Emotional and functional well-being in long-term breast cancer survivorship.

PURPOSE: Emotional and functional well-being (EWB and FWB) are important components of mental health and quality of life. This study aims to evaluate long-term EWB and FWB in breast cancer (BC) survivors. METHODS: The Carolina Breast Cancer Study Phase 3 oversampled Black and younger (< 50 years in age) women so that they each represent approximately 50% of the study population and assessed participants' EWB and FWB with the Functional Assessment of Cancer Therapy-Breast (FACT-B) at 5- (baseline), 25-, and 84-months post diagnosis. Multinomial logit models were used to estimate adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for associations between demographic and clinical characteristics and well-being change relative to baseline. RESULTS: Among 2,781 participants with BC, average EWB and FWB improved with time since diagnosis. Persistent FWB decrements were associated with Black race [OR 1.4 (95% CI 1.2-1.7) and 1.3 (95% CI 1.1-1.6), at 25-months and 84-months respectively], older age [OR 1.4 (95% CI 1.1-1.7) and 1.5 (95% CI 1.2-1.8), respectively], no chemotherapy, and recurrence [OR 2.9 (95% CI 1.8-4.8) and 3.1 (95% CI 2.1-4.6), respectively]. EWB decrements were associated with advanced stage and recurrence. Decrements in combined (FWB+EWB) well-being were associated with recurrence at both follow-up survey timepoints [ORs 4.7 (95% CI 2.7-8.0) and 4.3 (95% CI 2.8-6.6), respectively]. CONCLUSIONS: Long-term well-being varies by demographics and clinical features, with Black women and women with aggressive disease at greatest risk of long-term decrements.

A systematic scoping review of latent class analysis applied to accelerometry-assessed physical activity and sedentary behavior.

BACKGROUND: Latent class analysis (LCA) identifies distinct groups within a heterogeneous population, but its application to accelerometry-assessed physical activity and sedentary behavior has not been systematically explored. We conducted a systematic scoping review to describe the application of LCA to accelerometry. METHODS: Comprehensive searches in PubMed, Web of Science, CINHAL, SPORTDiscus, and Embase identified studies published through December 31, 2021. Using Covidence, two researchers independently evaluated inclusion criteria and discrepancies were resolved by consensus. Studies with LCA applied to accelerometry or combined accelerometry/self-reported measures were selected. Data extracted included study characteristics and both accelerometry and LCA methods. RESULTS: Of 2555 papers found, 66 full-text papers were screened, and 12 papers (11 cross-sectional, 1 cohort) from 8 unique studies were included. Study sample sizes ranged from 217-7931 (mean 2249, standard deviation 2780). Across 8 unique studies, latent class variables included measures of physical activity (100%) and sedentary behavior (75%). About two-thirds (63%) of the studies used accelerometry only and 38% combined accelerometry and self-report to derive latent classes. The accelerometer-based variables in the LCA model included measures by day of the week (38%), weekday vs. weekend (13%), weekly average (13%), dichotomized minutes/day (13%), sex specific z-scores (13%), and hour-by-hour (13%). The criteria to guide the selection of the final number of classes and model fit varied across studies, including Bayesian Information Criterion (63%), substantive knowledge (63%), entropy (50%), Akaike information criterion (50%), sample size (50%), Bootstrap likelihood ratio test (38%), and visual inspection (38%). The studies explored up to 5 (25%), 6 (38%), or 7+ (38%) classes, ending with 3 (50%), 4 (13%), or 5 (38%) final classes. CONCLUSIONS: This review explored the application of LCA to physical activity and sedentary behavior and identified areas of improvement for future studies leveraging LCA. LCA was used to identify unique groupings as a data reduction tool, to combine self-report and accelerometry, and to combine different physical activity intensities and sedentary behavior in one LCA model or separate models.

Haplotype-resolved genomes of two buckwheat crops provide insights into their contrasted rutin concentrations and reproductive systems.

BACKGROUND: Two widely cultivated annual buckwheat crops, Fagopyrum esculentum and F. tataricum, differ from each other in both rutin concentration and reproductive system. However, the underlying genetic mechanisms remain poorly elucidated. RESULTS: Here, we report the first haplotype-resolved chromosome-level genome assemblies of the two species. Two haplotype genomes of F. esculentum were assembled as 1.23 and 1.19 Gb with N50 = 9.8 and 12.4 Mb, respectively; the two haplotype genomes of F. tataricum were 453.7 and 446.2 Mb with N50 = 50 and 30 Mb, respectively. We further annotated protein-coding genes of each haplotype genome based on available gene sets and 48 newly sequenced transcriptomes. We found that more repetitive sequences, especially expansion of long terminal repeat retrotransposons (LTR-RTs), contributed to the large genome size of F. esculentum. Based on the well-annotated sequences, gene expressions, and luciferase experiments, we identified the sequence mutations of the promoter regions of two key genes that are likely to have greatly contributed to the high rutin concentration and selfing reproduction in F. tartaricum. CONCLUSIONS: Our results highlight the importance of high-quality genomes to identify genetic mutations underlying phenotypic differences between closely related species. F. tataricum may have been experienced stronger selection than F. esculentum through choosing these two non-coding alleles for the desired cultivation traits. These findings further suggest that genetic manipulation of the non-coding promoter regions could be widely employed for breeding buckwheat and other crops.

Do Patient-Reported Upper-Body Symptoms Predict Breast Cancer-Related Lymphoedema: Results from a Population-Based, Longitudinal Breast Cancer Cohort Study.

The objectives of this work were to (i) describe upper-body symptoms post-breast cancer; (ii) explore the relationship between symptoms and upper-body function, breast cancer-related lymphoedema (BCRL), physical activity levels, and quality of life; and (iii) determine whether the presence of upper-body symptoms predicts BCRL. Nine symptoms, upper-body function, lymphoedema, physical activity, and quality of life were assessed in women with invasive breast cancer at baseline (2- to 9-months post-diagnosis; n = 2442), and at 2- and 7-years post-diagnosis. Mann−Whitney tests, unpaired t-tests, and chi-squared analyses were used to assess cross-sectional relationships, while regression analyses were used to assess the predictive relationships between symptoms at baseline, and BCRL at 2- and 7-years post-diagnosis. Symptoms are common post-breast cancer and persist at 2- and 7-years post-diagnosis. Approximately two in three women, and one in three women, reported >2 symptoms of at least mild severity, and of at least moderate severity, respectively. The presence of symptoms is associated with poorer upper-body function, and lower physical activity levels and quality of life. One or more symptoms of at least moderate severity increases the odds of developing BCRL by 2- and 7-years post-diagnosis (p < 0.05). Consequently, improved monitoring and management of symptoms following breast cancer have the potential to improve health outcomes.

Burden of lymphedema in long-term breast cancer survivors by race and age.

BACKGROUND: Risk assessment for breast cancer-related lymphedema has emphasized upper-limb symptoms and treatment-related risk factors. This article examined breast cancer-related lymphedema after surgery, overall and in association with broader demographic and clinical features. METHODS: The Carolina Breast Cancer Study phase 3 followed participants for breast cancer-related lymphedema from baseline (on average, 5 months after breast cancer diagnosis) to 7 years after diagnosis. Among 2645 participants, 552 self-reported lymphedema cases were identified. Time-to-lymphedema curves and inverse probability weighted conditional Cox proportional hazards model were used to evaluate whether demographics and clinical features were associated with breast cancer-related lymphedema. RESULTS: Point prevalence of breast cancer-related lymphedema was 6.8% at baseline, and 19.9% and 23.8% at 2 and 7 years after diagnosis, respectively. Most cases had lymphedema in the arm (88%-93%), whereas 14% to 27% presented in the trunk and/or breast. Beginning approximately 10 months after diagnosis, younger Black women had the highest risk of breast cancer-related lymphedema and older non-Black women had the lowest risk. Positive lymph node status, larger tumor size (>5 cm), and estrogen receptor-negative breast cancer, as well as established risk factors such as higher body mass index, removal of more than five lymph nodes, mastectomy, chemotherapy, and radiation therapy, were significantly associated with increased hazard (1.5- to 3.5-fold) of lymphedema. CONCLUSIONS: Findings highlight that hazard of breast cancer-related lymphedema differs by demographic characteristics and clinical features. These factors could be used to identify those at greatest need of lymphedema prevention and early intervention. LAY SUMMARY: In this study, the aim was to investigate breast cancer-related lymphedema (BCRL) burden. This study found that risk of BCRL differs by race, age, and other characteristics.

Effect of Dual Trigger In Vitro Fertilization and Intracytoplasmic Sperm Injection During the Gonadotropin-releasing Hormone-Antagonist Cycle on Final Oocyte Maturation and Cumulative Live Birth Rate in Women with Diminished Ovarian Reserve.

OBJECTIVE: It is well known that a dual trigger treatment can improve clinical outcomes of in vitro fertilization (IVF) in high or normal ovarian responders. However, it is not clear whether dual triggering also benefits patients with diminished ovarian reserve (DOR). The aim of this study was to investigate whether a dual trigger treatment of gonadotropin-releasing hormone (GnRH) agonist combined with human chorionic gonadotropin (hCG) for final follicular maturation improves the cumulative live birth rate (CLBR) during the GnRH-antagonist cycle in patients with DOR. METHODS: This retrospective study included patients with DOR who received a GnRH-antagonist protocol during IVF and intracytoplasmic sperm injection (IVF-ICSI) cycles at Peking University People's Hospital from January 1, 2017 through December 31, 2017. Oocyte maturation was triggered by GnRH combined with hCG (n=110) or hCG alone (n=71). Embryos were transferred on the third day after oocyte retrieval or during a subsequent freeze-thaw cycle. Patients were followed up for 3 years. RESULTS: The dual trigger treatment did not affect CLBR, which is an overall determinant of the success rate of assisted reproductive technology (ART). Women in the dual trigger group had significantly higher rates of fertilization than those in the hCG group (90.1% vs. 83.9%, P=0.040). CONCLUSION: Dual trigger with GnRH agonist and hCG did not improve CLBR in patients with DOR, but did slightly improve fertilization rate, oocyte count, and embryo quality.

The chromosome-level genome assembly of Gentiana dahurica (Gentianaceae) provides insights into gentiopicroside biosynthesis.

Gentiana dahurica Fisch. is a perennial herb of the family Gentianaceae. This species is used as a traditional Tibetan medicine because of its rich gentiopicroside constituents. Here, we generate a high-quality, chromosome-level genome of G. dahurica with a total length of 1,416.54 Mb. Comparative genomic analyses showed that G. dahurica shared one whole-genome duplication (WGD) event with Gelsemium sempervirens of the family Gelsemiaceaei and had one additional species-specific WGD after the ancient whole-genome triplication with other eudicots. Further transcriptome analyses identified numerous enzyme coding genes and the transcription factors related to gentiopicroside biosynthesis. A set of candidate cytochrome P450 genes were identified for being involved in biosynthetic shifts from swertiamarin to gentiopicroside. Both gene expressions and the contents measured by high-performance liquid chromatography indicated that the gentiopicrosides were mainly synthesized in the rhizomes with the highest contents. In addition, we found that two above-mentioned WGDs, contributed greatly to the identified candidate genes involving in gentiopicroside biosynthesis. The first reference genome of Gentianaceae we generated here will definitely accelerate evolutionary, ecological, and pharmaceutical studies of this family.

A chromosome-level genome assembly of an alpine plant Crucihimalaya lasiocarpa provides insights into high-altitude adaptation.

It remains largely unknown how plants adapt to high-altitude habitats. Crucihimalaya (Brassicaceae) is an alpine genus occurring in the Qinghai-Tibet Plateau characterized by cold temperatures and strong ultraviolet radiation. Here, we generated a chromosome-level genome for C. lasiocarpa with a total size of 255.8 Mb and a scaffold N50 size of 31.9 Mb. We first examined the karyotype origin of this species and found that the karyotype of five chromosomes resembled the ancestral karyotype of the Brassicaceae family, while the other three showed strong chromosomal structural variations. In combination with the rough genome sequence of another congener (C. himalaica), we found that the significantly expanded gene families and positively selected genes involved in alpine adaptation have occurred since the origin of this genus. Our new findings provide valuable information for the chromosomal karyotype evolution of Brassicaceae and investigations of high-altitude environment adaptation of the genus.

A Premature Rise of Luteinizing Hormone Is Associated With a Reduced Cumulative Live Birth Rate in Patients ≥37 Years Old Undergoing GnRH Antagonist In Vitro Fertilization Cycles.

This is a retrospective cohort study included 1021 patients underwent a flexible GnRH antagonist IVF protocol from January 2017 to December 2017 to explore the effect of a premature rise in luteinizing hormone (LH) level on the cumulative live birth rate. All patients included received the first ovarian stimulation and finished a follow-up for 3 years. A premature rise in LH was defined as an LH level >10 IU/L or >50% rise from baseline during ovarian stimulation. The cumulative live birth rate was calculated as the number of women who achieved a live birth divided by the total number of women who had either delivered a baby or had used up all their embryos received from the first stimulated cycle. In the advanced patients (≥37 years), the cumulative live birth rate was reduced in patients with a premature rise of LH (ß: 0.20; 95% CI: 0.05-0.88; p=0.03), compared to patients (≥37 years) without the premature LH rise. The incidence of premature LH rise is associated with decreased rates of cumulative live birth rate in patients of advanced age (≥37 years) and aggravated the reduced potential of embryos produced by the advanced age, not the number of embryos.

Branched-Chain Amino Acids and Risk of Breast Cancer.

Background: Circulating branched-chain amino acid (BCAA) levels reflect metabolic health and dietary intake. However, associations with breast cancer are unclear. Methods: We evaluated circulating BCAA levels and breast cancer risk within the Nurses' Health Study (NHS) and NHSII (1997 cases and 1997 controls). A total of 592 NHS women donated 2 blood samples 10 years apart. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) of breast cancer risk in multivariable logistic regression models. We conducted an external validation in 1765 cases in the Women's Health Study (WHS). All statistical tests were 2-sided. Results: Among NHSII participants (predominantly premenopausal at blood collection), elevated circulating BCAA levels were associated with lower breast cancer risk (eg, isoleucine highest vs lowest quartile, multivariable OR = 0.86, 95% CI = 0.65 to 1.13, P trend = .20), with statistically significant linear trends among fasting samples (eg, isoleucine OR = 0.74, 95% CI = 0.53 to 1.05, P trend = .05). In contrast, among postmenopausal women, proximate measures (<10 years from blood draw) were associated with increased breast cancer risk (eg, isoleucine OR = 1.63, 95% CI = 1.12 to 2.39, P trend = .01), with stronger associations among fasting samples (OR = 1.73, 95% CI = 1.15 to 2.61, P trend = .01). Distant measures (10-20 years since blood draw) were not associated with risk. In the WHS, a positive association was observed for distant measures of leucine among postmenopausal women (OR = 1.23, 95% CI = 0.96 to 1.58, P trend = .04). Conclusions: No statistically significant associations between BCAA levels and breast cancer risk were consistent across NHS and WHS or NHSII and WHS. Elevated circulating BCAA levels were associated with lower breast cancer risk among predominantly premenopausal NHSII women and higher risk among postmenopausal women in NHS but not in the WHS. Additional studies are needed to understand this complex relationship.

A multi-scale gated multi-head attention depthwise separable CNN model for recognizing COVID-19.

Coronavirus 2019 (COVID-19) is a new acute respiratory disease that has spread rapidly throughout the world. In this paper, a lightweight convolutional neural network (CNN) model named multi-scale gated multi-head attention depthwise separable CNN (MGMADS-CNN) is proposed, which is based on attention mechanism and depthwise separable convolution. A multi-scale gated multi-head attention mechanism is designed to extract effective feature information from the COVID-19 X-ray and CT images for classification. Moreover, the depthwise separable convolution layers are adopted as MGMADS-CNN's backbone to reduce the model size and parameters. The LeNet-5, AlexNet, GoogLeNet, ResNet, VGGNet-16, and three MGMADS-CNN models are trained, validated and tested with tenfold cross-validation on X-ray and CT images. The results show that MGMADS-CNN with three attention layers (MGMADS-3) has achieved accuracy of 96.75% on X-ray images and 98.25% on CT images. The specificity and sensitivity are 98.06% and 96.6% on X-ray images, and 98.17% and 98.05% on CT images. The size of MGMADS-3 model is only 43.6 M bytes. In addition, the detection speed of MGMADS-3 on X-ray images and CT images are 6.09 ms and 4.23 ms for per image, respectively. It is proved that the MGMADS-3 can detect and classify COVID-19 faster with higher accuracy and efficiency.

Association between Low House Cleaning Frequency, Cough and Risk of Miscarriage: A Case Control Study in China.

This study investigated the association between house cleaning frequency and the risk of miscarriage in a case control sample of Chinese population. We recruited 59 pregnant women with clinical pregnancy loss as cases and 122 women who chose to conduct induced abortion as controls. All participants were aged 20~40 years and completed a questionnaire of lifestyle exposure with a trained nurse. The effect of frequency of cleaning up on risk of miscarriage was estimated using multivariable logistic regressions, adjusting for potential confounders. In the present study, it was shown that house cleaning of less than twice per week was significantly associated with cough during day or night with odds ratio (OR) of 2.97 (95% CI: 1.36~6.75, p = 0.007), and cough during day or night was significantly associated with risk of miscarriage with OR of 2.69 (95% CI: 1.22~6.02, p = 0.014). Thus, house cleaning of less than twice per week was statistically significantly associated with miscarriage with OR of 3.05 (95% CI: 1.51~6.31, p = 0.002). We found that females who have their house cleaned less than twice per week are at elevated risk for miscarriage. Therefore, the home of pregnant woman should be cleaned at least twice per week in order to avoid miscarriage.

Effect of a "Dual Trigger" Using a GnRH Agonist and hCG on the Cumulative Live-Birth Rate for Normal Responders in GnRH-Antagonist Cycles.

"Dual triggering" for final oocyte maturation using a combination of a gonadotropin-releasing hormone agonist (GnRHa) and human chorionic gonadotropin (hCG) can improve clinical outcomes in high responders during in vitro fertilization-intracytoplasmic sperm injection (IVF-ICSI) GnRH-antagonist cycles. However, whether this dual trigger is also beneficial to normal responders is not known. We retrospectively analyzed the data generated from 469 normal responders from 1 January to 31 December 2017. The final oocyte maturation was undertaken with a dual trigger with a GnRHa combined with hCG (n = 270) or hCG alone (n = 199). Patients were followed up for 3 years. The cumulative live-birth rate was calculated as the first live birth achieved after all cycles having an embryo transfer (cycles using fresh embryos and frozen-thawed embryos) among both groups. Women in the dual-trigger group achieved a slightly higher number of oocytes retrieved (11.24 vs. 10.24), higher number of two-pronuclear (2PN) embryos (8.37 vs. 7.67) and a higher number of embryos available (4.45 vs. 4.03). However, the cumulative live-birth rate and the all-inclusive success rate for assisted reproductive technology was similar between the two groups (54.07 vs. 59.30%). We showed that a dual trigger was not superior to a hCG-alone trigger for normal responders in GnRH-antagonist cycles in terms of the cumulative live-birth rate.