Multisite Pragmatic Cluster-Randomized Controlled Trial of the CONCERN Early Warning System.

Importance: Late predictions of hospitalized patient deterioration, resulting from early warning systems (EWS) with limited data sources and/or a care team's lack of shared situational awareness, contribute to delays in clinical interventions. The COmmunicating Narrative Concerns Entered by RNs (CONCERN) Early Warning System (EWS) uses real-time nursing surveillance documentation patterns in its machine learning algorithm to identify patients' deterioration risk up to 42 hours earlier than other EWSs. Objective: To test our a priori hypothesis that patients with care teams informed by the CONCERN EWS intervention have a lower mortality rate and shorter length of stay (LOS) than the patients with teams not informed by CONCERN EWS. Design: One-year multisite, pragmatic controlled clinical trial with cluster-randomization of acute and intensive care units to intervention or usual-care groups. Setting: Two large U.S. health systems. Participants: Adult patients admitted to acute and intensive care units, excluding those on hospice/palliative/comfort care, or with Do Not Resuscitate/Do Not Intubate orders. Intervention: The CONCERN EWS intervention calculates patient deterioration risk based on nurses' concern levels measured by surveillance documentation patterns, and it displays the categorical risk score (low, increased, high) in the electronic health record (EHR) for care team members. Main Outcomes and Measures: Primary outcomes: in-hospital mortality, LOS; survival analysis was used. Secondary outcomes: cardiopulmonary arrest, sepsis, unanticipated ICU transfers, 30-day hospital readmission. Results: A total of 60 893 hospital encounters (33 024 intervention and 27 869 usual-care) were included. Both groups had similar patient age, race, ethnicity, and illness severity distributions. Patients in the intervention group had a 35.6% decreased risk of death (adjusted hazard ratio [HR], 0.644; 95% confidence interval [CI], 0.532-0.778; P<.0001), 11.2% decreased LOS (adjusted incidence rate ratio, 0.914; 95% CI, 0.902-0.926; P<.0001), 7.5% decreased risk of sepsis (adjusted HR, 0.925; 95% CI, 0.861-0.993; P=.0317), and 24.9% increased risk of unanticipated ICU transfer (adjusted HR, 1.249; 95% CI, 1.093-1.426; P=.0011) compared with patients in the usual-care group. Conclusions and Relevance: A hospital-wide EWS based on nursing surveillance patterns decreased in-hospital mortality, sepsis, and LOS when integrated into the care team's EHR workflow. Trial Registration: ClinicalTrials.gov Identifier: NCT03911687.

Recent Advancements and Innovations in Pediatric Precision Oncology.

Precision oncology incorporates comprehensive genomic profiling into the individualized clinical care of pediatric cancer patients. In recent years, comprehensive pan-cancer analyses have led to the successful implementation of genomics-based pediatric trials and accelerated approval of novel targeted agents. In addition, disease-specific studies have resulted in molecular subclassification of myriad cancer types with subsequent tailoring of treatment intensity based on the patient's prognostic factors. This review discusses the progress of the field and highlights developments that are leading to more personalized cancer care and improved patient outcomes. Increased understanding of the evolution of precision oncology over recent decades emphasizes the tremendous impact of improved genomic applications. New technologies and improved diagnostic modalities offer further promise for future advancements within the field.

Engagement Along the PrEP Care Continuum Among Men Who Have Sex with Men in China: A Systematic Review and Meta-analysis.

Pre-exposure prophylaxis (PrEP), including daily oral, on-demand, and long-acting injectable (LAI), is a promising HIV prevention intervention for men who have sex with men (MSM). We conducted a systematic review on engagement with the PrEP continuum among MSM in China. A total of 756 studies were initially identified and 36 studies were included (N = 26,021). In the 20 studies (N = 13,886) examining PrEP awareness, 32.4% (95% CI: 25.1-40.7) of MSM were aware of PrEP. In the 25 studies (N = 18,587) examining willingness, 54.5% (95% CI: 41.9-66.5) MSM indicated they were willing to use PrEP. The pooled prevalence of PrEP uptake from 9 studies (N = 6,575) was 4.9% (95% CI: 1.4-15.8%), while pooled estimates of adequate adherence from five studies (N = 2,344) among MSM on PrEP was 40.7% (95% CI: 20.0-65.2%). Subgroup analyses suggested studies conducted after 2015 (versus before) tended to report higher awareness and uptake. Awareness was highest for daily oral PrEP, followed by on-demand, and LAI PrEP; willingness to use was highest for LAI PrEP. The operationalization of willingness and adherence constructs varied across studies and complicated the interpretation of pooled estimates. This review revealed gaps in the PrEP care continuum among MSM in China, with relatively low awareness and uptake (in contrast to willingness and adherence) as the major potential barriers to widespread implementation and the need for a unified approach to defining and measuring PrEP outcomes.

Discrimination and hypertension among a diverse sample of racial and sexual minority men living with HIV: baseline findings of a longitudinal cohort study.

Racial and sexual orientation discrimination may exacerbate the double epidemic of hypertension (HTN) and HIV that affects men of color who have sex with men (MSM). This was a cross-sectional analysis of African American, Asian American, Native Hawaiian, or Pacific Islander (NHPI) MSM living with HIV (PLWH) cohort in Honolulu and Philadelphia. Racial and sexual orientation discrimination, stress, anxiety, and depression were measured with computer-assisted self-interview questionnaires (CASI). We examined the associations between racial and sexual orientation discrimination with hypertension measured both in the office and by 24-h ambulatory blood pressure monitoring (ABPM) using multivariable logistic regression. Sixty participants (60% African American, 18% Asian, and 22% NHPI) completed CASIs and 24-h ABPM. African American participants (80%) reported a higher rate of daily racial discrimination than Asian American (36%) and NHPI participants (17%, p < 0.001). Many participants (51%) reported daily sexual orientation discrimination. Sixty-six percent of participants had HTN by office measurement and 59% had HTN by 24-h ABPM measurement. Participants who experienced racial discrimination had greater odds of having office-measured HTN than those who did not, even after adjustment (Odds Ratio 5.0 (95% Confidence Interval [1.2-20.8], p = 0.03)). This association was not seen with 24-h ABPM. Hypertension was not associated with sexual orientation discrimination. In this cohort, MSM of color PLWH experience significant amounts of discrimination and HTN. Those who experienced racial discrimination had higher in-office blood pressure. This difference was not observed in 24-h APBM and future research is necessary to examine the long-term cardiovascular effects.

A Cerebellar Tumor-to-Tumor Metastasis in a Patient With Von Hippel-Lindau Disease.

Tumor-to-tumor metastasis in the central nerve system is uncommon in our routine practice. Most reports include metastatic breast cancer into meningioma. Here we report a metastatic clear cell renal cell carcinoma (ccRCC) into a cerebellar hemangioblastoma in a patient with von Hippel-Lindau (VHL) disease. Imaging cannot distinguish metastatic ccRCC from primary cerebellar hemangioblastoma. Immuno-molecular studies are proven to be diagnostic. We also reviewed previously documented tumor-to-tumor metastasis of ccRCC to cerebellar hemangioblastoma in VHL disease. Lastly, we discussed potential mechanisms involved in the metastasis of ccRCC to hemangioblastoma in the cerebellum in patients with VHL.

Assessment of birth cohort screening of chronic hepatitis C in colorectal cancer screening patients in British Columbia.

Background: Since 2018, British Columbia (BC) has recommended chronic hepatitis C (HCV) screening for those born between 1945 and 1964, with a provincial prevalence of 2.31%. Combining HCV and colorectal cancer (CRC) screening can facilitate specialist referrals and follow-up. We assessed HCV screening uptake among CRC screening patients following the release of BC's birth cohort guidelines and examined the COVID-19 pandemic's impact on HCV screening practices. Methods: A retrospective review was conducted on patients referred to Vancouver Coastal Health Authority's CRC screening program. Two groups, Cohort A (October-December 2019) and Cohort B (December 2021), were studied to identify pandemic-related changes. Data on demographics, liver disease history, hepatitis B or HIV co-infection rates, and initial anti-hepatitis C and ribonucleic acid (RNA) testing dates were collected. Statistical analyses were performed with Stata 15.1. Results: A total of 579 patients were referred for the CRC screening program, of whom 465 were born between 1945 and 1964 and were included in the study. Among the 348 patients in cohort A, 144 (41%, 95% CI 36%-47%) were screened for HCV infection. Of these, four (1.2%) were positive for anti-hepatitis C, and one patient had positive RNA levels. Similar proportions of screenings were observed in cohort B (47.8%, 95% CI 39%-57%). Of those with liver disease, 66% had been screened for HCV. Conclusion: Birth cohort screening for HCV has been underutilized in British Columbia. Combining HCV and CRC screening could provide a practical approach to linking patients to health care.

Phase I Trial of GD2.CART Cells Augmented With Constitutive Interleukin-7 Receptor for Treatment of High-Grade Pediatric CNS Tumors.

PURPOSE: T cells modified with chimeric antigen receptors (CARTs) have demonstrated efficacy for hematologic malignancies; however, benefit for patients with CNS tumors has been limited. To enhance T cell activity against GD2+ CNS malignancies, we modified GD2-directed CART cells (GD2.CARTs) with a constitutively active interleukin (IL)-7 receptor (C7R-GD2.CARTs). METHODS: Patients age 1-21 years with H3K27-altered diffuse midline glioma (DMG) or other recurrent GD2-expressing CNS tumors were eligible for this phase I trial (ClinicalTrials.gov identifier: NCT04099797). All subjects received standard-of-care adjuvant radiation therapy or chemotherapy before study enrollment. The first treatment cohort received GD2.CARTs alone (1 × 107 cells/m2), and subsequent cohorts received C7R-GD2.CARTs at two dose levels (1 × 107 cells/m2; 3 × 107 cells/m2). Standard lymphodepletion with cyclophosphamide and fludarabine was included at all dose levels. RESULTS: Eleven patients (age 4-18 years) received therapy without dose-limiting toxicity. The GD2.CART cohort did not experience toxicity, but had disease progression after brief improvement of residual neurologic deficits (≤3 weeks). The C7R-GD2.CART cohort developed grade 1 tumor inflammation-associated neurotoxicity in seven of eight (88%) cases, controllable with anakinra. Cytokine release syndrome was observed in six of eight (75%, grade 1 in all but one patient) and associated with increased circulating IL-6 and IP-10 (P < .05). Patients receiving C7R-GD2.CARTs experienced temporary improvement from baseline neurologic deficits (range, 2 to >12 months), and seven of eight (88%) remained eligible for additional treatment cycles (range 2-4 cycles). Partial responses by iRANO criteria were observed in two of seven (29%) patients with DMG treated by C7R-GD2.CARTs. CONCLUSION: Intravenous GD2.CARTs with and without C7R were well tolerated. Patients treated with C7R-GD2.CARTs exhibited transient improvement of neurologic deficits and increased circulating cytokines/chemokines. Treatment with C7R-GD2.CARTs represents a novel approach warranting further investigation for children with these incurable CNS cancers.

Sinusoidal transmission grating spectrometer for extreme ultraviolet measurement.

Spectral measurements play a vital role in understanding laser-plasma interactions. The ability to accurately measure the spectrum of radiation sources is crucial for unraveling the underlying physics. In this article, we introduce a novel approach that significantly enhances the efficiency of binary sinusoidal transmission grating spectrometers . The grating was tailored especially for Extreme Ultraviolet (EUV) measurements. The new design, High Contrast Sinusoidal Transmission Grating (HCSTG), not only suppresses high diffraction orders and retains the advantageous properties of previous designs but also exhibits a fourfold improvement in first-order efficiency. In addition, the HCSTG offers exceptional purity in the first order due to effectively eliminating half-order contributions from the diffraction pattern. The HCSTG spectrometer was employed to measure the emission of laser-produced Sn plasma in the 1-50 nm spectral range, achieving a spectral resolution of λ/Δλ = 60. We provide a comprehensive analysis comparing the diffraction patterns of different STGs, highlighting the advantages offered by the HCSTG design. This novel, efficiency-enhanced HCSTG spectrometer opens up new possibilities for accurate and sensitive EUV spectral measurements.

Spin-orbit exciton-induced phonon chirality in a quantum magnet.

The interplay of charge, spin, lattice, and orbital degrees of freedom in correlated materials often leads to rich and exotic properties. Recent studies have brought new perspectives to bosonic collective excitations in correlated materials. For example, inelastic neutron scattering experiments revealed non-trivial band topology for magnons and spin-orbit excitons (SOEs) in a quantum magnet CoTiO3 (CTO). Here, we report phonon properties resulting from a combination of strong spin-orbit coupling, large crystal field splitting, and trigonal distortion in CTO. Specifically, the interaction between SOEs and phonons endows chirality to two [Formula: see text] phonon modes and leads to large phonon magnetic moments observed in magneto-Raman spectra. The remarkably strong magneto-phononic effect originates from the hybridization of SOEs and phonons due to their close energy proximity. While chiral phonons have been associated with electronic topology in some materials, our work suggests opportunities may arise by exploring chiral phonons coupled to topological bosons.

Mapping the Relationship between Health-related Beliefs, Fear, Avoidance, and Depression: Lessons from the Pandemic and Beyond.

The COVID-19 pandemic brought a mental health crisis, with depression symptoms increasing nearly three-fold compared to pre-pandemic levels. To explain this surge and to outline related novel treatment targets for post-pandemic psychiatric interventions, the current study examined cognitive, emotional, and behavioral predictors of depression (in the context of the recent pandemic). Participants completed measures assessing perceived danger, perceived infectiousness, and fear of the coronavirus (COVID-19). Participants also reported symptoms of depression and behavioral tendencies: pandemic-related compulsive checking, cleaning, and avoidance (of activities, situations, places, and people). A multiple mediation model revealed that the relationship between perceived infectiousness of the virus and depression was atemporally mediated by fear of the virus and pandemic-related avoidance of activities, situations, places, and people. Furthermore, avoidance played a uniquely important role in the mediation model. First, it directly mediated the relationship between perceived infectiousness and depression, even when omitting fear from the model. Second, avoidance was a discriminant predictor of depression, as neither pandemic-related checking and reassurance-seeking nor cleaning behavior mediated the relationship between cognition and depressive symptoms. Clinical implications are discussed, including how addressing the relationship between anxiety about viral infections and depression can prospectively increase treatment success as we move beyond the pandemic.

Elucidating Piezoelectricity and Strain in Monolayer MoS2 at the Nanoscale Using Kelvin Probe Force Microscopy.

Strain engineering modifies the optical and electronic properties of atomically thin transition metal dichalcogenides. Highly inhomogeneous strain distributions in two-dimensional materials can be easily realized, enabling control of properties on the nanoscale; however, methods for probing strain on the nanoscale remain challenging. In this work, we characterize inhomogeneously strained monolayer MoS2 via Kelvin probe force microscopy and electrostatic gating, isolating the contributions of strain from other electrostatic effects and enabling the measurement of all components of the two-dimensional strain tensor on length scales less than 100 nm. The combination of these methods is used to calculate the spatial distribution of the electrostatic potential resulting from piezoelectricity, presenting a powerful way to characterize inhomogeneous strain and piezoelectricity that can be extended toward a variety of 2D materials.

Intervention treatment reducing cellular senescence inhibits tubulointerstitial fibrosis in diabetic mice following acute kidney injury.

Senescence of kidney tubules leads to tubulointerstitial fibrosis (TIF). Proximal tubular epithelial cells undergo stress-induced senescence during diabetes and episodes of acute kidney injury (AKI), and combining these injuries promotes the progression of diabetic kidney disease (DKD). Since TIF is crucial to progression of DKD, we examined the therapeutic potential of targeting senescence with a senolytic drug (HSP90 inhibitor) and/or a senostatic drug (ASK1 inhibitor) in a model of TIF in which AKI is superimposed on diabetes. After 8 weeks of streptozotocin-induced diabetes, mice underwent bilateral clamping of renal pedicles to induce mild AKI, followed by 28 days of reperfusion. Groups of mice (n=10-12) received either vehicle, HSP90 inhibitor (alvespimycin), ASK1 inhibitor (GS-444217), or both treatments. Vehicle-treated mice displayed tubular injury at day 3 and extensive tubular cell senescence at day 10, which remained unresolved at day 28. Markers of senescence (Cdkn1a and Cdkn2a), inflammation (Cd68, Tnf, and Ccl2), and TIF (Col1a1, Col4a3, α-Sma/Acta2, and Tgfb1) were elevated at day 28, coinciding with renal function impairment. Treatment with alvespimycin alone reduced kidney senescence and levels of Col1a1, Acta2, Tgfb1, and Cd68; however, further treatment with GS-444217 also reduced Col4a3, Tnf, Ccl2, and renal function impairment. Senolytic therapy can inhibit TIF during DKD, but its effectiveness can be improved by follow-up treatment with a senostatic inhibitor, which has important implications for treating progressive DKD.

Electrostatic moiré potential from twisted hexagonal boron nitride layers.

Moiré superlattices host a rich variety of correlated electronic phases. However, the moiré potential is fixed by interlayer coupling, and it is dependent on the nature of carriers and valleys. In contrast, it has been predicted that twisted hexagonal boron nitride (hBN) layers can impose a periodic electrostatic potential capable of engineering the properties of adjacent functional layers. Here, we show that this potential is described by a theory of electric polarization originating from the interfacial charge redistribution, validated by its dependence on supercell sizes and distance from the twisted interfaces. This enables controllability of the potential depth and profile by controlling the twist angles between the two interfaces. Employing this approach, we further demonstrate how the electrostatic potential from a twisted hBN substrate impedes exciton diffusion in semiconductor monolayers, suggesting opportunities for engineering the properties of adjacent functional layers using the surface potential of a twisted hBN substrate.

Health Service Utilization and Its Associations with Depression and Sexual Risk Behaviors Among Transgender Women in Shanghai, China.

Purpose: Given the limited research on health care utilization among transgender women in China, we described the use of primary health care and gender-affirming health care, and the associations between utilization of gender-affirming health care and depression and sexual risk behaviors. Methods: We conducted a cross-sectional survey in 2017 among a purposive sample of transgender women in Shanghai, China (N=199). We examined correlates of health care utilization and its association with depression and sexual risk behaviors with Chi-square (χ2), Fisher's exact tests, and analysis of variance. Results: The majority of the sample (78.5%) only had physician appointments when having an illness, while about one-fifth of the sample had physician appointments for yearly checkups. Nineteen out of 199 participants (9.5%) received gender-affirming surgery, among which only five used hormone therapy prescribed by a doctor (26.3%). Receiving some form of gender-affirming surgery was associated with higher depression scores [Welch's F(2, 12.22)=4.16, p=0.04], engagement in sex work (p=0.001), having 7 or more male sexual partners in the last 30 days (p=0.003), lifetime unprotected sex with a man (p=0.050), and unprotected sex with a main partner (p=0.043). Compared with transgender women who received both breast augmentation and vulvo-vaginoplasty (mean=5.86), those who received breast augmentation only (mean=12.33) scored higher on depression (p=0.04). Conclusions: Access to gender-affirming health care is low among transgender women in this study. The utilization of gender-affirming surgery is associated with depression and sexual risk behaviors. Findings suggest China should establish national guidelines on transgender-related health care and set up more clinics to provide consultation and services for the transgender population in China.

A Multilevel Primary Care Intervention to Improve Follow-Up of Overdue Abnormal Cancer Screening Test Results: A Cluster Randomized Clinical Trial.

Importance: Realizing the benefits of cancer screening requires testing of eligible individuals and processes to ensure follow-up of abnormal results. Objective: To test interventions to improve timely follow-up of overdue abnormal breast, cervical, colorectal, and lung cancer screening results. Design, Setting, and Participants: Pragmatic, cluster randomized clinical trial conducted at 44 primary care practices within 3 health networks in the US enrolling patients with at least 1 abnormal cancer screening test result not yet followed up between August 24, 2020, and December 13, 2021. Intervention: Automated algorithms developed using data from electronic health records (EHRs) recommended follow-up actions and times for abnormal screening results. Primary care practices were randomized in a 1:1:1:1 ratio to (1) usual care, (2) EHR reminders, (3) EHR reminders and outreach (a patient letter was sent at week 2 and a phone call at week 4), or (4) EHR reminders, outreach, and navigation (a patient letter was sent at week 2 and a navigator outreach phone call at week 4). Patients, physicians, and practices were unblinded to treatment assignment. Main Outcomes and Measures: The primary outcome was completion of recommended follow-up within 120 days of study enrollment. The secondary outcomes included completion of recommended follow-up within 240 days of enrollment and completion of recommended follow-up within 120 days and 240 days for specific cancer types and levels of risk. Results: Among 11 980 patients (median age, 60 years [IQR, 52-69 years]; 64.8% were women; 83.3% were White; and 15.4% were insured through Medicaid) with an abnormal cancer screening test result for colorectal cancer (8245 patients [69%]), cervical cancer (2596 patients [22%]), breast cancer (1005 patients [8%]), or lung cancer (134 patients [1%]) and abnormal test results categorized as low risk (6082 patients [51%]), medium risk (3712 patients [31%]), or high risk (2186 patients [18%]), the adjusted proportion who completed recommended follow-up within 120 days was 31.4% in the EHR reminders, outreach, and navigation group (n = 3455), 31.0% in the EHR reminders and outreach group (n = 2569), 22.7% in the EHR reminders group (n = 3254), and 22.9% in the usual care group (n = 2702) (adjusted absolute difference for comparison of EHR reminders, outreach, and navigation group vs usual care, 8.5% [95% CI, 4.8%-12.0%], P < .001). The secondary outcomes showed similar results for completion of recommended follow-up within 240 days and by subgroups for cancer type and level of risk for the abnormal screening result. Conclusions and Relevance: A multilevel primary care intervention that included EHR reminders and patient outreach with or without patient navigation improved timely follow-up of overdue abnormal cancer screening test results for breast, cervical, colorectal, and lung cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT03979495.

Deletion of Ascl1 in pancreatic ß-cells improves insulin secretion, promotes parasympathetic innervation, and attenuates dedifferentiation during metabolic stress.

OBJECTIVE: ASCL1, a pioneer transcription factor, is essential for neural cell differentiation and function. Previous studies have shown that Ascl1 expression is increased in pancreatic ß-cells lacking functional KATP channels or after feeding of a high fat diet (HFD) suggesting that it may contribute to the metabolic stress response of ß-cells. METHODS: We generated ß-cell-specific Ascl1 knockout mice (Ascl1ßKO) and assessed their glucose homeostasis, islet morphology and gene expression after feeding either a normal diet or HFD for 12 weeks, or in combination with a genetic disruption of Abcc8, an essential KATP channel component. RESULTS: Ascl1 expression is increased in response to both a HFD and membrane depolarization and requires CREB-dependent Ca2+ signaling. No differences in glucose homeostasis or islet morphology were observed in Ascl1ßKO mice fed a normal diet or in the absence of KATP channels. However, male Ascl1ßKO mice fed a HFD exhibited decreased blood glucose levels, improved glucose tolerance, and increased ß-cell proliferation. Bulk RNA-seq analysis of islets from Ascl1ßKO mice from three studied conditions showed alterations in genes associated with the secretory function. HFD-fed Ascl1ßKO mice showed the most extensive changes with increased expression of genes necessary for glucose sensing, insulin secretion and ß-cell proliferation, and a decrease in genes associated with ß-cell dysfunction, inflammation and dedifferentiation. HFD-fed Ascl1ßKO mice also displayed increased expression of parasympathetic neural markers and cholinergic receptors that was accompanied by increased insulin secretion in response to acetylcholine and an increase in islet innervation. CONCLUSIONS: Ascl1 expression is induced by stimuli that cause Ca2+-signaling to the nucleus and contributes in a multifactorial manner to the loss of ß-cell function by promoting the expression of genes associated with cellular dedifferentiation, attenuating ß-cells proliferation, suppressing acetylcholine sensitivity, and repressing parasympathetic innervation of islets. Thus, the removal of Ascl1 from ß-cells improves their function in response to metabolic stress.

H3G34-Mutant Gliomas-A Review of Molecular Pathogenesis and Therapeutic Options.

The 2021 World Health Organization Classification of Tumors of the Central Nervous System reflected advances in understanding of the roles of oncohistones in gliomagenesis with the introduction of the H3.3-G34R/V mutant glioma to the already recognized H3-K27M altered glioma, which represent the diagnoses of pediatric-type diffuse hemispheric glioma and diffuse midline glioma, respectively. Despite advances in research regarding these disease entities, the prognosis remains poor. While many studies and clinical trials focus on H3-K27M-altered-glioma patients, those with H3.3-G34R/V mutant gliomas represent a particularly understudied population. Thus, we sought to review the current knowledge regarding the molecular mechanisms underpinning the gliomagenesis of H3.3-G34R/V mutant gliomas and the diagnosis, treatment, long-term outcomes, and possible future therapeutics.

Circulating tumor DNA sequencing of pediatric solid and brain tumor patients: An institutional feasibility study.

The potential of circulating tumor DNA (ctDNA) analysis to serve as a real-time "liquid biopsy" for children with central nervous system (CNS) and non-CNS solid tumors remains to be fully elucidated. We conducted a study to investigate the feasibility and potential clinical utility of ctDNA sequencing in pediatric patients enrolled on an institutional clinical genomics trial. A total of 240 patients had tumor DNA profiling performed during the study period. Plasma samples were collected at study enrollment from 217 patients and then longitudinally from a subset of patients. Successful cell-free DNA extraction and quantification occurred in 216 of 217 (99.5%) of these initial samples. Twenty-four patients were identified whose tumors harbored 30 unique variants that were potentially detectable on a commercially-available ctDNA panel. Twenty of these 30 mutations (67%) were successfully detected by next-generation sequencing in the ctDNA from at least one plasma sample. The rate of ctDNA mutation detection was higher in patients with non-CNS solid tumors (7/9, 78%) compared to those with CNS tumors (9/15, 60%). A higher ctDNA mutation detection rate was also observed in patients with metastatic disease (9/10, 90%) compared to non-metastatic disease (7/14, 50%), although tumor-specific variants were detected in a few patients in the absence of radiographic evidence of disease. This study illustrates the feasibility of incorporating longitudinal ctDNA analysis into the management of relapsed or refractory patients with childhood CNS or non-CNS solid tumors.

Depression as a mediator between intimate partner violence (IPV) and CD4 cell count among men who have sex with men (MSM) living with HIV in China.

Intimate partner violence (IPV) is associated with adverse mental and physical outcomes among men who have sex with men (MSM) living with HIV. Few studies focus on psychological IPV, such as verbal threats. This study examined the associations between different forms of IPV and depression and CD4+ cell count, with depression as a mediator for the association between IPV and CD4+ cell count. Data for these analyses were derived from a larger cross-sectional study on HIV-HCV co-infection among MSM in Shanghai, China (N = 1623). We estimated the average causal mediation effects (ACME) and average direct effects (ADE) through three steps. About 16% of participants experienced IPV, with forced sex (7%), verbal threats (5%), and thrown objects (4%) being most common. Verbal threats showed the strongest link with depression and low CD4+ cell count. Depression fully mediated the relationship between verbal abuse and low CD4+ cell count, suggesting it as a potential pathway between psychological IPV and poorer HIV-related health outcomes. More research on psychological IPV is warranted to examine its health impacts. Mental health could be a potential focus of intervention to enhance HIV-related health outcomes among MSM with IPV experience.