Healthy lifestyles, systemic inflammation and breast cancer risk: a mediation analysis.

BACKGROUND: Despite the known association between healthy lifestyles and reduced risk of breast cancer, it remains unclear whether systemic inflammation, as a consequence of unhealthy lifestyles, may mediate the association. METHODS: A cohort study of 259,435 female participants in the UK Biobank was conducted to estimate hazard ratio (HR) for breast cancer according to 9 inflammation markers using Cox regression models. We further estimated the percentage of total association between healthy lifestyle index (HLI) and breast cancer that is mediated by these inflammation markers. RESULTS: During 2,738,705 person-years of follow-up, 8,889 cases of breast cancer were diagnosed among 259,435 women in the UK Biobank cohort. Higher level of C-reactive protein (CRP), systemic immune-inflammation index (SII), CRP-to-albumin Ratio (CAR), CRP-to-lymphocyte Ratio (CLR), monocyte-to-HDL-c ratio (MHR), and neutrophil-to-HDL-c ratio (NHR) were associated with increased breast cancer risk, while a higher lymphocyte-to-monocyte ratio (LMR) was associated with a lower risk. The inverse association between HLI and breast cancer was weakly mediated by CRP (8.5%), SII (1.71%), CAR (8.66%), CLR (6.91%), MHR (6.27%), and NHR (7.33%). When considering individual lifestyle factors, CRP and CAR each mediated 16.58% and 17.20%, respectively, of the associations between diet score and breast cancer risk, while the proportion mediated for physical activity and breast cancer were 12.13% and 11.48%, respectively. Furthermore, MHR was found to mediate 13.84% and 12.01% of the associations between BMI, waist circumference, and breast cancer. CONCLUSION: The association of HLI and breast cancer is weakly mediated by the level of inflammation, particularly by CRP and CAR. Systemic inflammatory status may be an intermediate in the biological pathway of breast cancer development.

The interaction of diet, alcohol, genetic predisposition, and the risk of breast cancer: a cohort study from the UK Biobank.

BACKGROUND: Dietary factors have consistently been associated with breast cancer risk. However, there is limited evidence regarding their associations in women with different genetic susceptibility to breast cancer, and their interaction with alcohol consumption is also not well understood. METHODS: We analyzed data from 261,853 female participants in the UK Biobank. Multivariable adjusted Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations between dietary factors and breast cancer risk. Additionally, we assessed the interaction of dietary factors with alcohol consumption and polygenic risk score (PRS) for breast cancer. RESULTS: A moderately higher risk of breast cancer was associated with the consumption of processed meat (HR = 1.10, 95% CI 1.03, 1.18, p-trend = 0.016). Higher intake of raw vegetables and fresh fruits, and adherence to a healthy dietary pattern were inversely associated with breast cancer risk [HR (95% CI):0.93 (0.88-0.99), 0.87 (0.81, 0.93) and 0.93 (0.86-1.00), p for trend: 0.025, < 0.001, and 0.041, respectively]. Furthermore, a borderline significant interaction was found between alcohol consumption and the intake of processed meat with regard to breast cancer risk (P for interaction = 0.065). No multiplicative interaction was observed between dietary factors and PRS. CONCLUSION: Processed meat was positively associated with breast cancer risk, and vegetables, fruits, and healthy dietary patterns were negatively associated with breast cancer risk. We found no strong interaction of dietary factors with alcohol consumption and genetic predisposition for risk of breast cancer.

Breastfeeding in infancy and mortality in middle and late adulthood: A prospective cohort study and meta-analysis.

BACKGROUND: Breastfeeding in infancy is associated with a lower risk of mortality among children, but the impact on mortality in middle and late adulthood remains unknown. OBJECTIVES: To assess the association between breastfeeding in infancy and mortality in middle and late adulthood. METHODS: We included 383,627 participants aged 40-73 from the UK Biobank (2006-2010) and followed up until 2021. Hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality according to breastfeeding in infancy were estimated with Cox proportional hazards regression models. We further did a meta-analysis, including results from our present study and three other cohort studies (PROSPERO; number CRD42022348925). RESULTS: During a total of 4732,751 person-years of follow-up, 25,581 deaths were identified. Breastfeeding in infancy was associated with lower risks of mortality in middle and late adulthood, with adjusted HRs (95% CIs) of 0.95 (0.93-0.98) for all-cause mortality; 0.91 (0.87-0.96) for cardiovascular mortality and 0.94 (0.874-0.999) for respiratory mortality. Specifically, the association with mortality seemed to attenuate with age - stronger in middle-aged adults than in older adults. A similar association between breastfeeding in infancy and all-cause mortality was found in the meta-analysis. CONCLUSION: Breastfeeding in infancy is associated with a lower risk of mortality - even decades later - in middle and late adulthood.

Spatial patterns and the associated factors for breast cancer hospitalization in the rural population of Fujian Province, China.

BACKGROUND: Despite the known increasing incidence of breast cancer in China, evidence on the spatial pattern of hospitalization for breast cancer is scarce. This study aimed to describe the disparity of breast cancer hospitalization in the rural population of Southeast China and to explore the impacts of socioeconomic factors and heavy metal pollution in soil. METHODS: This study was conducted using the New Rural Cooperative Medical Scheme (NRCMS) claims data covering 20.9 million rural residents from 73 counties in Southeast China during 2015-2016. The associations between breast cancer hospitalization and socioeconomic factors and soil heavy metal pollutants were evaluated with quasi-Poisson regression models and geographically weighted Poisson regressions (GWPR). RESULTS: The annual hospitalization rate for breast cancer was 101.40/100,000 in the studied area and the rate varied across different counties. Overall, hospitalization for breast cancer was associated with road density (ß = 0.43, P = 0.02), urbanization (ß = 0.02, P = 0.002) and soil cadmium (Cd) pollution (ß = 0.01, P = 0.02). In the GWPR model, a stronger spatial association of Cd, road density and breast cancer hospitalization was found in the northeast regions of the study area while breast cancer hospitalization was mainly related to urbanization in the western regions. CONCLUSIONS: Soil Cd pollution, road density, and urbanization were associated with breast cancer hospitalization in different regions. Findings in this study might provide valuable information for healthcare policies and intervention strategies for breast cancer.

Effects of ambient air pollution on cause-specific hospitalizations in Wuhan during 2017-2019.

BACKGROUND: Few studies have focused on the associations between air pollutants and multiple organ system diseases in the entire hospitalized population. The present study aims to explore the short-term effects of six routinely monitored air pollutants on the broad causes of hospital admissions and estimate the resulting hospital admission burdens. METHODS: Daily hospital admission records from 2017 to 2019 were obtained from the Wuhan Information center of Health and Family Planning. Generalized additive models (GAMs) were employed to evaluate the effects of air pollutants on the percent increase in the cause-specific daily number of hospital admissions. Increased hospital admission numbers, days, and expenses were also estimated. RESULTS: A total of 2636,026 hospital admissions were identified. We found that both PM2.5 and PM10 increased the risk of hospital admissions for most disease categories. Short-term exposure to PM2.5 was positively associated with hospitalizations of several rarely studied disease categories, such as diseases of the eye and adnexa (2.83%, 95%CI: 0.96-4.73%, P < 0.01) and diseases of the musculoskeletal system and connective tissue (2.17%, 95% CI: 0.88-3.47%, P < 0.001). NO2 was observed to have a robust effect on diseases of the respiratory system (1.36%, 95%CI: 0.74-1.98%, P < 0.001). CO was significantly associated with hospital admissions for six disease categories. Furthermore, each 10-µg/m3 increase in PM2.5 was associated with an annual increase of 13,444 hospital admissions (95% CI: 6239-20,649), 124,344 admission days (95% CI: 57,705-190,983), and 166-million-yuan admission expenses (95% CI: 77-255). CONCLUSION: Our study suggested that particulate matter (PM) had a short-term effect on hospital admissions of most major disease categories and resulted in a considerable hospital admission burden. In addition, the health effects of NO2 and CO emissions require more attention in megacities.

Bone mineral density and risk of breast cancer: A cohort study and Mendelian randomization analysis.

BACKGROUND: Estrogen is involved in both bone metabolism and breast cancer proliferation. However, evidence about the risk of breast cancer according to women's bone mineral density (BMD) is scarce, and little is known about their causal associations. METHODS: Women participating in the UK Biobank cohort were used to investigate the association between BMD and the risk of breast cancer using Cox regression models. Instrumental variants associated with estimated BMD (eBMD) were extracted from genome-wide association studies with European ancestry. Logistic regression was used to calculate the genetic association with breast cancer in the UK Biobank and 2-sample Mendelian randomization (MR) analyses to assess their causal associations with breast cancer. Finally, the pleiotropic conditional false discovery rate (cFDR) method was conducted to further detect common genetic variants between BMD and breast cancer. RESULTS: Compared with the general population, postmenopausal women with BMD T scores <-2.5 had a lower risk of breast cancer (hazard ratio [HR], 0.77; 95% CI, 0.59-1.00), and this effect was stronger in women with fracture (HR, 0.31; 95% CI, 0.12-0.82). In MR analysis, no causal associations between eBMD and breast cancer were observed. The cFDR method identified 63 pleiotropic loci associated with both BMD and breast cancer, of which CCDC170, ESR1, and FTO might play crucial roles in their pleiotropy. CONCLUSIONS: An association between BMD and the risk of postmenopausal breast cancer in the UK Biobank was observed, whereas no evidence supported their causal association. Instead, their association could be explained by pleiotropic genetic variants leading to the pathology of osteoporosis and breast cancer.

Disease trajectories and mortality among individuals diagnosed with depression: a community-based cohort study in UK Biobank.

Patients with depression are at increased risk for a range of comorbid diseases, with, however, unclear explanations. In this large community-based cohort study of the UK Biobank, 24,130 patients diagnosed with depression were compared to 120,366 matched individuals without such a diagnosis. Follow-up was conducted from 6 months after the index date until death or the end of 2019, for the occurrence of 470 medical conditions and 16 specific causes of death. The median age at the time of the depression diagnosis was 62.0 years, and most of the patients were female (63.63%). During a median follow-up of 4.94 years, 129 medical conditions were found to be significantly associated with a prior diagnosis of depression, based on adjusted Cox regression models. Using disease trajectory network analysis to visualize the magnitude of disease-disease associations and the temporal order of the associated medical conditions, we identified three main affected disease clusters after depression (i.e., cardiometabolic diseases, chronic inflammatory diseases, and diseases related to tobacco abuse), which were further linked to a wider range of other conditions. In addition, we also identified three depression-mortality trajectories leading to death due to cardiovascular disease, respiratory system disease and malignant neoplasm. In conclusion, an inpatient diagnosis of depression in later life is associated with three distinct network-based clusters of medical conditions, indicating alterations in the cardiometabolic system, chronic status of inflammation, and tobacco abuse as key pathways to a wide range of other conditions downstream. If replicated, these pathways may constitute promising targets for the health promotion among depression patients.

Alcohol consumption, blood DNA methylation and breast cancer: a Mendelian randomisation study.

Alcohol intake is thought to be a risk factor for breast cancer, but the causal relationship and carcinogenic mechanisms are not clear. We performed an up-to-date meta-analysis of prospective studies to assess observational association, and then conducted MR analysis to make causal inference based on the genetic predisposition to alcohol consumption ("drinks per week") and pathological drinking behaviours ("alcohol use disorder" and "problematic alcohol use"), as well as genetically predicted DNA methylation at by alcohol-related CpG sites in blood. We found an observational dose-response association between alcohol intake and breast cancer incidence with an additional risk of 4% for per 10 g/day increase in alcohol consumption. Genetic predisposition to alcohol consumption ("drinks per week") was not causally associated with breast cancer incidence at the OR of 1.01 (95% CI 0.84, 1.23), but problematic alcohol use (PAU) was linked to a higher breast cancer risk at the OR of 1.76 (95% CI 1.04, 2.99) when conditioning on alcohol consumption. Epigenetic MR analysis identified four CpG sites, cg03260624 near CDC7 gene, cg10816169 near ZNF318 gene, cg03345232 near RIN3 gene, and cg26312998 near RP11-867G23.13 gene, where genetically predicted epigenetic modifications were associated with an increased breast cancer incidence risk. Our findings re-affirmed that alcohol consumption is of high risk for breast cancer incidence even at a very low dose, and the pathogenic effect of alcohol on breast cancer could be due to pathological drinking behaviour and epigenetic modification at several CpG sites, which could be potential intervention targets for breast cancer prevention.

Mammographic features are associated with cardiometabolic disease risk and mortality.

AIMS: In recent years, microcalcifications identified in routine mammograms were found to be associated with cardiometabolic disease in women. Here, we aimed to systematically evaluate the association of microcalcifications and other mammographic features with cardiometabolic disease risk and mortality in a large screening cohort and to understand a potential genetic contribution. METHODS AND RESULTS: This study included 57 867 women from a prospective mammographic screening cohort in Sweden (KARMA) and 49 583 sisters. Cardiometabolic disease diagnoses and mortality and medication were extracted by linkage to Swedish population registries with virtually no missing data. In the cardiometabolic phenome-wide association study, we found that a higher number of microcalcifications were associated with increased risk for multiple cardiometabolic diseases, particularly in women with pre-existing cardiometabolic diseases. In contrast, dense breasts were associated with a lower incidence of cardiometabolic diseases. Importantly, we observed similar associations in sisters of KARMA women, indicating a potential genetic overlap between mammographic features and cardiometabolic traits. Finally, we observed that the presence of microcalcifications was associated with increased cardiometabolic mortality in women with pre-existing cardiometabolic diseases (hazard ratio and 95% confidence interval: 1.79 [1.24-2.58], P = 0.002) while we did not find such effects in women without cardiometabolic diseases. CONCLUSIONS: We found that mammographic features are associated with cardiometabolic risk and mortality. Our results strengthen the notion that a combination of mammographic features and other breast cancer risk factors could be a novel and affordable tool to assess cardiometabolic health in women attending mammographic screening.

Effect of ambient fine particulates (PM2.5) on hospital admissions for respiratory and cardiovascular diseases in Wuhan, China.

BACKGROUND: Positive associations between ambient PM2.5 and cardiorespiratory disease have been well demonstrated during the past decade. However, few studies have examined the adverse effects of PM2.5 based on an entire population of a megalopolis. In addition, most studies in China have used averaged data, which results in variations between monitoring and personal exposure values, creating an inherent and unavoidable type of measurement error. METHODS: This study was conducted in Wuhan, a megacity in central China with about 10.9 million people. Daily hospital admission records, from October 2016 to December 2018, were obtained from the Wuhan Information center of Health and Family Planning, which administrates all hospitals in Wuhan. Daily air pollution concentrations and weather variables in Wuhan during the study period were collected. We developed a land use regression model (LUR) to assess individual PM2.5 exposure. Time-stratified case-crossover design and conditional logistic regression models were adopted to estimate cardiorespiratory hospitalization risks associated with short-term exposure to PM2.5. We also conducted stratification analyses by age, sex, and season. RESULTS: A total of 2,806,115 hospital admissions records were collected during the study period, from which we identified 332,090 cardiovascular disease admissions and 159,365 respiratory disease admissions. Short-term exposure to PM2.5 was associated with an increased risk of a cardiorespiratory hospital admission. A 10 µg/m3 increase in PM2.5 (lag0-2 days) was associated with an increase in hospital admissions of 1.23% (95% CI 1.01-1.45%) and 1.95% (95% CI 1.63-2.27%) for cardiovascular and respiratory diseases, respectively. The elderly were at higher PM-induced risk. The associations appeared to be more evident in the cold season than in the warm season. CONCLUSIONS: This study contributes evidence of short-term effects of PM2.5 on cardiorespiratory hospital admissions, which may be helpful for air pollution control and disease prevention in Wuhan.

Hyperthyroidism is associated with breast cancer risk and mammographic and genetic risk predictors.

BACKGROUND: Despite the biological link between thyroid hormones and breast cancer cell proliferation shown in experimental studies, little is known about the association between hyperthyroidism and breast cancer, as well as its association with the most common mammographic and genetic risk predictors for breast cancer. METHODS: This study estimates the incidence rate ratios (IRRs) of breast cancer among women diagnosed with hyperthyroidism, compared to those who are not, using two cohorts: a Swedish national cohort of the general female population (n = 3,793,492, 2002-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 69,598, 2002-2017). We used logistic regression to estimate the odds ratios (ORs) of hyperthyroidism according to the mammographic and genetic risk predictors for breast cancer. RESULTS: An increased risk of breast cancer was observed in patients in the national cohort with hyperthyroidism (IRR = 1.23, 95% CI = 1.12-1.36), particularly for toxic nodular goiter (IRR = 1.38, 95% CI = 1.16-1.63). Hyperthyroidism was associated with higher body mass index, early age at first birth, and lower breastfeeding duration. Higher mammographic density was observed in women with toxic nodular goiter, compared to women without hyperthyroidism. Additionally, among genotyped women without breast cancer in the KARMA cohort (N = 11,991), hyperthyroidism was associated with a high polygenic risk score (PRS) for breast cancer overall (OR = 1.98, 95% CI = 1.09-3.60) and for estrogen receptor-positive specific PRS (OR = 1.90, 95% CI = 1.04-3.43). CONCLUSION: Hyperthyroidism is associated with an increased risk of breast cancer, particularly for patients with toxic nodular goiter. The association could be explained by higher mammographic density among these women, as well as pleiotropic genetic variants determining shared hormonal/endocrine factors leading to the pathology of both diseases.

Disease trajectories and mortality among women diagnosed with breast cancer.

PURPOSE: Breast cancer is a common disease with a relatively good prognosis. Therefore, understanding the spectrum of diseases and mortality among breast cancer patients is important, though currently incomplete. We systematically examined the incidence and mortality of all diseases following a breast cancer diagnosis, as well as the sequential association of disease occurrences (trajectories). METHODS: In this national cohort study, 57,501 breast cancer patients (2001-2011) were compared to 564,703 matched women from the general Swedish population and followed until 2012. The matching criteria included year of birth, county of residence, and socioeconomic status. Based on information from the Swedish Patient and Cause of Death Registries, hazard ratios (HR) were estimated for disease incidence and mortality. Conditional logistic regression models were used to identify disease trajectories among breast cancer patients. RESULTS: Among 225 diseases, 45 had HRs > 1.5 and p < 0.0002 when comparing breast cancer patients with the general population. Diseases with highest HRs included lymphedema, radiodermatitis, and neutropenia, which are side effects of surgery, radiotherapy, and chemotherapy. Other than breast cancer, the only significantly increased cause of death was other solid cancers (HR = 1.16, 95% CI = 1.08-1.24). Two main groups of disease trajectories were identified, which suggest menopausal disorders as indicators for other solid cancers, and both neutropenia and dorsalgia as diseases and symptoms preceding death due to breast cancer. CONCLUSIONS: While an increased incidence of other diseases was found among breast cancer patients, increased mortality was only due to other solid cancers. Preventing death due to breast cancer should be a priority to prolong life in breast cancer patients, but closer surveillance of other solid cancers is also needed.

Inherited factors contribute to an inverse association between preeclampsia and breast cancer.

BACKGROUND: Preeclampsia is frequently linked to reduced breast cancer risk. However, little is known regarding the underlying genetic association and the association between preeclampsia and mammographic density. METHODS: This study estimates the incidence rate ratios (IRRs) of breast cancer in patients with preeclampsia, when compared to women without preeclampsia, using Poisson regression models in two cohorts of pregnant women: a Swedish nationwide cohort (n = 1,337,934, 1973-2011) and the Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA, n = 55,044, 1958-2015). To identify the genetic association between preeclampsia and breast cancer, we used logistic regression models to calculate the odds ratios (ORs) of preeclampsia in sisters of breast cancer patients, and in women with different percentiles of breast cancer polygenic risk scores (PRS). Linear regression models were used to estimate the mammographic density by preeclampsia status in the KARMA cohort. RESULTS: A decreased risk of breast cancer was observed among patients with preeclampsia in both the nationwide (IRR = 0.90, 95% CI = 0.85; 0.96) and KARMA cohorts (IRR = 0.75, 95% CI = 0.61; 0.93). Women with high breast cancer PRS and sisters of breast cancer patients had a lower risk of preeclampsia (OR = 0.89, 95% CI = 0.83; 0.96). Mammographic density was lower in women with preeclampsia compared to women without preeclampsia (-2.04%, 95% CI = -2.65; -1.43). Additionally, among sisters in the KARMA cohort (N = 3500), density was lower in sisters of patients with preeclampsia compared to sisters of women without preeclampsia (-2.76%, 95% CI = -4.96; -0.56). CONCLUSION: Preeclampsia is associated with reduced risk of breast cancer and mammographic density. Inherited factors contribute to this inverse association.

Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer.

Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in situ breast cancer (2001-2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46-1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in situ cancer only showed an increased incidence of stress-related disorders during the first 6 months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.

Risk and predictors of psoriasis in patients with breast cancer: a Swedish population-based cohort study.

BACKGROUND: The risk of psoriasis in patients with breast cancer is largely unknown, as available evidence is limited to case findings. We systematically examined the incidence and risk factors of psoriasis in patients with breast cancer. METHODS: A Swedish nationwide cohort of 56,235 breast cancer patients (2001-2012) was compared to 280,854 matched reference individuals from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. We also calculated HRs for psoriasis according to treatment, genetic, and lifestyle factors in a regional cohort of 8987 patients. RESULTS: In the nationwide cohort, 599 patients with breast cancer were diagnosed with psoriasis during a median follow-up of 5.1 years compared to 2795 cases in the matched reference individuals. This corresponded to an incidence rate of 1.9/1000 person-years in breast cancer patients vs. 1.7/1000 person-years in matched reference individuals. Breast cancer patients were at an increased risk of psoriasis (HR = 1.17; 95% confidence interval (CI) = 1.07-1.28), especially its most common subtype (psoriasis vulgaris; HR = 1.33; 95% CI = 1.17-1.52). The risk of psoriasis vulgaris was highest shortly after diagnosis but remained increased up to 12 years. Treatment-specific analyses indicated a higher risk of psoriasis in patients treated with radiotherapy (HR = 2.44; 95% CI = 1.44-4.12) and mastectomy (HR = 1.54, 95% CI = 1.03-2.31). Apart from treatment-specific effects, we identified genetic predisposition, obesity, and smoking as independent risk factors for psoriasis in breast cancer patients. CONCLUSIONS: The incidence of psoriasis is slightly elevated among patients with breast cancer, with treatment, lifestyle, and genetic factors defining the individual risk profile.

Enhanced SOFI algorithm achieved with modified optical fluctuating signal extraction.

In this paper, we present a modified SOFI algorithm with enhanced temporal resolution: the required number of raw images for SOFI is reduced from hundreds to tens. The modification is intended to eliminate the low-frequency fluctuation and readout noise from the raw image stack, and is achieved by separately utilizing two wavelet-based filters in the temporal and spatial domains of the raw image stack. The high-frequency stochastic fluctuating signal could be extracted effectively, and the efficiency of SOFI could be enhanced. The modified SOFI image could be generated with 25 frames of raw images, and the corresponding acquisition time was 1.25 s.

Development assistance for health given to Nepal by China and India: a comparative study.

BACKGROUND: Development assistance for health (DAH) promotes health development in low and middle income countries. China and India, as emerging donors, have scaled-up their DAH programs during the recent years. Nepal, as a neighboring country to China and India, has witnessed the history and development of China's and India's DAH. METHODS: This research uses a literature review and in-depth individual interviewing to compare the history and forms of DAH given from China and India to Nepal. RESULTS: During 60-years of DAH to Nepal, China and India have gradually increased the scale and forms of DAH, and both focus on dispatching medical teams or faculty, building health facilities and gifting medicines and equipment. However, the inclusiveness of Nepalese culture, diplomatic interests, and Nepal's cultural, linguistic and geographical closeness to India make the DAH of India different from that of China. India's DAH also includes support to grass roots NGOs and public health interventions. CONCLUSION: China's and India's insistence on a recipient-driven mechanism keeps the aid programs aligned with Nepal's health development plan and respects Nepal's "ownership". China can learn from India to start the development assistance for health related NGOs and public health intervention.

Hematological and biochemical markers influencing breast cancer risk and mortality: Prospective cohort study in the UK Biobank by multi-state models.

BACKGROUND: Breast cancer is the most common cancer and the leading cause of cancer-related death among women. However, evidence concerning hematological and biochemical markers influencing the natural history of breast cancer from in situ breast cancer to mortality is limited. METHODS: In the UK Biobank cohort, 260,079 women were enrolled during 2006-2010 and were followed up until 2019 to test the 59 hematological and biochemical markers associated with breast cancer risk and mortality. The strengths of these associations were evaluated using the multivariable Cox regression models. To understand the natural history of breast cancer, multi-state survival models were further applied to examine the effects of biomarkers on transitions between different states of breast cancer. RESULTS: Eleven biomarkers were found to be significantly associated with the risk of invasive breast cancer, including mainly inflammatory-related biomarkers and endogenous hormones, while serum testosterone was also associated with the risk of in-situ breast cancer. Among them, C-reactive protein (CRP) was more likely to be associated with invasive breast cancer and its transition to death from breast cancer (HR for the highest quartile = 1.46, 95 % CI = 1.07-1.97), while testosterone and insulin-like growth factor-1 (IGF-1) were more likely to impact the early state of breast cancer development (Testosterone: HR for the highest quartile = 1.31, 95 % CI = 1.12-1.53; IGF-1: HR for the highest quartile = 1.17, 95 % CI = 1.00-1.38). CONCLUSION: Serum CRP, testosterone, and IGF-1 have different impacts on the transitions of different breast cancer states, confirming the role of chronic inflammation and endogenous hormones in breast cancer progression. This study further highlights the need of closer surveillance for these biomarkers during the breast cancer development course.

Evaluating the features of breast lesions identified by bimodal breast examination: a real-world study.

Background: Several image-based diagnostic methods have been developed to examine the features of breast lesions among women, while the value of combining palpation imaging and ultrasound by a bimodal breast examination system is still unknown. Methods: A real-world study was conducted among 424 patients who visited Fujian Maternal and Child Health Hospital and Fujian Obstetrics and Gynecology Hospital, and used the Bimodal Breast Exam (BBE) systems which combines palpation imaging and ultrasound imaging. Among them, 97 patients had additional ultrasound, mammogram, or pathological examination. These patients were used to evaluate the consistency and efficacy of the BBE in interpreting the features of breast lesions as compared to results of ultrasound, mammogram, and pathological examinations. Results: The BBE system detected 1517 lesions with palpation imaging, 1126 lesions with ultrasound examination (950 solid lesions and 176 cysts), and 391 non mass lesions. Among them, 404 patients were diagnosed as benign and 20 were diagnosed as malignant tumor. However, 12, 9 and 4 cases were diagnosed as malignant tumors by ultrasound, mammogram and pathological examination, respectively. Compared with the integrative results of ultrasound, mammogram and pathology, the sensitivity of BBE is 55.6%, and the specificity is 90.9%, with a kappa coefficient of 0.387 (0.110, 0.665), indicating moderate consistency. Conclusions: In clinical practice, BBE can be used to evaluate features of breast lesions with a high specificity. The diagnostic efficacy is comparable to the integrative results of ultrasound, mammography, and pathological examination.

Breast Cancer Incidence After a False-Positive Mammography Result.

Importance: False-positive mammography results are common. However, long-term outcomes after a false-positive result remain unclear. Objectives: To examine long-term outcomes after a false-positive mammography result and to investigate whether the association of a false-positive mammography result with cancer differs by baseline characteristics, tumor characteristics, and time since the false-positive result. Design, Setting, and Participants: This population-based, matched cohort study was conducted in Sweden from January 1, 1991, to March 31, 2020. It included 45 213 women who received a first false-positive mammography result between 1991 and 2017 and 452 130 controls matched on age, calendar year of mammography, and screening history (no previous false-positive result). The study also included 1113 women with a false-positive result and 11 130 matched controls with information on mammographic breast density from the Karolinska Mammography Project for Risk Prediction of Breast Cancer study. Statistical analysis was performed from April 2022 to February 2023. Exposure: A false-positive mammography result. Main Outcomes and Measures: Breast cancer incidence and mortality. Results: The study cohort included 497 343 women (median age, 52 years [IQR, 42-59 years]). The 20-year cumulative incidence of breast cancer was 11.3% (95% CI, 10.7%-11.9%) among women with a false-positive result vs 7.3% (95% CI, 7.2%-7.5%) among those without, with an adjusted hazard ratio (HR) of 1.61 (95% CI, 1.54-1.68). The corresponding HRs were higher among women aged 60 to 75 years at the examination (HR, 2.02; 95% CI, 1.80-2.26) and those with lower mammographic breast density (HR, 4.65; 95% CI, 2.61-8.29). In addition, breast cancer risk was higher for women who underwent a biopsy at the recall (HR, 1.77; 95% CI, 1.63-1.92) than for those without a biopsy (HR, 1.51; 95% CI, 1.43-1.60). Cancers after a false-positive result were more likely to be detected on the ipsilateral side of the false-positive result (HR, 1.92; 95% CI, 1.81-2.04) and were more common during the first 4 years of follow-up (HR, 2.57; 95% CI, 2.33-2.85 during the first 2 years; HR, 1.93; 95% CI, 1.76-2.12 at >2 to 4 years). No statistical difference was found for different tumor characteristics (except for larger tumor size). Furthermore, associated with the increased risk of breast cancer, women with a false-positive result had an 84% higher rate of breast cancer death than those without (HR, 1.84; 95% CI, 1.57-2.15). Conclusions and Relevance: This study suggests that the risk of developing breast cancer after a false-positive mammography result differs by individual characteristics and follow-up. These findings can be used to develop individualized risk-based breast cancer screening after a false-positive result.