Nevin Manimala

J Natl Cancer Inst. 2022 Sep 20:djac180. doi: 10.1093/jnci/djac180. Online ahead of print.

ABSTRACT

BACKGROUND: The Pathways to Wellness trial tested the efficacy of two interventions for younger breast cancer survivors: mindful awareness practices (MAPs) and survivorship education (SE). This planned secondary analysis examines intervention effects on stress, positive psychological outcomes, and inflammation (Clincaltrials.gov NCT03025139).

METHODS: Women diagnosed with breast cancer at or before age 50 who had completed treatment and had elevated depressive symptoms were randomly assigned to 6 weeks of MAPs, SE, or wait-list control (WLC). Assessments conducted at pre- and post-intervention and at 3- and 6-month follow-up measured general stress perceptions, cancer-related intrusive thoughts and worry, positive affect, meaning/peace in life, altruism/empathy, and markers of inflammation. Analyses compared change in outcomes over time in each intervention group relative to WLC using linear mixed models.

RESULTS: 247 women were randomized to MAPS (n = 85), SE (n = 81), or WLC (n = 81). MAPs statistically significantly decreased intrusive thoughts and worry at post-intervention and 3-month follow up relative to WLC (ps < .027), and statistically significantly increased positive affect and meaning/peace at post-intervention, with positive affect persisting at 3-month follow up (ps < .027). SE statistically significantly decreased intrusive thoughts at 3-month follow up and statistically significantly increased positive affect at 6-month follow up relative to WLC (ps < .01). Pro-inflammatory gene expression increased in WLC relative to MAPs (p = .016) but did not differ from SE. There were no intervention effects on other outcomes.

CONCLUSION: MAPs had beneficial effects on psychological and immune outcomes in younger breast cancer survivors and is a promising approach for enhancing biobehavioral health.

PMID:36130057 | DOI:10.1093/jnci/djac180

Eur J Endocrinol. 2022 Sep 1:EJE-22-0449. doi: 10.1530/EJE-22-0449. Online ahead of print.

ABSTRACT

OBJECTIVE: To evaluate the safety and efficacy of weekly PEG-rhGH in children with idiopathic short stature (ISS) in China.

DESIGN AND METHODS: A multicenter, phase II study randomized subjects 1:1:1 to weekly subcutaneous injections of PEG-rhGH 0.1 (low dose [LD]) or 0.2 mg/kg/week (high dose [HD]) or control for 52 weeks. The primary endpoint was change in HT-SDS from baseline to week 52. Secondary endpoints were height velocity (HV), bone maturity, IGF-1 SDS, and IGF-1/IGFBP-3 ratio.

RESULTS: A total of 360 children with ISS were recruited in the study (n=120 in each group). At week 52, the mean change from baseline in HT-SDS was 0.56 ± 0.26, 0.98 ± 0.35, and 0.20 ± 0.26 in the LD, HD, and control groups, respectively (within-group P<0.0001; inter-group P<0.0001). Statistically significant changes in HV, IGF-1, IGF-1/IGFBP-3 ratio, and IGF-1 SDS at week 52 from baseline were observed in both treatment groups (P<0.0001). There were clear dose-dependent responses for all auxological variables. PEG-rhGH was well tolerated throughout the treatment period with treatment-emergent adverse events (TEAEs) reported in 86.5%, 84.6%, and 91.3% of children in the HD, LD, and control groups, respectively. The incidence of TEAEs was similar in all treatment groups despite the difference in doses. A total of 27 (8.7%) children experienced drug-related TEAEs.

CONCLUSION: Fifty-two-week treatment with PEG-rhGH 0.1 or 0.2 mg/kg/week achieved significant improvement in HT-SDS and other growth-related variables, including HV, IGF-1 SDS, and IGF-1/IGFBP-3 ratio, in a dose-dependent manner. Both doses were well tolerated with similar safety profiles.

PMID:36130048 | DOI:10.1530/EJE-22-0449

J Am Soc Mass Spectrom. 2022 Sep 21. doi: 10.1021/jasms.2c00218. Online ahead of print.

ABSTRACT

Mass spectrometry (MS) is uniquely powerful for measuring the mass of intact proteins and other biomolecules. New applications have expanded intact protein analysis into biopharmaceuticals, native MS, and top-down proteomics, all of which have driven the need for more automated data-processing pipelines. However, key metrics in the field are often not precisely defined. For example, there are different views on how to calculate uncertainty from spectra. This Critical Insight will explore the different definitions of mass, error, and uncertainty. It will discuss situations where different definitions may be more suitable and provide recommendations for best practices. Targeting both beginners and experts, the goal of the discussion is to provide a common foundation of terminology, enhance statistical rigor, and improve automation of data analysis.

PMID:36130030 | DOI:10.1021/jasms.2c00218

Sci Adv. 2022 Sep 23;8(38):eabm5952. doi: 10.1126/sciadv.abm5952. Epub 2022 Sep 21.

ABSTRACT

This work introduces a comprehensive approach to assess the sensitivity of model outputs to changes in parameter values, constrained by the combination of prior beliefs and data. This approach identifies stiff parameter combinations strongly affecting the quality of the model-data fit while simultaneously revealing which of these key parameter combinations are informed primarily by the data or are also substantively influenced by the priors. We focus on the very common context in complex systems where the amount and quality of data are low compared to the number of model parameters to be collectively estimated, and showcase the benefits of this technique for applications in biochemistry, ecology, and cardiac electrophysiology. We also show how stiff parameter combinations, once identified, uncover controlling mechanisms underlying the system being modeled and inform which of the model parameters need to be prioritized in future experiments for improved parameter inference from collective model-data fitting.

PMID:36129974 | DOI:10.1126/sciadv.abm5952

Nano Lett. 2022 Sep 21. doi: 10.1021/acs.nanolett.2c02275. Online ahead of print.

ABSTRACT

The physics of phase transitions in two-dimensional (2D) systems underpins research in diverse fields including statistical mechanics, nanomagnetism, and soft condensed matter. However, many aspects of 2D phase transitions are still not well understood, including the effects of interparticle potential, polydispersity, and particle shape. Magnetic skyrmions are chiral spin-structure quasi-particles that form two-dimensional lattices. Here, we show, by real-space imaging using in situ cryo-Lorentz transmission electron microscopy coupled with machine learning image analysis, the ordering behavior of Néel skyrmion lattices in van der Waals Fe₃GeTe₂. We demonstrate a distinct change in the skyrmion size distribution during field-cooling, which leads to a loss of lattice order and an evolution of the skyrmion liquid phase. Remarkably, the lattice order is restored during field heating and demonstrates a thermal hysteresis. This behavior is explained by the skyrmion energy landscape and demonstrates the potential to control the lattice order in 2D phase transitions.

PMID:36129969 | DOI:10.1021/acs.nanolett.2c02275

J Evol Biol. 2022 Sep 21. doi: 10.1111/jeb.14087. Online ahead of print.

ABSTRACT

Temperatures are increasing due to global changes, putting biodiversity at risk. Organisms are faced with a limited set of options to cope with this situation: adapt, disperse or die. We here focus on the first possibility, more specifically, on evolutionary adaptations to temperature. Ectotherms are usually characterized by a hump-shaped relationship between fitness and temperature, a non-linear reaction norm that is referred to as thermal performance curve (TPC). To understand and predict impacts of global change, we need to know whether and how such TPCs evolve. Therefore, we performed a systematic literature search and a statistical meta-analysis focusing on experimental evolution and artificial selection studies. This focus allows us to directly quantify relative fitness responses to temperature selection by calculating fitness differences between TPCs from ancestral and derived populations after thermal selection. Out of 7561 publications screened, we found 47 studies corresponding to our search criteria representing taxa across the tree of life, from bacteria, to plants and vertebrates. We show that, independently of species identity, the studies we found report a positive response to temperature selection. Considering entire TPC shapes, adaptation to higher temperatures traded off with fitness at lower temperatures, leading to niche shifts. Effects were generally stronger in unicellular organisms. By contrast, we do not find statistical support for the often discussed “Hotter is better” hypothesis. While our meta-analysis provides evidence for adaptive potential of TPCs across organisms, it also highlights that more experimental work is needed, especially for under-represented taxa, such as plants and non-model systems.

PMID:36129955 | DOI:10.1111/jeb.14087

PLoS One. 2022 Sep 21;17(9):e0274935. doi: 10.1371/journal.pone.0274935. eCollection 2022.

ABSTRACT

BACKGROUND: Breast cancer is still a recognized public health issue in Ethiopia. Despite this, the viewpoints and comprehensions of young women about the situation are unknown. Therefore, this study was carried out to assess the knowledge and perceptions of young adult women in Southwest Ethiopia about breast cancer and breast self-examination (BSE).

METHODS: A community-based cross-sectional study was carried out in the Gurage zone, southwest Ethiopia, in 2021. A total of 392 young adult women were randomly selected from both urban and rural strata using a three-stage stratified sampling process. A pretested questionnaire was used to collect the data. For data entry, Epi-data 4.6 with a double-entry approach was used, and for analysis, SPSS 26 was used. Bivariate and multivariable logistic regression analyses were performed to identify variables associated with BSE behavior. A p-value of 0.05 or below was considered statistically significant with a 95% CI.

RESULTS: The respondents’ ages ranged from 20 to 24, with a mean of 21.25 (±1.32) years. Breast cancer and BSE were unknown to more than 80% of the study participants. A large proportion of young adult women had low perceived susceptibility (97.6%), low threat of breast cancer (96%), and low self-efficacy to perform BSE (91.4%). BSE was conducted by 23.1% of the participants occasionally. Being married (AOR = 5.31, 95% CI = 2.19-12.90), having good outcome expectations of BSE (AOR = 2.05, 95% CI = 1.16-3.61), having good BSE knowledge (AOR = 1.22, 95% CI = 1.04-1.45), having high perceived susceptibility (AOR = 1.12, 95% CI = 1.05-1.20), high perceived severity (AOR = 1.78, 95% CI = 1.02-3.09), and having high self-efficacy to do BSE (AOR = 1.05, 95% CI = 1.01-1.09) were all significant predictors of BSE practice.

CONCLUSIONS: Young adult women were less concerned about breast cancer and had insufficient knowledge of breast cancer and breast self-examination. They have little knowledge of, confidence in, or experience with BSE. The practice of BSE was associated with increased perceived susceptibility, self-efficacy, severity, outcome expectations, and BSE knowledge. Therefore, these variables should be considered when developing educational interventions for young women.

PMID:36129946 | DOI:10.1371/journal.pone.0274935

Proc Natl Acad Sci U S A. 2022 Sep 27;119(39):e2205509119. doi: 10.1073/pnas.2205509119. Epub 2022 Sep 21.

ABSTRACT

Androgen receptor (AR) messenger RNA (mRNA) alternative splicing variants (AR-Vs) are implicated in castration-resistant progression of prostate cancer (PCa), although the molecular mechanism underlying the genesis of AR-Vs remains poorly understood. The CDK12 gene is often deleted or mutated in PCa and CDK12 deficiency is known to cause homologous recombination repair gene alteration or BRCAness via alternative polyadenylation (APA). Here, we demonstrate that pharmacological inhibition or genetic inactivation of CDK12 induces AR gene intronic (intron 3) polyadenylation (IPA) usage, AR-V expression, and PCa cell resistance to the antiandrogen enzalutamide (ENZ). We further show that AR binds to the CCNK gene promoter and up-regulates CYCLIN K expression. In contrast, ENZ decreases AR occupancy at the CCNK gene promoter and suppresses CYCLIN K expression. Similar to the effect of the CDK12 inhibitor, CYCLIN K degrader or ENZ treatment promotes AR gene IPA usage, AR-V expression, and ENZ-resistant growth of PCa cells. Importantly, we show that targeting BRCAness induced by CYCLIN K down-regulation with the PARP inhibitor overcomes ENZ resistance. Our findings identify CYCLIN K down-regulation as a key driver of IPA usage, hormonal therapy-induced AR-V expression, and castration resistance in PCa. These results suggest that hormonal therapy-induced AR-V expression and therapy resistance are vulnerable to PARP inhibitor treatment.

PMID:36129942 | DOI:10.1073/pnas.2205509119

JMIR Res Protoc. 2022 Sep 21;11(9):e39482. doi: 10.2196/39482.

ABSTRACT

BACKGROUND: The use of validated instruments means providing health professionals with reliable and valid tools. The Nurses’ Global Assessment of Suicide Risk (NGASR) scale has proven to be valid and reliable in supporting the nursing evaluation of suicide risk in different languages and cultural environments.

OBJECTIVE: The aims of our study are to translate and adapt the NGASR scale for the Spanish population and evaluate its psychometric properties in patients with suicide risk factors.

METHODS: The translation, adaptation, and modeling of the tool will be performed. The sample will include 165 participants. The psychometric analysis will include reliability and validity tests of the tool’s internal structure. The tool’s reliability will be assessed by exploring internal consistency and calculating the Cronbach α coefficient; significance values of .70 or higher will be accepted as indicators of good internal consistency. The underlying factor structure of the Spanish version of the NGASR scale will be assessed by performing an exploratory factor analysis. The Kaiser-Meyer-Olkin measure of sample adequacy and the Bartlett sphericity statistic will be calculated beforehand. For the latter, if P is <.05 for the null hypothesis of sphericity, the null hypothesis will be rejected.

RESULTS: Participants will be recruited between April 2022 and December 2022. Our study is expected to conclude in the first quarter of 2023.

CONCLUSIONS: We hope to find the same firmness that colleagues have found in other countries in order to consolidate and promote the use of the NGASR tool in the Spanish population. The prevention and treatment of suicidal behavior require holistic, multidisciplinary, and comprehensive management.

INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/39482.

PMID:36129752 | DOI:10.2196/39482

JMIR Mhealth Uhealth. 2022 Sep 21;10(9):e38368. doi: 10.2196/38368.

ABSTRACT

BACKGROUND: Despite several initiatives taken by government bodies, disparities in maternal health have been noticeable across India’s socioeconomic gradient due to poor health awareness.

OBJECTIVE: The aim of this study was to implement an easy-to-use mobile health (mHealth) app-Mobile for Mothers (MfM)-as a supporting tool to improve (1) maternal health awareness and (2) maternal health-related behavioral changes among tribal and rural communities in India.

METHODS: Pregnant women, aged 18 to 45 years, were selected from two rural villages of Jharkhand, India: (1) the intervention group received government-mandated maternal care through an mHealth app and (2) the control group received the same government-mandated care via traditional means (ie, verbally). A total of 800 accredited social health activists (ASHAs) were involved, of which 400 were allocated to the intervention group. ASHAs used the MfM app to engage with pregnant women during each home visit in the intervention group. The mHealth intervention commenced soon after the baseline survey was completed in February 2014. The end-line data were collected between November 2015 and January 2016. We calculated descriptive statistics related to demographics and the percentage changes for each variable between baseline and end line per group. The baseline preintervention groups were compared to the end-line postintervention groups using Pearson chi-square analyses. Mantel-Haenszel tests for conditional independence were conducted to determine if the pre- to postintervention differences in the intervention group were significantly different from those in the control group.

RESULTS: Awareness regarding the five cleans (5Cs) in the intervention group increased (P<.001) from 143 (baseline) to 555 (end line) out of 740 participants. Awareness about tetanus vaccine injections and the fact that pregnant women should receive two shots of tetanus vaccine in the intervention group significantly increased (P<.001) from 73 out of 740 participants (baseline) to 372 out of 555 participants (end line). In the intervention group, awareness regarding the fact that problems like painful or burning urination and itchy genitals during pregnancy are indicative of a reproductive tract infection increased (P<.001) from 15 (baseline) to 608 (end line) out of 740 participants. Similarly, knowledge about HIV testing increased (P<.001) from 39 (baseline) to 572 (end line) out of 740 participants. We also noted that the number of pregnant women in the intervention group who consumed the prescribed dosage of iron tablets increased (P<.001) from 193 (baseline) out of 288 participants to 612 (end line) out of 663 participants.

CONCLUSIONS: mHealth interventions can augment awareness of, and persistence in, recommended maternal health behaviors among tribal communities in Jharkhand, India. In addition, mHealth could act as an educational tool to help tribal societies break away from their traditional beliefs about maternal health and take up modern health care recommendations.

TRIAL REGISTRATION: OSF Registries 9U8D5; https://doi.org/10.17605/OSF.IO/9U8D5.

PMID:36129749 | DOI:10.2196/38368