Clinical features of prostate cancer by polygenic risk score.

Genome-wide association studies have identified more than 290 single nucleotide variants (SNVs) associated with prostate cancer. These SNVs can be combined to generate a Polygenic Risk Score (PRS), which estimates an individual's risk to develop prostate cancer. Identifying individuals at higher risk for prostate cancer using PRS could allow for personalized screening recommendations, improve current screening tools, and potentially result in improved survival rates, but more research is needed before incorporating them into clinical use. Our study aimed to investigate associations between PRS and clinical factors in affected individuals, including age of diagnosis, metastases, histology, International Society of Urological Pathology (ISUP) Grade Group (GG) and family history of prostate cancer, while taking into account germline genetic testing in known prostate cancer related genes. To evaluate the relationship between these clinical factors and PRS, a quantitative retrospective chart review of 250 individuals of European ancestry diagnosed with prostate cancer who received genetic counseling services at The Ohio State University's Genitourinary Cancer Genetics Clinic and a 72-SNV PRS through Ambry Genetics, was performed. We found significant associations between higher PRS and younger age of diagnosis (p = 0.002), lower frequency of metastases (p = 0.006), and having a first-degree relative diagnosed with prostate cancer (p = 0.024). We did not observe significant associations between PRS and ISUP GG, histology or a having a second-degree relative with prostate cancer. These findings provide insights into features associated with higher PRS, but larger multi-ancestral studies using PRS that are informative across populations are needed to understand its clinical utility.

Associations of Demographic and Social Factors on Health-Related Quality-of-Life Changes Among Older Women With Breast or Gynecologic Cancer.

OBJECTIVES: To examine associations of sociodemographic factors and social limitations with health-related quality of life (HRQOL) from pre- to postdiagnosis in older female cancer survivors. SAMPLE & SETTING: 9,807 women aged 65 years or older with breast or gynecologic cancer from the Surveillance, Epidemiology, and End Results-Medicare Health Outcomes Survey. METHODS & VARIABLES: Physical and mental HRQOL were assessed using the physical component summary (PCS) and mental component summary (MCS) of the Veterans RAND 12-Item Health Survey. Descriptive statistics and mixed-effects models for repeated measures were used. RESULTS: Social limitations were the only significant factor associated with changes in MCS scores. Race and ethnicity, rurality, and social interference were associated with significant decreases in PCS scores. IMPLICATIONS FOR NURSING: Nurses can assess mental and physical HRQOL after diagnosis and advocate for appropriate referrals. Oncology care should be tailored to cultural considerations, including race and ethnicity, rurality, and social support.

Prognosis significance and potential association between ALDOA and AKT expression in colorectal cancer.

Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract and a leading cause of cancer-related death worldwide. Since many CRC patients are diagnosed already in the advanced stage, and traditional chemoradiotherapy is prone to drug resistance, it is important to find new therapeutic targets. In this study, the expression levels of ALDOA and p-AKT were detected in cancer tissues and paired normal tissues, and it was found that they were significantly increased in CRC tissues, and their high expression indicated poor prognosis. Moreover, a positive correlation between the expression of ALDOA and p-AKT was found in CRC tissues and paired normal tissues. In addition, the Kaplan-Meier analysis revealed that the group with both negative of ALDOA/p-AKT expression had longer five-year survival rates compared with the other group. Besides, the group with both high expression of ALDOA/p-AKT had a worse prognosis compared with the other group. Based on the expression of ALDOA and p-AKT in tumor tissues, we can effectively distinguish tumor tissues from normal tissues through cluster analysis. Furthermore, we constructed nomograms to predict 3-year and 5-year overall survival, showing that the expression of ALDOA/p-AKT plays a crucial role in predicting the prognosis of CRC patients. Therefore, ALDOA/p-AKT may act as a crucial role in CRC, which may provide new horizons for targeted therapies for CRC.

Potent Estrogen Receptor ß Agonists with Inhibitory Activity In Vitro , Fail to Suppress Xenografts of Endocrine-Resistant Cyclin-dependent Kinase 4/6 inhibitor-Resistant Breast Cancer Cells.

Objective: Seventy percent of newly diagnosed breast cancers are estrogen receptor-α positive and HER2/neu negative [1]. First-line treatments incorporate endocrine therapy and cyclin-dependent kinase 4/6 inhibitors [2]. However, therapy resistance occurs in most patients [3-5]. Hence, there is an urgent need for effective second-line treatments. We previously showed that the potent estrogen receptor-ß agonists, OSU-ERb-12 and LY500307, synergized with the selective estrogen receptor modulator, tamoxifen, in vitro. Furthermore, we showed that these compounds inhibited endocrine-resistant and cyclin-dependent kinase 4/6-inhibitor-resistant estrogen receptor α-positive cell lines in vitro [6]. Here, we used fulvestrant- and abemaciclib-resistant T47D-derived cell line xenografts to determine the efficacy of the combination of OSU-ERb-12 and LY500307 with tamoxifen in vivo. Results: Despite efficacy in vitro, treatments failed to reduce xenograft tumor volumes. Hence, we conclude that this treatment strategy lacks direct cancer cell-intrinsic cytotoxic efficacy in vivo.

Identification and molecular evolution of the GLX genes in 21 plant species: a focus on the Gossypium hirsutum.

BACKGROUND: The glyoxalase system includes glyoxalase I (GLXI), glyoxalase II (GLXII) and glyoxalase III (GLXIII), which are responsible for methylglyoxal (MG) detoxification and involved in abiotic stress responses such as drought, salinity and heavy metal. RESULTS: In this study, a total of 620 GLX family genes were identified from 21 different plant species. The results of evolutionary analysis showed that GLX genes exist in all species from lower plants to higher plants, inferring that GLX genes might be important for plants, and GLXI and GLXII account for the majority. In addition, motif showed an expanding trend in the process of evolution. The analysis of cis-acting elements in 21 different plant species showed that the promoter region of the GLX genes were rich in phytohormones and biotic and abiotic stress-related elements, indicating that GLX genes can participate in a variety of life processes. In cotton, GLXs could be divided into two groups and most GLXIs distributed in group I, GLXIIs and GLXIIIs mainly belonged to group II, indicating that there are more similarities between GLXII and GLXIII in cotton evolution. The transcriptome data analysis and quantitative real-time PCR analysis (qRT-PCR) show that some members of GLX family would respond to high temperature treatment in G.hirsutum. The protein interaction network of GLXs in G.hirsutum implied that most members can participate in various life processes through protein interactions. CONCLUSIONS: The results elucidated the evolutionary history of GLX family genes in plants and lay the foundation for their functions analysis in cotton.

Trajectories of Daily Postconcussion Symptoms in Children.

OBJECTIVES: To identify trajectories of daily postconcussion symptoms (PCS) from the acute postinjury period to symptom resolution among concussed children and examine demographic factors and acute PCS associated with the identified symptom trajectories. SETTING AND PARTICIPANTS: Seventy-nine participants with a concussion were enrolled within 72 hours of injury and completed a daily survey that assessed PCS from enrollment until symptom resolution. DESIGN: This was a prospective cohort study among concussed children aged 11-17 years. MAIN MEASURES: Children rated their concussion symptoms daily using the Post-Concussion Symptom Scale. Symptom duration was assessed using participants' date of symptom resolution and coded as a dichotomous variable: (1) PCS duration 14 days or less or (2) PCS duration longer than 14 days. RESULTS: Of the 79 participants, most were male (n = 53, 67%), injured during a sporting activity (n = 67, 85%), or had PCS that persisted for more than 14 days post-injury (n = 41, 52%). Group-based trajectory modeling yielded 4 trajectory groups: (1) low acute/resolved PCS (n = 39, 49%), (2) moderate/persistent PCS (n = 19, 24%), (3) high acute/persistent PCS (n = 13, 16%), and (4) high acute/resolved PCS (n = 8, 10%). No significant associations were found between demographic factors and the trajectory group. A higher symptom burden at injury was associated with an increased odds of being in the high acute/resolved or high acute/persistent recovery groups than being in the low acute/resolved group (odds ratio [OR] 1.39, 95% CI = 1.11-1.74; OR = 1.33, 95% CI = 1.11-1.60, respectively), as was a higher symptom severity at injury (OR = 1.09, 95% CI = 1.03-1.15; OR = 1.06, 95% CI = 1.02-1.11, respectively). CONCLUSION: Our findings may help clinicians identify concussed children on slower recovery trajectories, and implement early, individualized treatment plans that foster optimal recovery for concussed children.

Overexpression of TYRO3 indicates poor prognosis and induces gastric cancer progression via AKT-mTOR pathway.

Gastric cancer (GC) is among of the leading causes of cancer mortality worldwide. This is because many patients are diagnosed with advanced GC and postoperative radiotherapy and chemotherapy have also exhibited limited effects on GC. TYRO3 has been considered carcinogenic and a potential therapeutic target for GC. However, TYRO3 function and mechanism in GC remains elusive. The study results indicated that TYRO3 was aberrantly elevated in GC tissues and predicted poor prognosis. TYRO3 is closely associated with clinicopathological indicators in GC tissues such as lymph node metastasis, venous invasion, neural invasion, and the tumor-node-metastasis stage. In addition, TYRO3 expression levels are closely related to the AKT-mTOR pathway in GC tissues. Moreover, the oncogenic role of TYRO3 was determined through in vitro and in vivo functional assays, and knockdown of the TYRO3 expression level in GC cell lines can effectively suppress the AKT-mTOR pathway and inhibit tumor cell proliferation and migration. In conclusion, this study provides a theoretical basis for establishing the potential association and regulatory mechanism between TYRO3 and AKT-mTOR and offers a new strategy for GC-targeted therapy.

Clinical markers of immunotherapy outcomes in advanced sarcoma.

BACKGROUND: Despite immunotherapy's promise in oncology, its use for sarcoma remains challenging. There are no sarcoma-specific biomarkers for immune checkpoint inhibitors (ICI). Previously, we reported our institutional experience highlighting ICI activity in 29 patients with sarcoma. In this study, we explore responses to ICI based on ICI regimen and other covariates to identify significant clinical factors in advanced sarcoma outcomes. METHODS: Patients in The Ohio State University Sarcoma Clinics were enrolled in the Sarcoma Retrospective ICI database from January 1, 2015 through November 1, 2021. Data included treatment regimen (single-agent ICI or ICI + combination) along with clinical covariates. ICI + combination was further categorized into ICI + medication, ICI + radiation, ICI + surgery, or ICI + multiple (more than 2 modalities). Statistical analysis included log-rank tests and proportional hazard regression. The primary objective was to evaluate overall survival (OS) and progression-free survival (PFS). RESULTS: Of the patients in the database, 135 met inclusion criteria. We demonstrated improved OS in patients treated with ICI + combination (p = 0.014, median 64 weeks), but no effect on PFS (p = 0.471, median 31 weeks). Patients with a documented immune-related adverse event (irAE) of dermatitis had improved OS, but only in the ICI + combination cohort (p = 0.021). Patients who received single-agent ICI and whose change in the neutrophil-to-lymphocyte ratio (NLR) was less than 5 had an improved OS (p = 0.002); this was not seen in patients who received ICI + combination therapy (p = 0.441). There were no differences in OS based on age, gender, histology, or subcategories of ICI + combination. This was not the case for PFS; patients who received any ICI regimen and were younger than 70 had a worse PFS (p = 0.036) compared with their older counterparts in this dataset. Patients who developed an irAE, specifically colitis (p = 0.009), hepatitis (p = 0.048), or dermatitis (p = 0.003), had an improved PFS. There were no differences in PFS based on ICI regimen (or subcategories of ICI + combination), gender, histology, change in NLR, or grade of irAE. CONCLUSIONS: This retrospective study demonstrates that ICI + combination therapy can improve OS in some patients with advanced sarcoma. This is consistent with our prior results of ICI in sarcoma.

Prognosis value and positive association of Rab1A/IL4Rα aberrant expression in gastric cancer.

Gastric cancer (GC) is the most common gastrointestinal cancer and the leading cause of worldwide cancer-associated mortality. Several GC patients are diagnosed at the advanced stage with an unsatisfactory 5-year survival rate. Rab1A was significantly associated with IL4Rα expression in non-small cell lung cancer. However, their potential correlation in expression and prognosis remains largely unknown in GC. In this study, Rab1A/IL-4Rα was significantly increased in GC than in para-cancerous tissues, and Rab1A/IL-4Rα overexpression caused poor prognosis among GC patients. Rab1A expression was significantly correlated with IL-4Rα expression in GC tissues, as determined by IHC analysis. In addition, the mRNA expression of Rab1A was closely linked with the IL-4Rα mRNA expression in GC tissue expressed by qPCR. Furthermore, the Kaplan-Meier analysis demonstrated that the group with negative Rab1A and IL-4Rα expression had longer 5-year survival rates than the other group. Besides, the group with positive Rab1A and IL-4Rα expression had a worse prognosis than the other group. Finally, nomograms revealed the overall 3 and 5-year survival determined crucial roles of Rab1A/IL-4Rα expression in predicting the prognosis of GC patients. Therefore, Rab1A/IL-4Rα is vital in GC, providing a novel perspective on targeted GC therapy.

Mediation Impact of Physical Literacy and Activity Between Psychological Distress and Life Satisfaction Among College Students During COVID-19 Pandemic.

The study aims to examine the mediation effects of physical literacy and physical activity behavior in a relationship between psychological distress and life satisfaction among Chinese college students during the real-life Coronavirus disease pandemic (COVID-19) circumstance. This study implemented a cross-sectional design, and 1,516 participants from 12 universities participated in this study. Structural equation modeling was used to examine a hypothesized model. The findings indicated an acceptable model fit (X 2[61] = 508.2, Comparative Fit Index [CFI] = 0.958, Tucker Lewis Index [TLI] = 0.946, Root Mean Square Error of Approximation [RMSEA] = 0.076, 90% CI [0.070, 0.082], Standardized Root Mean Square Residual [SRMR] = 0.047). The results indicated that college students with low participation in physical activity could experience less than healthy living conditions. The findings offered empirical support to the theory that physical literacy could advance individuals' healthy living by promoting physical activity participation. The study suggested that educational institutions and physical activity programs should cultivate individuals' physical literacy in order to promote lifelong healthy living.

Chemokine CCL7 mediates trigeminal neuropathic pain via CCR2/CCR3-ERK pathway in the trigeminal ganglion of mice.

BACKGROUND: Chemokine-mediated neuroinflammation plays an important role in the pathogenesis of neuropathic pain. The chemokine CC motif ligand 7 (CCL7) and its receptor CCR2 have been reported to contribute to neuropathic pain via astrocyte-microglial interaction in the spinal cord. Whether CCL7 in the trigeminal ganglion (TG) involves in trigeminal neuropathic pain and the involved mechanism remain largely unknown. METHODS: The partial infraorbital nerve transection (pIONT) was used to induce trigeminal neuropathic pain in mice. The expression of Ccl7, Ccr1, Ccr2, and Ccr3 was examined by real-time quantitative polymerase chain reaction. The distribution of CCL7, CCR2, and CCR3 was detected by immunofluorescence double-staining. The activation of extracellular signal-regulated kinase (ERK) was examined by Western blot and immunofluorescence. The effect of CCL7 on neuronal excitability was tested by whole-cell patch clamp recording. The effect of selective antagonists for CCR1, CCR2, and CCR3 on pain hypersensitivity was checked by behavioral testing. RESULTS: Ccl7 was persistently increased in neurons of TG after pIONT, and specific inhibition of CCL7 in the TG effectively relieved pIONT-induced orofacial mechanical allodynia. Intra-TG injection of recombinant CCL7 induced mechanical allodynia and increased the phosphorylation of ERK in the TG. Incubation of CCL7 with TG neurons also dose-dependently enhanced the neuronal excitability. Furthermore, pIONT increased the expression of CCL7 receptors Ccr1, Ccr2, and Ccr3. The intra-TG injection of the specific antagonist of CCR2 or CCR3 but not of CCR1 alleviated pIONT-induced orofacial mechanical allodynia and reduced ERK activation. Immunostaining showed that CCR2 and CCR3 are expressed in TG neurons, and CCL7-induced hyperexcitability of TG neurons was decreased by antagonists of CCR2 or CCR3. CONCLUSION: CCL7 activates ERK in TG neurons via CCR2 and CCR3 to enhance neuronal excitability, which contributes to the maintenance of trigeminal neuropathic pain. CCL7-CCR2/CCR3-ERK pathway may be potential targets for treating trigeminal neuropathic pain.

Preliminary Support for the Use of Motivational Interviewing to Improve Parent/Adult Caregiver Behavior for Obesity and Cancer Prevention.

Motivational interviewing (MI) is a promising behavioral intervention for improving parent and adult caregiver (PAC) health behavior for obesity and cancer prevention. This study explored the preliminary effects of MI from a registered dietitian (RDMI) within an obesity prevention intervention to promote PAC behavior change and positive proxy effects on children and the home environment. N = 36 PAC/child dyads from low-resource communities were enrolled in a randomized trial testing a 10-week obesity prevention intervention. Intervention dyads were offered RDMI sessions. Data were collected at baseline and post-intervention (PAC diet quality (Healthy Eating Index (HEI)), child skin carotenoids, home environment, and PAC ambivalence regarding improving diet). Results show that for every RDMI dose, PAC HEI scores increased (0.571 points, p = 0.530), child skin carotenoid scores improved (1.315%, p = 0.592), and the home food environment improved (3.559%, p = 0.026). There was a significant positive relationship between RDMI dose and change in ambivalence (ρ = 0.533, p = 0.007). Higher baseline ambivalence was associated with greater dose (ρ = -0.287, p = 0.173). Thus, RDMI for PACs may improve diets among PACs who are otherwise ambivalent, with potential effects on the diets of their children and the home food environment. Such intervention strategies have the potential for greater effect, strengthening behavioral interventions targeting obesity and cancer.

Excitatory Projections from the Prefrontal Cortex to Nucleus Accumbens Core D1-MSNs and κ Opioid Receptor Modulate Itch-Related Scratching Behaviors.

Itch is an uncomfortable and complex sensation that elicits the desire to scratch. The nucleus accumbens (NAc) activity is important in driving sensation, motivation, and emotion. Excitatory afferents from the medial prefrontal cortex (mPFC), amygdala, and hippocampus are crucial in tuning the activity of dopamine receptor D1-expressing and D2-expressing medium spiny neurons (Drd1-MSN and Drd2-MSN) in the NAc. However, a cell-type and neural circuity-based mechanism of the NAc underlying acute itch remains unclear. We found that acute itch induced by compound 48/80 (C48/80) decreased the intrinsic membrane excitability in Drd1-MSNs, but not in Drd2-MSNs, in the NAc core of male mice. Chemogenetic activation of Drd1-MSNs alleviated C48/80-induced scratching behaviors but not itch-related anxiety-like behaviors. In addition, C48/80 enhanced the frequency of spontaneous EPSCs (sEPSCs) and reduced the paired-pulse ratio (PPR) of electrical stimulation-evoked EPSCs in Drd1-MSNs. Furthermore, C48/80 increased excitatory synaptic afferents to Drd1-MSNs from the mPFC, not from the basolateral amygdala (BLA) or ventral hippocampus (vHipp). Consistently, the intrinsic excitability of mPFC-NAc projecting pyramidal neurons was increased after C48/80 treatment. Chemogenetic inhibition of mPFC-NAc excitatory synaptic afferents relieved the scratching behaviors. Moreover, pharmacological activation of κ opioid receptor (KOR) in the NAc core suppressed C48/80-induced scratching behaviors, and the modulation of KOR activity in the NAc resulted in the changes of presynaptic excitatory inputs to Drd1-MSNs in C48/80-treated mice. Together, these results reveal the neural plasticity in synapses of NAc Drd1-MSNs from the mPFC underlying acute itch and indicate the modulatory role of the KOR in itch-related scratching behaviors.SIGNIFICANCE STATEMENT Itch stimuli cause strongly scratching desire and anxiety in patients. However, the related neural mechanisms remain largely unclear. In the present study, we demonstrated that the pruritogen compound 48/80 (C48/80) shapes the excitability of dopamine receptor D1-expressing medium spiny neurons (Drd1-MSNs) in the nucleus accumbens (NAc) core and the glutamatergic synaptic afferents from medial prefrontal cortex (mPFC) to these neurons. Chemogenetic activation of Drd1-MSNs or inhibition of mPFC-NAc excitatory synaptic afferents relieves the scratching behaviors. In addition, pharmacological activation of κ opioid receptor (KOR) in the NAc core alleviates C48/80-induced itch. Thus, targeting mPFC-NAc Drd1-MSNs or KOR may provide effective treatments for itch.

Knockdown of LINC01279 Suppresses Gastric Cancer Proliferation and Migration by Inhibiting PI3K/Akt/mTOR Signaling Pathway.

Objective: To explore the functional and molecular mechanism of long noncoding RNA LINC01279 in gastric cancer (GC). Methods: The LINC01279 expression in GC and tissues of para-carcinoma was detected by qPCR (real-time fluorescent quantitative PCR), and the association between the LINC01279 expression and clinicopathological features of patients with GC was investigated. The colony formation, CCK-8, transwell assays, and cell cycle detection kit were used for detection of the effect of LINC01279 on GC cell proliferation, cell cycle, colony formation, and invasion. The effect of LINC01279 on PI3K/AKT/mTOR in the GC signaling pathway was identified by the Western blotting technique. The effect of LINC01279 on GC cell proliferation in vivo was evaluated by subcutaneous xenograft tumors in the nude mice. Results: The results of qPCR displayed the expression of LINC01279 was higher in tissues of GC patients. Furthermore, the tumor size, TNM stage, and metastasis of lymph nodes were also closely related to LINC01279 expression. The experiments on cell function showed that the LINC01279 knockdown significantly inhibited the colony formation, invasion, and proliferation of GC cells and induced the cell cycle arrest in G0 and G1 phases. The Western blotting technique also showed that LINC01279 knockdown significantly inhibited the phosphorylation of PI3K, Akt, and mTOR in GC cells. Furthermore, in vivo experiments displayed that the LINC01279 knockdown significantly inhibited the GC growth. Conclusion: Knockdown of LINC01279 plays a significant role in inhibiting the PI3K/AKT/mTOR signaling pathway which affects the GC invasion and proliferation. The LINC01279 expression can be utilized as a biomarker for the prediction of the GC prognosis.

The Value-Added Contribution of Exercise Commitment to College Students' Exercise Behavior: Application of Extended Model of Theory of Planned Behavior.

The aim of this study was to investigate the applicability of the planned behavior theory model (TPB-5) and TPB-6 model of enhanced physical exercise in college students, and to explore the role of exercise commitment in the relationship between exercise intention and behavior, so as to provide theoretical and empirical support for college students to promotion exercise. The study participants were 581 college students (male = 243, female = 338, age = 19.27 ± 0.94) are investigated with Theory of Planned Behavior (TPB) Scale, Exercise Commitment Scale, and Physical Activity Rating Scale. Results showed that the explanatory power of the TPB to exercise intention and exercise behavior is 0.70 and 0.52, respectively, and exercise intention was the primary factor to predict exercise behavior of college students. The Model fit of TPB-6 model is acceptable, compared with TPB 5-factor model, the predictive power of TPB-6 (with the mediator: exercise commitment) on behavioral intention increases from 70.0 to 75.0%, and the predictive power towards behavior raises from 52.0 to 59.0%. Exercise commitment has a partial mediating effect between exercise intention and behavior, which accounts for 26.89% of the total effect, but it has no moderating effect. In conclusion, this research demonstrates the TPB-5 model has good applicability among the college students, with exercise commitment variables, exercise intention can better predict college students' exercise behavior, which can be used as the theoretical basis for the intervention on their exercise behavior.

An Evaluation of Clinical Efficacy of Immune Checkpoint Inhibitors for Patients with Anaplastic Thyroid Carcinoma.

Background: Anaplastic thyroid carcinoma (ATC) is an aggressive thyroid malignancy that is associated with poor prognosis. Current treatment options include surgery, radiation, cytotoxic chemotherapy, and multikinase inhibitor therapy. The role of immunotherapy in ATC is an area of active interest and recent evidence suggests that it may be a potentially effective treatment option. Methods: We report a case series of 13 patients with locally advanced or metastatic unresectable ATC who received immune checkpoint inhibitor therapy (pembrolizumab or nivolumab) at a single institution. Results: The patients' median age was 70 years, 54% (7/13) were male, and 85% (11/13) had stage IVC disease with lungs and lymph nodes being the most common sites of metastases. Ten patients had tumor tissue available for programmed death-ligand 1 (PD-L1) expression testing, all of which were positive for PD-L1, and seven of these patients also had a BRAFV600E mutation. The median progression-free survival was 1.9 months and median overall survival (OS) was 4.4 months. The objective response rate was 16% (2/13). Two patients had partial response (PR), and three patients had durable stable disease. Among patients with a clinical benefit, after a median follow-up of 13.5 months, median OS had not been reached (range 4+ to 29+ months). Responses were ongoing in four subjects. The one-year survival rate was 38% (5/13). Six patients (46%) experienced an immune-related adverse event, and 15% (2/13) experienced a grade 3 or higher adverse event, including one patient with grade 5 immune checkpoint-related thyroiditis. Conclusions: Immune checkpoint blockade was well tolerated with a toxicity profile consistent with published literature on PD-1/PD-L1-targeting therapies. For ATC patients, immune checkpoint inhibition may represent an effective treatment option with robust sustained responses seen in a subset of patients.

Treatment with soluble CD24 attenuates COVID-19-associated systemic immunopathology.

BACKGROUND: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) through direct lysis of infected lung epithelial cells, which releases damage-associated molecular patterns and induces a pro-inflammatory cytokine milieu causing systemic inflammation. Anti-viral and anti-inflammatory agents have shown limited therapeutic efficacy. Soluble CD24 (CD24Fc) blunts the broad inflammatory response induced by damage-associated molecular patterns via binding to extracellular high mobility group box 1 and heat shock proteins, as well as regulating the downstream Siglec10-Src homology 2 domain-containing phosphatase 1 pathway. A recent randomized phase III trial evaluating CD24Fc for patients with severe COVID-19 (SAC-COVID; NCT04317040) demonstrated encouraging clinical efficacy. METHODS: Using a systems analytical approach, we studied peripheral blood samples obtained from patients enrolled at a single institution in the SAC-COVID trial to discern the impact of CD24Fc treatment on immune homeostasis. We performed high dimensional spectral flow cytometry and measured the levels of a broad array of cytokines and chemokines to discern the impact of CD24Fc treatment on immune homeostasis in patients with COVID-19. RESULTS: Twenty-two patients were enrolled, and the clinical characteristics from the CD24Fc vs. placebo groups were matched. Using high-content spectral flow cytometry and network-level analysis, we found that patients with severe COVID-19 had systemic hyper-activation of multiple cellular compartments, including CD8+ T cells, CD4+ T cells, and CD56+ natural killer cells. Treatment with CD24Fc blunted this systemic inflammation, inducing a return to homeostasis in NK and T cells without compromising the anti-Spike protein antibody response. CD24Fc significantly attenuated the systemic cytokine response and diminished the cytokine coexpression and network connectivity linked with COVID-19 severity and pathogenesis. CONCLUSIONS: Our data demonstrate that CD24Fc rapidly down-modulates systemic inflammation and restores immune homeostasis in SARS-CoV-2-infected individuals, supporting further development of CD24Fc as a novel therapeutic against severe COVID-19.

Assessing Differential Effects of Somatic Amplification to Positive Affect in Midlife and Late Adulthood-A Regression Mixture Approach.

This study aims to provide an empirical demonstration of a novel method, regression mixture model, by examining differential effects of somatic amplification to positive affect and identifying the predictors that contribute to the differential effects. Data derived from the second wave of Midlife in the United States. The analytic sample consisted of 1,766 adults aged from 33 to 84 years. Regression mixture models were fitted using Mplus 7.4, and a two-step model-building approach was adopted. Three latent groups were identified consisting of a maladaptive (32.1%), a vulnerable (62.5%), and a resilient (5.4%) group. Six covariates (i.e., age, education level, positive relations with others, purpose in life, depressive symptoms, and physical health) significantly predicted the latent class membership in the regression mixture model. The study demonstrated the regression mixture model to be a flexible and efficient statistical tool in assessing individual differences in response to adversity and identifying resilience factors, which contributes to aging research.

White and Black Differences in Perceived Access to Health and Community Services and Self-Rated Health in an Age-Friendly Community Assessment.

OBJECTIVES: This study sought to identify the race differences in perceived access to health and community services and self-rated health (SRH) among White and Black older adult participants of an age-friendly community assessment. METHODS: Responses (n = 313) to a baseline assessment of Columbus, Ohio, residents aged ≥50 years were analyzed. RESULTS: Significant differences were found between White and Black older adults regarding SRH, with Black older adults reporting lower SRH. Black older adults reported significantly lower perceived access to 11 out of the 13 health and community services. There were no significant differences by race regarding ratings of Columbus and personal neighborhoods as a place for people to live as they age. Regression analyses found income was a significant predictor of SRH for both White and Black older adults. DISCUSSION: Opportunities to increase perceived access and knowledge of health and community services for older adults through targeted, equitable interventions are warranted.