 0.05. The results of the project-end satisfaction survey further revealed that all of the teacher participants were satisfied with the OER, which also enhanced their teaching practices. The results of the study offer a theoretical foundation that OER developers can ground upon to enhance their OER design. They also provide practical insights into the application of formative evaluation in the OER development that OER developers can adopt to create resources that are finely attuned to the needs of frontline teachers. [ABSTRACT FROM AUTHOR]

Fine-grained visual classification (FGVC) necessitates expert knowledge,which is expensive and requires a large training sample size. Consequently, using sample data acquired through the web has emerged as a novel approach for augmenting training samples. However, the web data often includes noisy samples, leading to misclassification of deep learning models. This paper presents a a meta-learning-base method called Data Reweighting Net (DR-Net). It enables the use of small, clean meta set as a guiding mechanism to accurately learn web image datasets that contain noise. More specifically, the DR-Net fully learns from small, clean meta set to discard noisy samples and obtain clean web samples through low similarity properties. DR-Net enables classification networks to adaptively learn training sets through sample weighting, mitigating the impact of noisy labels on classification learning. Our experiments on Web-bird, Web-aircraft, Web-car, CIFAR-10, and CIFAR-100 datasets demonstrate the feasibility of our proposed method. [ABSTRACT FROM AUTHOR]

This large community-based cohort study investigates the impact of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), specifically Liraglutide and Semaglutide, on the risk of developing psychiatric conditions such as depression, anxiety, and suicidal behaviors in patients with obesity. Utilizing post-marketing data, this research compares patients prescribed GLP-1 RAs (cases) with those not taking these medications (controls). The analysis spanned data from January 1, 2015, to December 31, 2023. To minimize selection bias, we employed 1:1 propensity score matching to account for demographic factors such as age, sex, race, and comorbidities. After matching, the study included 162,253 case and control patients. This study showed a significant association between GLP-1 RA treatment and an 98% increased risk of any psychiatric disorders. Notably, patients on GLP-1 RAs exhibited a 195% higher risk of major depression, a 108% increased risk for anxiety, and a 106% elevated risk for suicidal behavior. These findings underscore the critical need for physicians to thoroughly assess patient history before prescribing GLP-1 RAs and highlight the urgent requirement for further prospective clinical trials to fully understand the implications of GLP-1 RA use on mental health in the obese patient population. [ABSTRACT FROM AUTHOR]

cFLIP, a master anti-apoptotic regulator, targets the FADD-induced DED complexes of procaspase-8 in death receptor and ripoptosome signaling pathways. Several tumor cells maintain relatively high levels of cFLIP in achieving their immortality. However, understanding the three-dimensional regulatory mechanism initiated or mediated by elevated levels of cFLIP has been limited by the absence of the atomic coordinates for cFLIP-induced DED complexes. Here we report the crystal plus cryo-EM structures to uncover an unconventional mechanism where cFLIP and procaspase-8 autonomously form a binary tandem DED complex, independent of FADD. This complex gains the ability to recruit FADD, thereby allosterically modulating cFLIP assembly and partially activating caspase-8 for RIPK1 cleavage. Our structure-guided mutagenesis experiments provide critical insights into these regulatory mechanisms, elucidating the resistance to apoptosis and necroptosis in achieving immortality. Finally, this research offers a unified model for the intricate bidirectional hierarchy-based processes using multiprotein helical assembly to govern cell fate decisions. FADD binds Casp-8 and then cFLIP to form the FADD-Casp8-cFLIP complex. The authors found that the DED complex could assemble in reverse order, where cFLIP oligomerizes to bind Casp-8. The resultant complex could bind FADD, generating the cFLIP-Casp-8-FADD complex by a different mechanism. [ABSTRACT FROM AUTHOR]

The canonical G406R mutation that increases Ca2+ influx through the CACNA1C-encoded CaV1.2 Ca2+ channel underlies the multisystem disorder Timothy syndrome (TS), characterized by life-threatening arrhythmias. Severe episodic hypoglycemia is among the poorly characterized non-cardiac TS pathologies. While hypothesized from increased Ca2+ influx in pancreatic beta cells and consequent hyperinsulinism, this hypoglycemia mechanism is undemonstrated because of limited clinical data and lack of animal models. We generated a CaV1.2 G406R knockin mouse model that recapitulates key TS features, including hypoglycemia. Unexpectedly, these mice do not show hyperactive beta cells or hyperinsulinism in the setting of normal intrinsic beta cell function, suggesting dysregulated glucose homeostasis. Patient data confirm the absence of hyperinsulinism. We discover multiple alternative contributors, including perturbed counterregulatory hormone responses with defects in glucagon secretion and abnormal hypothalamic control of glucose homeostasis. These data provide new insights into contributions of CaV1.2 channels and reveal integrated consequences of the mutant channels driving life-threatening events in TS. Gain of function mutant CaV1.2 channels drive life-threatening hypoglycemia in the multisystem disorder Timothy syndrome, but the underlying mechanisms are unknown. Here the authors show the mutant channels have adverse effects on counterregulatory hormones and CNS control of glucose homeostasis. [ABSTRACT FROM AUTHOR]

Introduction and Hypothesis: To assess the outcomes of mid-urethral sling (MUS) procedures for urodynamic stress incontinence (USI) following extensive pelvic reconstructive surgery (PRS) and identify risk factors for persistent USI (P-USI). Methods: This retrospective study analyzed 84 women who underwent a staged approach to MUS for USI after PRS for advanced pelvic organ prolapse (Pelvic Organ Prolapse Quantification III and IV). The primary outcome was objective cure rate, defined by negative urine leakage on urodynamic study and a 1-h pad test weight of < 2 g. Subjective cure rate was through a negative response to question 3 of UDI-6. Results: The overall objective cure rate was 81.0%. The highest cure rate was observed in de novo USI (MUS-D; 89.7%) compared with women with persistent USD (MUS-P). Patients with overt SUI exhibited lower cure rates than those with occult SUI. Predictive factors for persistent USI were lower pre-operative maximum urethral closure pressure (MUCP; p = 0.031) and higher BMI in the MUS-P group than in the MUS-D group (p = 0.008). Subjective improvement was noted, especially in the MUS-D group, with a subjective cure rate of 78.6%. Those with MUS-D reported a higher impact on patient well-being post-surgery. No complications were observed after MUS surgery at follow-up. Conclusions: Overt USI, low MUCP and high BMI are independent predictors of persistent USI after a staged MUS approach after pelvic reconstructive surgery. [ABSTRACT FROM AUTHOR]

Emerging research suggests that first-generation queer and trans (QT) students experience disproportionate discrimination in schooling leading to disengagement early on in their educational trajectories. Although labeled as "at risk", first-generation QT students are actually more cognitively engaged in academics than their cisgender and heterosexual peers. Administrators, teachers, counselors, and guardians (validating agents) have an ethical responsibility to foster inclusive schooling contexts for first-generation QT students. This study examines how validating agents impact first-generation QT students' school engagement, high school GPA, and postsecondary enrollment. We posit a queer theorizing of the ecological validation model of student success and through principles of QuantCrit, we examine the High School Longitudinal Study of 2009 through a path analysis. Our results reveal that both talking to parents about college and high school GPA had a positive association with college enrollment for first-generation QT students. We provide recommendations for future research and practice that demand further exploration of first-generation QT students. [ABSTRACT FROM AUTHOR]

Haemolytic Uraemic Syndrome (HUS) is a rare medical condition characterised by microangiopathic haemolytic anaemia, thrombocytopenia, and acute kidney injury. Neurological complications are documented but rarely involve the cerebellum. We present a unique case of a 23-month-old male with HUS triggered by Escherichia coli-O157 (E.coli-O157) infection leading to an isolated cerebellar stroke. The patient initially presented with fever, bloody stools, and seizures. Confirmation of E.coli-O157 infection was obtained, and MRI revealed an isolated cerebellar stroke. Treatment included supportive care, anticoagulation for a right atrial thrombus, with gradual improvement observed. This case highlights the unusual occurrence of isolated cerebellar stroke in HUS patients, emphasising the importance of promptly recognizing manifestations of the central nervous system and the necessity for a multidisciplinary approach. Finally, a comprehensive literature review was conducted to identify cases of HUS patients with cerebellar involvement. [ABSTRACT FROM AUTHOR]

Aim: To analyze the prevalence of anxiety and depression in a large cohort of adults with autoimmune diabetes, identifying sex-driven associated factors. Materials and methods: In this cross-sectional study, we enrolled 553 consecutive adults with Type 1 diabetes mellitus or latent autoimmune diabetes in adults who came to the Division of Endocrinology of the S.Orsola-Malpighi Polyclinic, Bologna (Italy), to receive their second dose of SARS-CoV-2 vaccine. We administered the questionnaires: Hospital Anxiety and Depression Scale, Diabetes Distress Scale, Diabetes-related Quality of Life, Diabetes Treatment Satisfaction Questionnaire. We collected clinical and biochemical data and 14 days glucose metrics in patients with sensor use > 70% in a time span of ± 4 months from the questionnaires' administration. We excluded 119 patients from our analyses with missing data (final cohort n = 434: 79% of those enrolled). Results: Anxiety and depression prevalence was respectively 30.4% and 10.8%. According to the multivariate analysis, higher diabete-related emotional burden, lower treatment satisfaction, but not physician-related distress, were risk factors for anxiety and depression; female sex was associated with anxiety (OR 0.51, 95% 0.31–0.81; p = 0.005); in women, depression was associated with increasing age (males vs. females OR 0.96 per 1 year increase, 95% CI 0.92–1.00; p = 0.036), whilst in men with HbA1c (OR 1.08 per 1 mmol/mol increase, 95% CI 1.03–1.13; p = 0.002). Conclusion: Nearly 1/3 of patients with autoimmune diabetes suffers from anxiety and 1/10 from depression. These conditions are associated with independent modifiable and non-modifiable characteristics. For depression, these characteristics differ between males and females. [ABSTRACT FROM AUTHOR]

Background: Older inpatients with dementia are at an increased risk of an adverse drug reaction (ADR) during hospitalization. Objective: To quantify the prevalence of ADRs in older inpatients according to dementia status and ADR definition approach and to identify risk factors of ADRs during hospitalization. Methods: This was a retrospective cohort study of 2000 inpatients aged ≥ 75 years admitted consecutively to six Sydney hospitals (1 July 2016 to 31 May 2017). Dementia was defined by diagnosis in electronic medical records. ADRs were defined according to two approaches: the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification (ICD-10-AM) and classification by a research pharmacist (subset cohort, n = 600). A binary logistic regression was conducted to determine risk factors of ADRs. Results: Among 2000 patients, 25.9% (n = 517) were reported to have dementia. ADRs defined by ICD-10-AM were identified in 8.3% (n = 43) and 14.6% (n = 217) of inpatients with and without dementia respectively (p < 0.001). A total of 13.0% (n = 260) and 12.5% (n = 75) of patients had ADRs defined by ICD-10-AM and a research pharmacist, respectively. Key risk factors of ADRs were longer hospital stay [odds ratio (OR) 1.01, 95% confidence interval (CI) 1.01, 1.02) and a greater number of regular potentially inappropriate medicines (PIMs) on admission (OR 1.17, 95% CI 1.00, 1.38). Conclusions: ADRs were more prevalent among inpatients without dementia and when assessed by a research pharmacist. Our findings underline the need for improved ADR detection in older inpatients. [ABSTRACT FROM AUTHOR]

Purpose: Evaluate the agreement between bone age assessments conducted by two distinct machine learning system and standard Greulich and Pyle method. Materials and methods: Carpal radiographs of 225 patients (mean age 8 years and 10 months, SD = 3 years and 1 month) were retrospectively analysed at two separate institutions (October 2018 and May 2022) by both expert radiologists and radiologists in training as well as by two distinct AI software programmes, 16-bit AItm and BoneXpert® in a blinded manner. Results: The bone age range estimated by the 16-bit AItm system in our sample varied between 1 year and 1 month and 15 years and 8 months (mean bone age 9 years and 5 months SD = 3 years and 3 months). BoneXpert® estimated bone age ranged between 8 months and 15 years and 7 months (mean bone age 8 years and 11 months SD = 3 years and 3 months). The average bone age estimated by the Greulich and Pyle method was between 11 months and 14 years, 9 months (mean bone age 8 years and 4 months SD = 3 years and 3 months). Radiologists' assessments using the Greulich and Pyle method were significantly correlated (Pearson's r > 0.80, p < 0.001). There was no statistical difference between BoneXpert® and 16-bit AItm (mean difference = − 0.19, 95%CI = (− 0.45; 0.08)), and the agreement between two measurements varies between − 3.45 (95%CI = (− 3.95; − 3.03) and 3.07 (95%CI − 3.03; 3.57). Conclusions: Both AI methods and GP provide correlated results, although the measurements made by AI were closer to each other compared to the GP method. [ABSTRACT FROM AUTHOR]

Coronary artery disease (CAD), particularly three-vessel coronary disease (3VD), is the main cause of death in industrialized countries. Chronic kidney disease is an independent risk factor for CAD. The CHA2DS2-VASc score shows a good ability to predict CV events in high-risk population independently from atrial fibrillation. The aim of the present study was to evaluate the association between the R2CHA2DS2-VASc score and 3VD in a population of patients at high cardiovascular risk. Monocentric prospective study evaluated 1017 patients undergoing coronary angiography. The R2CHA2DS2-VASc score was obtained by adding 2 points to the CHA2DS2-VASc score in case of eGFR < 60 ml/min/1.73m2. Coronary lesions causing ≥ 50% reduction of a major epicardial vessel diameter were considered significant. Patients were grouped based on R2CHA2DS2-VASc tertiles and according to the severity of CAD: 3VD vs No-3VD. The 3VD group showed significantly higher R2CHA2DS2-VASc score than the No-3VD group (4.20 ± 2.18 vs 3.36 ± 2.06, p < 0.001). The risk of 3VD increased by 21% for every 1-point increase in the score (OR 1.21; 95% CI 1.13–1.28, p < 0.001). The prevalence of 3VD was higher among patients belonging to higher tertiles of R2CHA2DS2-VASc (17.2% vs 26.7% vs 33.6% for first, second, and third tertile respectively, p < 0.001) with a risk more than doubled for the third tertile compared to the first one (OR 2.45; 95% CI 1.71–3.49, p < 0.001). The R2CHA2DS2-VASc score is independently associated with 3VD in patients at high cardiovascular risk. The score could be considered a useful tool for clinicians to identify patients who are at high risk of 3VD. [ABSTRACT FROM AUTHOR]

Spacecraft trajectories near the south pole of Enceladus violate the Brillouin sphere associated with the convergence radius of spherical harmonics models. In this study, a shifted coordinate frame is demonstrated to ensure a convergent model is available in regions of operational interest. Hypothetical experiments are performed around a simulated celestial body where the truth exterior gravity fields are known exactly. The divergence of the harmonics below the Brillouin sphere of the unshifted models is confirmed, while the shifted harmonics model converges. The method is next applied to the Cassini-derived gravity field for Enceladus, including uncertainties. Using these low-degree and low-order reference models, expected for use in an operational setting, the results show that the shifted and body-centered harmonics models agree to near machine precision for all evaluations at or above the surface, and no divergence is noticed. The results imply that mission designers and navigation engineers can safely use a traditional spherical harmonics field for Enceladus, even in regions that dip below the Brillouin sphere. For low-flying missions to celestial bodies besides Enceladus, the experiments conducted in this study can be repeated. The need for an alternative to the traditional spherical harmonics, such as the presented shifted model, increases for bodies that are increasingly non-spherical and orbits that are deeper inside the Brillouin sphere. [ABSTRACT FROM AUTHOR]

Background: Surgical treatments of refractory gastroparesis include pyloromyotomy and gastric electrical stimulator (GES). It is unclear if patients may benefit from a combined approach with concomitant GES and pyloromyotomy. Methods: Retrospective cohort analysis of all patients with refractory gastroparesis treated with GES implantation with and without concomitant pyloromyotomy at Cleveland Clinic Florida from January 2003 to January 2023. Primary endpoint was efficacy (clinical response duration and success rate) and secondary endpoints included safety (postoperative morbidity) and length of stay. Success rate was defined as the absence of one of the following reinterventions during follow-up: Roux-en-Y gastric bypass (RYGB), pyloromyotomy, GES removal. Results: During a period of 20 years, 134 patients were treated with GES implantation. Three patients with history of previous surgical pyloromyotomy or RYGB were excluded from the analysis. Median follow-up was 31 months (IQR 10, 72). Forty patients (30.5%) had GES with pyloromyotomy, whereas 91 (69.5%) did not have pyloromyotomy. Most of the patients had idiopathic (n = 68, 51.9%) or diabetic (n = 58, 43.3%) gastroparesis. Except for preoperative use of opioids (47.5 vs 14.3%; p < 0.001), patient's characteristics were similar in both groups. There were no significant differences between the two groups in terms of overall postoperative complications (17.5% vs 14.3%; p = 0.610), major postoperative complications (0% vs 2.2%; p = 1), and length of stay (2(IQR 1, 2) vs 2(IQR 1, 3) days; p = 0.068). At 5 years, success rate was higher in patients with than without pyloromyotomy however not statistically significant (82% versus 62%, p = 0.066). Especially patients with diabetic gastroparesis seemed to benefit from pyloromyotomy during GES (100% versus 67%, p = 0.053). In an adjusted Cox regression, GES implantation without pyloromyotomy was associated with a 2.66 times higher risk of treatment failure compared to GES implantation with pyloromyotomy (HR 2.66, 95% CI 1.03–6.94, p = 0.044). Conclusion: Pyloromyotomy during GES implantation for gastroparesis seems to be associated with a longer clinical response with similar postoperative morbidity and length of hospital stay than GES without pyloromyotomy. Patient with diabetic gastroparesis might benefit from a combination of GES implantation and pyloromyotomy. [ABSTRACT FROM AUTHOR]

'Active' and 'non-active' secondary progressive MS (SPMS) have distinct pathophysiological mechanisms and clinical characteristics, but there is still no consensus regarding the frequency of these MS forms in the real-world setting. We aimed to evaluate the frequency of 'active' and 'non-active' SPMS in a large cohort of Italian MS patients and the differences in terms of clinical and MRI characteristics and disease progression. This multicenter study collected data about MS patients who have transitioned to the SP form in the period between 1st January 2014 and 31st December 2019 and followed by the MS centers contributing to the Italian MS Registry. Patients were divided into 'active SPMS' and 'non-active SPMS', based on both reported MRI data and relapse activity in the year before conversion to SPMS. Out of 68,621, 8,316 (12.1%) patients were diagnosed with SPMS. Out of them, 872 (10.5%) were classified into patients with either 'active' or 'non-active' SPMS. A total of 237 were classified into patients with 'active SPMS' (27.2%) and 635 as 'non-active SPMS' (72.8%). 'Non-active SPMS' patients were older, with a longer disease duration compared to those with 'active SPMS'. The percentages of patients showing progression independent of relapse activity (PIRA) at 24 months were similar between 'active' and 'non-active' SPMS patients (67 [27.4%] vs 188 [29.6%]; p = 0.60). In the 'active' group, 36 (15.2%) patients showed relapse-associated worsening (RAW). Comparison of the survival curves to EDSS 6 and 7 according to disease activity did not show significant differences (p = 0.68 and p = 0.71). 'Active' and 'non-active' SPMS patients had a similar risk of achieving disability milestones, suggesting that progression is primarily attributed to PIRA and only to a small extent to disease activity. [ABSTRACT FROM AUTHOR]

Objective: Nordalbergin is a coumarin extracted from Dalbergia sissoo DC. To date, the biological effects of nordalbergin have not been well investigated. To investigate the anti-inflammatory responses and the anti-oxidant abilities of nordalbergin using lipopolysaccharide (LPS)-activated macrophages and LPS-induced sepsis mouse model. Materials and methods: Production of nitrite oxide (NO), prostaglandin E2 (PGE2), pro-inflammatory cytokines (tumor necrosis factor (TNF)-α, interleukin (IL)-6 and IL-1β), reactive oxygen species (ROS), tissue damage and serum inflammatory markers, and the activation of the NLRP3 inflammasome were examined. Results: Our results indicated that nordalbergin reduced the production of NO and pro-inflammatory cytokines in vitro and ex vivo. Nordalbergin also suppressed iNOS and cyclooxygenase-2 expressions, decreased NF-κB activity, and attenuated MAPKs signaling pathway activation by decreasing JNK and p38 phosphorylation by LPS-activated J774A.1 macrophages. Notably, nordalbergin diminished NLRP3 inflammasome activation via repressing the maturation of IL-1β and caspase-1 and suppressing ROS production by LPS/ATP- and LPS/nigericin-activated J774A.1 macrophages. Furthermore, nordalbergin exhibited protective effects against the infiltration of inflammatory cells and also inhibited the levels of organ damage markers (AST, ALT, BUN) by LPS-challenged mice. Conclusion: Nordalbergin possesses anti-inflammatory effects in macrophage-mediated innate immune responses, alleviates ROS production, decreases NLRP3 activation, and exhibits protective effects against LPS-induced tissue damage in mice. [ABSTRACT FROM AUTHOR]