Nicotinamide in Combination with EGFR-TKIs for the Treatment of Stage IV Lung Adenocarcinoma with EGFR Mutations: A Randomized Double-Blind (Phase IIb) Trial.

PURPOSE: RUNX3 is a tumor suppressor gene, which is inactivated in approximately 70% of lung adenocarcinomas. Nicotinamide, a sirtuin inhibitor, has demonstrated potential in re-activating epigenetically silenced RUNX3 in cancer cells. This study assessed the therapeutic benefits of combining nicotinamide with first-generation EGFR-tyrosine kinase inhibitors (TKI) for patients with stage IV lung cancer carrying EGFR mutations. PATIENTS AND METHODS: We assessed the impact of nicotinamide on carcinogen-induced lung adenocarcinomas in mice and observed that nicotinamide increased RUNX3 levels and inhibited lung cancer growth. Subsequently, 110 consecutive patients with stage IV lung cancer who had EGFR mutations were recruited: 70 females (63.6%) and 84 never-smokers (76.4%). The patients were randomly assigned to receive either nicotinamide (1 g/day, n = 55) or placebo (n = 55). The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. RESULTS: After a median follow-up of 54.3 months, the nicotinamide group exhibited a median PFS of 12.7 months [95% confidence interval (CI), 10.4-18.3], while the placebo group had a PFS of 10.9 months (9.0-13.2; P = 0.2). The median OS was similar in the two groups (31.0 months with nicotinamide vs. 29.4 months with placebo; P = 0.2). Notably, subgroup analyses revealed a significant reduction in mortality risk for females (P = 0.01) and never-smokers (P = 0.03) treated with nicotinamide. CONCLUSIONS: The addition of nicotinamide with EGFR-TKIs demonstrated potential improvements in PFS and OS, with notable survival benefits for female patients and those who had never smoked (ClinicalTrials.gov Identifier: NCT02416739).

Efficacy and safety of BVAC-C in HPV type 16- or 18-positive cervical carcinoma who failed 1st platinum-based chemotherapy: a phase I/IIa study.

Background: BVAC-C, a B cell- and monocyte-based immunotherapeutic vaccine transfected with recombinant HPV E6/E7, was well tolerated in HPV-positive recurrent cervical carcinoma patients in a phase I study. This phase IIa study investigates the antitumor activity of BVAC-C in patients with HPV 16- or 18-positive cervical cancer who had experienced recurrence after a platinum-based combination chemotherapy. Patients and methods: Patients were allocated to 3 arms; Arm 1, BVAC-C injection at 0, 4, 8 weeks; Arm 2, BVAC-C injection at 0, 4, 8, 12 weeks; Arm 3, BVAC-C injection at 0, 4, 8, 12 weeks with topotecan at 2, 6, 10, 14 weeks. Primary endpoints were safety and objective response rate (ORR) as assessed by an independent radiologist according to Response Evaluation Criteria in Solid Tumors version 1.1. Secondary endpoints included the disease control rate (DCR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Of the 30 patients available for analysis, the ORR was 19.2% (Arm 1: 20.0% (3/15), Arm 2: 33.3% (2/6), Arm3: 0%) and the DCR was 53.8% (Arm 1: 57.1%, Arm 2: 28.6%, Arm3: 14.3%). The median DOR was 7.5 months (95% CI 7.1-not reported), the median PFS was 5.8 months (95% CI 4.2-10.3), and the median OS was 17.7 months (95% CI 12.0-not reported). All evaluated patients showed not only inflammatory cytokine responses (IFN-γ or TNF-α) but also potent E6/E7-specific T cell responses upon vaccinations. Immune responses of patients after vaccination were correlated with their clinical responses. Conclusion: BVAC-C represents a promising treatment option and a manageable safety profile in the second-line setting for this patient population. Further studies are needed to identify potential biomarkers of response. Clinical trial registration: ClinicalTrials.gov, identifier NCT02866006.

Impact of Co-Doping on the Visible Light-Driven Photocatalytic and Photoelectrochemical Activities of Eu(OH)3.

The microwave-assisted synthesis approach was used to synthesize Eu(OH)3 and Co-Eu(OH)3 nanorods. Various techniques were used to investigate the structural, optical, and morphological features of the Eu(OH)3 and Co-Eu(OH)3 NRs. Both Eu(OH)3 and Co-Eu(OH)3 NRs were found to be hexagonal with crystallite sizes ranging from 21 to 35 nm. FT-IR and Raman spectra confirmed the formation of Eu(OH)3 and Co-Eu(OH)3. Rod-shaped Eu(OH)3 and Co-Eu(OH)3 with average lengths and diameters ranging from 27 to 50 nm and 8 to 12 nm, respectively, were confirmed by TEM. The addition of Co was found to increase the particle size. Furthermore, with increased Co doping, the band gap energies of Co-Eu(OH)3 NRs were lowered (3.80-2.49 eV) in comparison to Eu(OH)3, and the PL intensities with Co doping were quenched, suggesting the lessening of electron/hole recombination. The effect of these altered properties of Eu(OH)3 and Co-Eu(OH)3 was observed through the photocatalytic degradation of brilliant green dye (BG) and photoelectrochemical activity. In the photocatalytic degradation of BG, 5% Co-Eu(OH)3 had the highest response. However, photoelectrochemical experiments suggested that 10% Co-Eu(OH)3 NRs showed improved activity when exposed to visible light. As a result, Co-Eu(OH)3 NRs have the potential to be a promising visible-light active material for photocatalysis.

Effect of modification methods on the physical properties and immunomodulatory activity of particulate ß-glucan.

ß-Glucan is an immunoenhancing agent whose biological activities are linked to molecular structure. On that basis, the polysaccharide can be physiochemically modified to produce valuable functional materials. This study investigated the physical properties and immunostimulatory activity of modified ß-glucan. Alkali-treated ß-glucan had a distinct shape and smaller particle size than untreated ß-glucan. The reduced particle size was conducive to the stability of the suspension because the ß-glucan appeared to be completely dissolved by this treatment, forming an amorphous mass. Furthermore, alkali treatment improved the immunostimulating activity of ß-glucan, whereas exposure of macrophages to heat-treated ß-glucan decreased their immune activity. ß-Glucan with reduced particle size by wet-grinding also displayed immunomodulatory activities. These results suggested that the particle size of ß-glucan is a key factor in ß-glucan-induced immune responses of macrophages. Thus, the modification of the ß-glucan particle size provides new opportunities for developing immunoenhancing nutraceuticals or pharmacological therapies in the future.

The Diversity of Surgical Trainees Index Identifies Racial and Ethnic Disparities Among Surgical Specialties.

BACKGROUND: Racial and ethnic disparities have been well-described among surgical specialties, however, variations in underrepresented minority (URiM) representation between these specialties have not previously been quantified. METHODS: Data collected from Accreditation Council for Graduate Medical Education (ACGME) annual reports were used to derive the Diversity of Surgical Trainee Index (DoSTI) metric, which was calculated as the proportion of URiM resident and fellow physicians within a given surgical specialty, relative to the overall proportion of URiM trainees within all surgical and non-surgical ACGME-accredited programs in the same academic year. RESULTS: From 2013 to 2022, a total of 108,193 ACGME-accredited residency programs trained 1,296,204 residents and fellows in the United States. Of these, 14.1% (n=182,680) of trainees self-identified as URiM over the study period. The mean DoSTI among all surgical specialties was 0.80 (standard error, 0.01) compared with all ACGME-accredited programs. High DoSTI specialties incorporated significantly higher proportions of Hispanic (8.7% vs 6.3%) and Black (5.2% vs 2.5%) trainees compared with low DoSTI specialties (p<0.0001 each). General surgery (1.06±0.01), plastic surgery (traditional) (1.12±0.06), vascular surgery (integrated) (0.96±0.03), and vascular surgery (traditional) (0.94±0.06) had the highest DoSTI indices (p<0.05 each vs composite). On linear regression analysis, only ophthalmology (+0.01/year, R2=0.41, p=0.019), orthopedic surgery (+0.01/year, R2=0.33, p=0.047), otolaryngology (+0.02/year, R2=0.86, p<0.001), and pediatric surgery (+0.06/year, R2=0.33, p=0.048) demonstrated an annual increase in DoSTI. CONCLUSION: The Diversity of Surgical Trainees Index is a novel metric used to quantify the degree of URiM representation among surgical specialties. DoSTI has revealed specialty-specific variations in racial/ethnic minority representation among surgical training programs. This metric may be used to improve provider awareness, identify high performing DoSTI specialties to highlight their best practices, and ultimately, recruit a more diverse surgical workforce.

Evaluating cardiovascular disease risk stratification using multiple-polygenic risk scores and pooled cohort equations: insights from a 17-year longitudinal Korean cohort study.

Cardiovascular disease (CVD) remains the leading cause of mortality worldwide, caused by a complex interplay of genetic and environmental factors. This study aimed to evaluate the combined efficacy of multi-polygenic risk scores and pooled cohort equations (PCE) for predicting future CVD risks in the Korean population. In this longitudinal study, 7,612 individuals from the Ansan and Ansung cohorts were analyzed over a 17-year follow-up period. The participants were genotyped using the Korea Biobank Array, and quality-controlled genetic data were subjected to imputation analysis. The weighted sum of the PRSs (wPRSsum) was calculated using PRS-CS with summary statistics from myocardial infarction, ischemic stroke, coronary artery disease, and hypertension genome-wide association studies. The recalibrated PCE was used to assess clinical risk, and the participants were stratified into risk groups based on the wPRSsum and PCE. Associations between these risk scores and incident CVD were evaluated using Cox proportional hazards models and Kaplan-Meier analysis. The wPRSsum approach showed a significant association with incident CVD (HR = 1.15, p = 7.49 × 10-5), and the top 20% high-risk genetic group had an HR of 1.50 (p = 5.04 × 10-4). The recalibrated PCE effectively differentiated between the low and high 10-year CVD risk groups, with a marked difference in survival rates. The predictive models constructed using the wPRSsum and PCE demonstrated a slight improvement in prediction accuracy, particularly among males aged <55 years (C-index = 0.640). We demonstrated that while the integration of wPRSsum with PCE did not significantly outperform the PCE-only model (C-index: 0.703 for combined and 0.704 for PCE-only), it provided enhanced stratification of CVD risk. The highest risk group, identified through the combination of high wPRSsum and PCE scores, exhibited an HR of 4.99 for incident CVD (p = 1.45 × 10-15). These findings highlight the potential of integrating genetic risk assessments with traditional clinical tools for effective CVD risk stratification. Although the addition of wPRSsum to the PCE provided a marginal predictive improvement, it proved valuable in identifying high-risk individuals and supporting personalized treatment strategies. This study reinforces the utility of multi-PRS in conjunction with clinical risk assessment tools, paving the way for more tailored approaches for CVD prevention and management in diverse populations.

2024 European Heart Rhythm Association/Heart Rhythm Society/Asia Pacific Heart Rhythm Society/Latin American Heart Rhythm Society expert consensus statement on catheter and surgical ablation of atrial fibrillation.

In the last three decades, ablation of atrial fibrillation (AF) has become an evidence-based safe and efficacious treatment for managing the most common cardiac arrhythmia. In 2007, the first joint expert consensus document was issued, guiding healthcare professionals involved in catheter or surgical AF ablation. Mounting research evidence and technological advances have resulted in a rapidly changing landscape in the field of catheter and surgical AF ablation, thus stressing the need for regularly updated versions of this partnership which were issued in 2012 and 2017. Seven years after the last consensus, an updated document was considered necessary to define a contemporary framework for selection and management of patients considered for or undergoing catheter or surgical AF ablation. This consensus is a joint effort from collaborating cardiac electrophysiology societies, namely the European Heart Rhythm Association, the Heart Rhythm Society (HRS), the Asia Pacific HRS, and the Latin American HRS.

Unipolar myomectomy for congenital muscular torticollis: A retrospective study.

In this study, unipolar myomectomy was used to address limited neck movement and tight muscles in pediatric, adolescent, and adult patients. A retrospective chart review was performed for patients from January 2006 to February 2023, who were diagnosed with congenital muscular torticollis and underwent a unipolar myomectomy. Outcome evaluation, adapted from the Cheng and Tang system - cervicomandibular angle (CMA), facial asymmetry, cranial asymmetry, tilting limitation (TL), rotation limitation (RL), subjective assessment, and residual contracture - included various parameters scored from 0 to 3 points and categorized as poor, fair, good, or excellent. In total, the data for 36 patients (21 males and 15 females) were analyzed. Participants were aged 0.8-38 years. Surgery improved CMA, RL, and TL, with no complications (12.2°-1.2°, 18.6°-5.2°, and 17.6°-6.5° for CMA, RL, and TL, respectively; p < 0.001). The mean overall score was comparable among different age groups (2.8 ± 0.5, 2.2 ± 0.62, and 2.1 ± 0.37 for the pediatric, adolescent, and adult groups, respectively). Within the limitations of the study it seems that unipolar myomectomy is a promising, effective surgical option for individuals of multiple age groups.

Clinical Utility of a CT-based AI Prognostic Model for Segmentectomy in Non-Small Cell Lung Cancer.

Background Currently, no tool exists for risk stratification in patients undergoing segmentectomy for non-small cell lung cancer (NSCLC). Purpose To develop and validate a deep learning (DL) prognostic model using preoperative CT scans and clinical and radiologic information for risk stratification in patients with clinical stage IA NSCLC undergoing segmentectomy. Materials and Methods In this single-center retrospective study, transfer learning of a pretrained model was performed for survival prediction in patients with clinical stage IA NSCLC who underwent lobectomy from January 2008 to March 2017. The internal set was divided into training, validation, and testing sets based on the assignments from the pretraining set. The model was tested on an independent test set of patients with clinical stage IA NSCLC who underwent segmentectomy from January 2010 to December 2017. Its prognostic performance was analyzed using the time-dependent area under the receiver operating characteristic curve (AUC), sensitivity, and specificity for freedom from recurrence (FFR) at 2 and 4 years and lung cancer-specific survival and overall survival at 4 and 6 years. The model sensitivity and specificity were compared with those of the Japan Clinical Oncology Group (JCOG) eligibility criteria for sublobar resection. Results The pretraining set included 1756 patients. Transfer learning was performed in an internal set of 730 patients (median age, 63 years [IQR, 56-70 years]; 366 male), and the segmentectomy test set included 222 patients (median age, 65 years [IQR, 58-71 years]; 114 male). The model performance for 2-year FFR was as follows: AUC, 0.86 (95% CI: 0.76, 0.96); sensitivity, 87.4% (7.17 of 8.21 patients; 95% CI: 59.4, 100); and specificity, 66.7% (136 of 204 patients; 95% CI: 60.2, 72.8). The model showed higher sensitivity for FFR than the JCOG criteria (87.4% vs 37.6% [3.08 of 8.21 patients], P = .02), with similar specificity. Conclusion The CT-based DL model identified patients at high risk among those with clinical stage IA NSCLC who underwent segmentectomy, outperforming the JCOG criteria. © RSNA, 2024 Supplemental material is available for this article.

Prediction of postoperative cerebral infarction after combined bypass surgery in adult moyamoya disease: combining quantitative parameters on RAPID perfusion CT with clinically related factors.

OBJECTIVE: The aim of this study was to identify predictive factors of postoperative cerebral infarction (PostCI) following combined bypass (CB) surgery in adult patients with moyamoya disease (MMD) using quantitative parameters from the rapid processing of perfusion and diffusion (RAPID) perfusion CT (PCT) software. METHODS: The authors retrospectively reviewed 276 total hemispheres in patients with MMD who underwent CB. Preoperative volumes of time-to-maximum (Tmax) > 4 sec and > 6 sec were obtained from the RAPID analysis of PCT. These quantitative parameters, along with other clinical and angiographic factors, were statistically analyzed to determine the significant predictors for PostCI following CB. RESULTS: PostCI occurred in 17 hemispheres (6.16%). PCA involvement (p = 0.016), and the volume of Tmax > 6 sec (p < 0.001) and Tmax > 4 sec (p < 0.001), were identified as variables related to PostCI in the univariable analysis. In the multivariable analysis, the volume of Tmax > 6 sec (OR 1.013, 95% confidence interval 1.007-1.019, p < 0.001) was determined to be an independent predictive factor significantly associated with PostCI after CB in adult patients with MMD. In the receiver operating characteristic (ROC) curve, the cutoff value of the preoperative volume of Tmax > 6 sec was determined to be 59.5 ml (sensitivity 82.4%, specificity 71.9%, area under the ROC curve 0.811). CONCLUSIONS: For adult patients with MMD and a large volume of Tmax > 6 sec over 59.5 ml, more caution is required when deciding to undergo bypass surgery and in postoperative management.

Clinical and Genetic Characteristics Associated With Survival Outcome in Late-Onset Huntington's Disease in South Korea.

BACKGROUND AND PURPOSE: The onset of Huntington's disease (HD) usually occurs before the age of 50 years, and the median survival time from onset is 15 years. We investigated survival in patients with late-onset HD (LoHD) (age at onset ≥60 years) and the associations of the number of mutant CAG repeats and age at onset (AAO) with survival in patients with HD. METHODS: Patients with genetically confirmed HD at six referral centers in South Korea between 2000 and 2020 were analyzed retrospectively. Baseline demographic, clinical, and genetic characteristics and the survival status as at December 2020 were collected. RESULTS: Eighty-seven patients were included, comprising 26 with LoHD (AAO=68.77±5.91 years, mean±standard deviation; 40.54±1.53 mutant CAG repeats) and 61 with common-onset HD (CoHD) (AAO=44.12±8.61 years, 44.72±4.27 mutant CAG repeats). The ages at death were 77.78±7.46 and 53.72±10.86 years in patients with LoHD and CoHD, respectively (p<0.001). The estimated survival time was 15.21±2.49 years for all HD patients, and 10.74±1.95 and 16.15±2.82 years in patients with LoHD and CoHD, respectively. More mutant CAG repeats and higher AAO were associated with shorter survival (hazard ratio [HR]=1.05, 95% confidence interval [CI]=1.01-1.09, p=0.019; and HR=1.17, 95% CI=1.03-1.31, p=0.013; respectively) for all HD patients. The LoHD group showed no significant factors associated with survival after disease onset, whereas the number of mutant CAG repeats had a significant effect (HR=1.12, 95% CI=1.01-1.23, p=0.034) in the CoHD group. CONCLUSIONS: Survival after disease onset was shorter in patients with LoHD than in those with CoHD. More mutant CAG repeats and higher AAO were associated with shorter survival in patients with HD.

Complexation of Poly(ethylene glycol)-(ds)OligoDNA Conjugates with Ionic Liquids.

We report the complexation of poly(ethylene glycol) conjugated double-stranded oligoDNA (PEG-(ds)oligoDNA) with imidazolium-based ionic liquids (ILs) to form polyelectrolyte complex aggregates (PCAs). The PEG-(ds)oligoDNA conjugates are prepared following a solution-phase coupling reaction. The binding of PEG-(ds)oligoDNA with either 1-butyl-3-methylimidazolium tetrafluoroborate ([BMIM][BF4]) or 1-hexyl-3-methylimidazolium tetrafluoroborate ([HMIM][BF4]) is confirmed by a fluorescence displacement assay. Both ILs show stronger binding affinity to PEG-(ds)oligoDNA than bare (ds)oligoDNA due to the PEG-assisted increase in IL cation concentration in the vicinity of (ds)oligoDNA. The complex morphology formed at various amine (N) to phosphate (P) ratios is also examined. At high N/P ratios above 4, nanosized PCAs are formed, driven by a counterion-mediated attraction among the IL-bound (ds)oligoDNA segments and stabilized by the conjugated PEG segments. The PCAs exhibit near-neutral surface charges and resistance to DNase degradation, suggesting their potential use in gene delivery applications.

Total Synthesis and Cytotoxicity Evaluation of Pareitropone and Analogues.

A concise synthesis of pareitropone by oxidative cyclization of a phenolic nitronate is delineated. The use of TMSOTf as an additive to promote the facile formation of a strained norcaradiene intermediate provides convenient access to highly condensed multicyclic tropones in high yields. This synthesis is modular, efficient, and scalable, highlighting the synthetic utility of radical anion coupling reactions in annulation reactions. This work is discussed in the context of total syntheses of the tropoloisoquinoline alkaloids. Also included are the preparation of several congeners and a brief description of their biological activities.

Impact of the COVID-19 pandemic on clinical and psychological aspects of temporomandibular disorders.

BACKGROUND: The Coronavirus 2019 disease (COVID-19) caused drastic changes in people's lifestyle that affected TMD characteristics through its physical and psychological influences. The aim of this study was to define the clinical and psychological characteristics of a large group of well-defined TMD patients and seek their differences between before and during the COVID-19 pandemic to establish points of care to be emphasized in the post-pandemic era. METHODS: TMD patients diagnosed by the Diagnostic Criteria for Temporomandibular Disorders (DC/TMD) aged ≥ 18 were analyzed. Samples between September, 2017 to July, 2019 (n = 455) and March, 2021 to June, 2022 (n = 338) were collected to represent before and during COVID-19, respectively. The Graded Chronic Pain Scale (GCPS) and Symptom Checklist-90-Revision (SCL-90-R) were used to evaluate disability levels and psychological status. Clinical indices were compared between COVID periods and factors related to higher pain levels were investigated according to pandemic period. RESULTS: More patients reported pain on palpation of the masticatory muscles during the pandemic (p = 0.021) while the number decreased for neck muscles (p = 0.001) and TMJ (p < 0.001) areas. Patients reporting nocturnal bruxism (23.3-29.6%) and clenching (45.1-54.7%) significantly increased during the pandemic. TMD patients with pain without disability were more common during the pandemic regardless of pain intensity (p < 0.001). The number of patients expressing interference in daily activities decreased drastically during COVID-19 regardless of disability level (p < 0.001). Factors associated with higher than moderate pain intensity (CPI ≥ 50) were insomnia (odds ratio [OR] = 1.603, p = 0.047) and somatization (OR = 1.082, p < 0.001) before the pandemic. During the pandemic, age (OR = 1.024, p = 0.007), somatization (OR = 1.070, p = 0.006), and paranoid ideation (OR = 1.117, p = 0.003) were significantly associated with higher pain intensity. CONCLUSIONS: The results of our study underline the importance of evaluating psychological profiles of TMD patients, especially somatization, paranoid ideation and psychoticism, in exceptional situations that may cause a change in individual mental status. This will lead to a better understanding of the individual TMD patient and help in planning personalized treatment strategies that will assist the patient in adjusting to changes occurring in special environments such as the COVID-19 pandemic.

Mapping cutaneous field carcinogenesis of nonmelanoma skin cancer using mesoscopic imaging of pro-inflammation cues.

Nonmelanoma skin cancers remain the most widely diagnosed types of cancers globally. Thus, for optimal patient management, it has become imperative that we focus our efforts on the detection and monitoring of cutaneous field carcinogenesis. The concept of field cancerization (or field carcinogenesis), introduced by Slaughter in 1953 in the context of oral cancer, suggests that invasive cancer may emerge from a molecularly and genetically altered field affecting a substantial area of underlying tissue including the skin. A carcinogenic field alteration, present in precancerous tissue over a relatively large area, is not easily detected by routine visualization. Conventional dermoscopy and microscopy imaging are often limited in assessing the entire carcinogenic landscape. Recent efforts have suggested the use of noninvasive mesoscopic (between microscopic and macroscopic) optical imaging methods that can detect chronic inflammatory features to identify pre-cancerous and cancerous angiogenic changes in tissue microenvironments. This concise review covers major types of mesoscopic optical imaging modalities capable of assessing pro-inflammatory cues by quantifying blood haemoglobin parameters and hemodynamics. Importantly, these imaging modalities demonstrate the ability to detect angiogenesis and inflammation associated with actinically damaged skin. Representative experimental preclinical and human clinical studies using these imaging methods provide biological and clinical relevance to cutaneous field carcinogenesis in altered tissue microenvironments in the apparently normal epidermis and dermis. Overall, mesoscopic optical imaging modalities assessing chronic inflammatory hyperemia can enhance the understanding of cutaneous field carcinogenesis, offer a window of intervention and monitoring for actinic keratoses and nonmelanoma skin cancers and maximise currently available treatment options.

A Revision of the Phylogeny of Helicotylenchus Steiner, 1945 (Tylenchida: Hoplolaimidae) as Inferred from Ribosomal and Mitochondrial DNA.

Identification of Helicotylenchus species is very challenging due to phenotypic plasticity and existence of cryptic species complexes. Recently, the use of rDNA barcodes has proven to be useful for identification of Helicotylenchus. Molecular markers are a quick diagnostic tool and are crucial for discriminating related species and resolving cryptic species complexes within this speciose genus. However, DNA barcoding is not an error-free approach. The public databases appear to be marred by incorrect sequences, arising from sequencing errors, mislabeling, and misidentifications. Herein, we provide a comprehensive analysis of the newly obtained, and published DNA sequences of Helicotylenchus, revealing the potential faults in the available DNA barcodes. A total of 97 sequences (25 nearly full-length 18S-rRNA, 12 partial 28S-rRNA, 16 partial internal transcribed spacer [ITS]-rRNA, and 44 partial cytochrome c oxidase subunit I [COI] gene sequences) were newly obtained in the present study. Phylogenetic relationships between species are given as inferred from the analyses of 103 sequences of 18S-rRNA, 469 sequences of 28S-rRNA, 183 sequences of ITS-rRNA, and 63 sequences of COI. Remarks on suggested corrections of published accessions in GenBank database are given. Additionally, COI gene sequences of H. dihystera, H. asiaticus and the contentious H. microlobus are provided herein for the first time. Similar to rDNA gene analyses, the COI sequences support the genetic distinctness and validity of H. microlobus. DNA barcodes from type material are needed for resolving the taxonomic status of the unresolved taxonomic groups within the genus.

A compendium of multi-omics data illuminating host responses to lethal human virus infections.

Human infections caused by viral pathogens trigger a complex gamut of host responses that limit disease, resolve infection, generate immunity, and contribute to severe disease or death. Here, we present experimental methods and multi-omics data capture approaches representing the global host response to infection generated from 45 individual experiments involving human viruses from the Orthomyxoviridae, Filoviridae, Flaviviridae, and Coronaviridae families. Analogous experimental designs were implemented across human or mouse host model systems, longitudinal samples were collected over defined time courses, and global multi-omics data (transcriptomics, proteomics, metabolomics, and lipidomics) were acquired by microarray, RNA sequencing, or mass spectrometry analyses. For comparison, we have included transcriptomics datasets from cells treated with type I and type II human interferon. Raw multi-omics data and metadata were deposited in public repositories, and we provide a central location linking the raw data with experimental metadata and ready-to-use, quality-controlled, statistically processed multi-omics datasets not previously available in any public repository. This compendium of infection-induced host response data for reuse will be useful for those endeavouring to understand viral disease pathophysiology and network biology.

Age-stratified analysis of temporomandibular joint osteoarthritis using cone-beam computed tomography.

Purpose: This study aimed to evaluate age-stratified radiographic features in temporomandibular joint osteoarthritis using cone-beam computed tomography. Materials and Methods: In total, 210 joints from 183 patients (144 females, 39 males, ranging from 12 to 88 years old with a mean age of 44.75±19.97 years) diagnosed with temporomandibular joint osteoarthritis were stratified by age. Mandibular condyle position and bony changes (flattening, erosion, osteophytes, subchondral sclerosis, and subchondral pseudocysts in both the condyle and articular eminence, thickening of the glenoid fossa, joint space narrowing, and joint loose bodies) were evaluated through cone-beam computed tomography. After adjusting for sex, the association between age groups and radiographic findings was analyzed using both a multiple regression model and a multinomial logistic regression model (α=0.05). Results: The prevalence of joint space narrowing and protruded condyle position in the glenoid fossa significantly increased with age (P<0.05). The risks of bony changes, including osteophytes and subchondral pseudocysts in the condyle; flattening, erosion, osteophyte, and subchondral sclerosis in the articular eminence; joint loose bodies; and thickening of the glenoid fossa, also significantly rose with increasing age (P<0.05). The number of radiographic findings increased with age; in particular, the increase was more pronounced in the temporal bone than in the mandibular condyle (P<0.05). Conclusion: Increasing age was associated with a higher frequency and greater diversity of bony changes in the temporal bone, as well as a protruded condyle position in the glenoid fossa, resulting in noticeable joint space narrowing in temporomandibular joint osteoarthritis.

Improvement in Health-Related Quality of Life Following Antibiotic Treatment in Nontuberculous Mycobacterial Pulmonary Disease: Initial Analysis of the NTM-KOREA Cohort.

BACKGROUND: Improving health-related quality of life (HRQOL) has emerged as a priority in the management of nontuberculous mycobacterial pulmonary disease (NTM-PD). We aimed to evaluate HRQOL and its changes after 6 months' treatment in patients with NTM-PD. METHODS: The NTM-KOREA is a nationwide prospective cohort enrolling patients initiating treatment for NTM-PD in 8 institutions across South Korea. We conducted the Quality of Life-Bronchiectasis (QOL-B) at 6-month intervals and evaluated baseline scores (higher scores indicate better quality of life) and changes after 6 months' treatment. Multivariate logistic regression was performed to identify factors associated with improvement in the QOL-B physical functioning and respiratory symptoms domains. RESULTS: Between February 2022 and August 2023, 411 patients were included in the analysis. Baseline scores (95% confidence interval [CI]) for physical functioning and respiratory symptoms were 66.7 (46.7-86.7) and 81.5 (70.4-92.6), respectively. Among 228 patients who completed the QOL-B after 6 months' treatment, improvements in physical functioning and respiratory symptoms were observed in 61 (26.8%) and 71 (31.1%) patients, respectively. A lower score (adjusted odds ratio; 95% CI) for physical functioning (0.93; 0.91-0.96) and respiratory symptoms (0.92; 0.89-0.95) at treatment initiation was associated with a greater likelihood of physical functioning and respiratory symptom improvement, respectively; achieving culture conversion was not associated with improvement in physical functioning (0.62; 0.28-1.39) or respiratory symptoms (1.30; 0.62-2.74). CONCLUSIONS: After 6 months of antibiotic treatment for NTM-PD, HRQOL improved in almost one-third, especially in patients with severe initial symptoms, regardless of culture conversion. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov identifier: NCT03934034.