Tag: nevin manimala

Methods Protoc. 2023 Mar 28;6(2):35. doi: 10.3390/mps6020035.

ABSTRACT

Increasing evidence strongly supports the key role of the tumour microenvironment in response to systemic therapy, particularly immune checkpoint inhibitors (ICIs). The tumour microenvironment is a complex tapestry of immune cells, some of which can suppress T-cell immunity to negatively impact ICI therapy. The immune component of the tumour microenvironment, although poorly understood, has the potential to reveal novel insights that can impact the efficacy and safety of ICI therapy. Successful identification and validation of these factors using cutting-edge spatial and single-cell technologies may enable the development of broad acting adjunct therapies as well as personalised cancer immunotherapies in the near future. In this paper we describe a protocol built upon Visium (10x Genomics) spatial transcriptomics to map and characterise the tumour-infiltrating immune microenvironment in malignant pleural mesothelioma. Using ImSig tumour-specific immune cell gene signatures and BayesSpace Bayesian statistical methodology, we were able to significantly improve immune cell identification and spatial resolution, respectively, improving our ability to analyse immune cell interactions within the tumour microenvironment.

PMID:37104017 | DOI:10.3390/mps6020035

Noncoding RNA. 2023 Mar 30;9(2):22. doi: 10.3390/ncrna9020022.

ABSTRACT

Long non-coding RNAs (lncRNAs) play important roles in the maintenance of metabolic homeostasis. Recently, many studies have suggested that lncRNAs, such as Metastasis Associated Lung Adenocarcinoma Transcript 1 (MALAT1) and Imprinted Maternally Expressed Transcript (H19), might participate in the pathogenesis of metabolic disorders such as obesity. We conducted a case-control study with 150 Russian children and adolescents aged between 5 and 17 years old in order to assess the statistical association between the single nucleotide polymorphisms (SNPs) rs3200401 in MALAT1 and rs217727 in H19, and the risk of developing obesity in this population. We further explored the possible association of rs3200401 and rs217727 with BMI Z-score and insulin resistance. The MALAT1 rs3200401 and H19 rs217727 SNPs were genotyped using Taqman SNP genotyping assay. The MALAT1 rs3200401 SNP was identified as a risk factor for childhood obesity (p < 0.05) under the dominant and allelic models, and the CT heterozygous genotype was associated with the risk of increased BMI and with insulin resistance. The H19 rs217727 SNP had no significant association with obesity risk (all p > 0.05). Our findings thus suggest that MALAT1 SNP rs3200401 is a potential indicator of obesity susceptibility and pathogenesis in children and adolescents.

PMID:37104004 | DOI:10.3390/ncrna9020022

JMIR Form Res. 2023 Apr 27;7:e44857. doi: 10.2196/44857.

ABSTRACT

BACKGROUND: Social skills training by human trainers is a well-established method of teaching appropriate social and communication skills and strengthening social self-efficacy. Specifically, human social skills training is a fundamental approach to teaching and learning the rules of social interaction. However, it is cost-ineffective and offers low accessibility, since the number of professional trainers is limited. A conversational agent is a system that can communicate with a human being in a natural language. We proposed to overcome the limitations of current social skills training with conversational agents. Our system is capable of speech recognition, response selection, and speech synthesis and can also generate nonverbal behaviors. We developed a system that incorporated automated social skills training that completely adheres to the training model of Bellack et al through a conversational agent.

OBJECTIVE: This study aimed to validate the training effect of a conversational agent-based social skills training system in members of the general population during a 4-week training session. We compare 2 groups (with and without training) and hypothesize that the trained group’s social skills will improve. Furthermore, this study sought to clarify the effect size for future larger-scale evaluations, including a much larger group of different social pathological phenomena.

METHODS: For the experiment, 26 healthy Japanese participants were separated into 2 groups, where we hypothesized that group 1 (system trained) will make greater improvement than group 2 (nontrained). System training was done as a 4-week intervention where the participants visit the examination room every week. Each training session included social skills training with a conversational agent for 3 basic skills. We evaluated the training effect using questionnaires in pre- and posttraining evaluations. In addition to the questionnaires, we conducted a performance test that required the social cognition and expression of participants in new role-play scenarios. Blind ratings by third-party trainers were made by watching recorded role-play videos. A nonparametric Wilcoxson Rank Sum test was performed for each variable. Improvement between pre- and posttraining evaluations was used to compare the 2 groups. Moreover, we compared the statistical significance from the questionnaires and ratings between the 2 groups.

RESULTS: Of the 26 recruited participants, 18 completed this experiment: 9 in group 1 and 9 in group 2. Those in group 1 achieved significant improvement in generalized self-efficacy (P=.02; effect size r=0.53). We also found a significant decrease in state anxiety presence (P=.04; r=0.49), measured by the State-Trait Anxiety Inventory (STAI). For ratings by third-party trainers, speech clarity was significantly strengthened in group 1 (P=.03; r=0.30).

CONCLUSIONS: Our findings reveal the usefulness of the automated social skills training after a 4-week training period. This study confirms a large effect size between groups on generalized self-efficacy, state anxiety presence, and speech clarity.

PMID:37103996 | DOI:10.2196/44857

JMIR Public Health Surveill. 2023 Apr 27;9:e42820. doi: 10.2196/42820.

ABSTRACT

BACKGROUND: China is the most populous country globally and has made significant achievements in the control of infectious diseases over the last decades. The 2003 SARS epidemic triggered the initiation of the China Information System for Disease Control and Prevention (CISDCP). Since then, numerous studies have investigated the epidemiological features and trends of individual infectious diseases in China; however, few considered the changing spatiotemporal trends and seasonality of these infectious diseases over time.

OBJECTIVE: This study aims to systematically review the spatiotemporal trends and seasonal characteristics of class A and class B notifiable infectious diseases in China during 2005-2020.

METHODS: We extracted the incidence and mortality data of 8 types (27 diseases) of notifiable infectious diseases from the CISDCP. We used the Mann-Kendall and Sen’s methods to investigate the diseases’ temporal trends, Moran I statistic for their geographical distribution, and circular distribution analysis for their seasonality.

RESULTS: Between January 2005 and December 2020, 51,028,733 incident cases and 261,851 attributable deaths were recorded. Pertussis (P=.03), dengue fever (P=.01), brucellosis (P=.001), scarlet fever (P=.02), AIDS (P<.001), syphilis (P<.001), hepatitis C (P<.001) and hepatitis E (P=.04) exhibited significant upward trends. Furthermore, measles (P<.001), bacillary and amebic dysentery (P<.001), malaria (P=.04), dengue fever (P=.006), brucellosis (P=.03), and tuberculosis (P=.003) exhibited significant seasonal patterns. We observed marked disease burden-related geographic disparities and heterogeneities. Notably, high-risk areas for various infectious diseases have remained relatively unchanged since 2005. In particular, hemorrhagic fever and brucellosis were largely concentrated in Northeast China; neonatal tetanus, typhoid and paratyphoid, Japanese encephalitis, leptospirosis, and AIDS in Southwest China; BAD in North China; schistosomiasis in Central China; anthrax, tuberculosis, and hepatitis A in Northwest China; rabies in South China; and gonorrhea in East China. However, the geographical distribution of syphilis, scarlet fever, and hepatitis E drifted from coastal to inland provinces during 2005-2020.

CONCLUSIONS: The overall infectious disease burden in China is declining; however, hepatitis C and E, bacterial infections, and sexually transmitted infections continue to multiply, many of which have spread from coastal to inland provinces.

PMID:37103994 | DOI:10.2196/42820

J Med Internet Res. 2023 Apr 27;25:e44256. doi: 10.2196/44256.

ABSTRACT

BACKGROUND: Long-term daily health monitoring and management play a more significant role in telehealth management systems nowadays, which require evaluation indicators to present patients’ general health conditions and become applicable to multiple chronic diseases.

OBJECTIVE: This study aims to evaluate the effectiveness of subjective indicators of telehealth chronic disease management system (TCDMS).

METHODS: We selected Web of Science, ScienceDirect, Scopus, Cochrane library, IEEE, and Chinese National Knowledge Infrastructure and Wanfang, a Chinese medical database, and searched papers published from January 1, 2015, to July 1, 2022, regarding randomized controlled trials on the effectiveness of the telehealth system on patients with chronic diseases. The narrative review summarized the questionnaire indicators presented in the selected studies. In the meta-analysis, Mean Difference (MD) and Standardized Mean Difference (SMD) with a 95% CI were pooled depending on whether the measurements were the same. Subgroup analysis was conducted if the heterogeneity was significant, and the number of studies was sufficient.

RESULTS: Twenty RCTs with 4153 patients were included in the qualitative review. Seventeen different questionnaire-based outcomes were found, within which quality of life, psychological well-being (including depression, anxiety, and fatigue), self-management, self-efficacy, and medical adherence were most frequently used. Ten RCTs with 2095 patients remained in meta-analysis. Compared to usual care, telehealth system can significantly improve the quality of life (SMD 0.44; 95% CI 0.16-0.73; P=.002), whereas no significant effects were found on depression (SMD -0.25; 95% CI -0.72 to 0.23; P=.30), anxiety (SMD -0.10; 95% CI -0.27 to 0.07; P=.71), fatigue (SMD -0.36; 95% CI -1.06 to 0.34; P<.001), and self-care (SMD 0.77; 95% CI -0.28-1.81; P<.001). In the subdomains of quality of life, telehealth statistically significantly improved physical functioning (SMD 0.15; 95% CI 0.02 to 0.29; P=.03), mental functioning (SMD 0.37; 95% CI 0.13-0.60; P=.002), and social functioning (SMD 0.64; 95% CI 0.00-1.29; P=.05), while there was no difference on cognitive functioning (MD 8.31; 95% CI -7.33 to 23.95; P=.30) and role functioning (MD 5.30; 95% CI -7.80 to 18.39; P=.43).

CONCLUSIONS: TCDMS positively affected patients’ physical, mental, and social quality of life across multiple chronic diseases. However, no significant difference was found in depression, anxiety, fatigue, and self-care. Subjective questionnaires had the potential ability to evaluate the effectiveness of long-term telehealth monitoring and management. However, further well-designed experiments are warranted to validate TCDMS’s effects on subjective outcomes, especially when tested among different chronically ill groups.

PMID:37103993 | DOI:10.2196/44256

Hum Vaccin Immunother. 2023 Dec 31;19(1):2206774. doi: 10.1080/21645515.2023.2206774.

ABSTRACT

Universal infant hepatitis B vaccination has been implemented more than three decades. This study aimed to determine the prevalence of antibodies to hepatitis B surface antigen (anti-HBs) and to hepatitis B core antigen (anti-HBc) in qualified blood donors in Nanjing, China. Plasmas of 815 qualified blood donors, collected from February through May 2019, were measured for anti-HBs and anti-HBc by enzyme-linked immunosorbent assay. There were 449 (55.1%) male and 366 (44.9%) female blood donors, with a median age of 28.9 years (18-60). The seroprevalence of anti-HBs was 58.8%, with no significant difference in different genders and different age groups. The overall prevalence of anti-HBc was 7.0%, with an increasing trend with age, from 0% in 18-20 years old group to 17.9% in 51-60 years old group (χ² = 46.7965, p < .0001). The prevalence of anti-HBc in donors born after the implementation of universal hepatitis B vaccination was significantly lower than that in donors born before (1.0% vs 15.5%; χ² = 63.6033, p < .0001). Our data suggest that more than half of the blood donors in Nanjing are anti-HBs positive. Since a blood recipient usually receives more than one unit of red blood cells or plasma, passively acquired anti-HBs in blood recipients may neutralize hepatitis B virus potentially presented in blood donors with occult hepatitis B infection. In addition, the presence of anti-HBs and/or anti-HBc in blood donors may cause unique hepatitis B serological profile in blood recipients.

PMID:37103976 | DOI:10.1080/21645515.2023.2206774

JAMA Ophthalmol. 2023 Apr 27. doi: 10.1001/jamaophthalmol.2023.1007. Online ahead of print.

ABSTRACT

IMPORTANCE: Racial and ethnic differences in the association between myopia and primary open-angle glaucoma (POAG) are not well understood.

OBJECTIVE: To investigate the association between myopia and POAG in the 2019 California Medicare population and to investigate whether there was evidence of effect measure modification of this association by race and ethnicity.

DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study used administrative claims data from 2019 California Medicare beneficiaries 65 years or older with California residence and active coverage with Medicare parts A and B. Analysis took place between October 2021 and October 2023.

EXPOSURES: The primary exposure was myopia, which was defined by International Statistical Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis codes.

MAIN OUTCOMES AND MEASURES: The outcome of interest was POAG, which was defined by ICD-10-CM code.

RESULTS: Of 2 717 346 California Medicare beneficiaries in 2019, 1 440 769 (53.0%) were aged 65 to 74 years, 1 544 479 (56.8%) identified as female, 60 211 (2.2%) had myopia, and 171 988 (6.3%) had POAG. Overall, 346 723 individuals (12.8%) identified as Asian, 117 856 (4.3%) as Black, 430 597 (15.8%) as Hispanic, 1 705 807 (62.8%) as White, and 115 363 (4.2%) as other race and ethnicity. In adjusted logistic regression analyses, beneficiaries with myopia had higher odds of POAG compared with beneficiaries without myopia (odds ratio [OR], 2.41; 95% CI, 2.35-2.47). In multivariable models stratified by race and ethnicity, the association between myopia and POAG was stronger in Asian (OR, 2.74; 95% CI, 2.57-2.92), Black (OR, 2.60; 95% CI, 2.31-2.94), and Hispanic (OR, 3.28; 95% CI, 3.08-3.48) beneficiaries compared with non-Hispanic White beneficiaries (OR, 2.14; 95% CI, 2.08-2.21).

CONCLUSIONS AND RELEVANCE: In the 2019 California Medicare population, myopia was associated with greater adjusted odds of POAG. This association was stronger among Asian, Black, and Hispanic beneficiaries compared with non-Hispanic White beneficiaries. These findings suggest possible disparities in glaucoma risk by race and ethnicity in individuals with myopia and may indicate greater need for glaucoma screening in individuals with myopia from racial and ethnic minority backgrounds.

PMID:37103940 | DOI:10.1001/jamaophthalmol.2023.1007

JAMA Oncol. 2023 Apr 27. doi: 10.1001/jamaoncol.2023.0768. Online ahead of print.

ABSTRACT

IMPORTANCE: While the characteristics of COVID-19 infection and mortality among patients with a malignant neoplasm have previously been examined, little data are available for gender-specific COVID-19 mortality.

OBJECTIVE: To examine the gender-specific COVID-19 case fatality risks among patients with a malignant neoplasm.

DESIGN, SETTING, AND PARTICIPANTS: In this cohort study using the Healthcare Cost and Utilization Project’s National Inpatient Sample, patients admitted to the hospital from April to December 2020 with a diagnosis of COVID-19 infection were identified by the World Health Organization’s International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code U07.1. Data analysis was performed from November 2022 to January 2023.

EXPOSURE: Diagnosis of malignant neoplasm, identified and classified according to the National Cancer Institute’s definition.

MAIN OUTCOME AND MEASURE: COVID-19 in-hospital case fatality rate, defined as the number of deaths that occurred during index hospital admissions.

RESULTS: There were 1 622 755 patients who were admitted to the hospital from April 1 to December 31, 2020, with a diagnosis of COVID-19. The cohort-level COVID-19 in-hospital case fatality rate was 12.9% with a median time to death of 5 days (IQR, 2-11 days). Frequently reported morbidities among the patients with COVID-19 included pneumonia (74.3%), respiratory failure (52.9%), cardiac arrythmia or cardiac arrest (29.3%), acute kidney injury (28.0%), sepsis (24.6%), shock (8.6%), cerebrovascular accident (5.2%), and venous thromboembolism or pulmonary embolism (5.0%). In a multivariable analysis, gender (male vs female, 14.5% vs 11.2%; adjusted odds ratio [aOR], 1.28; 95% CI, 1.27-1.30) and malignant neoplasm (17.9% vs 12.7%; aOR, 1.29; 95% CI, 1.27-1.32) were both associated with increased COVID-19 in-hospital case fatality risk at the cohort level. Among the group of female patients, there were 5 malignant neoplasms in which the COVID-19 in-hospital case fatality risk was greater than 2-fold higher. These included anal cancer (23.8%; aOR, 2.94; 95% CI, 1.84-4.69), Hodgkin lymphoma (19.5%; aOR, 2.79; 95% CI, 1.90-4.08), non-Hodgkin lymphoma (22.4%; aOR, 2.23; 95% CI, 2.02-2.47), lung cancer (24.3%; aOR, 2.21; 95% CI, 2.03-2.39), and ovarian cancer (19.4%; aOR, 2.15; 95% CI, 1.79-2.59). Among the group of male patients, Kaposi sarcoma (33.3%; aOR, 2.08; 95% CI, 1.18-3.66) and malignant neoplasm in the small intestine (28.6%; aOR, 2.04; 95% CI, 1.18-3.53) had a greater than 2-fold increased COVID-19 in-hospital case mortality risk.

CONCLUSIONS AND RELEVANCE: The results of this cohort study confirmed the substantial case fatality rate among patients with COVID-19 in the early pandemic experience in 2020 in the US. While COVID-19 in-hospital case fatality risks were lower among women compared with men, the associations of a concurrent malignant neoplasm with the COVID-19 case fatality were overall more substantial for women than for men.

PMID:37103920 | DOI:10.1001/jamaoncol.2023.0768

JAMA Oncol. 2023 Apr 27. doi: 10.1001/jamaoncol.2023.0187. Online ahead of print.

ABSTRACT

IMPORTANCE: Biomarkers to guide the use of pertuzumab in the treatment of early-stage ERBB2 (formerly HER2)-positive breast cancer beyond simple ERBB2 status are needed.

OBJECTIVE: To determine if use of the HER2DX genomic assay (Reveal Genomics) in pretreatment baseline tissue samples of patients with ERBB2-positive breast cancer is associated with response to neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab.

DESIGN, SETTING, AND PARTICIPANTS: This is a retrospective diagnostic/prognostic analysis of a multicenter academic observational study in Spain performed during 2018 to 2022 (GOM-HGUGM-2018-05). In addition, a combined analysis with 2 previously reported trials of neoadjuvant cohorts with results from the assay (DAPHNe and I-SPY2) was performed. All patients had stage I to III ERBB2-positive breast cancer, signed informed consent, and had available formalin-fixed paraffin-embedded tumor specimens obtained prior to starting therapy.

EXPOSURES: Patients received intravenous trastuzumab, 8 mg/kg, loading dose, followed by 6 mg/kg every 3 weeks in combination with intravenous docetaxel, 75 mg/m2, every 3 weeks and intravenous carboplatin area under the curve of 6 every 3 weeks for 6 cycles, or this regimen plus intravenous pertuzumab, 840 mg, loading dose, followed by an intravenous 420-mg dose every 3 weeks for 6 cycles.

MAIN OUTCOME AND MEASURES: Association of baseline assay-reported pathologic complete response (pCR) score with pCR in the breast and axilla, as well as association of baseline assay-reported pCR score with response to pertuzumab.

RESULTS: The assay was evaluated in 155 patients with ERBB2-positive breast cancer (mean [range] age, 50.3 [26-78] years). Clinical T1 to T2 and node-positive disease was present in 113 (72.9%) and 99 (63.9%) patients, respectively, and 105 (67.7%) tumors were hormone receptor positive. The overall pCR rate was 57.4% (95% CI, 49.2%-65.2%). The proportion of patients in the assay-reported pCR-low, pCR-medium, and pCR-high groups was 53 (34.2%), 54 (34.8%), and 48 (31.0%), respectively. In the multivariable analysis, the assay-reported pCR score (as a continuous variable from 0-100) showed a statistically significant association with pCR (odds ratio [OR] per 10-unit increase, 1.43; 95% CI, 1.22-1.70; P < .001). The pCR rates in the assay-reported pCR-high and pCR-low groups were 75.0% and 28.3%, respectively (OR, 7.85; 95% CI, 2.67-24.91; P < .001). In the combined analysis (n = 282), an increase in pCR rate due to pertuzumab was found in the assay-reported pCR-high tumors (OR, 5.36; 95% CI, 1.89-15.20; P < .001) but not in the assay-reported pCR-low tumors (OR, 0.86; 95% CI, 0.30-2.46; P = .77). A statistically significant interaction between the assay-reported pCR score and the effect of pertuzumab in pCR was observed.

CONCLUSIONS AND RELEVANCE: This diagnostic/prognostic study demonstrated that the genomic assay predicted pCR following neoadjuvant trastuzumab-based chemotherapy with or without pertuzumab. This assay could guide therapeutic decisions regarding the use of neoadjuvant pertuzumab.

PMID:37103916 | DOI:10.1001/jamaoncol.2023.0187

J Clin Psychiatry. 2023 Apr 24;84(3):22m14739. doi: 10.4088/JCP.22m14739.

ABSTRACT

Objective: A post hoc analysis of a phase 3, randomized, double-blind, placebo-controlled outpatient study investigated efficacy of lumateperone 42 mg in patients with bipolar I or bipolar II disorder and experiencing a major depressive episode (MDE) stratified by the presence of mixed features.

Methods: Adults (18-75 years) with bipolar I or bipolar II disorder experiencing an MDE, defined by Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, criteria, were randomized 1:1 to 6-week oral lumateperone 42 mg/d or placebo (conducted November 2017-March 2019). Montgomery-Asberg Depression Rating Scale (MADRS) total score, Clinical Global Impression Scale-Bipolar Version-Severity (CGI-BP-S) total score, and Quality of Life Enjoyment and Satisfaction Questionnaire-Short Form (Q-LES-Q-SF) were analyzed in patients (N = 376) categorized as having mixed features (Young Mania Rating Scale [YMRS] score ≥ 4 and ≤ 12, 41.5%) or not having mixed features (YMRS < 4, 58.5%) at baseline. Treatment-emergent adverse events (TEAEs) including mania/hypomania were assessed.

Results: At day 43, lumateperone significantly improved MADRS and CGI-BP-S total scores change from baseline compared with placebo for patients with mixed features (MADRS least squares mean difference [LSMD] = -4.4, P < .01; CGI-BP-S LSMD = -0.7, P < .05) and without mixed features (MADRS LSMD = -4.2, P < .001, CGI-BP-S LSMD = -1.0, P < .001). Q-LES-Q-SF percent score significantly improved at day 43 with lumateperone vs placebo in patients with mixed features (LSMD = 5.9, P < .05), with numerical improvements in patients without mixed features (LSMD = 2.6, P = .27). TEAEs of mania/hypomania were rare.

Conclusions: Lumateperone 42 mg significantly improved symptoms of depression and disease severity in patients with an MDE associated with bipolar I or bipolar II disorder, with or without mixed features.

Trial Registration: ClinicalTrials.gov identifier: NCT03249376.

PMID:37103915 | DOI:10.4088/JCP.22m14739