Gender differences in PTSD severity and pain outcomes: Baseline results from the LAMP trial.

BACKGROUND: Post-traumatic stress disorder (PTSD) and chronic pain are highly prevalent comorbid conditions. Veterans dually burdened by PTSD and chronic pain experience more severe outcomes compared to either disorder alone. Few studies have enrolled enough women Veterans to test gender differences in pain outcomes [catastrophizing, intensity, interference] by the severity of PTSD symptoms. AIM: Examine gender differences in the association between PTSD symptoms and pain outcomes among Veterans enrolled in a chronic pain clinical trial. METHODS: Participants were 421 men and 386 women Veterans with chronic pain who provided complete data on PTSD symptoms and pain outcomes. We used hierarchical linear regression models to examine gender differences in pain outcomes by PTSD symptoms. RESULTS: Adjusted multivariable models indicated that PTSD symptoms were associated with higher levels of pain catastrophizing (0.57, 95% CI [0.51, 0.63]), pain intensity (0.30, 95% CI [0.24, 0.37]), and pain interference (0.46, 95% CI [0.39, 0.52]). No evidence suggesting gender differences in this association were found in either the crude or adjusted models (all interaction p-values<0.05). CONCLUSION: These findings may reflect the underlying mutual maintenance of these conditions whereby the sensation of pain could trigger PTSD symptoms, particularly if the trauma and pain are associated with the same event. Clinical implications and opportunities testing relevant treatments that may benefit both chronic pain and PTSD are discussed.

Long-term survival in patients with brain-only metastatic non-small cell lung cancer undergoing upfront intracranial stereotactic radiosurgery and definitive treatment to the thoracic primary site.

BACKGROUND AND PURPOSE: To evaluate modern clinical outcomes for patients with brain-only metastatic non-small cell lung cancer (NSCLC) treated with intracranial stereotactic radiosurgery (SRS) with or without definitive treatment of the primary site. MATERIALS AND METHODS: Patients with synchronously diagnosed NSCLC and brain-only metastatic disease treated with intracranial SRS at a single institution were retrospectively identified. Patients were stratified based on whether they did (A) or did not (B) receive definitive primary site treatment. Patient characteristics and clinical outcomes were compared. RESULTS: From 2008 to 2022, 103 patients were identified, 53 of whom received definitive primary site treatment. Median follow-up was 2.1 y (A) and 0.8 y (B) (p < 0.001). 28 (53 %) patients in Group A received immune checkpoint inhibitor (ICI) therapy versus 19 (38 %) in Group B (p = 0.13) and there were no other statistically significant baseline or treatment characteristic differences between the groups. 5-year local-PFS was 34.5 % (A) versus 0 % (B) (p < 0.001). 5-year regional-PFS was 33.0 % (A) versus 0 % (B) (p < 0.001). 5-year distant body-PFS was 34.0 % (A) versus 0 % (B) (p < 0.001). 5-year CNS-PFS was 14.7 % (A) versus 0 % (B) (p = 0.12). 5-year OS was 40.2 % (A) versus 0 % (B) (p = 0.001). 5-year CSS was 67.6 % (A) versus 0 % (B) (p = 0.002). On multivariable analysis, lack of definitive treatment to the primary site (HR = 2.40), AJCC T3-4 disease (HR = 2.73), and lack of ICI therapy (HR = 2.86) were significant predictors of death. CONCLUSION: Definitive treatment to the thoracic primary site in patients with brain-only metastatic NSCLC after intracranial radiosurgery was associated with slower progression of disease and improved survival.

Exploring Gender Differences in Veterans in a Secondary Analysis of a Randomized Controlled Trial of Mindfulness for Chronic Pain.

Background: Although studies have documented higher rates of chronic pain among women Veterans compared to men Veterans, there remains a lack of comprehensive information about potential contributors to these disparities. Materials and Methods: This study examined gender differences in chronic pain and its contributors among 419 men and 392 women Veterans, enrolled in a mindfulness trial for chronic pain. We conducted descriptive analyses summarizing distributions of baseline measures, obtained by survey and through the electronic health record. Comparisons between genders were conducted using chi-square tests for categorical variables and t-tests for continuous measures. Results: Compared to men, women Veterans were more likely to have chronic overlapping pain conditions and had higher levels of pain interference and intensity. Women had higher prevalence of psychiatric and sleep disorder diagnoses, greater levels of depression, anxiety, post-traumatic stress disorder, fatigue, sleep disturbance, stress and pain catastrophizing, and lower levels of pain self-efficacy and participation in social roles and activities. However, women were less likely to smoke or have a substance abuse disorder and used more nonpharmacological pain treatment modalities. Conclusion: Among Veterans seeking treatment for chronic pain, women differed from men in their type of pain, had greater pain intensity and interference, and had greater prevalence and higher levels of many known biopsychosocial contributors to pain. Results point to the need for pain treatment that addresses the comprehensive needs of women Veterans.Clinical Trial Registration Number: NCT04526158. Patient enrollment began on December 4, 2020.

Epigenetic Regulation of Ameloblast Differentiation by HMGN Proteins.

Dental enamel formation is coordinated by ameloblast differentiation, production of enamel matrix proteins, and crystal growth. The factors regulating ameloblast differentiation are not fully understood. Here we show that the high mobility group N (HMGN) nucleosomal binding proteins modulate the rate of ameloblast differentiation and enamel formation. We found that HMGN1 and HMGN2 proteins are downregulated during mouse ameloblast differentiation. Genetically altered mice lacking HMGN1 and HMGN2 proteins show faster ameloblast differentiation and a higher rate of enamel deposition in mice molars and incisors. In vitro differentiation of induced pluripotent stem cells to dental epithelium cells showed that HMGN proteins modulate the expression and chromatin accessibility of ameloblast-specific genes and affect the binding of transcription factors epiprofin and PITX2 to ameloblast-specific genes. Our results suggest that HMGN proteins regulate ameloblast differentiation and enamel mineralization by modulating lineage-specific chromatin accessibility and transcription factor binding to ameloblast regulatory sites.

Structural vulnerabilities and PrEP awareness among Boston heterosexuals and people who inject drugs at risk for HIV: findings from 2018 to 2019 cycles from the Boston, MA site of the NHBS.

Little is known about biopsychosocial factors relating to pre-exposure prophylaxis (PrEP) awareness among people with either heterosexual or injection drug use HIV risk behaviors. Participants engaged in vaginal/anal sex with a person of the opposite sex (N = 515) or were people who injected drugs (PWID; N = 451) in the past 12 months from 2018-2019 in Boston, MA. We examined associations between PrEP awareness and: homelessness; perceived HIV-related stigma; country of birth; bacterial STDs, chlamydia, and/or gonorrhea in the past 12 months, lifetime hepatitis C virus (HCV) infection, sexual orientation, and poverty. More PWID (36.8%) were aware of PrEP than people with heterosexual HIV risk (28%; p = .001). Among people with heterosexual risk, homelessness (aOR = 1.99, p = .003), and among PWID: homelessness (aOR = 2.11, p = .032); bacterial STD (aOR = 2.96, p = .012); chlamydia (aOR = 6.14, p = .008); and HCV (aOR = 2.40, p < .001) were associated with increased likelihood of PrEP awareness. In the combined sample: homelessness (aOR = 2.25, p < .001); HCV (aOR = 2.18, p < .001); identifying as homosexual (aOR = 3.71, p = .036); and bisexual (aOR = 1.55, p = .016) were each associated with PrEP awareness. Although having an STD, HCV, identifying as homosexual or bisexual, and experiencing homelessness were associated with increased PrEP awareness, most participants were unaware of PrEP. Efforts to increase PrEP awareness could engage PWID and heterosexual HIV risk behavior.

An individual patient data meta-analysis of wound care in patients with toxic epidermal necrolysis.

Toxic epidermal necrolysis (TEN) involves extensive mucocutaneous loss, and care is supportive. The approach to wound care includes surgical debridement or using dressings while leaving the epidermis intact. Robust evidence for either approach is lacking. We compared surgical debridement to the use of dressings while leaving the epidermis in situ (referred to hereon as dressings) in adult patients with TEN. The primary outcome assessed was mortality. The secondary outcome was time to re-epithelialisation. The impact of medications was evaluated. An individual patient data (IPD) systematic review and meta-analysis was undertaken. A random effects meta-analysis and survival analysis for IPD data examined mortality, re-epithelisation time and the effect of systemic medications. The quality of evidence was rated per the Grading of Recommendations Assessment, Development and Evaluation (GRADE). PROSPERO: CRD42021266611 Fifty-four studies involving 227 patients were included in the systematic review and meta-analysis, with a GRADE from very low to moderate. There was no difference in survival in patients who had surgical debridement or dressings (univariate: p = 0.91, multivariate: p = 0.31). Patients who received dressings re-epithelialised faster than patients who underwent debridement (multivariate HR: 1.96 [1.09-3.51], p = 0.023). Intravenous immunoglobulin (univariate HR: 0.21 [0.09-0.45], p < 0.001; multivariate HR: 0.22 [0.09-0.53], p < 0.001) and cyclosporin significantly reduced mortality (univariate HR: 0.09 [0.01-0.96], p = 0.046; multivariate HR: 0.06 [0.01-0.73], p = 0.028) irrespective of the wound care. This study supports the expert consensus of the dermatology hospitalists, that wound care in patients with TEN should be supportive with the epidermis left intact and supported with dressings, which leads to faster re-epithelialisation.

Comparison of the Physical Function Trajectories in Three Birth Cohorts of Chinese Older Adults: A 14-Year Longitudinal Study.

OBJECTIVES: It remains uncertain whether the favorable trend of reduction in physical disabilities has become reversed in the recent-born cohorts of older adults. This study aimed to compare the rate of decline with time in self-reported Instrumental Activity of Daily Living (IADL) difficulties, objective measurement of gait speed and grip strength, in three birth cohorts of Chinese older adults. DESIGN: A prospective cohort study. SETTING AND PARTICIPANTS: Four thousand Chinese older adults aged 65 years or above in three birth cohorts (1934-1938, 1929-1933, 1905-1928) were recruited from the community in Hong Kong. MEASUREMENTS: Grip strength, gait speed and IADL difficulties were measured between 2001 to 2017. Joint models were used to examine the trajectories of grip strength, gait speed and IADL difficulties over time, and the interaction effect of age-by-cohort (or also age2-by-cohort) was also examined. RESULTS: The recently born cohort (1934 - 1938) had worse grip strength and more IADL difficulties at the same age than the earlier two cohorts (1929 - 1933; 1905 - 1928). Furthermore, the most recently born cohort also followed a more rapid decline longitudinally with a greater decline observed in gait speed, grip strength and IADL difficulties for women whereas a greater decline in grip strength and IADL difficulties for men. CONCLUSIONS: The continuous improvement of physical limitations in old age may have halted and there appears to be a reversal of this favourable trend in the recent born cohort of older adults living in Hong Kong.

Monitoring environmental microbiomes: Alignment of microbiology and computational biology competencies within a culturally integrated curriculum and research framework.

We have developed a flexible undergraduate curriculum that leverages the place-based research of environmental microbiomes to increase the number of Indigenous researchers in microbiology, data science and scientific computing. Monitoring Environmental Microbiomes (MEM) provides a curriculum and research framework designed to integrate an Indigenous approach when conducting authentic scientific research and to build interest and confidence at the undergraduate level. MEM has been successfully implemented as a short summer workshop to introduce computing practices in microbiome analysis. Based on self-assessed student knowledge of topics and skills, increased scientific confidence and interest in genomics careers were observed. We propose MEM be incorporated in a scalable course-based research experience for undergraduate institutions, including tribal colleges and universities, community colleges and other minority serving institutions. This coupled curricular and research framework explicitly considers cultural perspectives, access and equity to train a diverse future workforce that is more informed to engage in microbiome research and to translate microbiome science to benefit community and environmental health.

Microbiologically influenced corrosion-more than just microorganisms.

Microbiologically influenced corrosion (MIC) is a phenomenon of increasing concern that affects various materials and sectors of society. MIC describes the effects, often negative, that a material can experience due to the presence of microorganisms. Unfortunately, although several research groups and industrial actors worldwide have already addressed MIC, discussions are fragmented, while information sharing and willingness to reach out to other disciplines are limited. A truly interdisciplinary approach, which would be logical for this material/biology/chemistry-related challenge, is rarely taken. In this review, we highlight critical non-biological aspects of MIC that can sometimes be overlooked by microbiologists working on MIC but are highly relevant for an overall understanding of this phenomenon. Here, we identify gaps, methods, and approaches to help solve MIC-related challenges, with an emphasis on the MIC of metals. We also discuss the application of existing tools and approaches for managing MIC and propose ideas to promote an improved understanding of MIC. Furthermore, we highlight areas where the insights and expertise of microbiologists are needed to help progress this field.

Healthcare workers' acceptance of and adherence to latent tuberculosis treatment.

BACKGROUND: Healthcare workers (HCWs) with latent tuberculosis infection (LTBI) have a high risk of active tuberculosis and need systematic LTBI screening and treatment. However, acceptance and adherence rates of LTBI treatment are low. AIMS: To examine the specific reasons for the loss at each LTBI treatment-cascade stage: acceptance, continuation and completion of LTBI treatment in HCWs. METHODS: This retrospective descriptive study was conducted among 61 HCWs with an interferon-gamma release assay-confirmed LTBI diagnosis who were prescribed LTBI treatment at a tertiary hospital in the Republic of Korea. Data were analysed using Pearson's chi-square, Fisher's exact, independent t-test and Mann-Whitney U-test. A word cloud analysis was used to describe the perceived meaning of LTBI in HCWs. RESULTS: HCWs who refused or discontinued LTBI treatment perceived LTBI as 'not a big deal', whereas HCWs who completed LTBI treatment had a high-risk perception of the LTBI prognosis, such as 'frightened about adverse prognosis'. Determinants of non-adherence to the recommended LTBI treatment included a busy work schedule, side effects of anti-tuberculosis agents and the inconvenience of regularly taking anti-tuberculosis agents. CONCLUSIONS: To ensure LTBI treatment adherence in HCWs, effective interventions that are customized to each stage of the LTBI treatment should be developed, with due consideration of the stage-specific perceived facilitators and barriers in the LTBI treatment cascade.

Enhanced charge density wave with mobile superconducting vortices in La1.885Sr0.115CuO4.

Superconductivity in the cuprates is found to be intertwined with charge and spin density waves. Determining the interactions between the different types of order is crucial for understanding these important materials. Here, we elucidate the role of the charge density wave (CDW) in the prototypical cuprate La1.885Sr0.115CuO4, by studying the effects of large magnetic fields (H) up to 24 Tesla. At low temperatures (T), the observed CDW peaks reveal two distinct regions in the material: a majority phase with short-range CDW coexisting with superconductivity, and a minority phase with longer-range CDW coexisting with static spin density wave (SDW). With increasing magnetic field, the CDW first grows smoothly in a manner similar to the SDW. However, at high fields we discover a sudden increase in the CDW amplitude upon entering the vortex-liquid state. Our results signify strong coupling of the CDW to mobile superconducting vortices and link enhanced CDW amplitude with local superconducting pairing across the H - T phase diagram.

Long-term survival with first-line nivolumab plus ipilimumab in patients with advanced non-small-cell lung cancer: a pooled analysis.

BACKGROUND: First-line nivolumab plus ipilimumab prolongs survival versus chemotherapy in advanced non-small-cell lung cancer (NSCLC). We further characterized clinical benefit with this regimen in a large pooled patient population and assessed the effect of response on survival. PATIENTS AND METHODS: Data were pooled from four studies of first-line nivolumab plus ipilimumab in advanced NSCLC (CheckMate 227 Part 1, 817 cohort A, 568 Part 1, and 012). Overall survival (OS), progression-free survival (PFS), objective response rate, duration of response, and safety were assessed. Landmark analyses of OS by response status at 6 months and by tumor burden reduction in responders to nivolumab plus ipilimumab were also assessed. RESULTS: In the pooled population (N = 1332) with a minimum follow-up of 29.1-58.9 months, median OS was 18.6 months, with a 3-year OS rate of 35%; median PFS was 5.4 months (3-year PFS rate, 17%). Objective response rate was 36%; median duration of response was 23.7 months, with 38% of responders having an ongoing response at 3 years. In patients with tumor programmed death-ligand 1 (PD-L1) <1%, ≥1%, 1%-49%, or ≥50%, 3-year OS rates were 30%, 38%, 30%, and 48%. Three-year OS rates were 30% and 38% in patients with squamous or non-squamous histology. Efficacy outcomes in patients aged ≥75 years were similar to the overall pooled population (median OS, 20.1 months; 3-year OS rate, 34%). In the pooled population, responders to nivolumab plus ipilimumab at 6 months had longer post-landmark OS than those with stable or progressive disease; 3-year OS rates were 66%, 22%, and 14%, respectively. Greater depth of response was associated with prolonged survival; in patients with tumor burden reduction ≥80%, 50% to <80%, or 30% to <50%, 3-year OS rates were 85%, 72%, and 44%, respectively. No new safety signals were identified in the pooled population. CONCLUSION: Long-term survival benefit and durable response with nivolumab plus ipilimumab in this large patient population further support this first-line treatment option for advanced NSCLC.

Preoperative Chemoradiotherapy With Capecitabine With or Without Temozolomide in Patients With Locally Advanced Rectal Cancer: A Prospective, Randomised Phase II Study Stratified by O6-Methylguanine DNA Methyltransferase Status: KCSG-CO17-02.

AIMS: To evaluate the clinical efficacy of adding temozolomide (TMZ) to preoperative capecitabine (CAP)-based chemoradiotherapy in patients with locally advanced rectal cancer (LARC) and validate O6-methylguanine DNA methyltransferase (MGMT) methylation status as a predictive marker for TMZ combined regimens. MATERIALS AND METHODS: LARC patients with clinical stage II (cT3-4N0) or III (cTanyN+) disease were enrolled. They were stratified into unmethylated MGMT (uMGMT) and methylated MGMT (mMGMT) groups by methylation-specific polymerase chain reaction before randomisation and were then randomly assigned (1:1) to one of four treatment arms: uMGMT/CAP (arm A), uMGMT/TMZ + CAP (arm B), mMGMT/CAP (arm C) and mMGMT/TMZ + CAP (arm D). The primary end point was the pathological complete response (pCR) rate. RESULTS: Between November 2017 and July 2020, 64 patients were randomised. Slow accrual caused early study termination. After excluding four ineligible patients, 60 were included in the full analysis set. The pCR rate was 15.0% (9/60), 0%, 14.3%, 18.8% and 26.7% for the entire cohort, arms A, B, C and D, respectively (P = 0.0498 between arms A and D). The pCR rate was 9.7% in the CAP group (arms A + C), 20.7% in the TMZ + CAP group (arms B + D), 6.9% in the uMGMT group (arms A + B) and 22.6% in the mMGMT group (arms C + D). Grade 1-2 nausea or vomiting was significantly more frequent in the TMZ + CAP treatment groups (arms B + D) than in the CAP treatment groups (arms A + C, P < 0.001) with no difference in grade 3 adverse events. There were no grade 4 or 5 adverse events. CONCLUSION: The addition of TMZ to CAP-based chemoradiotherapy tended to improve pCR rates, particularly in those with mMGMT LARC. MGMT status may warrant further investigation as a predictive biomarker for chemotherapeutic agents and radiotherapy.

An Analysis of the Role of Mental Health in a Randomized Trial of a Walking Intervention for Black Veterans With Chronic Pain.

Black patients and those with co-occurring mental health disorders are disproportionately affected by chronic pain, but few interventions target these populations. This is a secondary analysis of a randomized trial of a walking-focused proactive counseling intervention for Black Veterans with chronic musculoskeletal pain (ACTION). The primary aim was to examine intervention effectiveness among Veterans with an electronic health record-documented mental health diagnosis [depressive disorder, anxiety disorder, substance use disorder, post-traumatic stress disorder or serious mental illness (n = 205)] and those without a diagnosis (n = 175). About 380 Black Veterans receiving care at the Atlanta VA Health Care System were enrolled from 2016 to 2019 and randomized to the intervention or usual care (UC) (1:1). The intervention featured 6 telephone coaching sessions over 8-14 weeks to encourage walking. Participants with a mental health disorder were more likely to complete all counseling sessions (56% vs 38%) and reported improvements in global perceptions of pain and pain intensity/interference (secondary outcomes) at 3-months vs UC. Among participants without a mental health disorder, the intervention was associated with an improvement in pain-related disability at 6-months (primary outcome). Black chronic pain patients with co-occurring mental health disorders may require more intensive treatment to affect improvement in pain-related disability. PERSPECTIVE: This study examines the effectiveness of a walking intervention for chronic pain among Black Veterans with a mental health disorder. These patients were more engaged with the intervention than those without a mental health disorder. However, they did not experience reductions in pain-related disability, suggesting more intensive treatment is needed.

Evaluation of the MolecuTech® REBA MTB-XMDR kit for detection of pre-extensively drug-resistant TB.

BACKGROUND: Rapid diagnosis of drug-resistant TB is critical for early initiation of effective therapy. YD Diagnostics in South Korea recently developed the MolecuTech® REBA MTB-XMDR test to rapidly detect multidrug-resistant TB (MDR-TB), pre-extensively drug-resistant TB (pre-XDR-TB) and resistance to second-line injectable drugs (SLIDs) simultaneously using a fully automated test platform. This study aimed to evaluate the MolecuTech® test for the detection of MDR- and pre-XDR-TB, as well as SLID resistance.METHODS: A total of 151 clinical Mycobacterium tuberculosis isolates from South Korea were tested using the MolecuTech test, and the results were analysed by comparing these with phenotypic drug susceptibility testing (pDST) and sequencing.RESULTS: Compared to pDST, the MolecuTech test showed a sensitivity and specificity of respectively 97.7% and 100.0% for rifampicin (RIF), 82.4% and 100.0% for isoniazid (INH), 97.5% and 97.2% for fluoroquinolones (FQs), and 94.0% and 98.8% for SLIDs. Concordances with the sequencing results of each resistance determinant were 99.3% for RIF, 96.7% for INH, 98.7% for FQs and 99.3% for SLIDs.CONCLUSION: The MolecuTech test is an efficient and reliable rapid molecular diagnostic tool for the simultaneous screening of MDR- and pre-XDR-TB.

Isolated posterior inferior cerebellar artery dissection with ischaemic stroke: evaluating the radiological features and diagnostic feasibility of high-resolution vessel wall imaging.

AIM: To evaluate the radiological features of isolated posterior inferior cerebellar artery dissection (PICAD) and the feasibility of using high-resolution vessel-wall imaging (HR-VWI) for diagnosing PICAD. MATERIALS AND METHODS: Three hundred and nine patients with arterial dissection involving the posterior cerebral circulation, who underwent HR-VWI between March 2012 and July 2019 were reviewed retrospectively. Among them, 44 patients (14.2%) were diagnosed with isolated PICAD in consensus among a neuroradiologist, a neurointerventionist, and a neurologist. Two neuroradiologists reviewed the vessel wall images independently for evidence of dissection (dissection flap, outer diameter enlargement on T2-weighted imaging [WI], mural haematoma). Diagnostic confidence was also scored on a five-point scale. Intra- and interobserver agreement for diagnosing PICAD and detecting evidence of dissection were evaluated. RESULTS: Dissection flaps were seen on T2WI in all cases (100%) and on contrast-enhanced T1WI in 34 patients (79.1%). Outer diameter enlargement of the steno-occlusive lesions on angiography was detected in most cases (97.7%). A mural haematoma was detected on three-dimensional (3D) contrast-enhanced motion-sensitised driven-equilibrium T1WI in 97.1% of the cases. The mean diagnostic confidence score derived by two neuroradiologists was 4.72. The two reviewers showed substantial to almost perfect agreement (weighted kappa coefficient: 0.62-0.97). CONCLUSION: Use of HR-VWI as a diagnostic tool for PICAD is feasible, and a dissection flap with outer wall enlargement on HR-T2WI allows confident dissection diagnosis. The present data suggest that PICAD might be considered as a stroke aetiology in patients with unexplained ischaemic stroke in the PICA territory, and that PICA evaluation with HR-VWI is both necessary and feasible.

Trends in body mass index changes among Korean adolescents between 2005-2020, including the COVID-19 pandemic period: a national representative survey of one million adolescents.

OBJECTIVE: The impact of the coronavirus disease 2019 (COVID-19) pandemic on weight gain in children and adolescents remains unknown. We aimed to identify an estimated 15-year trend in mean body mass index (BMI) changes and prevalence of obesity and overweight among Korean adolescents from 2005 to 2020, including the period of the COVID-19 pandemic. PATIENTS AND METHODS: We analyzed data taken from a nationwide survey (Korea Youth Risk Behavior Survey), between 2005 and 2020. Representative samples of one million Korean adolescents aged 13-18 years (n=1,057,885) were examined. The 15-year trends in mean BMI and proportion of obesity or overweight, and the changes due to the COVID-19 pandemic were analyzed. RESULTS: The data of 1,057,885 Korean adolescents were analyzed (mean age: 14.98 years; females, 48.4%). The estimated weighted mean BMI was 20.5 kg/m2 [95% confidence interval (CI), 20.4-20.5] from 2005 to 2008 and 21.5 kg/m2 (95% CI, 21.4-21.6) in 2020 (during the COVID-19 pandemic). Although the 15-year trend of mean BMI gradually increased, the change in mean BMI before and during the pandemic significantly lessened (ßdiff, -0.027; 95% CI, -0.028 to -0.026). The 15-year (2005-2020) trend changes in the prevalence of obesity and overweight were similar (obesity prevalence from 2005-2008, 3.2%; 95% CI, 3.1-3.3 vs. obesity prevalence in 2020, 8.6%; 95% CI, 8.2-9.0; ßdiff, -0.309; 95% CI, -0.330 to -0.288). CONCLUSIONS: The 15-year trend of overall mean BMI and obesity and overweight prevalence demonstrated a significant increase; however, its slope decreased during the pandemic. These landmark results suggest the need for the development of precise strategies to prevent pediatric obesity and overweight during the COVID-19 pandemic.

Enhanced charge density wave coherence in a light-quenched, high-temperature superconductor.

Superconductivity and charge density waves (CDWs) are competitive, yet coexisting, orders in cuprate superconductors. To understand their microscopic interdependence, a probe capable of discerning their interaction on its natural length and time scale is necessary. We use ultrafast resonant soft x-ray scattering to track the transient evolution of CDW correlations in YBa2Cu3O6+x after the quench of superconductivity by an infrared laser pulse. We observe a nonthermal response of the CDW order characterized by a near doubling of the correlation length within ≈1 picosecond of the superconducting quench. Our results are consistent with a model in which the interaction between superconductivity and CDWs manifests inhomogeneously through disruption of spatial coherence, with superconductivity playing the dominant role in stabilizing CDW topological defects, such as discommensurations.

First-line nivolumab + ipilimumab in advanced NSCLC: CheckMate 227 subpopulation analyses in Asian patients.

BACKGROUND: Nivolumab plus ipilimumab demonstrated clinically meaningful improvement in efficacy versus chemotherapy with a manageable safety profile in patients with advanced non-small cell lung cancer (NSCLC) and tumor programmed death-ligand 1 (PD-L1) expression ≥1% or <1% in Part 1 of CheckMate 227. Here we report efficacy and safety results for the Asian subpopulation. METHODS: Patients with stage IV/recurrent NSCLC were randomized 1 : 1 : 1 to nivolumab plus ipilimumab, nivolumab monotherapy, or chemotherapy (PD-L1 ≥1%) or nivolumab plus ipilimumab, nivolumab plus chemotherapy, or chemotherapy (PD-L1 <1%). Overall survival (OS), progression-free survival, objective response rate, duration of response, and safety were evaluated among patients in Japan, South Korea, and Taiwan. RESULTS: In the Asian subpopulation with PD-L1 ≥1%, 81 patients received nivolumab plus ipilimumab and 81 received chemotherapy. Median OS was not reached with nivolumab plus ipilimumab versus 24.8 months with chemotherapy; 3-year OS rate was 53% versus 37% [hazard ratio (HR), 0.72; 95% confidence interval (CI) 0.47-1.11]. The 3-year progression-free survival rate was 26% versus 7% (HR, 0.65; 95% CI 0.45-0.96), objective response rate was 56% versus 37%, and median duration of response was 29.0 months (95% CI 15.0 months-not reached) versus 6.9 months (95% CI 3.9-11.1 months). Similar results were observed regardless of tumor PD-L1 expression and in Japanese patients. Grade 3-4 treatment-related adverse events occurred in 40% of patients receiving nivolumab plus ipilimumab and 36% receiving chemotherapy, in the overall Asian subpopulation (tumor PD-L1 expression ≥1% and <1%); no new safety signals were identified. CONCLUSIONS: At 3-year follow-up, nivolumab plus ipilimumab provided durable long-term efficacy benefits versus chemotherapy regardless of tumor PD-L1 expression in the Asian subpopulation, including Japanese patients. Consistent with findings for all randomized patients, these data support the use of nivolumab plus ipilimumab as first-line treatment of Asian patients with advanced NSCLC.