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Abstract Purpose We aimed at analysing the risk of congestive heart failure (CHF) among first‐ and second‐generation immigrants in younger age groups. Methods All individuals aged 18–54 years, n = 3 973 454 in the first‐generation study and n = 3 817 560 in the second‐generation study, were included. CHF was defined as at least one registered diagnosis in the National Patient Register between 1 January 1998 and 31 December 2018. Cox regression analysis was used to estimate the relative risk [hazard ratios (HRs) with 99% confidence intervals (CIs)] of incident CHF with adjustments for age, co‐morbidities and socio‐demographics. Results In the first‐generation study, a total of 85 719 cases of CHF were registered, 54 369 men and 31 350 women, where fully adjusted models showed HRs for all foreign‐born men of 1.12 (99% CI 1.06–1.17) and for women of 0.99 (0.92–1.05). Groups with higher risk included men from Eastern Europe, Central Europe, Africa and Asia and women from Africa and Asia, and a lower risk was found among Latin American women. In the second‐generation study, a total of 88 999 cases of CHF were registered, 58 403 men and 30 596 women, where fully adjusted models showed HRs for second‐generation men of 1.04 (0.99–1.09) and women of 0.97 (0.90–1.04). Conclusions The higher risk in some foreign‐born groups needs to be paid attention to in clinical practice. The fact that almost all increased risks were attenuated and absent in second‐generation immigrants suggests that lifestyle and environmental factors are more important than genetic differences in the risk of CHF.

Purpose: We aimed to analyze the risk of hereditary hemochromatosis (HH) among first-generation and second-generation immigrants in Sweden using Swedish-born individuals and Swedish-born individuals with Swedish-born parents as referents, respectively. Methods: All individuals aged 18 years of age and older, n = 6,180,500 in the first-generation study, and n = 4,589,930 in the second-generation study were included in the analyses. HH was defined as at least one registered diagnosis International Classification of Diseases 10th edition (E83.1) in the National Patient Register between January 1, 1998 and December 31, 2018. Cox regression was used to estimate the hazard ratios (HRs) with 99% confidence intervals (CI) owing to multiple testing, of incident HH with adjustments for age, cancer, other comorbidities, and socio-demographics. Results: In the first-generation study, there were 5,112 cases of HH, and in the second-generation study 4,626 cases of HH. The adjusted HRs for first-generation men and women overall were 0.72 (99% CI: 0.63–0.82) and 0.61 (99% CI: 0.52–0.72), respectively, and for the second-generation men and women 0.72 (99% CI: 0.62–0.83) and 0.97 (99% CI: 0.83–1.14), respectively, with a higher risk found only among first-generation men from Western Europe, HR 1.47 (99% CI: 1.05–2.06), compared to the control group. Conclusions: Our findings indicate that the overall risk of HH was lower among both first-generation and second-generation immigrants when compared to individuals born in Sweden or with Swedish-born parents. An elevated risk for HH was observed exclusively among first-generation men originating from Western Europe. These findings represent new knowledge and should be of global interest.

Using wind energy in the natural environment provides a promising solution for wireless sensor power supply for ecological, meteorological, environmental, and infrastructure monitoring. However, the uncertainty and disorder of natural wind restrict the further development of wind energy harvester systems and self-powered wireless sensor technology. Hence, this paper proposes a self-regulation blade wind energy harvester system (SBWEHS) for self-powered wireless monitoring sensors in remote field areas with power shortages. The system is mainly composed of three parts: wind harvesting mechanism, generator module, and energy storage module. The device can control the blade overlap ratio according to the wind speed while generating electricity to maximize the power coefficient. The system can control the blade’s closure in bad weather to protect the device. Based on the computational fluid dynamics technology of Ansys Fluent software, this study evaluated the impact of wind speed and blade overlap ratio on the two-stage blades. Experiments revealed that when the overlap ratio of the blades is fixed at 0.2 and the wind speed is set at 16 m/s, the maximum average power will reach 0.79 W, which fulfills the power requirements of wireless sensors. These results illustrate that the SBWEHS can effectively supply power for wireless monitoring sensors, especially in remote natural environments.

Abstract Background Associations between different cancer types are known. The affirmation of the risk for non-ovarian cancer after ovarian borderline tumors (BOT) is, however, sparse. Aim To analyze the risk of subsequent or simultaneous cancers in women with BOTs compared with the general female Swedish population. Methods An open cohort study (1995–2018) was conducted where a diagnosis of BOTs as well as subsequent or simultaneous cancer diagnoses were obtained from the Swedish Cancer Register and matched to the Total Population Register. Each woman with BOT was followed until non-ovarian cancer, death or emigration and could only be included once for the outcome. Standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for specific non-ovarian cancers were analyzed. Results The 4998 women with serous and mucinous BOTs were diagnosed during 1995–2018 with a mean age of 55.7 years (SD 16.0) at diagnosis. Compared with the general female population, women with BOTs had increased risks for non-ovarian cancer in colon (SIR = 2.5; 95% CI 2.0–3.1), rectum (SIR = 1.7; 95% CI 1.1–2.5), small intestine (SIR = 5.0; 95% CI 2.3–9.5), cervix (SIR = 2.5; 95% CI 1.4–4.2), endometrium (SIR = 2.4; 95% CI 1.9–3.1), pancreas (SIR = 2.3; 95% CI 1.4–3.5), upper aerodigestive tract (SIR = 2.2; 95% CI 1.2–3.8), lung (SIR = 1.8; 95% CI 1.4–2.3), kidney (SIR = 2.3; 95% CI 1.4–3.7) and bladder (SIR = 1.8; 95% CI 1.1–2.8). Among women with serous BOTs, the risk of thyroid gland cancer (SIR = 3.1; 95% CI 1.2–6.4) was also increased. Lung and pancreas cancer showed increased risks more than 1 year after a diagnosis of BOT. Conclusions This Swedish population-based study demonstrated an increased risk of multiple malignancies including lung and pancreatic cancers beyond the first year of diagnosis in patients with borderline ovarian tumors (BOTs), suggesting a potential shared etiology.

Efficient degradation of organic compounds in water is also challenge for wastewater treatment. Photocatalytic degradation based on multifunctional semiconductor materials has attracted great attention as a prospective method and is highly desirable. Here, we investigated the photocatalytic performance of Pt-supported TiO2 photocatalyst in different crystal structures (rutile, rutile/anatase, anatase) for degradation of methylene blue dye. The morphology and structural properties of TiO2 nanoparticles were tested using field emission scanning electron microscope (FESEM) and X-ray diffraction analysis (XRD) techniques. Moreover, the photocatalytic activities over noble metal supported anatase/rutile titania catalysts (Pd/TiO2, Pt/TiO2, and Ru/TiO2) were evaluated by degrading the methylene blue dye under solar light irradiation, and Pt/TiO2 contributed the highest decomposition efficiency within 20 min irradiation. A possible reaction mechanism for the catalytic oxidation of methylene blue was proposed.

Background Little is known about risks of hypertensive disorders of pregnancy in both first‐ and second‐generation immigrant women in Europe and other Western countries; such knowledge may help elucidate the influence of genetic versus social factors on such risks. We aimed to study both first‐ and second‐generation immigrant women for the presence of all types of hypertension (preexisting hypertension, gestational hypertension, preeclampsia, and eclampsia) during pregnancy. Methods and Results A cohort study was conducted using data derived from the Swedish National Birth Register, the National Patient Register, and the Total Population Register. We used Cox regression analysis to compute hazard ratios (HRs) and 99% CIs while adjusting for sociodemographic factors and comorbidities. The first‐generation study included a total of 1 084 212 deliveries and 68 311 hypertension cases, and the second‐generation study included 989 986 deliveries and 67 505 hypertension cases. The fully adjusted HR (with 99% CI) for hypertension in pregnancy among first‐generation immigrant women was 0.69 (0.66–0.72), and among second‐generation immigrant women, it was 0.88 (0.86–0.91), compared with Swedish‐born women with 2 Swedish‐born parents. Women born in Finland or with parent(s) from Finland had higher risks, with fully adjusted HRs (99% CIs) of 1.30 (1.18–1.43) and 1.12 (1.07–1.17), respectively. Conclusions Both first‐ and second‐generation immigrant women had overall lower risks of hypertension in pregnancy compared with other Swedish women. However, the risk reduction was less pronounced in second‐generation compared with first‐generation immigrant women, suggesting that environmental factors in Sweden may have an important influence on risk of hypertension during pregnancy.

BackgroundThe impact of bacterial vaginosis on women's health is an increasing concern; however, the effect of the obesity index on bacterial vaginosis is controversial. We investigated the association between body mass index and bacterial vaginosis in women in the United States.MethodsThis was a cross-sectional study which obtained the data from the National Health and Nutrition Examination Survey from 2001 to 2004, in which weighted multivariate regression and logistic regression analyses were performed to explore the independent relationship between body mass index and bacterial vaginosis. Subgroup analyses and smoothed curve fitting were also performed.ResultsA total of 5,428 participants were enrolled, and the findings show that the participants with higher body mass index tended to have a higher incidence of bacterial vaginosis. In the fully adjusted model, a positive association between bacterial vaginosis and body mass index was observed (Odd's ratio = 1.03, 95% Confidence interval, 1.01-1.04). The subgroup analysis showed that this positive association was significant in non-Hispanic White individuals (Odd's ratio = 1.0327, 95% Confidence interval, 1.0163, 1.0493).ConclusionIncreased bacterial vaginosis positivity may be associated with an increased body mass index.

Colovesical fistula (CVF) is usually developed from colonic diverticulitis, followed by tumor. Traditional surgery is usually completed in one or more stages. For complex cancerous CVF, radical resection is more difficult. We report a 62-year-old male patient diagnosed with sigmoid colon cancer combined with sigmoid vesical fistula. In the course of treatment, in addition to conventional surgery, neoadjuvant chemotherapy (NAC) was innovatively used. The sigmoid tumor and fistula were significantly shrunken. Radical surgery achieved negative margins.

Abstract To examine the risk of post-polio syndrome (PPS) in immigrant groups using native Swedish-born individuals as referents. This is a retrospective study. The study population included all individuals aged 18 years and older registered in Sweden. PPS was defined as having at least one registered diagnosis in the Swedish National Patient Register. The incidence of post-polio in different immigrant groups, using Swedish-born individuals as referents, was assessed by Cox regression, with hazard ratios (HRs) and 99% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, co-morbidities, and neighbourhood socioeconomic status. In total 5300 post-polio cases were registered, 2413 males and 2887 females. Fully adjusted HRs (99% CI) in immigrants versus Swedish-born were 1.77 in men (1.52–2.07) and 1.39 (1.19–1.62) in women. Statistically significant excess risks of post-polio were found in the following subgroups: men and women from Africa, HRs (with 99% CI) 7.40 (5.17–10.59) and 8.39 (5.44–12.95), respectively, and Asia, HRs 6.32 (5.11–7.81) and 4.36 (3.38–5.62) respectively, and in men from Latin America, HR 3.66 (2.17–6.18). It is of importance to be aware of risks of PPS in immigrants settled in Western countries, and that it is more common in immigrants from regions of the world where polio is still prevalent. Patients with PPS need treatment and proper follow-up until polio has been eradicated through global vaccination programs.

Sepsis is a severe condition, representing a significant public health concern, especially in the elderly. There is, however, little insight into the potential effects of sociodemographic factors and comorbidities on sepsis incidence and how these factors interact. This was a nationwide open cohort study including individuals (N = 6 746 010) in Sweden ≥ 18 years of age spanning from 1997 to 2018, with 116 175 995 person years of follow-up. The outcome was time to first occurrence of sepsis. The following variables were included in the analysis: sociodemographic factors (age, sex, income, education, marital status, region of residency, and country of origin), severe mental disorders (schizophrenia and bipolar disorders), and Charlson Comorbidity Index. Interaction tests were conducted. A total of 161 558 individuals were diagnosed with sepsis during the study period, corresponding to an incidence rate of 13.9 per 10 000 person years (95% CI: 13.8 – 14.0). The main findings were that male sex, high age, low education, and comorbid conditions were positively associated with sepsis, after adjustments for the other covariates. Being aged 80 years and above yielded a HR of 18.19 (95% CI: 17.84 – 18.55) and the effect of high age was more than twice as high in men than in women. In conclusion, this large nationwide cohort found that several sociodemographic factors and comorbid conditions were independently associated with sepsis and men were more affected by higher age than women. These findings can help improve sepsis awareness and preventive work in risk groups.

Abstract Large amounts of germline sequencing data have recently become available and we sought to compare these results with population-based family history data. Family studies are able to describe aggregation of any defined cancers in families. The Swedish Family-Cancer Database is the largest of its kind in the world, covering the Swedish families through nearly a century with all cancers in family members since the start of national cancer registration in 1958. The database allows estimation of familial risks, ages of cancer onset and the proportion of familial cancer in different family constellations. Here, we review the proportion of familial cancer for all common cancers and specify them based on the number of affected individuals. With the exception of a few cancers, age of onset of familial cancer is not different from all cancers combined. The highest proportions of familial cancer were found for prostate (26.4%), breast (17.5%) and colorectal (15.7%) cancers, but the proportions of high-risk families with multiple affected individuals were only 2.8%, 1% and 0.9%, respectively. A large sequencing study on female breast cancer found that BRCA1 and BRCA2 mutations could account for 2% of the cases (subtracting the proportions in healthy individuals) and that all germline mutations accounted for 5.6% of the cases. Early age of onset was a distinct feature of only BRCA mutations. In heritable colorectal cancer, Lynch syndrome genes dominate. Large studies on penetrance in Lynch syndrome have shown an approximately linear increase in risk from 40–50 years up to age 80 years. Interesting novel data revealed a strong modification of familial risk by unknown factors. High-risk germline genetics of prostate cancer is characterized by BRCA and other DNA repair genes. HOXB13 encodes a transcription factor which contributes to germline risk of prostate cancer. A strong interaction was shown with a polymorphism in the CIP2A gene. The emerging germline landscape of common cancers can be reasonably accommodated by family data on these cancers as to high-risk proportions and age of onset.

The thermal comfort of passengers in the carriage cannot be ignored. Thus, this research aims to establish a prediction model for the thermal comfort of the internal environment of a subway car and find the optimal input combination in establishing the prediction model of the predicted mean vote (PMV) index. Data-driven modeling utilizes data from experiments and questionnaires conducted in Nanjing Metro. Support vector machine (SVM), decision tree (DT), random forest (RF), and logistic regression (LR) were used to build four models. This research aims to select the most appropriate input variables for the predictive model. All possible combinations of 11 input variables were used to determine the most accurate model, with variable selection for each model comprising 102 350 iterations. In the PMV prediction, the RF model was the best when using the correlation coefficients square (R2) as the evaluation indicator (R2: 0.7680, mean squared error (MSE): 0.2868). The variables include clothing temperature (CT), convective heat transfer coefficient between the surface of the human body and the environment (CHTC), black bulb temperature (BBT), and thermal resistance of clothes (TROC). The RF model with MSE as the evaluation index also had the highest accuracy (R2: 0.7676, MSE: 0.2836). The variables include clothing surface area coefficient (CSAC), CT, BBT, and air velocity (AV). The results show that the RF model can efficiently predict the PMV of the subway car environment.

Abstract Purpose We aimed to analyze the risk of cardiomyopathies (CMPs) among first-generation and second-generation immigrants. Methods All individuals aged 18 years of age and older, n = 6,123,661 in the first-generation study, and n = 4,587,764 in the second-generation study were analyzed. CMP was defined as at least one registered diagnosis in the National Patient Register between January 1, 1998 and December 31, 2018. Cox regression analysis was used to estimate the relative risk (hazard ratios (HR) with 99% confidence intervals (CI)) of incident CMP with adjustments made for age, cancer, other comorbidities, and sociodemographic factors. Results In the first-generation study, a total of 33,321 CMP cases were registered, 20,780 men and 12,541 women, where the fully adjusted models showed HRs (99% CI) for all foreign-born men of 0.92 (0.86–0.98) and for women of 0.90 (0.83–0.98). For dilated CMP, the risk was higher for men from Nordic countries, more specifically men from Finland, and lower for men and women from Asia. For hypertrophic CMP, the risk was higher for men from Africa and Asia. For other types of CMPs, the risk was lower in men and women from Asia. In the second-generation study, a total of 26,559 cases were registered (17,620 men and 8939 women), with no significant differences overall or among specific groups, when Swedish-born with foreign-born parents were compared to Swedish-born with Swedish-born parents. Conclusions We observed a generally lower risk of CMPs among foreign-born individuals, but with a higher risk especially for hypertrophic CMPs for men from Africa and Asia, and a higher risk of dilated CMP for men from Nordic countries.

Objectives: We aimed to explore the association between various physiological factors and pyelonephritis in parous women. Methods: Swedish nationwide registers were used to identify 1,073,467 parous women aged 15-50 years. The study period began in 1997 and ended in 2018, or at the first incidence of pyelonephritis, death, or emigration. Cox proportional hazards methods were used to determine hazard ratios (HRs) and 95% confidence intervals (CIs) of pyelonephritis in relation to body mass index (BMI) and body height adjusted for age, parity, and individual-level sociodemographic variables. Results: A total of 21,625 women (2.0%) were diagnosed with pyelonephritis during follow-up. In the fully adjusted model, low BMI (

Abstract The aim was to study the potential effect of neighborhood deprivation on incident and fatal coronary heart disease (CHD) in patients with bipolar disorder. This was a nationwide cohort study which included all adults aged 30 years or older with bipolar disorder (n = 61,114) in Sweden (1997–2017). The association between neighborhood deprivation and the outcomes was explored using Cox regression analysis, with hazard ratios (HRs) and 95% confidence intervals (CIs). Patients with bipolar disorder living in neighborhoods with high or moderate levels of deprivation were compared with those living in neighborhoods with low deprivation scores. There was an association between level of neighborhood deprivation and incident and fatal CHD among patients with bipolar disorder. The HRs were 1.24 (95% CI 1.07–1.44) for men and 1.31 (1.13–1.51) for women for incident CHD among patients with bipolar disorder living in high deprivation neighborhoods compared to those from low deprivation neighborhoods, after adjustments for potential confounders. The corresponding HR for fatal CHD were 1.35 (1.22–1.49) in men and 1.30 (1.19–1.41) in women living in high deprivation neighborhoods. Increased incident and fatal CHD among patients with bipolar disorder living in deprived neighborhoods raises important clinical and public health concerns.

Poorly cohesive duodenal carcinoma mixed with signet ring cell carcinoma is very rare, and no cases have been reported. When distant metastasis occurs, it is very easy to be misdiagnosed. We report the first case of a 52-year-old man with poorly cohesive carcinoma of the duodenum mixed with signet ring cell carcinoma with systemic metastasis. The process of its diagnosis and differential diagnosis is highlighted.

The spin–orbit torques within a Pt/Tm _3 Fe _5 O _12 (TmIG) bilayer offer an expedient method for manipulating the magnetization of TmIG. However, the practical application of TmIG is hindered by the presence of an external field during switching. Here, we demonstrate field-free magnetization switching in Pt/TmIG bilayer on a vicinal substrate with minimal sacrifice to the perpendicular magnetic anisotropy (PMA) of TmIG. With the assistance of tilt PMA, reversible perpendicular magnetization switching is realized in the absence of an external field. Our results offer an alternative solution for achieving field-free perpendicular magnetization switching in a Pt/TmIG bilayer, thereby fostering the advancement of emerging SOT-based devices.

Gleason Score (GS) 3 + 4 prostate cancer (PCa) is heterogeneous in clinical course and molecular features. Risk stratification of indolent and aggressive PCa with GS 3 + 4 is critical, especially those with bone metastasis (BM) potential. Microarray-based microRNA(miRNA) profiling with eight PCa cases with or without BM was used to screen the candidate miRNAs associated with BM. Transwell and MTS assays were used to characterize the function of miRNAs and target gene LASP1. RT-qPCR and immunohistochemistry assays were utilized to illustrate the clinical significance of miRNAs and target gene in a cohort of 309 Chinese PCa cases. In the current study, we identified that miR-1-3p, miR-143–3p and miR-145–5p are associated with BM of GS 3 + 4 PCa. Through functional experiments, we show that miR-1-3p/143–3p/145–5p promotes proliferation and migration of PCa in vitro. LASP1 was predicted as the common target of these three miRNAs which was further confirmed by a luciferase assay. Overexpression of LASP1 was correlated with higher GS, higher pathological stage, and the presence of metastasis by immunohistochemistry. siRNA knockdown of LASP1 significantly suppressed proliferation and migration, whereas overexpression of LASP1 promoted it. Bioinformatics analysis revealed the involvement of Wnt signaling pathway in LASP1 mediated function. LASP1 may activate Wnt signaling by interacting with β-catenin. In all, we suggest that miR-1-3p/143–3p/145–5p are associated with BM of Gleason 3 + 4 PCa. LASP1 is the common target of these miRNAs and may active Wnt signaling by interacting with β-catenin.

Since efficient hydrogenation was valued for manufacture of pharmaceutical intermediates and fragrances in recent years, the development of easily accessible heterogeneous catalysts was preferably made. Here we designed a facile one-pot synthesis of Ni modified COF-derived catalyst for selective catalytic hydrogenation of cinnamaldehyde. The nickel-based COFs catalyst reduced at 600 °C exhibited better catalytic activity for the selective production of hydrocinnamyl with an excellent yield of 98%, and the nickel-based COFs reduced at 500 °C and 700 °C preferred to selectively produce benzenepropanal. Overall, this work proves cost-effective and sustainable access to the wide application of selective hydrogenation reaction.

To promote the application of bio-materials and provide a direction for their further researches, this paper comprehensively summarizes the research progress of biomaterials in recent years. The review results show that bio-oil is a mixture obtained from different biomasses through pyrolysis, alcoholysis, acidolysis, high liquefaction, etc., and those biomasses mainly include wood fiber type, waste oil type and animal manure type. Bio-binder refers to the product of bio-oil processed by distillation, extraction oxidation and polymer modification, and it can be served as a modifier, diluent or substitute material of asphalt; the main chemical components of bio-oil include ethers, esters, aldehydes, ketones, phenols, organic acids, alcohols and sugars. Bio-asphalt is obtained by adding bio-binder into the petroleum asphalt for modification or blending, and the shear temperature and shear rate of bio-asphalt derived from wood fiber type and waste oil type are usually higher than that of bio-asphalt derived from swine manure. Compared with petroleum asphalt, bio-asphalt binder usually shows lower high-temperature performance as well as higher low-temperature performance and aging resistance. Also, bio-asphalt mixture generally exhibits lower high-temperature stability, higher low-temperature crack resistance and water stability than petroleum asphalt mixture. Future studies should be conducted combining with the source, composition, preparation, properties and oil production rate of bio-oil. First, how to raise the bio-binder content in bio-asphalt as much as possible while ensuring the sufficient performance becomes the focus of future researches. Second, the micro reaction mechanism between bio-binder and petroleum asphalt should be illustrated in depth. Moreover, developing a complete and unifying technical standard and application specification of bio-asphalt technology is necessary for future researches. Furthermore, determining the optimum bio-binder potentially used as the substitute of petroleum asphalt is also an interesting topic.

Studying the mechanisms of the spin Hall effect (SHE) is essential for the fundamental understanding of spintronic physics. By now, despite the intensive studies of SHE on heavy metal (HM)/metallic magnet heterostructures, the SHE on HM/ferrimagnetic insulator (FMI) heterostructures still remains elusive. Here, we study the mechanism of SHE in the Pt/Tm3Fe5O12 (TmIG) heterostructure. We first tune the crystallinity and resistivity of Pt by an annealing method, and then study the spin–orbit torque (SOT) in the tuned-Pt/TmIG devices. The SOT generation efficiency per unit electric field and spin Hall angle were obtained, which are insensitive to the annealing temperature. We further demonstrate that the intrinsic contribution in the moderately dirty regime is responsible for the SHE in our Pt/TmIG bilayer. Our study provides an important piece of information for the SHE in FMI-based spintronic physics.

Objective: This study aimed to estimate the association between potential risk factors and common vaginal infections using nationwide primary health care and other national registers. Methods: An open cohort study consisting of 2,357,711 women aged 15 years to 50 years (2001 to 2018) was conducted in Sweden. The outcomes were first event of vulvovaginal candidiasis (VVC) and bacterial vaginosis (BV) in relation to sociodemographic factors. Cox regression models were used. Sensitivity analyses including diabetes mellitus, contraceptive use, and cervical cancer were conducted. Results: The incidence rates per 1,000 person-years for VVC and BV were 3.3 (95% confidence interval [CI] 3.2-3.3) and 3.4 (95% CI 3.4-3.4), respectively. In the fully adjusted model, sociodemographic factors were significantly associated with both outcomes. Compared with Swedish-born women, women from Middle East/North Africa had the highest risk of VVC (hazard ratio [HR] 2.77, 95% CI, 2.72-2.83), followed by Africa (excluding North Africa) (HR 2.53, 95% CI, 2.45-2.61), and Latin America and the Caribbean (HR 2.18, 95% CI, 2.09-2.27). For BV, women from Latin America and the Caribbean had the highest risk (HR 1.83, 95% CI, 1.75-1.92). Conclusion: This study presents novel risk factors associated with medically attended vaginal infections. Women from non-Western countries seem to develop these conditions disproportionately.

Abstract In this nationwide cohort of one million fertile women, BMI, height, and parity only had minor but statistically significant effects on the risk of uncomplicated cystitis. The results indicate that underweight women and certain sociodemographic groups might have higher risks, which could have underlying explanations that need further studying.

Degradation pathway models constructed using network structural equation modeling (netSEM) are used to study degradation modes and pathways active in photovoltaic (PV) system variants in exposure conditions of high humidity and temperature. This data-driven modeling technique enables the exploration of simultaneous pairwise and multiple regression relationships between variables in which several degradation modes are active in specific variants and exposure conditions. Durable and degrading variants are identified from the netSEM degradation mechanisms and pathways, along with potential ways to mitigate these pathways. A combination of domain knowledge and netSEM modeling shows that corrosion is the primary cause of the power loss in these glass/backsheet PV minimodules. We show successful implementation of netSEM to elucidate the relationships between variables in PV systems and predict a specific service lifetime. The results from pairwise relationships and multiple regression show consistency. This work presents a greater opportunity to be expanded to other materials systems.

Since selective control in catalytic reductive aminations of aldehyde for the synthesis of functional amines was highly valued, we developed three kinds of COFs supported catalysts (Pt/COF, Pd/COF, and Rh/COF) for selectively catalytic reductive amination of benzaldehyde. Results indicated that Pd/COF and Pt/COF exhibited good selectivity towards secondary amines with a 1.2/1 M proportion of aldehyde and ammonia, while Rh/COF catalyst can selectively convert benzaldehyde to secondary imine with an excellent yield of 90%. Furthermore, an improved yield of primary amine could be obtained over Rh/COF catalyst with a 1.2/60 M proportion of aldehyde and ammonia.

Objective: To study the relationship between sociodemographic factors and pyelonephritis.Methods: A nationwide open cohort study consisting of 2,052,873 women (76.2% Swedish-born) aged 15-50 years was conducted (1997-2018). The outcome was the first event of acute uncomplicated pyelonephritis diagnosed in primary healthcare settings in relation to the sociodemographic factors. Cox regression models were used in the analyses.Results: The study identified 40,724 cases. In the fully adjusted model, women from non-Western countries had a higher risk of pyelonephritis compared to Swedish-born women. Women from Latin America/the Caribbean had the highest risk (Hazard ratio = 1.60; 95% CI 1.49-1.72), followed by Eastern Europe (HR = 1.26; 95% CI 1.21-1.32) and the Middle East/North Africa (HR = 1.25; 95% CI 1.19-1.30). Low education, low income, urban living, and young age were also associated with higher risks of pyelonephritis.Conclusion: This study presents novel risk factors associated with pyelonephritis. Women from non-Western countries and with low socioeconomic status might disproportionately suffer from this serious infection. This might be due to biological predispositions and the fact that immigrant women do not acquire the same level of health or might receive less healthcare compared to native women, even in the presence of universal healthcare.

FAM83A gene is related to the invasion and metastasis of various tumors. However, the abnormal immune cell infiltration associated with the gene is poorly understood in the pathogenesis and prognosis of NSCLC. Based on the TCGA and GEO databases, we used COX regression and machine learning algorithms (CIBERSORT, random forest, and back propagation neural network) to study the prognostic value of FAM83A and immune infiltration characteristics in NSCLC. High FAM83A expression was significantly associated with poor prognosis of NSCLC patients (p = 0.00016), and had excellent prognostic independence. At the same time, the expression level of FAM83A is significantly related to the T, N, and Stage. Subsequently, based on machine learing strategies, we found that the infiltration level of naive B cells was negatively correlated with the expression of FAM83A. The low infiltration of naive B cells was significantly related to the poor overall survival rate of NSCLC (p = 0.0072). In addition, Cox regression confirmed that FAM83A and naive B cells are risk factors for the prognosis of NSCLC patients. The nomogram combining FAM83A and naive B cells (C-index = 0.748) has a more accurate prognostic ability than the Stage (C-index = 0.651) system. Our analysis shows that abnormal infiltration of naive B cells associated with FAM83A is a key factor in the prognostic prediction of NSCLC patients.

Abstract Acute lymphoblastic leukemia (ALL) is the most common childhood leukemia, while the other types, acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), and chronic myeloid leukemia (CML) are much rarer. While data on familial risks for childhood ALL have been emerging, such data for the other childhood leukemias are hardly available. We aim to fill in the gap of knowledge by assessing familial clustering of each childhood leukemia with childhood and adult leukemia and with any cancer. We identified 4461 childhood leukemias from the Swedish Cancer Registry and obtained their family members from the Multigeneration Register. Standardized incidence ratios (SIRs) were 3.34 for singleton siblings both diagnosed with ALL before age 20 years and 1.64 for those who had a family member diagnosed with ALL in adult age. Other childhood leukemias showed no familial risk, but childhood ALL risk was increased to 1.40 when adult family members were diagnosed with CLL. Childhood ALL was associated with endometrial cancer, and female ALL patients showed increased risk when family members were diagnosed with testicular cancer, melanoma, and skin squamous cell carcinoma. Childhood CLL was associated with rectal cancer, and childhood AML was associated with pancreatic and bladder cancers. As most of these associations are reported for the first time, there is a need to replicate the findings from independent sources.

Abstract Childhood acute lymphoblastic leukemia (ALL) has an origin in the fetal period which may distinguish it from ALL diagnosed later in life. We wanted to test whether familial risks differ in ALL diagnosed in the very early childhood from ALL diagnosed later. The Swedish nation-wide family-cancer data were used until year 2016 to calculate standardized incidence ratios (SIRs) for familial risks in ALL in three diagnostic age-groups: 0–4, 5–34 and 35 + years. Among 1335 ALL patients diagnosed before age 5, familial risks were increased for esophageal (4.78), breast (1.42), prostate (1.40) and connective tissue (2.97) cancers and leukemia (2.51, ALL 7.81). In age-group 5–34 years, rectal (1.73) and endometrial (2.40) cancer, myeloma (2.25) and leukemia (2.00, ALL 4.60) reached statistical significance. In the oldest age-group, the only association was with Hodgkin lymphoma (3.42). Diagnostic ages of family members of ALL patients were significantly lower compared to these cancers in the population for breast, prostate and rectal cancers. The patterns of increased familial cancers suggest that BRCA2 mutations could contribute to associations of ALL with breast and prostate cancers, and mismatch gene PMS2 mutations with rectal and endometrial cancers. Future DNA sequencing data will be a test for these familial predictions.

Summary: Background: Cervical cancer is a major cause of mortality and morbidity in women worldwide. This study aimed to estimate the association between common urogenital infections and cervical neoplasia. Methods: A multi-register national cohort study of 4,120,557 women aged ≥15 years (2002–2018) was conducted. The outcomes were cervical cancer and carcinoma in situ (Swedish Cancer Register). The main predictors were urogenital infections—(urinary) cystitis, (bacterial) vaginosis, (candida) vulvovaginitis. Incidence rates per 10,000 person-years were calculated (using the European Standard Population). Cox regression was used to estimate hazard ratios (HR) while adjusting for possible confounders—other genital infections (e.g., cervicitis, salpingitis, urogenital herpes), parity, and sociodemographic factors. Findings: In 39·0 million person-years of follow-up, the incidence rate for cervical cancer was 1·2 (95% CI 1·1–1·2) per 10,000 person-years and the figure for cervical carcinoma in situ was more than tenfold higher. The fully adjusted HRs for cervical cancer were 1·31 (95% CI 1·15 and 1·48) and 1·22 (95% CI 1·16 and 1·29) for vaginosis and cystitis, respectively. Vaginosis showed a gradient association to carcinoma in situ. Vulvovaginitis was inversely associated with cervical cancer, but not significantly related with carcinoma in situ in the fully adjusted model. A temporal association with cervical cancer was observed for vaginosis and vulvovaginitis (inversely) but not for cystitis. Interpretation: In this large nationwide cohort of women, medically attended common urogenital infections were independently associated with cervical neoplasia, but cystitis was not temporally associated with cervical neoplasia. These findings could be used to increase focus on preventive measures, HPV-vaccination programmes, HPV-analyses- and cervical cancer screening, especially in women suffering from vaginosis. Future studies on the causal mechanism are warranted before generalized public health recommendations can be made. Funding: Region Skåne, Tore Nilsons Stiftelse, and Swedish Society of Medicine.

Design: Addison’s disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, present as an isolated AD or part of autoimmune polyendocrine syndromes (APSs) 1 and 2. Although AD patients present with a number of AID co-morbidities, population-based family studies are scarce, and we aimed to carry out an unbiased study on AD and related AIDs. Methods: We collected data on patients diagnosed with AIDs in Swedish hospitals and calculated standardized incidence ratios (SIRs) in families for concordant AD and for other AIDs, the latter as discordant relative risks. Results: The number of AD patients was 2852, which accounted for 0.4% of all hospitalized AIDs. A total of 62 persons (3.6%) were diagnosed with familial AD. The SIR for siblings was remarkably high, reaching 909 for singleton siblings diagnosed before age 10 years. It was 32 in those diagnosed past age 29 years and the risk for twins was 323. SIR was 9.44 for offspring of affected parents. AD was assoc iated with 11 other AIDs, including thyroid AIDs and type 1 diabetes and some rarer AIDs such as Guillain–Barre syndrome, myasthenia gravis, polymyalgia rheumatica and Sjögren’s syndrome. Conclusions: The familial risk for AD was very high implicating genetic etiology, which for juvenile siblings may be ascribed to APS-1. The adult part of sibling risk was probably contributed by recessive polygenic inheritance. AD was associated with many common AIDs; some of these were known co-morbidities in AD patients while some other appeared to more specific for a familial setting.

ObjectivesTo analyze the risk of hearing impairment in adult first-generation immigrants, i.e., foreign-born individuals as compared to Swedish-born individuals.Study designA register-based study follow-up study.MethodsA nationwide study of individuals 25 years of age and older (N = 5 464 245; 2 627 364 men and 2 836 881 women) in Sweden. Hearing impairment was defined as at least one registered diagnosis in the National Patient Register between January 1st, 1998 and December 31st, 2015. Cox regression analysis was used to estimate the relative risk (hazard ratios (HR) with 95% confidence intervals (CI)) of incident hearing impairment in foreign-born compared to Swedish-born individuals. Cox regression models were stratified by sex and adjusted for age, comorbidities, and socioeconomic status.ResultsA total of 244 171 cases (124 349 men and 119 822 women) of hearing impairment were registered. Hearing impairment risk expressed as fully adjusted HRs (99% CI) was somewhat lower among immigrant men 0.95 (0.92-97) but not among immigrant women 0.97 (0.95-1.00), with significantly higher fully adjusted HRs among men and women from Asia, and Eastern Europe, and women from Africa.ConclusionsWe observed a somewhat lower risk of hearing impairment among foreign-born men, but there was a higher risk among men and women from some regions.

Background: The risk of pyelonephritis following uncomplicated lower urinary tract infection (cystitis) in women has not been studied in well-powered samples. This is likely due to the previous lack of nationwide primary healthcare data. We aimed to examine the risks of pyelonephritis following cystitis in women and explore if antibiotic treatment, cervical cancer, parity, and sociodemographic factors are related to these risks. Methods: This was a nationwide cohort study (2006–2018) of 752,289 women diagnosed with uncomplicated cystitis in primary healthcare settings. Of these, 404 696 did not redeem an antibiotic prescription within five days from cystitis. Logistic regression models were used to calculate odds ratios for pyelonephritis within 30 days and 90 days following the cystitis event. Results: Around one percent (7454) of all women with cystitis were diagnosed with pyelonephritis within 30 days, of which 78.2% had not redeemed an antibiotic for their cystitis. Antibiotic treatment was inversely associated with both outpatient registration and hospitalization due to pyelonephritis, with odds ratios of 0.85 (95% CI 0.80 to 0.91) and 0.65 (95% CI 0.55 to 0.77), respectively. Sociodemographic factors, parity, and cervical cancer were, with few exceptions (e.g., age and region of residency), not associated with pyelonephritis. Conclusions: Antibiotic treatment was inversely associated with pyelonephritis, but the absolute risk reduction was low. Non-antibiotic treatment for cystitis might be a safe option for most women. Future studies identifying the women at the highest risks will help clinicians in their decision making when treating cystitis, while keeping the ecological costs of antibiotics in mind.

Abstract Background Cancer stem-like traits contribute to prostate cancer (PCa) progression and metastasis. Deciphering the novel molecular mechanisms underlying stem-like traits may provide important insight for developing novel therapeutics. Methods Immunohistochemistry and immunofluorescence assays in prostatic tissues; gain- and loss-of-function analyses using ectopic overexpression and shRNAs in PCa cell lines; measurements of tumorigenic and stemness properties, and transcription in vitro and in vivo; transcriptional analysis in public databases. Results We identified that overexpression of BTF3 in PCa tissues and BTF3 expression highly correlates to stem-like traits. Cancer stem-like characteristics in PCa including self-renewal and metastatic potential were impaired by BTF3 loss and promoted by BTF3 overexpression. Mechanistically, BTF3 could stabilize BMI1, which is a crucial regulator of prostate stem cell self-renewal. More importantly, our data revealed that BTF3 is highly predictive of poor prognosis and may help in risk stratification of PCa patients. Conclusions BTF3 promotes PCa progression though modeling stem-like traits in PCa. BTF3 represents a stratification marker in PCa progression and outcomes.

Abstract Background Bariatric surgery is considered to be the most effective method of weight loss today. The aim of the present Swedish study, which was performed in a country that has universal health care, was to investigate if there is an association between socioeconomic factors and bariatric surgery by taking body mass index (BMI) into account. Methods In this prospective cohort study, BMI data were collected for the period 1985–2010 from the Military Service Conscription Register (for men) and from the Medical Birth Register in the first trimester (for women). The follow-up period started in 2005 and continued until 2012. Age-standardized cumulative incidence rates (CR) of bariatric surgery were compared between different BMI groups by considering individual variables. We analyzed the association between the individual variables and bariatric surgery using Cox proportional hazard models. Results In the study population of 814,703 women and 787,027 men, a total of 7433 women and 1961 men underwent bariatric surgery. In women, the hazard ratios (HRs) for bariatric surgery were higher for low and middle income and educational levels, compared to high income and educational levels. In men, the highest HR for bariatric surgery was found among those with a high income. The HRs when comparing the different socioeconomic groups in those with BMI > 40 kg/m2 showed no significant results, except for middle education in women. Conclusion Differences in bariatric surgery between socioeconomic groups were found, favoring those with a low socioeconomic status. However, very few socioeconomic differences were found amongst those who had a BMI > 40 kg/m2. This indicates that the Swedish healthcare system seems to have achieved equal access to health care for bariatric surgery.

Background The number and rank order of siblings could be of importance for risk of cardiovascular disease and mortality. Previous studies have used only fatal events for risk prediction. We, therefore, aimed to use also non-fatal coronary and cardiovascular events in fully adjusted models.Methods From the Multiple-Generation Register in Sweden, data were used from 1.36 million men and 1.32 million women (born 1932–1960), aged 30–58 years at baseline and with follow-up from 1990 to 2015. Mean age at follow-up was 67 years (range 55–83 years). Fatal and non-fatal events were retrieved from national registers.Results Compared with men with no siblings, those with 1–2 siblings had a lower, and those with four or more siblings had a higher adjusted risk of cardiovascular events. Again, compared with men with no siblings, those with more than one sibling had a lower total mortality risk, and those with three or more siblings had an increased risk of coronary events.Correspondingly, compared with women with no siblings those women with three siblings or more had an increased risk of cardiovascular events, and those with two siblings or more had an increased risk of coronary events. Women with one sibling or more were at lower total mortality risk, following full adjustment.Conclusion Being first born is associated with a favourable effect on non-fatal cardiovascular and coronary events for both men and women. The underlying biological mechanisms for this should be studied in a sociocultural context.

Background: Symptoms suggestive of uncomplicated cystitis constitutes one of the most common reasons to seek health care in otherwise healthy women. Previous studies regarding the relationship between sociodemographic factors and uncomplicated cystitis are limited, mainly because of the lack of nationwide population-based data from primary healthcare settings, where most uncomplicated cystitis are diagnosed. Methods: A Swedish nation-wide open cohort study consisting of 2 044 065 females who were 15–50 years of age during the study period (1997–2018) was conducted. The outcome was first event uncomplicated cystitis diagnosed in primary health care rather than an assessment of the ''true'' incidence, which is not feasible in nationwide datasets. Cox regression models were used in the statistical analyses. Findings: The study identified 546 076 first events of uncomplicated cystitis (26•7% of the study population), corresponding to an incidence rate per 100 person-years of 2•91 (95% CI 2•90–2•91). In fully adjusted models, rural living was associated with lower risks of uncomplicated cystitis (Hazard ratio, HR, 0•67; 95% CI, 0•66–0•68) compared to urban living, while both Middle Eastern/North African (HR, 1•15; 95% CI, 1•14–1•16) and Latin American/Caribbean (HR, 1•24; 95% CI, 1•22–1•27) women had higher risks compared to Swedish women. Low education and low income were also associated with higher risks compared to high education and high income. Interpretation: This study presents novel risk factors associated with uncomplicated cystitis in women. The findings may help health care workers in the treatment of women with symptoms of uncomplicated cystitis. Funding: The Primary Healthcare Management and ALF funding (Region Skåne, Sweden) and the Swedish Research Council.

Single-cell Hi-C (scHi-C) sequencing technologies allow us to investigate three-dimensional chromatin organization at the single-cell level. However, we still need computational tools to deal with the sparsity of the contact maps from single cells and embed single cells in a lower-dimensional Euclidean space. This embedding helps us understand relationships between the cells in different dimensions, such as cell-cycle dynamics and cell differentiation. We present an open-source computational toolbox, scHiCTools, for analyzing single-cell Hi-C data comprehensively and efficiently. The toolbox provides two methods for screening single cells, three common methods for smoothing scHi-C data, three efficient methods for calculating the pairwise similarity of cells, three methods for embedding single cells, three methods for clustering cells, and a build-in function to visualize the cells embedding in a two-dimensional or three-dimensional plot. scHiCTools, written in Python3, is compatible with different platforms, including Linux, macOS, and Windows.

Background. Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients. Methods. We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks. Results. The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs. Conclusions. The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease.

Background It remains unclear whether heritable factors can contribute to risk stratification for ischemic stroke in patients with atrial fibrillation (AF). We examined whether having a sibling with ischemic stroke was associated with increased risk of ischemic stroke and mortality in patients with AF. Methods and Results In this nationwide study of the Swedish population, patients with AF and their siblings were identified from the Swedish patient registers and the Swedish MGR (Multi‐Generation Register). Ischemic stroke events were retrieved from the Swedish patient registers and CDR (Cause of Death Register). Risk of ischemic stroke was compared between patients with AF with and without a sibling affected by ischemic stroke, AF, or both ischemic stroke and AF. The total study population comprised 113 988 subjects (mean age, 60±12 years) diagnosed with AF between 1989 and 2012. In total, 11 709 of them were diagnosed with a first ischemic stroke and 20 097 died during a mean follow‐up time of 5.5 years for ischemic stroke and 5.9 years for mortality. After adjustment for covariates having a sibling with ischemic stroke, or both ischemic stroke and AF, was associated with increased risk of ischemic stroke (hazard ratio, 1.31; 95% CI, 1.23–1.40 or hazard ratio, 1.36; 95% CI, 1.24–1.49, respectively). Furthermore, ischemic stroke in a sibling was associated with all‐cause mortality (hazard ratio, 1.09; 95% CI, 1.05–1.14). In contrast, the risk of stroke was only marginally increased for patients with AF with a spouse affected by ischemic stroke. Conclusions Having a sibling affected by ischemic stroke confers an increased risk of ischemic stroke and death independently of traditional risk factors in patients with AF.

Genetic and family studies have indicated that Graves disease and Hashimoto thyroiditis have a heritable component which appears to be shared to some extend also with some other autoimmune diseases (AIDs). In the present nation-wide study we describe familial risk for Graves disease and Hashimoto thyroiditis identified from the Swedish Hospital Discharge Register (years 1964 through 2012) and the Outpatient Register (2001 through 2012). Family relationships were obtained from the Multigeneration Register and cancers from the Cancer Registry. Familial standardized incidence ratios (SIRs) were calculated for 29,005 offspring with Graves disease and for 25,607 offspring with Hashimoto thyroiditis depending on any of 43 AIDs in parents or siblings. The concordant familial risks for Graves disease and Hashimoto thyroiditis were 3.85 and 4.75, higher for men than for women. The familial risks were very high (11.35, Graves and 22.06, Hashimoto) when both a parent and a sibling were affected. Spousal familial risks were higher for Hashimoto thyroiditis (1.98/1.93) than for Graves disease (1.48/1.50). For Graves disease, 24 discordant AIDs showed a significant association; for Hashimoto thyroiditis, 20 discordant associations were significant. All significant discordant associations were positive for the two thyroid AIDs, with the exception of Hashimoto thyroiditis with Reiter disease. Overall 8 associations were significant only for Graves disease and 6 Hashimoto thyroiditis. The overall high concordant familial risks for Graves disease and Hashimoto thyroiditis suggest a strong genetic contribution to the familial risk. Significant familial associations among more than half of the 43 AIDs attest to the extensive polyautoimmunity among thyroid AIDs.

Autoimmune hepatitis (AH) and primary biliary cirrhosis (PBC) are autoimmune diseases (AIDs) targeting cellular components of the liver. Being rare diseases, limited data are available about familial risks among these AIDs (concordant) or between them and other AIDs (discordant). We aimed to carry out an unbiased study on these AIDs based on medically diagnosed patients. We collected data on patients diagnosed in Swedish hospitals with AH, PBC and other AIDs and calculated familial standardized incidence ratios (SIRs) for concordant and discordant familial relative risks. The number of AH patients was 6,269, of whom 43.0% were male; patient numbers for PBC were 4,269, with 17.8% males. AH accounted for 0.8% and 0.6% of all hospitalized AIDs in Sweden. For AH only the familial risk between siblings was significant (3.83). For PBC the risks for offspring of parents (9.05) and siblings (10.88) were high, but only risk for females was significant. Spousal risks were very high, 5.91 and 6.07 for AH. Risk for AH was 2.21 in families of PBC, and it was 2.47 for PBC in families of AH patients. Among other AIDs, 14 showed a significant association with AH, compared to 16 AIDs with PBC. The surprising finding in this nation-wide family study on medically diagnosed patients was the high risk for AH (6.0) between spouses, which exceed the risk between siblings, suggesting the existence of strong environmental risk factors. AH and PBC were associated with multiple other AIDs. The results call attention to environmental factors in AID etiology which should also be in focus in taking anamnestic data from patients.

Background: Antibiotics are commonly prescribed for outpatient management of cystitis. Previous evidence suggests that certain factors likely beyond the infection seem to influence the choice of antimicrobial treatment. However, studies on the specific antibiotic treatments for cystitis are lacking. This study aimed to explore the antibiotic treatments for cystitis using nationwide primary healthcare data and investigate if factors beyond the infection could be associated with fluoroquinolone treatment. Methods: This nationwide follow-up cohort study consisted of 352,507 women with cystitis. The primary aim was to investigate what specific classes of antibiotics were redeemed by patients within five days from the cystitis diagnosis. Each patient could only be included once. Logistic regression models were also used to examine the relationship between fluoroquinolone (FQ) treatment, parity, and sociodemographic factors. Results: In total, 192,065 antibiotic prescriptions were redeemed. Pivmecillinam (58.4%) followed by nitrofurantoin (22.2%), trimethoprim (12.0%), fluoroquinolone (5.6%), and cephalosporins (1.5%) were the most redeemed antibiotics. Sociodemographic factors were weakly associated with fluoroquinolone treatment; young age was inversely associated with fluoroquinolone treatment. Parity and cervical cancer history were not associated with fluoroquinolone treatment. The proportion of fluoroquinolone and trimethoprim treatments decreased over time, while pivmecillinam and nitrofurantoin increased. Conclusions: The treatment trends of antibiotics redeemed within five days from a cystitis diagnosis were similar to the national surveillance program of these antibiotics (not diagnosis linked). Fluoroquinolones were weakly associated with sociodemographic factors, which likely is only of historical relevance.

Abstract Background According to the literature the three stone diseases, sialolithiasis (SL), urolithiasis (UL) and cholelithiasis (CL) share comorbidities. We assess familial and spouse risks between these stone disease and compare them to familial risks for concordant (same) stone disease. Methods Study population including familiar relationships was obtained from the Swedish Multigeneration Register and stone disease patients were identified from nation-wide medical records. Standardized incidence ratios (SIRs) were calculated for 0–83 year old offspring when their first-degree relatives were diagnosed with stone disease and the rates were compared to individuals without a family history of stone disease. Numbers of offspring with SL were 7906, for UL they were 170,757 and for CL they were 204,369. Results SIRs for concordant familial risks were 2.06 for SL, 1.94 for UL and 1.82 for CL. SIRs for SL and UL were slightly higher for women than for men. Familial risks between stone diseases were modest. The highest risk of 1.17 was for UL when family members were diagnosed with CL, or vice versa. The SIR for UL was 1.15 when family members were diagnosed with SL. Familial risks among spouses were increased only for UL-CL pairs (1.10). Conclusions Familial risks for concordant SL were 2.06 and marginally lower for the other diseases. Familial risks between stone diseases were low but higher than risks between spouses. The data show that familial clustering is unique to each individual stone disease which would imply distinct disease mechanisms. The results cast doubt on the reported comorbidities between these diseases.

Risk stratification using molecular features could potentially help distinguish indolent from aggressive prostate cancer (PCa). Mutations in isocitrate dehydrogenase (IDH) acquire an abnormal enzymatic activity, resulting in the production of 2-hydroxyglutarate and alterations in cellular metabolism, histone modification, and DNA methylation. Mutant IDH1 has been identified in various human malignancies, and IDH1R132H constituted the vast majority of mutational events of IDH1. Most recent studies suggested that IDH1 mutations define a methylator subtype in PCa. However, the function of IDH1R132H in PCa development and progression is largely unknown. In this study, we showed that the prevalence of IDH1R132H in Chinese PCa patients is 0.6% (2/336). Of note, IDH1R132H-mutant PCa patients lacked other canonical genomic lesions (e.g., ERG rearrangement, PTEN deletion) that are common in most other PCa patients. The in vitro experiment suggested that IDH1R132H can promote proliferation of benign prostate epithelial cell RWPE-1 when under the situation of low cytokine. It could also promote migration capacity of RWPE-1 cells. Mechanistically, IDH1R132H was an important regulator of insulin-like growth factor 1receptor (IGF1R) by downregulating a set of microRNAs (miR-141-3p, miR-7-5p, miR-223-3p). These microRNAs were repressed by the alteration of epigenetic modification to decrease the enrichment of active marker H3K4me3 or to increase repressive marker H3K27me3 at their promoters. Collectively, we proposed a novel model for an IDH1R132H-microRNAs-IGF1R regulatory axis, which might provide insight into the function of IDH1R132H in PCa development.

Background: Uncomplicated cystitis is one of the most common reasons for antibiotic treatment in otherwise healthy women. Nationwide studies on antibiotic treatment for this infection and in relation to factors beyond the infection itself have hitherto not been available. Methods: This was a nationwide open cohort study consisting of 352,507 women aged 15–50 years with uncomplicated cystitis (2006–2018). The outcome was a redeemed antibiotic prescription within five days from the cystitis diagnosis. Logistic regression models were used to examine the relationship between the outcome and the predictor variables. Results: This study identified 192,065 redeemed treatments (54.5%). Several sociodemographic variables were associated with antibiotic treatment. For example, women with the lowest income had an odds ratio (OR) of 1.26 (95% CI 1.23–1.28) compared to those with the highest income. History of cervical cancer and high parity were also associated with lower treatment rates. Conclusion: This study presents novel factors beyond the infection which seem to affect the antibiotic treatment for uncomplicated cystitis in women. Future studies to investigate possible mechanisms are warranted in order to properly use our findings. This may help healthcare workers and planners to provide a more equal treatment plan for this common infection, which may reduce misuse of antibiotics, decrease costs and improve efforts against antibiotic resistance.

Objectives: The aim of this 6-year follow-up study was to examine whether neighbourhood accessibility to fast-food outlets was associated with diagnosed childhood obesity, after adjustment for neighbourhood- and individual-level socio-demographic factors. Methods: This 6-year follow-up study comprised 484,677 boys and 459,810 girls aged 0-14 years in Sweden. The follow-up period ran from January 1, 2005, until hospitalisation/out-patient treatment for obesity, death, emigration or the end of the study period on December 31, 2010. Multilevel logistic regression models (individual-level factors at the first level and neighbourhood-level factors at the second level) were used to calculate odds ratios (ORs) with 95% confidence intervals (95% CIs). Results: We identified 6,968 obesity cases (3,878 boys and 3,090 girls) during the follow-up period. Higher odds of childhood obesity for those living in neighbourhoods with accessibility to fast-food outlets was observed (OR = 1.14, 95% CI = 1.07-1.22) that remained significant after adjustments (OR = 1.06, 95% CI = 1.00-1.13). Conclusions: This prospective nationwide study showed that the neighbourhood accessibility to fast-food outlets was independently associated with increased odds of diagnosed childhood obesity. This finding implicates that residential environments should be considered when developing health promotion programmes.

Abstract We analysed cancer risks in patients with urinary tract stones but some features of the generated results alarmed us about possible surveillance bias, which we describe in this report. We used nationwide Swedish hospital records to identify patients with urinary tract stones (N = 211,718) and cancer registration data for cancer patients for years 1987 to 2012. Standardized incidence ratios (SIRs) for cancer were calculated after the last medical contact for urinary tract stones. All cancers were increased after kidney (SIR 1.54, 95%CI: 1.50–1.58), ureter (1.44, 1.42–1.47), mixed (1.51, 1.44–1.58) and bladder stones (1.63, 1.57–1.70). The risk of kidney cancer was increased most of all cancers after kidney, ureter and mixed stones while bladder cancer was increased most after bladder stones. All SIRs decreased steeply in the course of follow-up time. Tumour sizes were smaller in kidney cancer and in situ colon cancers were more common in patients diagnosed after urinary tract stones compared to all patients. The results suggest that surveillance bias influenced the result which somewhat surprisingly appeared to extend past 10 years of follow-up and include cancers at distant anatomical sites. Surveillance bias may be difficult to avoid in the present type of observational studies in clinical settings.