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Background: Worldwide, cardiovascular diseases are the primary cause of death, with hypertension as a key contributor. In 2019, cardiovascular diseases led to 17.9 million deaths, predicted to reach 23 million by 2030., Objective: This study presents a new method to predict hypertension using demographic data, using 6 machine learning models for enhanced reliability and applicability. The goal is to harness artificial intelligence for early and accurate hypertension diagnosis across diverse populations., Methods: Data from 2 national cohort studies, National Health Insurance Service-National Sample Cohort (South Korea, n=244,814), conducted between 2002 and 2013 were used to train and test machine learning models designed to anticipate incident hypertension within 5 years of a health checkup involving those aged ≥20 years, and Japanese Medical Data Center cohort (Japan, n=1,296,649) were used for extra validation. An ensemble from 6 diverse machine learning models was used to identify the 5 most salient features contributing to hypertension by presenting a feature importance analysis to confirm the contribution of each future., Results: The Adaptive Boosting and logistic regression ensemble showed superior balanced accuracy (0.812, sensitivity 0.806, specificity 0.818, and area under the receiver operating characteristic curve 0.901). The 5 key hypertension indicators were age, diastolic blood pressure, BMI, systolic blood pressure, and fasting blood glucose. The Japanese Medical Data Center cohort dataset (extra validation set) corroborated these findings (balanced accuracy 0.741 and area under the receiver operating characteristic curve 0.824). The ensemble model was integrated into a public web portal for predicting hypertension onset based on health checkup data., Conclusions: Comparative evaluation of our machine learning models against classical statistical models across 2 distinct studies emphasized the former's enhanced stability, generalizability, and reproducibility in predicting hypertension onset., (©Seung Ha Hwang, Hayeon Lee, Jun Hyuk Lee, Myeongcheol Lee, Ai Koyanagi, Lee Smith, Sang Youl Rhee, Dong Keon Yon, Jinseok Lee. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 05.11.2024.)

An 8-year-old spayed female Maltese dog was referred with a 4-month history of multifocal pruritic erosive or ulcerative lesions on the head, ventral neck, chest, and abdomen; and chronic otitis externa. Biopsy revealed cytotoxic dermatitis and apoptotic keratinocytes with occasional lymphocytic satellitosis. Bacterial culture and antimicrobial susceptibility tests revealed multidrug-resistant Pseudomonas aeruginosa infection of the skin and ears. The skin lesions regressed after treatment of P. aeruginosa infection with ciprofloxacin. Based on the skin lesions, histological characteristics, and response to therapy, the dog was presumed to have erythema multiforme induced by P. aeruginosa infection. This case report emphasizes that P. aeruginosa infection could be a trigger of erythema multiforme in dogs. Key clinical message: Erythema multiforme caused by infection is rare and poorly characterized in the veterinary literature. This case report describes the clinical characteristics of, diagnostic approach to, and treatment of erythema multiforme caused by Pseudomonas aeruginosa ., (Copyright and/or publishing rights held by the Canadian Veterinary Medical Association.)

Background: Current treatment paradigms recommend surgical intervention when conventional medical management proves ineffective in resolving chronic rhinosinusitis with nasal polyposis., Objectives: To assess and compare the efficacy of dupilumab and functional endoscopic sinus surgery (FESS) for the treatment of chronic rhinosinusitis with nasal polyp (CRSwNP) over time., Methods: Studies comparing CRSwNP patients who received dupilumab with those who underwent FESS were included. Outcome measures included the nasal congestion score (NCS), Sino-nasal Outcome Test-22 (SNOT-22), University of Pennsylvania Smell Identification Test-40 (UPSIT-40), and nasal polyp score (NPS). The risk of bias was evaluated using the Newcastle-Ottawa Scale., Results: A total of 4 studies with 724 participants were included. The dupilumab group had a superior NCS, but an inferior NPS, compared to the FESS group during the follow-up period. The SNOT-22 score of the dupilumab group was inferior to that of the FESS group until 6 months posttreatment, but the scores were similar at around 1 year. A similar trend was observed for the UPSIT-40 score, but the score of the dupilumab group was higher at around 1 year., Conclusion: Functional endoscopic sinus surgery was more effective than dupilumab for several months after treatment. However, at 1 year after treatment, the effects of the 2 treatments became similar, with greater olfactory improvement seen in the dupilumab group., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aimed to compare the clinical and radiological outcomes of medial patellofemoral ligament (MPFL) reconstruction (MPFLR) between anatomic femoral tunnel positions: proximal (near adductor tubercle [AT]) and distal (near medial epicondyle [ME])., Hypothesis: MPFLR with the proximal femoral tunnel position has worse clinical and radiological outcomes than those with the distal femoral tunnel position., Patients and Methods: Fifty-five patients who underwent isolated MPFLR with proximal or distal femoral tunnels with at least 2 years of follow-up were retrospectively analyzed. Based on postoperative CT images, 28 patients were classified as group AT and the remaining 27 patients were classified as group ME. The International Knee Documentation Committee, Lysholm, Tegner, Kujala scores, and complications were evaluated. Radiologically, the Caton-Deschamps Index (CDI), patellar tilt angle, patellofemoral osteoarthritis (PFOA), patellofemoral cartilage status by the International Cartilage Repair Society (ICRS) grade, bone contusion, and MPFL graft signal intensity were evaluated., Results: All clinical scores significantly improved in both groups (p<0.01). No statistically significant difference was noted between the two groups in regards to their preoperative demographic data, postoperative clinical scores, complications, or radiological findings (CDI, patellar tilt angle, PFOA, bone contusion, and graft signal intensity). The group AT had worse cartilage status on the medial facet of the patella (p=0.02). The ICRS grade for the medial facet of the patella statistically progressed in group AT compared to group ME (p=0.04) as well., Discussion: Both groups showed significantly improved clinical outcomes. However, for the medial facet of the patella, MPFLR with the proximal femoral tunnel position had worse cartilage status and ICRS grade progression than those with the distal femoral tunnel position., Level of Evidence: III; retrospective comparative study., (Copyright © 2024 Elsevier Masson SAS. All rights reserved.)

Topologically protected magnetic skyrmions in magnetic materials are stabilized by an interfacial or bulk Dzyaloshinskii-Moriya interaction (DMI). Interfacial DMI decays with an increase of the magnetic layer thickness in just a few nanometers, and bulk DMI typically stabilizes magnetic skyrmions at low temperatures. Consequently, more flexibility in the manipulation of DMI is required for utilizing nanoscale skyrmions in energy-efficient memory and logic devices at room temperature (RT). Here, we demonstrate the observation of RT skyrmions stabilized by gradient DMI (g-DMI) in composition gradient-engineered CoPt single-layer films by employing the topological Hall effect, magnetic force microscopy, and nitrogen-vacancy scanning magnetometry. Skyrmions remain stable over a wide range of applied magnetic fields and are confirmed to be nearly Bloch-type from micromagnetic simulation and analytical magnetization reconstruction. Furthermore, we observe skyrmion pairs, which may be explained by skyrmion-antiskyrmion interactions. Our findings expand the family of magnetic materials hosting RT magnetic skyrmions by tuning g-DMI via gradient polarity and a choice of magnetic elements.

Objective: To evaluate the clinical efficacy of vidian neurectomy (VN) or posterior nasal neurectomy (PNN) combined with endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis with nasal polyps (CRSwNP)., Data Sources: A systematic search of six databases (PubMed, SCOPUS, Embase, Web of Science, Google Scholar, and Cochrane) was conducted to identify relevant studies up to May 2024., Review Methods: The effects of combining VN or PNN with ESS were evaluated in comparison to ESS alone. Outcomes were assessed by evaluating changes in Lund-Kennedy score, patient-reported symptom scores (VAS), quality of life, as well as adverse effects and recurrence rate of CRSwNP., Results: A total of 6 studies, comprising 407 patients, were included in the analysis. The neurectomy group showed significant improvements in Lund-Kennedy score (SMD = 0.7276 [0.5695; 0.8857]), with statistically significant improvements maintained at 6, 12, and 24 months postoperatively. The treatment group maintained better improvements in sinusitis-related quality of life (SMD = 0.4540 [0.1784; 0.7297]) and VAS (SMD = 0.7096 [0.4356; 0.9837]) until 12 months postoperatively, but not at 24 months. Regarding adverse effects, additional neurectomy did not significantly induce epistaxis (odds ratio [OR] = 0.9806 [0.2348; 4.0960]) or dry eye (OR = 2.4194 [0.1114; 52.5255]) compared to the control group. On the other hand, there was no difference in the recurrence rate of CRSwNP between the 2 groups during the follow-up periods., Conclusion: Additional neurectomy shows better efficacy in improving endoscopic findings and symptoms in patients with CRSwNP and appears to be a safe and effective treatment., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Animals can discriminate diverse sensory values with a limited number of neurons, raising questions about how the brain utilizes neural resources to efficiently process multi-dimensional inputs for decision-making. Here, we demonstrate that this efficiency is achieved by reducing sensory dimensions and converging towards the value dimension essential for goal-directed behavior in the putamen. Humans and monkeys performed tactile and visual value discrimination tasks while their neural responses were examined. Value information, whether originating from tactile or visual stimuli, was found to be processed within the human putamen using fMRI. Notably, at the single-neuron level in the macaque putamen, half of the individual neurons encode values independently of sensory inputs, while the other half selectively encode tactile or visual value. The responses of bimodal value neurons correlate with value-guided finger insertion behavior in both tasks, whereas modality-selective value neurons show task-specific correlations. Simulation using these neurons reveals that the presence of bimodal value neurons enables value discrimination with a significantly reduced number of neurons compared to simulations without them. Our data indicate that individual neurons in the primate putamen process different values in a convergent manner, thereby facilitating the efficient use of constrained neural resources for value-guided behavior., (© 2024. The Author(s).)

Background: Few studies have been conducted on the prevention of bile reflux in gastric cancer patients who have undergone gastrectomy. The aim of this study was to evaluate the efficacy and safety of ursodeoxycholic acid (UDCA) in preventing bile reflux after gastrectomy in patients with gastric cancer., Methods: This study was a secondary analysis of the PEGASUS-D trial, a randomized, double-blind, placebo-controlled clinical trial. Adults with a diagnosis of gastric cancer who underwent gastrectomy were enrolled. Eligible participants were randomly assigned to receive 300 mg of UDCA, 600 mg of UDCA, or placebo at a ratio of 1:1:1. UDCA and placebo were administered daily for 52 weeks. The primary outcomes included bile reflux symptoms at each time point, percentage of participants with bile reflux, and the grade of gastritis., Results: Among 521 participants who underwent randomization, 151, 164, and 150 participants were analyzed from the 300 mg UDCA, 600 mg UDCA, and placebo groups, respectively. The difference in symptoms between the three groups was not significant. Bile reflux was less evident in the UDCA group than in the placebo group; however, this difference was significant only in the 300-mg group at 12 months post-operation (odds ratio, 0.44; P = 0.0076). A significant reduction in gastritis was also observed in the 300-mg group at 12 months post-operation (odds ratio, 0.50; P = 0.0368) compared to the placebo group., Conclusions: This study showed that UDCA administration significantly reduced bile reflux and gastritis by approximately 50% at the 12 months-postoperative follow-up in patients who underwent gastrectomy for gastric cancer., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Ginseng has anti-hyperglycemic effects. Gintonin, a glycolipoprotein derived from ginseng, also stimulates insulin release from pancreatic beta cells. However, the role of gintonin in glucose metabolism within skeletal muscle is unknown. Here, we showed the effect of gintonin on glucose uptake, glycogen content, glucose transporter (GLUT) 4 expression, and adenosine triphosphate (ATP) content in C2C12 myotubes. Gintonin (3-30 μg/mL) dose-dependently stimulated glucose uptake in myotubes. The expression of GLUT4 on the cell membrane was increased by gintonin treatment. Treatment with 1-3 μg/mL of gintonin increased glycogen content in myotubes, but the content was decreased at 30 μg/mL of gintonin. The ATP content in myotubes increased following treatment with 10-100 μg/mL gintonin. Gintonin transiently elevated intracellular calcium concentrations and increased the phosphorylation of extracellular signal-regulated kinase (ERK). Gintonin-induced transient calcium increases were inhibited by treatment with the lysophosphatidic acid receptor inhibitor Ki16425, the phospholipase C inhibitor U73122, and the inositol 1,4,5-trisphosphate receptor antagonist 2-aminoethoxydiphenyl borate. Gintonin-stimulated glucose uptake was decreased by treatment with U73122, the intracellular calcium chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid tetra(acetoxymethyl) ester, and the ERK inhibitor PD98059. These results show that gintonin plays a role in glucose metabolism by increasing glucose uptake through transient calcium increases and ERK signaling pathways. Thus, gintonin may be beneficial for glucose metabolism control.

Endoscopic submucosal dissection (ESD) plays a pivotal role in treating early gastric cancer (EGC). Some patients require additional gastrectomy because of non-curative ESD. This study aimed to analyze the clinical factors associated with non-curative ESD and to re-evaluate the role of ESD according to its indication criteria. Altogether, 134 patients who had undergone additional gastrectomy with lymphadenectomy for non-curative ESD based on the pathological results of ESD specimens were included. Their data including pre-ESD diagnosis, reasons for requesting additional gastrectomy, and surgical outcomes were analyzed retrospectively. Of the 134 patients with EGC in the final pathology of ESD specimens, 56 underwent staging ESD for a diagnostic approach, of whom 28 were diagnosed with atypical glands and 28 with high-grade dysplasia (HGD) prior to ESD. The remaining 78 patients of the 134 were identified to have EGC and received ESD for therapy. Based on the pathological results of ESD specimens, additional gastrectomy was commissioned with non-curative ESD because of one or more causes such as deep submucosal invasion, lymphatic invasion, positive vertical margin, undifferentiated histology, positive lateral margin, and venous invasion. Regarding surgical specimens, 13 patients had lymph node metastasis (LNM) and 9 had local residual tumor; one of them had both LNM and a local residual tumor. In patients with atypical glands, 4 had LNM and 3 had a local residual tumor; one of them had both LNM and a local residual tumor, and then died of multiple organ metastasis. In patients with HGD, 4 had LNM and 1 had a local residual tumor. Additionally, 4 patients who were absolutely indicated for ESD had LNM, of whom 2 had atypical glands, and the other 2 had HGD. Similarly, in 6 patients with a local residual tumor absolutely indicated for ESD, 2 had atypical glands and 1 had HGD. Positive vertical margin, lymphatic invasion, and deep submucosal invasion were identified as independent risk factors for LNM. ESD may play diagnostic and therapeutic roles in determining the optimal treatment of EGC when the diagnosis is equivocal or insufficient in endoscopic assessments for gastric cancer screening., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Sjögren's syndrome (SS) is an autoimmune disease caused by infiltrating lymphocytes. FTY720 affects the S1P signaling pathway, which plays a role in T and B cell migration from secondary lymphoid tissues to target organs. In this study, we investigate the regulatory mechanism of FTY720 in the context of SS., Method: FTY720 was given orally every day to NOD mice. The salivary flow rate (SFR) and blood glucose level were assayed every 3 weeks. Histopathological features were investigated at the end of the study. In vitro, FTY720 was added to mouse splenocytes, and changes in the lymphocyte subsets were assessed., Results: In vivo, FTY720 increased the SFR and reduced the blood glucose level. The salivary gland histological score and infiltration of the salivary glands by B and T cells were dramatically decreased. Furthermore, STAT expression in the salivary gland was decreased. In vitro, FTY720 inhibited Th17 cells, while increasing regulatory T (Treg) cells, respectively. Also, FTY720 decreased and increased the numbers of germinal center (GC) B cells and regulatory B cells (Breg cells), respectively. FTY720 decreased the IgG level in culture supernatants. Also, STAT3 activation was decreased by FTY720., Conclusion: Our results show the therapeutic potential of FTY720 in the context of SS; FTY720 prevents lymphocyte migration from secondary lymphoid organs to target organs., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Background: Assessing breast cancer risks from lifestyle and reproductive factors is critical for developing population-specific risk prediction tools. However, limited studies have evaluated these risks in recent Asian birth cohorts., Methods: We systematically reviewed articles published from January 2010 to December 2023, examining breast cancer risk factors in Asian women. Data were described narratively, estimates pooled, and prevalence and attributable proportions compared across Asian populations., Results: Of the 128 studies reviewed, 103 reported adjusted effect sizes for meta-analysis. Lifestyle and reproductive factors were predictive of breast cancer risk in Asian women, with varying impacts on premenopausal and postmenopausal women. Relative risks were similar within Asian populations and in comparison to European populations, except for menarche, menopause, and hormone receptor therapy. However, risk factor distributions differed across populations. While alcohol intake (21%) and oral contraceptive use (20%) emerged as the most attributable modifiable risk factors in Europeans, passive smoking (24%) and higher BMI (17%, ≥24 kg/m2 among postmenopausal women) were predominant in Asians., Conclusions: Our study shows that while the effects of lifestyle and reproductive breast cancer risk factors are largely similar across different populations, their distributions vary., Impact: Our analysis underscores the importance of considering population-specific risk factor distributions when developing risk prediction tools for Asian populations., (©2024 American Association for Cancer Research.)

The diagnosis and awareness of transthyretin amyloidosis cardiomyopathy (ATTR-CM) in heart failure with left ventricular ejection fraction (LVEF) > 40% remains under-recognized. This study aimed to investigate the prevalence and characteristics of ATTR-CM in patients with heart failure with LVEF > 40%. Patients with LVEF > 40% and maximal left ventricular wall thickness (MWT) > 10 mm who underwent bone scintigraphy were retrospectively investigated. Patients with a definite cause of heart failure were excluded. ATTR-CM was diagnosed when grade 2 or 3 myocardial uptake was observed on scintigraphy. Among 97 patients (male, 62.5%; median age, 69 years), 13 (13.4%) were diagnosed with ATTR-CM (wild type, 69.2%; hereditary type, 30.8%). Age or biomarker levels did not differ significantly; however, all patients with ATTR-CM were male. The ATTR-CM group had a significantly higher prevalence of polyneuropathy or carpal tunnel syndrome than the non-ATTR-CM group, accompanied by a longer PR interval, thicker MWT, larger left atrial volume index, and higher E/e'. Accordingly, ATTR was present in a substantial number, particularly among men. Clinicians should suspect ATTR when a male patient exhibits neurologic symptoms, diastolic dysfunction, and a long PR interval., (© 2024. The Author(s).)

Cryptosporidium and Giardia duodenalis are common gastrointestinal protozoan parasites that cause diarrhea in humans and animals. Although dogs in animal shelters in South Korea can be reintroduced into human society as companions, no continuous investigations have been conducted on the prevalence and genetic characteristics of the protozoan parasites. In the present study, 345 fecal samples from dogs were obtained from animal shelters in six provinces between January and December 2022. The prevalence of Cryptosporidium and G. duodenalis were molecularly identified at the 18S rRNA gene. Cryptosporidium canis isolates were subtyped at the gp60 locus, and G. duodenalis assemblages were identified at the tpi, bg and gdh loci. Overall, 6.67% of the fecal samples tested positive for Cryptosporidium spp. and two species were identified: C. canis (5.51%) and Cryptosporidium parvum (1.16%). Significant regional differences in prevalence were identified for C. canis. Subtyping analysis of C. canis isolates revealed a predominance of the subtype families XXa and XXe over XXb, and XXc. G. duodenalis was detected in 17.68% of the samples, and significant regional differences were identified; its prevalence was also significantly highest in diarrhoeic animals. Molecular characterization of G. duodenalis reveal that most isolates belonged to the canine-specific assemblages C and D. The present results can contribute to further insights into the prevalence and genotypes of Cryptosporidium and G. duodenalis in shelter dogs in South Korea., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

While evidence indicates that exposure to oil spill incidents can affect mental health, it is unclear whether the mental health effects result from the incident itself or from exposure to associated chemicals. Oil contains chemicals that can impact mental health and these chemicals may have long-term effects due to their persistence in the environment. To address the gap in current knowledge, we conducted cross-sectional and prospective analyses of data from adults who participated in the Health Effects of the Hebei Spirit Oil Spill study. To assess chemical exposure from oil spills, we used indirect exposure indicators such as distance from the contaminated oil band to residences and duration of clean-up work, along with direct exposure indicators such as urine metabolite concentrations of volatile organic compounds and polycyclic aromatic hydrocarbons. Mental health assessments covered posttraumatic stress disorder (PTSD), depression, state anxiety, and trait anxiety. In the cross-sectional analyses, all four mental health issues were found to be associated with proximity to the oil band (p-value<0.05) and showed a positive association with clean-up work duration (p-value<0.05). Cox regression analysis revealed that higher urinary t, t-muconic acid levels were associated with an increased risk of depression (Hazard Ratio [HR] = 1.55, 95 % Confidence Interval [CI] = 1.05-2.28), and elevated 1-hydroxypyrene levels increased the risk of PTSD (HR = 1.60, 95 % CI = 1.03-2.48). Additionally, higher urinary 2-naphthol levels were associated with increased state anxiety (HR = 1.39, 95 % CI = 1.00-1.93) and trait anxiety (HR = 1.64, 95 % CI = 1.15-2.32). These associations persisted even after controlling for distance and duration variables related to psychosocial exposure. Our findings suggest that environmental disaster response plans should prioritize minimizing chemical exposure while also considering the duration and nature of the mental health impacts., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Contact lenses have been instrumental in vision correction and are expected to be utilized in augmented reality (AR) displays through the integration of electronic and optical components. In optics, metasurfaces, an array of sub-wavelength nanostructures, have offered optical multifunctionality in an ultra-compact form factor, facilitating integration into various imaging, and display systems. However, transferring metasurfaces onto contact lenses remains challenging due to the non-biocompatible materials of extant imprinting methods and the structural instability caused by the swelling and shrinking of the wetted surface. Here, a biocompatible method is presented to transfer metasurfaces onto contact lenses using hyaluronic acid (HA) as a soft mold and to allow for holographic light projection. A high-efficiency metahologram is obtained with an all-metallic 3D meta-atom enhanced by the anisotropy of a rectangular structure, and a reflective background metal layer. A corrugated metal layer on the HA mold is supported with a SiO 2 capping layer, to avoid unwanted wrinkles and to ensure structural stability when transferred to the surface of pliable and wettable contact lenses. Biocompatible method of transferring metasurfaces onto contact lenses promises the integration of diverse optical components, including holograms, lenses, gratings and more, to advance the visual experience for AR displays and human-computer interfaces., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Purpose: This study aimed to compare tumor tissue DNA (ttDNA) and circulating tumor DNA (ctDNA) to explore the clinical applicability of ctDNA and to better understand clonal evolution in patients with metastatic colorectal cancer undergoing palliative first-line systemic therapy., Materials and Methods: We performed targeted sequencing analysis of 88 cancer-associated genes using germline DNA, ctDNA at baseline (baseline-ctDNA), and ctDNA at progressive disease (PD-ctDNA). The results were compared with ttDNA data., Results: Among 208 consecutively enrolled patients, we selected 84 (41 males; median age, 59 years; range, 35 to 90 years) with all four sample types available. A total of 202 driver mutations were found in 34 genes. ttDNA exhibited the highest mutation frequency (n=232), followed by baseline-ctDNA (n=155) and PD-ctDNA (n=117). Sequencing ctDNA alongside ttDNA revealed additional mutations in 40 patients (47.6%). PD-ctDNA detected 13 novel mutations in 10 patients (11.9%) compared to ttDNA and baseline-ctDNA. Notably, seven mutations in five patients (6.0%) were missense or nonsense mutations in APC, TP53, SMAD4, and CDH1 genes. In baseline-ctDNA, higher maximal variant allele frequency (VAF) values (p=0.010) and higher VAF values of APC (p=0.012), TP53 (p=0.012), and KRAS (p=0.005) mutations were significantly associated with worse overall survival., Conclusion: While ttDNA remains more sensitive than ctDNA, our ctDNA platform demonstrated validity and potential value when ttDNA was unavailable. Post-treatment analysis of PD-ctDNA unveiled new pathogenic mutations, signifying cancer's clonal evolution. Additionally, baseline-ctDNA's VAF values were prognostic after treatment.

Background: Orbital apex syndrome (OAS) is a condition characterised by lesions within the orbital apex, leading to various ophthalmologic symptoms. This study aimed to analyse the clinical characteristics and treatment strategies of OAS with respect to aetiology., Methods: This retrospective analysis utilised data from 5 medical institutions between 2013 and 2022. Patients who were diagnosed with OAS were initially enrolled, but patients who failed to follow up at least 1 month were excluded. The prevalence of initial ophthalmologic symptoms and visual improvement after treatment was compared according to aetiology. Factors related to visual improvement were analysed., Results: Among 73 enrolled patients, the leading aetiology was tumours, followed by fungal infections and inflammation. Visual impairment and proptosis were prevalent in tumour-related OAS cases. Inflammation-related OAS exhibited a higher likelihood of painful eye movements and ophthalmoplegia. Ptosis was most frequently observed in fungal infection-related OAS. Notably, fungal infections emerged as the sole significant factor negatively impacting vision progression. In inflammation-related OAS, the time interval between symptom onset and the administration of steroids was longer in patients without visual improvement, even though there was no statistically significant difference., Conclusions: Tumours were the predominant cause of OAS. Visual impairment was a common manifestation in tumour-related OAS, while fungal infections were strongly associated with a poor visual prognosis. The timely administration of steroids might be helpful for improving vision in patients with inflammation-related OAS. However, further studies are needed to enhance understanding and management of OAS.

Background: Elevated mammographic density (MD) for a woman's age and body mass index (BMI) is an established breast cancer risk factor. The relationship of parity, age at first birth, and breastfeeding with MD is less clear. We examined the associations of these factors with MD within the International Consortium of Mammographic Density (ICMD)., Methods: ICMD is a consortium of 27 studies with pooled individual-level epidemiological and MD data from 11,755 women without breast cancer aged 35-85 years from 22 countries, capturing 40 country-& ethnicity-specific population groups. MD was measured using the area-based tool Cumulus. Meta-analyses across population groups and pooled analyses were used to examine linear regression associations of square-root (√) transformed MD measures (percent MD (PMD), dense area (DA), and non-dense area (NDA)) with parity, age at first birth, ever/never breastfed and lifetime breastfeeding duration. Models were adjusted for age at mammogram, age at menarche, BMI, menopausal status, use of hormone replacement therapy, calibration method, mammogram view and reader, and parity and age at first birth when not the association of interest., Results: Among 10,988 women included in these analyses, 90.1% (n = 9,895) were parous, of whom 13% (n = 1,286) had ≥ five births. The mean age at first birth was 24.3 years (Standard deviation = 5.1). Increasing parity (per birth) was inversely associated with √PMD (β: - 0.05, 95% confidence interval (CI): - 0.07, - 0.03) and √DA (β: - 0.08, 95% CI: - 0.12, - 0.05) with this trend evident until at least nine births. Women who were older at first birth (per five-year increase) had higher √PMD (β:0.06, 95% CI:0.03, 0.10) and √DA (β:0.06, 95% CI:0.02, 0.10), and lower √NDA (β: - 0.06, 95% CI: - 0.11, - 0.01). In stratified analyses, this association was only evident in women who were post-menopausal at MD assessment. Among parous women, no associations were found between ever/never breastfed or lifetime breastfeeding duration (per six-month increase) and √MD., Conclusions: Associations with higher parity and older age at first birth with √MD were consistent with the direction of their respective associations with breast cancer risk. Further research is needed to understand reproductive factor-related differences in the composition of breast tissue and their associations with breast cancer risk., (© 2024. The Author(s).)

Objectives: This study aimed to evaluate whether a 2-week period of daily isoagglutinin titer testing after ABO-incompatible kidney transplantation (ABOi-KT) is sufficient to ensure successful engraftment and to advocate for an extension of the monitoring duration in specific situations., Methods: We reviewed patients from January 2022 to December 2023 at Asan Medical Center who underwent therapeutic plasma exchange (TPE) due to elevated ABO antibody titers and suspected acute antibody-mediated rejection (AMR) after ABOi-KT. Data collected included pre- and posttransplantation laboratory results, clinical and procedural information, imaging studies, and needle biopsy results of the renal graft., Results: We encountered 3 cases of acute AMR 2 weeks after transplantation. All cases exhibited simultaneous increases in anti-ABO antibody isoagglutinin titers, creatinine, and C-reactive protein levels. Clinical signs, including fever, suggested possible infection, and renal graft biopsy, confirmed AMR in all cases. Two cases underwent graftectomy, while the third recovered renal function after conservative treatment, including TPE., Conclusions: Our findings suggest that a 2-week monitoring period for isoagglutinin titers after ABOi-KT may not be sufficient to detect late AMR. Extending the monitoring duration and considering lifelong fresh-frozen plasma transfusion with graft-compatible blood types, along with periodic isoagglutinin titer testing in cases of suspected AMR, may improve long-term graft outcomes., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: EW-7197, a potent oral ALK5 inhibitor, was assessed for its impact on transforming growth factor beta 1 (TGF-β1)-induced fibrosis in a three-dimensional (3D) renal fibrosis-on-a-chip and a mouse model. The evaluation included tubular epithelial-mesenchymal transition, angiogenesis, and inflammatory cytokine expression., Methods: In a 3D renal fibrosis-on-a-chip model, three cell types (kidney fibroblasts, human proximal tubular cell line, and human umbilical vein endothelial cells) were cultured and treated with TGF-β1 and EW-7197. Expression of alpha smooth muscle actin (α-SMA) and keratin 8 (KRT-8) was assessed, angiogenesis was observed via confocal microscopy, and cytokine levels were measured using real-time polymerase chain reaction, immunoassay, and enzyme-linked immunosorbent assay. In a cisplatin-induced renal fibrosis mouse model, blood urea nitrogen levels, TGF-β, and Smad 2/3 were determined, and renal fibrosis was assessed with Masson's trichrome stain., Results: The α-SMA expression was significantly lower in the EW-7197 group than in the TGF-β fibrosis group. TGF-β decreased the expression of the epithelial marker KRT-8, an effect that was reversed by EW-7197 and SB431542. In the TGF-β-induced fibrosis model, the length of the thick vessels was reduced, and the diameter of both thick and thin vessels was decreased, but EW-7197 reversed these effects. EW-7197 significantly reduced the messenger RNA expression of TGF-β and increased the levels of vascular endothelial growth factor receptor 2, interleukin (IL)-10, and IL-6. EW-7197 reduced the levels of secretory cytokines TGF-β1, TGF-β3, IL-1β. In the cisplatin-induced renal fibrosis mouse model, EW-7197 reduced renal fibrosis by down-regulating TGF-β signaling., Conclusion: EW-7197 attenuated the TGF-β1-induced fibrotic cellular response in the 3D chip model and animal model. These findings indicate the potential effect of EW-7197 in attenuating renal fibrosis.

Many pathogenic bacteria form biofilms that are resistant to not only host immune defenses but also antibiotics, posing a need for the development of strategies to control biofilms. In this study, to prevent biofilm formation of the fulminating foodborne pathogen Vibrio vulnificus , chemical libraries were extensively screened to identify a small molecule inhibiting the activity of BrpR, a transcriptional regulator for biofilm genes. Accordingly, the BrpR inhibitor BFstatin [N1-(2-chloro-5-fluorophenyl)-N3-propylmalonamide], with a half-maximal effective concentration of 8.01 μM, was identified. BFstatin did not interfere with bacterial growth or exhibit cytotoxicity to the human epithelial cell line. BFstatin directly bound to BrpR and interrupted its binding to the target promoter DNAs of the downstream genes. Molecular dynamics simulation of the interaction between BFstatin and BrpR proposed that BFstatin modifies the structure of BrpR, especially the DNA-binding domain. Transcriptomic analyses revealed that BFstatin reduces the expression of the BrpR regulon including the cabABC operon and brp locus which contribute to the production of biofilm matrix of V. vulnificus . Accordingly, BFstatin diminished the biofilm levels of V. vulnificus by inhibiting the matrix development in a concentration-dependent manner. Altogether, BFstatin could be an anti-biofilm agent targeting BrpR, thereby rendering V. vulnificus more susceptible to host immune defenses and antibiotics., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lee, Hwang, Shin, Ha, Wang and Choi.)

Co-observation of a gene variant with a pathogenic variant in another gene that explains the disease presentation has been designated as evidence against pathogenicity for commonly used variant classification guidelines. Multiple variant curation expert panels have specified, from consensus opinion, that this evidence type is not applicable for the classification of breast cancer predisposition gene variants. Statistical analysis of sequence data for 55,815 individuals diagnosed with breast cancer from the BRIDGES sequencing project was undertaken to formally assess the utility of co-observation data for germline variant classification. Our analysis included expected loss-of-function variants in 11 breast cancer predisposition genes and pathogenic missense variants in BRCA1, BRCA2, and TP53. We assessed whether co-observation of pathogenic variants in two different genes occurred more or less often than expected under the assumption of independence. Co-observation of pathogenic variants in each of BRCA1, BRCA2, and PALB2 with the remaining genes was less frequent than expected. This evidence for depletion remained after adjustment for age at diagnosis, study design (familial versus population-based), and country. Co-observation of a variant of uncertain significance in BRCA1, BRCA2, or PALB2 with a pathogenic variant in another breast cancer gene equated to supporting evidence against pathogenicity following criterion strength assignment based on the likelihood ratio and showed utility in reclassification of missense BRCA1 and BRCA2 variants identified in BRIDGES. Our approach has applicability for assessing the value of co-observation as a predictor of variant pathogenicity in other clinical contexts, including for gene-specific guidelines developed by ClinGen Variant Curation Expert Panels., Competing Interests: Declaration of interests P.A.F. conducts research funded by Amgen, Novartis, and Pfizer. He received Honoraria from Roche, Novartis, and Pfizer. A.R.M. received funds from AstraZeneca for contribution to sponsored quality assessments and variant interpretation of VUSs in BRCA1 and BRCA2. The funds were paid to the institution., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Clinical genetic testing identifies variants causal for hereditary cancer, information that is used for risk assessment and clinical management. Unfortunately, some variants identified are of uncertain clinical significance (VUS), complicating patient management. Case-control data is one evidence type used to classify VUS, and previous findings indicate that case-control likelihood ratios (LRs) outperform odds ratios for variant classification. As an initiative of the Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) Analytical Working Group we analyzed germline sequencing data of BRCA1 and BRCA2 from 96,691 female breast cancer cases and 303,925 unaffected controls from three studies: the BRIDGES study of the Breast Cancer Association Consortium, the Cancer Risk Estimates Related to Susceptibility consortium, and the UK Biobank. We observed 11,227 BRCA1 and BRCA2 variants, with 6,921 being coding, covering 23.4% of BRCA1 and BRCA2 VUS in ClinVar and 19.2% of ClinVar curated (likely) benign or pathogenic variants. Case-control LR evidence was highly consistent with ClinVar assertions for (likely) benign or pathogenic variants; exhibiting 99.1% sensitivity and 95.4% specificity for BRCA1 and 92.2% sensitivity and 86.6% specificity for BRCA2 . This approach provides case-control evidence for 785 unclassified variants, that can serve as a valuable element for clinical classification.

Shared appraisals and collaboration within couples play important roles in optimizing health. Less is known about concordance regarding collaboration, factors associated with concordance, and implications for health. Data from 2,761 couples from the Health and Retirement Study (2014/2016 and 2016/2018 waves) were examined to determine within-couple concordance in completion of two tasks (family decisions and medical forms). The majority of couples were concordant regarding who makes family decisions (69.7%) and who completes medical forms (64.4%); 62% agreed they make family decisions collaboratively versus 25.5% completing medical forms collaboratively. Concordance was significantly associated with greater marital support and longer marital duration. Concordance was not significantly associated with depressive symptoms 2 years later, but the link between concordance in making major family decisions and self-rated health differed by age and gender. Future research at the intersection of concordance and collaboration may shed important light on how older couples navigate tasks and decisions., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Chronic pain represents a significant unmet medical need, affecting one-fifth of the U.S. population. EC5026 is a small molecule inhibitor of the enzyme soluble epoxide hydrolase (sEH) which is being developed as a novel non-opioid, non-NSAID analgesic. EC5026 prolongs the action of epoxy fatty acids, endogenous analgesic lipid mediators that are rapidly metabolized by sEH. We evaluated the safety and pharmacokinetic profile of EC5026 in two phase I trials, a single-ascending dose (SAD) study and a fed-fasted study. The SAD study evaluated EC5026 doses ranging from 0.5 to 24 mg in healthy volunteers. EC5026 was well tolerated. No treatment-emergent adverse events were considered related to EC5026. No apparent treatment- or dose-related trends in laboratory results, vital signs, physical examinations, or electrocardiograms were observed. A linear, near-dose-proportional increase in exposure was observed with progressive doses in the SAD study; plasma exposure was below or near the lower limit of quantification after 0.5-2 mg doses. Mean half-lives ranged from 41.8 to 59.1 h. for doses of 8-24 mg, supporting a once-daily dosing regimen. In the fed-fasted study using 8 mg EC5026 tablets, higher peak concentrations (66%) and total exposures (53%) were observed under the fed condition. Plasma concentrations declined in a monoexponential manner with mean half-lives of 59.5 h. in the fed state and 66.9 h. in the fasted state. Future clinical trials using EC5026 for the treatment of pain are justified based on the favorable outcomes from both clinical trials along with preclinical evidence of analgesic activity., (© 2024 EicOsis Human Health, Inc. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Nanomaterial-based yarns have been actively developed owing to their advantageous features, namely, high surface-area-to-volume ratios, flexibility, and unusual material characteristics such as anisotropy in electrical/thermal conductivity. The superior properties of the nanomaterials can be directly imparted and scaled-up to macro-sized structures. However, most nanomaterial-based yarns have thus far, been fabricated with only organic materials such as polymers, graphene, and carbon nanotubes. This paper presents a novel fabrication method for fully inorganic nanoribbon yarn, expanding its applicability by bundling highly aligned and suspended nanoribbons made from various inorganic materials (e.g., Au, Pd, Ni, Al, Pt, WO 3 , SnO 2 , NiO, In 2 O 3 , and CuO). The process involves depositing the target inorganic material on a nanoline mold, followed by suspension through plasma etching of the nanoline mold, and twisting using a custom-built yarning machine. Nanoribbon yarn structures of various functional inorganic materials are utilized for chemical sensors (Pd-based H 2 and metal oxides (MOx)-based green gas sensors) and green energy transducers (water splitting electrodes/triboelectric nanogenerators). This method is expected to provide a comprehensive fabrication strategy for versatile inorganic nanomaterials-based yarns., (© 2024 Wiley‐VCH GmbH.)

Lateral spinal artery (LSA) aneurysms are extremely rare lesions that can rupture and cause subarachnoid hemorrhage (SAH) even though the spinal arteries communicate directly with the subarachnoid space. To date, six cases of LSA aneurysms have been reported in the literature. Herein, three such cases are reported. All patients presented to the emergency department with headaches. The patients in the first two cases were confirmed to have SAH and LSA aneurysms on a brain computed tomography (CT) angiography performed at the hospital. Two patients had prior instances of cerebral infarction and coronary disease, respectively, and were undergoing antiplatelet therapy. The antiplatelet medication was stopped for 2 weeks and 1 week, respectively, while conservative care was provided. Subsequently, a suboccipital craniectomy was performed, followed by aneurysm clipping. Following the surgery, both patients were discharged without any significant neurological deficits. Regarding the third patient, no aneurysm was found on brain CT angiography, and cerebral angiography was performed during the patient's hospital stay. She was hospitalized, where she received medication and conservative care, and was discharged with an improvement in bleeding without neurological symptoms. Subsequently, a LSA aneurysm was identified on a brain CT angiography performed at an outpatient clinic; however, the patient was transferred because she wanted to be treated at another hospital. LSA aneurysms are difficult to visualize using CT angiography; therefore, careful angiographic studies are required. Surgical clipping is the treatment of choice if the aneurysm is inaccessible by the endovascular treatment.

Objectives: To assess the safety and effectiveness of perioperative ibuprofen in pediatric tonsillectomy through a meta-analysis of relevant randomized controlled trials., Methods: We conducted a comprehensive review of studies available in PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases up to June 2024. This analysis compared perioperative ibuprofen administration to control groups (saline, acetaminophen, or opioids). Outcomes assessed were postoperative pain management, as indicated by the frequency of analgesic use, and morbidity rates, which included the incidence of postoperative nausea and vomiting and post-tonsillectomy hemorrhage (PTH). PTH was further categorized as primary (occurring on the day of operation) or secondary (occurring after the day of operation), and classified as type 1 (observed at home or evaluated in the emergency department without further intervention), type 2 (requiring readmission for observation), or type 3 (necessitating a return to the operating room for hemorrhage control)., Results: This analysis included nine studies involving a total of 1545 patients. Incidences of primary PTH (OR = 1.0949, 95 % CI [0.4169; 2.8755], I 2  = 0.0 %), secondary PTH (OR = 1.6433 95 % CI [0.7783; 3.4695], I 2  = 0.1 %), and overall PTH (OR = 1.4296 95 % CI [0.8383; 2.4378], I 2  = 0.0 %) were not significantly higher in the ibuprofen group than the control groups. Administration of ibuprofen led to a significant decrease in postoperative nausea and vomiting (OR = 0.4228 95 % CI [0.2500; 0.7150], I 2  = 40.0 %) and frequency of postoperative analgesic uptake (OR = 0.4734 95 % CI [0.2840; 0.7893]; I 2  = 19.8 %). There was no difference in bleeding by type between the ibuprofen and control groups., Conclusions: Our meta-analysis demonstrated that administration of ibuprofen for pediatric tonsillectomy did not significantly increase the incidence of postoperative bleeding but did decrease postoperative emesis and improve pain control., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: To investigate the risk factors for varus progression after arthroscopic medial meniscal posterior root tear (MMPRT) repair and to compare the clinical outcomes between two groups: one with more varus progression and the other with less varus progression., Methods: Patients who underwent isolated arthroscopic repair of MMPRT between 2015 and 2020 were enroled, and 2-year follow-up data were collected. Participants were categorized into two groups based on preoperative values of the weight-bearing line (WBL) ratio: group A with <5.9% increase and group B with ≥5.9% increase. Various factors, including demographic features and radiological findings, were analysed and compared between the two groups. Intra-meniscal signal intensity, meniscal healing, medial meniscal extrusion (MME), and articular cartilage grade were assessed preoperatively and 1-year postoperatively using coronal magnetic resonance imaging., Results: The final cohort consisted of 34 patients in group A and 46 in group B, with a mean age of 55.8 ± 11.2 and 59.8 ± 6.6 years, respectively. Preoperative WBL ratio and cartilage lesions in the medial compartment did not differ between the groups. Preoperative MME were significantly lower in group A than those in group B (2.6 ± 0.6 mm in group A and 3.5 ± 0.7 mm in group B, p < 0.05). Patient-reported outcomes at the 2-year follow-up did not differ between the two groups (n. s.). In a logistic analysis, the odds ratio of MME was 2.1 (p < 0.05), and the cutoff value of MME was 3.02 mm., Conclusion: Preoperative MME is a risk factor for varus progression. However, no differences in patient-reported outcomes were observed at 2-year follow-up, even in the group with greater varus progression., Level of Evidence: Level IV., (© 2024 European Society of Sports Traumatology, Knee Surgery and Arthroscopy.)

Accurate segmentation of the left atrium (LA) from late gadolinium-enhanced cardiac magnetic resonance (LGE CMR) images is crucial for aiding the treatment of patients with atrial fibrillation. Few-shot learning holds significant potential for achieving accurate LA segmentation with low demand on high-cost labeled LGE CMR data and fast generalization across different centers. However, accurate LA segmentation with few-shot learning is a challenging task due to the low-intensity contrast between the LA and other neighboring organs in LGE CMR images. To address this issue, we propose an Adaptive Dynamic Inference Network (ADINet) that explicitly models the differences between the foreground and background. Specifically, ADINet leverages dynamic collaborative inference (DCI) and dynamic reverse inference (DRI) to adaptively allocate semantic-aware and spatial-specific convolution weights and indication information. These allocations are conditioned on the support foreground and background knowledge, utilizing pixel-wise correlations, for different spatial positions of query images. The convolution weights adapt to different visual patterns based on spatial positions, enabling effective encoding of differences between foreground and background regions. Meanwhile, the indication information adapts to the background visual pattern to reversely decode foreground LA regions, leveraging their spatial complementarity. To promote the learning of ADINet, we propose hierarchical supervision, which enforces spatial consistency and differences between the background and foreground regions through pixel-wise semantic supervision and pixel-pixel correlation supervision. We demonstrated the performance of ADINet on three LGE CMR datasets from different centers. Compared to state-of-the-art methods with ten available samples, ADINet yielded better segmentation performance in terms of four metrics., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Alzheimer's Disease and Alzheimer's Disease-related dementias (AD/ADRD) pose major global healthcare challenges, with diabetes mellitus (DM) being a key risk factor. Both AD and DM-related ADRD are characterized by reduced cerebral blood flow, although the exact mechanisms remain unclear. We previously identified compromised cerebral hemodynamics as early signs in TgF344-AD and type 2 DM-ADRD (T2DN) rat models. Genome-wide studies have linked AD/ADRD to SNPs in soluble epoxide hydrolase (sEH). This study explored the effects of sEH inhibition with TPPU on cerebral vascular function and cognition in AD and DM-ADRD models. Chronic TPPU treatment improved cognition in both AD and DM-ADRD rats without affecting body weight. In DM-ADRD rats, TPPU reduced plasma glucose and HbA1C levels. Transcriptomic analysis of primary cerebral vascular smooth muscle cells from AD rats treated with TPPU revealed enhanced pathways related to cell contraction, alongside decreased oxidative stress and inflammation. Both AD and DM-ADRD rats exhibited impaired myogenic responses and autoregulation in the cerebral circulation, which were normalized with chronic sEH inhibition. Additionally, TPPU improved acetylcholine-induced vasodilation in the middle cerebral arteries (MCA) of DM-ADRD rats. Acute TPPU administration unexpectedly caused vasoconstriction in the MCA of DM-ADRD rats at lower doses. In contrast, higher doses or longer durations were required to induce effective vasodilation at physiological perfusion pressure in both control and ADRD rats. Additionally, TPPU decreased reactive oxygen species production in cerebral vessels of AD and DM-ADRD rats. These findings provide novel evidence that chronic sEH inhibition can reverse cerebrovascular dysfunction and cognitive impairments in AD/ADRD, offering a promising avenue for therapeutic development., Competing Interests: DECLARATIONS Conflict of Interest B.D. Hammock is a founder and S.H. Hwang, and J. Yang are employees of EicOsis L.L.C., a startup company with an sEH inhibitor in human clinical trials.

Background and Objectives : We investigated the effects of using a BiZact™ device for tonsillectomy on operating time, intraoperative blood loss, postoperative bleeding rate, and pain through a meta-analysis of the relevant literature. Materials and Methods : We reviewed studies retrieved from the databases of PubMed, SCOPUS, Google Scholar, Embase, Web of Science, and Cochrane up to March 2024. The results were analyzed following PRISMA guidelines. Six studies that compared the outcomes of patients receiving perioperative BiZact™ tonsillectomy with those in control groups (cold steel dissection or bipolar tonsillectomy) were included for this analysis of the outcomes, which included intraoperative bleeding and time, postoperative pain, and frequency of postoperative bleeding. Results : The operative time (SMD -11.5985, 95%CI [-20.3326; -2.8644], I 2 = 99.5%) in the treatment group was significantly reduced compared to the control group. However, BiZact™ showed no significant efficacy in reducing intraoperative bleeding when compared with the control group (SMD -0.0480, 95%CI [-1.8200; 1.7240], I 2 = 98.6%). Postoperative pain on day 1 (SMD -0.0885, 95%CI [-0.4368; 0.2598], I 2 = 98.9%), day 3 (SMD -0.2118, 95%CI [-0.6110; 0.1873], I 2 = 99.5%), and later than day 7 (SMD 0.0924, 95%CI [-0.2491; 0.4338], I 2 = 98.6%) in the treatment group was not significantly reduced relative to the control group. When compared to the control group, BiZact™ did not reduce the incidence of secondary postoperative bleeding control in the operation room (OR 0.5711, 95%CI [0.2476; 1.3173], I 2 = 32.1%), primary bleeding (OR 0.4514, 95%CI [0.0568; 3.5894], I 2 = 0.0%), or all postoperative bleeding events (OR 0.8117, 95%CI [0.5796; 1.1368], I 2 = 26.3%). Conclusions : This study demonstrated that using the BiZact™ device for tonsillectomy significantly decreased the operative time but could not effectively reduce intraoperative bleeding or postoperative pain and bleeding., Competing Interests: The authors declare no conflicts of interest.

Autoinhibition, a crucial allosteric self-regulation mechanism in cell signaling, ensures signal propagation exclusively in the presence of specific molecular inputs. The heightened focus on autoinhibited proteins stems from their implication in human diseases, positioning them as potential causal factors or therapeutic targets. However, the absence of a comprehensive knowledgebase impedes a thorough understanding of their roles and applications in drug discovery. Addressing this gap, we introduce Autoinhibited Protein Database (AiPD), a curated database standardizing information on autoinhibited proteins. AiPD encompasses details on autoinhibitory domains (AIDs), their targets, regulatory mechanisms, experimental validation methods, and implications in diseases, including associated mutations and post-translational modifications. AiPD comprises 698 AIDs from 532 experimentally characterized autoinhibited proteins and 2695 AIDs from their 2096 homologs, which were retrieved from 864 published articles. AiPD also includes 42 520 AIDs of computationally predicted autoinhibited proteins. In addition, AiPD facilitates users in investigating potential AIDs within a query sequence through comparisons with documented autoinhibited proteins. As the inaugural autoinhibited protein repository, AiPD significantly aids researchers studying autoinhibition mechanisms and their alterations in human diseases. It is equally valuable for developing computational models, analyzing allosteric protein regulation, predicting new drug targets, and understanding intervention mechanisms AiPD serves as a valuable resource for diverse researchers, contributing to the understanding and manipulation of autoinhibition in cellular processes. Database URL: http://ssbio.cau.ac.kr/databases/AiPD., (© The Author(s) 2024. Published by Oxford University Press.)

Background: We evaluated the radiologic, pulmonary functional, and antibody statuses of coronavirus disease 2019 (COVID-19) patients 6 and 18 months after discharge, comparing changes in status and focusing on risk factors for residual computed tomography (CT) abnormalities., Methods: This prospective cohort study was conducted on COVID-19 patients discharged between April 2020 and January 2021. Chest CT, pulmonary function testing (PFT), and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunoglobulin G (IgG) measurements were performed 6 and 18 months after discharge. We evaluated factors associated with residual CT abnormalities and the correlation between lesion volume in CT (lesion volume ), PFT, and IgG levels., Results: This study included 68 and 42 participants evaluated 6 and 18 months, respectively, after hospitalizations for COVID-19. CT abnormalities were noted in 22 participants (32.4%) at 6 months and 13 participants (31.0%) at 18 months. Lesion volume was significantly lower at 18 months than 6 months ( P < 0.001). Patients with CT abnormalities at 6 months showed lower forced expiratory volume in 1 second (FEV1) and FEV1/forced vital capacity (FVC), and patients with CT abnormalities at 18 months exhibited lower FVC. FVC significantly improved between 6 and 18 months of follow-up (all P < 0.0001). SARS-CoV-2 IgG levels were significantly higher in patients with CT abnormalities at 6 and 18 months ( P < 0.001). At 18-month follow-up assessments, age was associated with CT abnormalities (odds ratio, 1.17; 95% confidence interval, 1.03-1.32; P = 0.01), and lesion volume showed a positive correlation with IgG level ( r = 0.643, P < 0.001)., Conclusion: At 18-month follow-up assessments, 31.0% of participants exhibited residual CT abnormalities. Age and higher SARS-CoV-2 IgG levels were significant predictors, and FVC was related to abnormal CT findings at 18 months. Lesion volume and FVC improved between 6 and 18 months., Trial Registration: Clinical Research Information Service Identifier: KCT0008573., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Accurate forecasting of clinical outcomes after kidney transplantation is essential for improving patient care and increasing the success rates of transplants. Our study employs advanced machine learning (ML) algorithms to identify crucial prognostic indicators for kidney transplantation. By analyzing complex datasets with ML models, we aim to enhance prediction accuracy and provide valuable insights to support clinical decision-making., Materials and Methods: Analyzing data from 4077 KT patients (June 1990 - May 2015) at a single center, this research included 27 features encompassing recipient/donor traits and peri-transplant data. The dataset was divided into training (80%) and testing (20%) sets. Four ML models-eXtreme Gradient Boosting (XGBoost), Feedforward Neural Network, Logistic Regression, and Support Vector Machine-were trained on carefully selected features to predict the success of graft survival. Performance was assessed by precision, sensitivity, F1 score, Area Under the Receiver Operating Characteristic (AUROC), and Area Under the Precision-Recall Curve., Results: XGBoost emerged as the best model, with an AUROC of 0.828, identifying key survival predictors like T-cell flow crossmatch positivity, creatinine levels two years post-transplant and human leukocyte antigen mismatch. The study also examined the prognostic importance of histological features identified by the Banff criteria for renal biopsy, emphasizing the significance of intimal arteritis, interstitial inflammation, and chronic glomerulopathy., Conclusion: The study developed ML models that pinpoint clinical factors crucial for KT graft survival, aiding clinicians in making informed post-transplant care decisions. Incorporating these findings with the Banff classification could improve renal pathology diagnosis and treatment, offering a data-driven approach to prioritizing pathology scores., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: To assess the short-term effects of topical platelet-rich plasma (PRP) injection on persistent refractory olfactory dysfunction., Methods: A comprehensive literature search of the PubMed, SCOPUS, EMBASE, Web of Science, Google Scholar, and Cochrane databases was conducted for articles up to November 2023. The search focused on studies that compared the amelioration of olfactory dysfunction between a topical PRP treatment cohort and a control group (receiving either placebo or no treatment), along with pre- and post-treatment comparisons. Subgroup analysis of the evaluation of olfactory function was also performed., Results: The improvement in olfactory scores 1-3 months post-treatment (standardized mean difference = 1.5354 [95% confidence interval: 0.7992; 2.2716], I 2  = 83.8%) was greater in the treatment group than in the control group. In the treatment group, PRP increased the threshold, discrimination, and identification (TDI) score for Sniffin' Sticks by > 5.5 (minimum clinically significant difference; mean difference = 6.1789 [3.9788; 8.3789], I 2  = 0.0%), indicating clinically significant improvement based on verified examinations. The rate of significant improvement among patients was 0.6683 [0.5833; 0.7436] after treatment. All TDI subdomains were significantly and similarly improved after treatment., Conclusion: This meta-analysis suggests that injection of PRP into the olfactory fissure or surrounding mucosal areas is an effective treatment for persistent refractory olfactory dysfunction in the short term., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Objectives: This study aimed to evaluate the safety and efficacy of perioperative ibuprofen administration by conducting a meta-analysis of pertinent literature., Methods: We conducted a comprehensive review of studies sourced from PubMed, SCOPUS, Embase, Web of Science, and Cochrane databases. The studies covered the period from database inception to June 2024. A perioperative ibuprofen administration group was compared to a control group administered either saline, acetaminophen, paracetamol, or opioids. The primary outcome was post-tonsillectomy bleeding that was categorized into overall bleeding and further classified as type 1 (observed at home or evaluated in the emergency department without additional intervention), type 2 (necessitating readmission for observation), and type 3 (requiring a return to the operating room for hemorrhage control). Morbidity incidence rates for postoperative nausea and vomiting were also assessed. The secondary outcomes assessed were postoperative pain management and the frequency of analgesic drug usage. Postoperative pain management was assessed from the incidence of emergency department visits or nurses' calls for pain independent of the presence or absence of dehydration., Results: Twenty-two studies with 27,149 patients were included and reviewed for this meta-analysis. Post-tonsillectomy bleeding (OR = 0.9954, 95 % CI [0.8800; 1.1260], I 2  = 0.0 %) was not significantly higher in the ibuprofen administration group compared to the control group. In subgroup analysis of post-tonsillectomy bleeding severity, ibuprofen caused clinically insignificant type 1 post-tonsillectomy bleeding that did not require intervention (OR = 1.1310 [0.7398; 1.7289]). Clinically significant bleeding requiring hospital admission (type 2) or surgical control (type 3) was not observed. Administration of ibuprofen has demonstrated efficacy in reducing the need for analgesic drugs (OR = 0.4734, 95 % CI [0.2840; 0.7893]; I 2  = 19.8 %) and is associated with a significant decrease in the incidence of postoperative nausea and vomiting (OR = 0.4886, 95 % CI [0.3156; 0.7562], I 2  = 34.3 %)., Conclusion: This study demonstrated that administration of ibuprofen for pediatric tonsillectomy did not increase the incidence of clinically significant postoperative bleeding. Ibuprofen administration decreased the incidence and severity of postoperative pain, nausea, and vomiting., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: To compare the effects of doxycycline (DOX) and conventional management in patients with refractory chronic rhinosinusitis and nasal polyps (CRSwNP)., Methods: Six databases were searched to September 2023. We retrieved studies that compared improvements in refractory chronic sinusitis-related symptoms between DOX-treated and control groups., Results: DOX significantly reduced the Lund-Kennedy (LK) score [- 0.3670 (range - 0.6173; - 0.1166); I 2  = 92.8%], the nasal polyposis score [- 0.9484 (- 1.2287; - 0.6680); I 2  = 92.5%], the patient-reported Sinonasal Outcome Test (SNOT) score [- 0.3141 (- 0.4622; - 0.1660); I 2  = 91.2%], and the nasal obstruction score [- 0.1813 (- 0.3382; - 0.0243); I 2  = 86.2%]. On subgroup analyses by the measurement timepoints, the extent of nasal polyposis was significantly lower in the DOX group during treatment, at the end of treatment, and 4 and 8 weeks later. The LK scores also indicated improvements during treatment and at the end of treatment. The SNOT score tended to decrease with time in the treatment group. Nasal obstruction symptoms improved during treatment and 4 weeks later., Conclusion: DOX enhances the postoperative endoscopic outcomes of refractory CRSwNP patients by reducing recurrent polyposis and inflammation., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Backgrounds: Strong evidence is lacking as no confirmatory randomized controlled trials (RCTs) have compared the efficacy of totally laparoscopic distal gastrectomy (TLDG) with laparoscopy-assisted distal gastrectomy (LADG). The authors performed an RCT to confirm if TLDG is different from LADG., Methods: The KLASS-07 trial is a multi-centre, open-label, parallel-group, phase III, RCT of 442 patients with clinical stage I gastric cancer. Patients were enroled from 21 cancer care centres in South Korea between January 2018 and September 2020 and randomized to undergo TLDG or LADG using blocked randomization with a 1:1 allocation ratio, stratified by the participating investigators. Patients were treated through R0 resections by TLDG or LADG as the full analysis set of the KLASS-07 trial. The primary endpoint was morbidity within postoperative day 30, and the secondary endpoint was quality of life (QoL) for 1 year. This trial is registered at ClinicalTrials.gov (NCT03393182)., Results: Four hundred forty-two patients were randomized (222 to TLDG, 220 to LADG), and 422 patients were included in the pure analysis (213 and 209, respectively). The overall complication rate did not differ between the two groups (TLDG vs. LADG: 12.2% vs. 17.2%). However, TLDG provided less postoperative ileus and pulmonary complications than LADG (0.9% vs. 5.7%, P= 0.006; and 0.5% vs. 4.3%, P= 0.035, respectively). The QoL was better after TLDG than after LADG regarding emotional functioning at 6 months, pain at 3 months, anxiety at 3 and 6 months, and body image at 3 and 6 months (all P< 0.05). However, these QoL differences were resolved at 1 year., Conclusions: The KLASS-07 trial confirmed that TLDG is not different from LADG in terms of postoperative complications but has the advantages to reduce ileus and pulmonary complications. TLDG can be a good option to offer better QoL in terms of pain, body image, emotion, and anxiety at 3-6 months., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Despite the high potential of one-dimensional (1D) donor-acceptor (D-A) coaxial nanostructures in bulk-heterojunction solar cell applications, the preparation of such 1D nanostructures using π-conjugated polymers has remained elusive. Herein, we demonstrate the first example of D-A semiconducting nanoribbons based on fully conjugated block copolymers (BCPs) prepared in a highly efficient procedure with controllable width and length via living crystallization-driven self-assembly (CDSA). Initially, Suzuki-Miyaura catalyst-transfer polymerization was employed to successfully synthesize BCPs containing two types of acceptor shells as the first block, followed by a donor poly(3-propylthiophene) core as the second block. The limited solubility and high crystallinity of the core induced a polymerization-induced crystallization-driven self-assembly (PI-CDSA) of the BCPs into nanoribbons during polymerization, providing a tunable width (7.6-39.6 nm) depending on the length of the polymer backbone. Surprisingly, purifying as-synthesized BCPs via simple precipitation directly yielded short and uniform seed structures, greatly shortening the overall protocol by eliminating the time-consuming process of initial aging and breaking down to the seed required for the conventional CDSA. With this new highly efficient method, we achieved length control over a broad range from 169 to 2210 nm, with high precision ( L w / L n < 1.20). Furthermore, combining self-seeding and seeded growth from two different D-A-type BCPs enabled continuous living epitaxial growth from each end of the nanoribbons, resulting in B-A-B triblock D-A semiconducting comicelles with controlled length.

Triple-negative breast cancers (TNBCs) are a subset of breast cancers that have remained difficult to treat. A proportion of TNBCs arising in non-carriers of BRCA pathogenic variants have genomic features that are similar to BRCA carriers and may also benefit from PARP inhibitor treatment. Using genomic data from 129 TNBC samples from the Malaysian Breast Cancer (MyBrCa) cohort, we developed a gene expression-based machine learning classifier for homologous recombination deficiency (HRD) in TNBCs. The classifier identified samples with HRD mutational signature at an AUROC of 0.93 in MyBrCa validation datasets and 0.84 in TCGA TNBCs. Additionally, the classifier strongly segregated HRD-associated genomic features in TNBCs from TCGA, METABRIC, and ICGC. Thus, our gene expression classifier may identify triple-negative breast cancer patients with homologous recombination deficiency, suggesting an alternative method to identify individuals who may benefit from treatment with PARP inhibitors or platinum chemotherapy., (© 2024. The Author(s).)

The use of naturally sourced organic materials with chirality, such as the M13 bacteriophage, holds intriguing implications, especially in the field of nanotechnology. The chirality properties of bacteriophages have been demonstrated through numerous studies, particularly in the analysis of liquid crystal phase transitions, developing specific applications. However, exploring the utilization of the M13 bacteriophage as a template for creating chiral nanostructures for optics and sensor applications comes with significant challenges. In this study, the chirality of the M13 bacteriophage was leveraged as a valuable tool for generating helical hybrid structures by combining it with nanoparticles through an evaporation-induced three-dimensional (3D) printing process. Utilizing on the self-assembly property of the M13 bacteriophage, metal nanoparticles were organized into a helical chain under the influence of the M13 bacteriophage at the meniscus interface. External parameters, including nanoparticle shape, the ratio between the bacteriophage and nanoparticles, and pulling speed, were demonstrated as crucial factors affecting the fabrication of helical nanostructures. This study aimed to explore the potential of chiral nanostructure fabrication by utilizing the chirality of the M13 bacteriophage and manipulating external parameters to control the properties of the resulting hybrid structures.

Detection of per- and polyfluoroalkyl substances (PFAS) in food is crucial for ensuring food safety. Therefore, we combined a quick, easy, cheap, rugged, and safe (QuEChERS) extraction method with liquid chromatography-triple-quadrupole mass spectrometry (LC-MS/MS) to detect 35 PFAS in rice. The solvents (water and acetonitrile) were adjusted to pH 2.4, a mixture of anhydrous MgSO 4 , NaCl, and NaOAc was used for extraction, and anhydrous MgSO 4 , a primary/secondary amine, and graphitized carbon black were applied for purification. The limits of detection and recovery were 0.005-0.100 ng·g -1 and 86.5 %-126.4 %, respectively. When this method was used to detect PFAS in packaged instant rice cooked in a microwave or boiled in water, the microwaved sample showed a lower PFAS content. However, both samples had PFAS contents within WHO guidelines and were safe for consumption. This method can be extended to detect PFAS levels in other foods exposed to packaging materials containing PFAS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Objectives: The primary aim of this study was to assess disparities in nasal nitric oxide (NO) levels between individuals diagnosed with eosinophilic chronic rhinosinusitis (ECRS) and those without ECRS. The second aim was to ascertain the comparative predictive efficacy of these nasal NO levels for the presence of ECRS., Methods: A systematic analysis was conducted on relevant studies that compared nasal NO levels in individuals with ECRS and those without. Furthermore, the discriminatory capacity of nasal NO in distinguishing ECRS from non-ECRS cohorts was quantified. The risk of bias across studies was evaluated utilizing the Newcastle-Ottawa scale., Results: The comprehensive review encompassed a total of 5 studies involving 470 participants. Findings revealed that patients diagnosed with ECRS exhibited significantly higher levels of nasal NO, as measured in parts per billion (ppb), compared to their non-ECRS patients. The mean difference was 130.03 ppb (95% confidence interval: [66.30, 193.75], I2 = 58.7%). The diagnostic odds ratio for nasal NO in identifying ECRS was 9.29 ([5.85, 14.75], I2 = 26.4%). The area under the summary receiver operating characteristic curve was 0.82. The correlation between sensitivity and false positive rate was 0.53, suggesting a lack of heterogeneity. Sensitivity, specificity, negative predictive value, and positive predictive value were 69% ([0.55, 0.79], I2   = 77.0%), 83% ([0.73, 0.90], I 2 = 68.5%), 77% ([0.69, 0.83], I 2   = 50.1%), and 75% ([0.67, 0.82], I 2   = 41.5%), respectively., Conclusion: Nasal NO has the potential as a noninvasive diagnostic measure and endotype tool for ECRS., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: We conducted a randomized prospective trial (KLASS-07 trial) to compare laparoscopy-assisted distal gastrectomy (LADG) and totally laparoscopic distal gastrectomy (TLDG) for gastric cancer. In this interim report, we describe short-term results in terms of morbidity and mortality., Methods and Methods: The sample size was 442 participants. At the time of the interim analysis, 314 patients were enrolled and randomized. After excluding patients who did not undergo planned surgeries, we performed a modified per-protocol analysis of 151 and 145 patients in the LADG and TLDG groups, respectively., Results: The baseline characteristics, including comorbidity status, did not differ between the LADG and TLDG groups. Blood loss was somewhat higher in the LADG group, but statistical significance was not attained (76.76±72.63 vs. 62.91±65.68 mL; P=0.087). Neither the required transfusion level nor the operation or reconstruction time differed between the 2 groups. The mini-laparotomy incision in the LADG group was significantly longer than the extended umbilical incision required for specimen removal in the TLDG group (4.79±0.82 vs. 3.89±0.83 cm; P<0.001). There were no between-group differences in the time to solid food intake, hospital stay, pain score, or complications within 30 days postoperatively. No mortality was observed in either group., Conclusions: Short-term morbidity and mortality rates did not differ between the LADG and TLDG groups. The KLASS-07 trial is currently underway., Trial Registration: ClinicalTrials.gov Identifier: NCT03393182., Competing Interests: No potential conflict of interest relevant to this article was reported., (Copyright © 2024. Korean Gastric Cancer Association.)

In breast tumors, somatic mutation frequencies in TP53 and PIK3CA vary by tumor subtype and ancestry. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somatic TP53 or PIK3CA mutation status in breast tumors. A genome-wide association study was conducted in 2,850 women of European ancestry with breast cancer using TP53 and PIK3CA mutation status (positive or negative) as well as specific functional categories [e.g., TP53 gain-of-function (GOF) and loss-of-function, PIK3CA activating] as phenotypes. Germline variants showing evidence of association were selected for validation analyses and tested in multiple independent datasets. Discovery association analyses found five variants associated with TP53 mutation status with P values <1 × 10-6 and 33 variants with P values <1 × 10-5. Forty-four variants were associated with PIK3CA mutation status with P values <1 × 10-5. In validation analyses, only variants at the ESR1 locus were associated with TP53 mutation status after multiple comparisons corrections. Combined analyses in European and Malaysian populations found ESR1 locus variants rs9383938 and rs9479090 associated with the presence of TP53 mutations overall (P values 2 × 10-11 and 4.6 × 10-10, respectively). rs9383938 also showed association with TP53 GOF mutations (P value 6.1 × 10-7). rs9479090 showed suggestive evidence (P value 0.02) for association with TP53 mutation status in African ancestry populations. No other variants were significantly associated with TP53 or PIK3CA mutation status. Larger studies are needed to confirm these findings and determine if additional variants contribute to ancestry-specific differences in mutation frequency., Significance: Emerging data show ancestry-specific differences in TP53 and PIK3CA mutation frequency in breast tumors suggesting that germline variants may influence somatic mutational processes. This study identified variants near ESR1 associated with TP53 mutation status and identified additional loci with suggestive association which may provide biological insight into observed differences., (© 2024 The Authors; Published by the American Association for Cancer Research.)

Background: Despite significant advancements in treatments such as surgery, radiotherapy, and chemotherapy, the survival rate for patients with asbestos-related cancers remains low. Numerous studies have provided evidence suggesting that air pollution induces oxidative stress and inflammation, affecting acute respiratory diseases, lung cancer, and overall mortality. However, because of the high case fatality rate, there is limited knowledge regarding the effects of air pollution exposures on survival following a diagnosis of asbestos-related cancers. This study aimed to determine the effect of air pollution on the survival of patients with malignant mesothelioma and asbestos-related lung cancer., Methods: We followed up with 593 patients with malignant mesothelioma and 998 patients with lung cancer identified as asbestos victims between 2009 and 2022. Data on five air pollutants-sulfur dioxide, carbon monoxide, nitrogen dioxide, fine particulate matter with a diameter < 10 μm, and fine particulate matter with a diameter < 2.5 μm-were obtained from nationwide atmospheric monitoring stations. Cox proportional hazard models were used to estimate the association of cumulative air pollutant exposure with patient mortality, while adjusting for potential confounders. Quantile-based g-computation was used to assess the combined effect of the air pollutant mixture on mortality., Results: The 1-, 3-, and 5-year survival rates for both cancer types decreased with increasing exposure to all air pollutants. The estimated hazard ratios rose significantly with a 1-standard deviation increase in each pollutant exposure level. A quartile increase in the pollutant mixture was associated with a 1.99-fold increase in the risk of malignant mesothelioma-related mortality (95% confidence interval: 1.62, 2.44). For lung cancer, a quartile increase in the pollutant mixture triggered a 1.87-fold increase in the mortality risk (95% confidence interval: 1.53, 2.30)., Conclusion: These findings support the hypothesis that air pollution exposure after an asbestos-related cancer diagnosis can negatively affect patient survival., (© 2024. The Author(s).)

To identify credible causal risk variants (CCVs) associated with different histotypes of epithelial ovarian cancer (EOC), we performed genome-wide association analysis for 470,825 genotyped and 10,163,797 imputed SNPs in 25,981 EOC cases and 105,724 controls of European origin. We identified five histotype-specific EOC risk regions (p value <5 × 10 -8 ) and confirmed previously reported associations for 27 risk regions. Conditional analyses identified an additional 11 signals independent of the primary signal at six risk regions (p value <10 -5 ). Fine mapping identified 4,008 CCVs in these regions, of which 1,452 CCVs were located in ovarian cancer-related chromatin marks with significant enrichment in active enhancers, active promoters, and active regions for CCVs from each EOC histotype. Transcriptome-wide association and colocalization analyses across histotypes using tissue-specific and cross-tissue datasets identified 86 candidate susceptibility genes in known EOC risk regions and 32 genes in 23 additional genomic regions that may represent novel EOC risk loci (false discovery rate <0.05). Finally, by integrating genome-wide HiChIP interactome analysis with transcriptome-wide association study (TWAS), variant effect predictor, transcription factor ChIP-seq, and motifbreakR data, we identified candidate gene-CCV interactions at each locus. This included risk loci where TWAS identified one or more candidate susceptibility genes (e.g., HOXD-AS2, HOXD8, and HOXD3 at 2q31) and other loci where no candidate gene was identified (e.g., MYC and PVT1 at 8q24) by TWAS. In summary, this study describes a functional framework and provides a greater understanding of the biological significance of risk alleles and candidate gene targets at EOC susceptibility loci identified by a genome-wide association study., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Background: This study aimed to evaluate the clinical outcomes and efficacy of enhanced recovery after surgery (ERAS) protocol in patients undergoing distal gastrectomy for gastric cancer (GC)., Methods: Patients were randomly assigned to the ERAS group (EG) and the conventional care group (CG) by stratified randomization according to age and sex. The primary endpoint was adjusted postoperative hospital stay, calculated using discharge criteria developed to evaluate recovery. Nutritional data and quality of life (QoL) (European Organisation for Research and Treatment of Cancer [EORTC] C30 and STO22) during the perioperative period were also analyzed., Results: We enrolled 198 eligible patients with GC for the study between June 2017 and January 2019. A total of 147 patients were finally enrolled in this study (full analysis set) and were assigned to EG (n = 71) and CG (n = 76). First flatus was faster significantly in EG (3.6 ± 1.5 vs 4.1 ± 1.2 days, P = .019). EG showed a faster start of the sips and soft diet than CG (1.3 ± 0.7 vs 3.1 ± 0.4 days, P < .001; 2.4 ± 0.9 vs 5.2 ± 0.7 days, P < .001) according to the protocol. The recorded hospital stay was not significantly different; however, adjusted hospital stay was significantly shorter in EG than in CG (6.5 ± 3.1 vs 7.8 ± 2.1 days, P = .005). There was no difference in morbidity, and no mortality occurred in both groups. EG did not show significant superiority in nutritional outcome and QoL improvement, except for pain scale in EORTC-STO22., Conclusion: The application of the ERAS protocol could reduce the adjusted hospital stay without an increase in postoperative complications. There was no significant difference in long-term nutritional outcome and QoL of the 2 groups., Competing Interests: Declaration of competing interest The authors declare no competing interest., (Copyright © 2024. Published by Elsevier Inc.)