bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of PCOS with offspring morbidity: a longitudinal cohort study
Authors: Wei Shu Qin , Bilodeau-Bertrand Marianne , Auger Nathalie 
Published: July 2022

Abstract

STUDY QUESTION
Do children whose mothers have polycystic ovary syndrome (PCOS) have an increased risk of morbidity?

SUMMARY ANSWER
Maternal PCOS is associated with an increased risk of infection, allergy and other childhood morbidity.

WHAT IS KNOWN ALREADY
PCOS is associated with higher rates of gestational diabetes, pre-eclampsia and preterm delivery, but the long-term impact on child health is poorly understood.

STUDY DESIGN, SIZE, DURATION
We conducted a retrospective longitudinal cohort study of 1 038 375 children in Quebec between 2006 and 2020.

PARTICIPANTS/MATERIALS, SETTING, METHODS
We included 7160 children whose mothers had PCOS and 1 031 215 unexposed children. Outcomes included child hospitalization for infectious, allergic, malignant and other diseases before 13 years of age. We estimated hazard ratios (HRs) and 95% CI for the association of PCOS with childhood morbidity in adjusted Cox proportional hazards regression models.

MAIN RESULTS AND THE ROLE OF CHANCE
Children exposed to PCOS were hospitalized at a rate of 68.9 (95% CI 66.2–71.8) per 1000 person-years, whereas unexposed children were hospitalized at a rate of 45.3 (95% CI 45.1–45.5) per 1000 person-years. Compared with no exposure, maternal PCOS was associated with 1.32 times the risk of any childhood hospitalization (95% CI 1.26–1.40), 1.31 times the risk of infectious disease hospitalization (95% CI 1.25–1.38) and 1.47 times the risk of allergy-related hospitalization (95% CI 1.31–1.66). Risk of hospitalization was also elevated for childhood metabolic (HR 1.59, 95% CI 1.16–2.18), gastrointestinal (HR 1.72, 95% CI 1.53–1.92), central nervous system (HR 1.74, 95% CI 1.46–2.07) and otologic disorders (HR 1.34, 95% CI 1.26–1.43). Subgroup analyses suggested that there was little difference in the association of PCOS with hospitalization among boys (HR 1.31, 95% CI 1.24–1.39) and girls (HR 1.34, 95% CI 1.26–1.43).

LIMITATIONS, REASONS FOR CAUTION
We analyzed severe childhood morbidity requiring hospitalization, not mild diseases treated in ambulatory clinics. We lacked data on ethnicity, education and physical activity, and cannot rule out residual confounding.

WIDER IMPLICATIONS OF THE FINDINGS
Our findings suggest that maternal PCOS is associated with an increased risk of childhood morbidity.

STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by grant PJT-162300 from the Canadian Institutes of Health Research. N.A. acknowledges a career award from the Fonds de recherche du Québec-Santé (296785). The authors declare no competing interests.

TRIAL REGISTRATION NUMBER
N/A.
Heterogeneous effects and spillovers of macroprudential policy in an agent-based model of the UK housing market
Authors: Carro Adrian , Hinterschweiger Marc , Uluc Arzu , Farmer J Doyne 
Published: July 2022

AbstractWe develop an agent-based model of the UK housing market to study the impact of macroprudential policy experiments on key housing market indicators. The heterogeneous nature of this model enables us to assess the effects of such experiments on the housing, rental, and mortgage markets not only in the aggregate, but also at the level of individual households and sub-segments, such as first-time buyers, homeowners, buy-to-let (BTL) investors, and renters. This approach can, therefore, offer a broad picture of the disaggregated effects of financial stability policies. The model is calibrated using a large selection of micro-data, including data from a leading UK real-estate online search engine as well as loan-level regulatory data. With a series of comparative static exercises, we investigate the impact of (i) a hard loan-to-value limit and (ii) a soft loan-to-income limit, allowing for a limited share of unconstrained new mortgages. We find that, first, these experiments tend to mitigate the house price cycle by reducing credit availability and therefore leverage. Second, an experiment targeting a specific risk measure may also affect other risk metrics, thus necessitating a careful calibration of the policy to achieve a given reduction in risk. Third, experiments targeting the owner-occupier housing market can spill over to the rental sector, as a compositional shift in home ownership from owner-occupiers to BTL investors affects both the supply of and the demand for rental properties.
Population pharmacokinetic study of benzathine penicillin G administration in Indigenous children and young adults with rheumatic heart disease in the Northern Territory, Australia
Authors: Kado Joseph , Salman Sam , Hand Robert , O’Brien Margaret , Ralph Anna , Bowen Asha C , Page-Sharp Madhu , Batty Kevin T , Dolman Veronica , Francis Joshua R , Carapetis Jonathan , Manning Laurens 
Published: July 2022

Abstract

Background
Benzathine penicillin G (BPG) is the cornerstone of secondary prophylaxis to prevent Streptococcus pyogenes infections, which precede acute rheumatic fever (ARF). The paucity of pharmacokinetic (PK) data from children and adolescents from populations at the highest risk of ARF and rheumatic heart disease (RHD) poses a challenge for determining the optimal dosing and frequency of injections and undermines efforts to develop improved regimens.

Methods
We conducted a 6 month longitudinal PK study of young people receiving BPG for secondary prophylaxis. Throat and skin swabs were collected for microbiological culture along with dried blood spot (DBS) samples for penicillin concentrations. DBSs were assayed using LC-MS/MS. Penicillin concentration datasets were analysed using non-linear mixed-effects modelling and simulations performed using published BMI-for-age and weight-for-age data.

Results
Nineteen participants provided 75 throat swabs, 3 skin swabs and 216 penicillin samples. Throat cultures grew group C and G Streptococcus. Despite no participant maintaining penicillin concentration &gt;20 ng/mL between doses, there were no S. pyogenes throat infections and no ARF. The median (range) observed durations &gt;20 ng/mL for the low- and high-BMI groups were 14.5 (11.0–24.25) and 15.0 (7.5–18.25) days, respectively.

Conclusions
Few patients at highest risk of ARF/RHD receiving BPG for secondary prophylaxis maintain penicillin concentrations above the target of 20 ng/mL beyond 2 weeks during each monthly dosing interval. These PK data suggest that some high-risk individuals may get inadequate protection from every 4 week dosing. Future research should explore this gap in knowledge and PK differences between different populations to inform future dosing schedules.
An ethico-legal assessment of intellectual property rights and their effect on COVID-19 vaccine distribution: an Australian case study
Authors: Scheibner James , Nielsen Jane , Nicol Dianne 
Published: July 2022

Abstract
This article posits that Australia, as an affluent country with increasing capacity to manufacture vaccines, has an obligation to assist its regional (and global) counterparts in implementing vaccination programs that protect their populations. First, the article explores the capacity of high-income nations to meet their obligations, assist their neighbours and refrain from vaccine nationalism. This inquiry involves an analysis of the optimal ethical strategy for distributing vaccines globally, and the role that Australia might play in this distribution strategy. Secondly, the article examines the intellectual property landscape for vaccines in Australia, focusing on the patents that cover vaccine compositions and manufacturing techniques (recognizing the potential for know-how and access to materials as well as patents to affect manufacturing capacity). This article then discusses the strategies the Australian Government has at its disposal to counter potential intellectual property impediments whilst complying with existing obligations under the Agreement on Trade-related Aspects of Intellectual Property Rights (TRIPS), as an ethically appropriate response to the pandemic. This article also considers whether a so-called TRIPS waiver could provide better options and concludes that the challenge of compelling disclosure of know-how remains.
Diver Underwater Cycling Endurance After Short-Term Warm and Hot Water Acclimation
Authors: Wheelock Courtney E , Looney David P , Potter Adam W , Pryor Riana R , Pryor J Luke , Florian John , Hostler David 
Published: July 2022

ABSTRACT

Introduction
It is unclear whether immersion heat acclimation benefits exercise in warm water conditions. This study examined the effects of heat acclimation strategies on heart rate (HR), core temperature, and time to exhaustion (TTE) during cycling exercise in varying warm water conditions.

Methods
Twenty male divers completed this study at the Navy Experimental Diving Unit. Subjects were randomly assigned to one of two 9-day heat acclimation groups. The first group (WARM; n = 10) cycled for 2 hours at 50 W in 34.4 °C water, while the second group (HOT; n = 10) cycled for 1 hour against minimal resistance in 36.7 °C water. Following acclimation, TTE was tested by underwater cycling (30 W) in 35.8 °C, 37.2 °C, and 38.6 °C water.

Results
Throughout acclimation, the rate of core temperature rise in the first 30 minutes of exercise increased (P = .02), but the maximum core temperature reached was not different for either group. Time to exhaustion (TTE) was reduced, and the rate of core temperature rise during performance testing increased (both P &lt; .001) with increasing water temperature but was not different between groups. Core temperature and HR increased throughout performance testing in each water condition and were lower in the HOT compared to the WARM acclimation group (all P &lt; .05) with the exception of core temperature in the 37.2 °C condition.

Conclusions
Underwater exercise performance did not differ between the two acclimation strategies. This study suggests that passive acclimation to a higher water temperature may improve thermoregulatory and cardiovascular responses to exercise in warm water. Hot water immersion adaptations are dependent on exercise intensity and water temperature.
Enhancement of CRISPR/Cas12a trans-cleavage activity using hairpin DNA reporters
Authors: Rossetti Marianna , Merlo Rosa , Bagheri Neda , Moscone Danila , Valenti Anna , Saha Aakash , Arantes Pablo R , Ippodrino Rudy , Ricci Francesco , Treglia Ida , Delibato Elisabetta , van der Oost John , Palermo Giulia , Perugino Giuseppe , Porchetta Alessandro 
Published: July 2022

Abstract
The RNA programmed non-specific (trans) nuclease activity of CRISPR-Cas Type V and VI systems has opened a new era in the field of nucleic acid-based detection. Here, we report on the enhancement of trans-cleavage activity of Cas12a enzymes using hairpin DNA sequences as FRET-based reporters. We discover faster rate of trans-cleavage activity of Cas12a due to its improved affinity (Km) for hairpin DNA structures, and provide mechanistic insights of our findings through Molecular Dynamics simulations. Using hairpin DNA probes we significantly enhance FRET-based signal transduction compared to the widely used linear single stranded DNA reporters. Our signal transduction enables faster detection of clinically relevant double stranded DNA targets with improved sensitivity and specificity either in the presence or in the absence of an upstream pre-amplification step.
The Topography of Subnational Inequality
Authors: VanHeuvelen Tom 
Published: July 2022

AbstractIn this study, I examine inequality divergence, or the inequality of inequalities across local labor markets. While divergence trends of central tendencies such as per capita income have been well documented, less is known about the descriptive trends or contributing mechanisms for inequality itself. In this study, I construct wage inequality measures in 722 commuting zones covering the entire contiguous United States across 22 waves of Census and American Community Survey data from 1940 to 2019 to assess the historical trends of inequality divergence. I synthesize counterfactual and variance decomposition techniques to develop main conclusions. Results show two eras, one of convergence between 1950 and 1990, and divergence between 1990 and 2019, resulting in rates of divergence today as high as any time in the past 80 years. With a brief exception from 1990 to 2007, most changes occurred through the geographical mobility of wages across labor markets. In the 1950–1990 period, this primarily occurred through equalization of wages across regions and within the US South, while the takeoff of highly urban and unequal labor markets made a novel contribution to the 1990–2019 era. In total, results point to the fundamental importance of what I term the topography of inequality, or the contours of inequality levels across spatial locations and the change in the size and location of peaks and valleys across time, for understanding the full nature of long run inequality change.
Cancer mortality and predictions for 2022 in selected Australasian countries, Russia, and Ukraine with a focus on colorectal cancer
Authors: Pizzato Margherita , La Vecchia Carlo , Malvezzi Matteo , Levi Fabio , Boffetta Paolo , Negri Eva , Dalmartello Michela 
Published: July 2022

Objective
We aimed at predicting cancer mortality rates for the current year for the Russian Federation, Ukraine, Israel, Hong Kong SAR, Japan, Korea, and Australia, with a focus on colorectal cancer.

Methods
We retrieved official death certification and population data from the WHO and the United Nations Population Division databases. We analyzed mortality for all cancers combined and for 10 major cancer sites from 1970 to 2019, or the latest available year. We predicted numbers of deaths and age-standardized mortality rates for 2022 using Poisson joinpoint regression models. We estimated the number of averted deaths over the period 1994–2022 because of the decline in mortality rates.

Results
Total cancer mortality declined in all countries and both sexes. Russia had the highest total cancer predicted rates for 2022: 156.4/100 000 (world standard) in men and 81.4 in women; the lowest rates were reported in Israeli men (90.6/100 000) and Korean women (44.5/100 000). Between 1994 and 2022, a total of 1 487 000 deaths were estimated to be avoided in Russia, 502 000 in Ukraine, 58 000 in Israel, 102 000 in Hong Kong SAR, 1 020 000 in Japan, 533 000 in the Republic of Korea, and 263 000 in Australia. Colorectal cancer mortality trends were downward for the last decades with favorable predictions for 2022 in both sexes.

Conclusion
In the countries considered, predicted downward trends started later and were less marked than those in the European Union and the USA. Despite overall favorable predictions, colorectal cancer remains one of the major causes of cancer mortality.
A trial of arbidol hydrochloride in adults with COVID-19
Authors: Zhao Jingya , Zhang Jinnong , Jin Yang , Tang Zhouping , Hu Ke , Sun Hui , Shi Mengmeng , Yang Qingyuan , Gu Peiyu , Guo Hongrong , Li Qi , Zhang Haiying , Li Chenghong , Yang Ming , Xiong Nian , Dong Xuan , Xu Juanjuan , Lin Fan , Wang Tao , Yang Chao , Huang Bo , Zhang Jingyi , Chen Shi , He Qiong , Zhou Min , Qu Jieming 
Published: July 2022

Abstract

Background:
To date, there is no effective medicine to treat coronavirus disease 2019 (COVID-19), and the antiviral efficacy of arbidol in the treatment for COVID-19 remained equivocal and controversial. The purpose of this study was to evaluate the efficacy and safety of arbidol tablets in the treatment of COVID-19.

Methods:
This was a prospective, open-label, controlled and multicenter investigator-initiated trial involving adult patients with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Patients were stratified 1:2 to either standard-of-care (SOC) or SOC plus arbidol tablets (oral administration of 200 mg per time, three times a day for 14 days). The primary endpoint was negative conversion of SARS-CoV-2 within the first week. The rates and 95% confidential intervals were calculated for each variable.

Results:
A total of 99 patients with laboratory-confirmed SARS-CoV-2 infection were enrolled; 66 were assigned to the SOC plus arbidol tablets group, and 33 to the SOC group. The negative conversion rate of SARS-CoV-2 within the first week in patients receiving arbidol tablets was significantly higher than that of the SOC group (70.3% [45/64] vs. 42.4% [14/33]; difference of conversion rate 27.9%; 95% confidence interval [CI], 7.7%–48.1%; P
= 0.008). Compared to those in the SOC group, patients receiving arbidol tablets had a shorter duration of clinical recovery (median 7.0 days vs. 12.0 days; hazard ratio [HR]: 1.877, 95% CI: 1.151–3.060, P = 0.006), symptom of fever (median 3.0 days vs. 12.0 days; HR: 18.990, 95% CI: 5.350–67.410, P < 0.001), as well as hospitalization (median 12.5 days vs. 20.0 days; P < 0.001). Moreover, the addition of arbidol tablets to SOC led to more rapid normalization of declined blood lymphocytes (median 10.0 days vs. 14.5 days; P > 0.05). The most common adverse event in the arbidol tablets group was the elevation of transaminase (5/200, 2.5%), and no one withdrew from the study due to adverse events or disease progression.

Conclusions:
SOC plus arbidol tablets significantly increase the negative conversion rate of SARS-CoV-2 within the first week and accelerate the recovery of COVID-19 patients. During the treatment with arbidol tablets, we find no significant serious adverse events.

Trial registration:
Chinese Clinical Trial Registry, NCT04260594, www.clinicaltrials.gov/ct2/show/NCT04260594?term=NCT04260594&draw=2&rank=1
Associations of toluidine red unheated serum test response to the treatment of syphilis in pregnancy and congenital syphilis: a 10-year real-world study
Authors: Wei Jin , Pang Mengyao , Lun Wenhui 
Published: July 2022

Abstract

Background:
So far, there is a paucity of real-world data on the syphilis serological responses to the first-line treatment during pregnancy, and there is no relevant study on the necessity of anti-syphilis treatment during pregnancy for those patients who have been treated for syphilis before pregnancy for the prevention of mother-to-child transmission, which might provide valuable insight into treatment effectiveness and optimal management of pregnant women with syphilis.

Methods:
A retrospective study on 10 years of real-world data was performed for accumulative 410 Chinese pregnant women with syphilis. The descriptive statistics were conducted in the study, and toluidine red unheated serum test (TRUST) titer responses to penicillin treatment in syphilis-infected pregnant women, and the associations with congenital syphilis were investigated. We divided the patients into two groups according to the history of anti-syphilis treatment before pregnancy (patients diagnosed with syphilis who had received anti-syphilis treatment before pregnancy, and patients screened and diagnosed with syphilis during pregnancy who had no previous history of anti-syphilis treatment).

Results:
The rate of congenital syphilis in this study was 6.2% (25/406). There was no significant difference in the rate of congenital syphilis between patients who received anti-syphilis treatment before pregnancy and those who did not. Secondary syphilis and high baseline serum TRUST titer (≥1:8) in pregnant women were independent risk factors for congenital syphilis.

Conclusions:
For the prevention of congenital syphilis, anti-syphilis treatment during pregnancy for syphilis seropositive pregnant women is needed, regardless of whether the patient has received anti-syphilis treatment before pregnancy, especially for those patients with secondary syphilis or high baseline serum TRUST titer, thus, timely surveillance, early diagnosis to timely treatment, and close syphilis reexamination during posttreatment follow-up, may help to reduce the above-mentioned risk factors for congenital syphilis.
Sex disparity of lung cancer risk in non-smokers: a multicenter population-based prospective study based on China National Lung Cancer Screening Program
Authors: Wu Zheng , Tan Fengwei , Yang Zhuoyu , Wang Fei , Cao Wei , Qin Chao , Dong Xuesi , Zheng Yadi , Luo Zilin , Zhao Liang , Yu Yiwen , Xu Yongjie , Ren Jiansong , Shi Jufang , Chen Hongda , Li Jiang , Tang Wei , Shen Sipeng , Wu Ning , Chen Wanqing , Li Ni , He Jie 
Published: July 2022

Abstract

Background:
Non-smokers account for a large proportion of lung cancer patients, especially in Asia, but the attention paid to them is limited compared with smokers. In non-smokers, males display a risk for lung cancer incidence distinct from the females—even after excluding the influence of smoking; but the knowledge regarding the factors causing the difference is sparse. Based on a large multicenter prospective cancer screening cohort in China, we aimed to elucidate the interpretable sex differences caused by known factors and provide clues for primary and secondary prevention.

Methods:
Risk factors including demographic characteristics, lifestyle factors, family history of cancer, and baseline comorbidity were obtained from 796,283 Chinese non-smoking participants by the baseline risk assessment completed in 2013 to 2018. Cox regression analysis was performed to assess the sex difference in the risk of lung cancer, and the hazard ratios (HRs) that were adjusted for different known factors were calculated and compared to determine the proportion of excess risk and to explain the existing risk factors.

Results:
With a median follow-up of 4.80 years, 3351 subjects who were diagnosed with lung cancer were selected in the analysis. The lung cancer risk of males was significantly higher than that of females; the HRs in all male non-smokers were 1.29 (95% confidence interval [CI]: 1.20–1.38) after adjusting for the age and 1.38 (95% CI: 1.28–1.50) after adjusting for all factors, which suggested that known factors could not explain the sex difference in the risk of lung cancer in non-smokers. Known factors were 7% (|1.29–1.38|/1.29) more harmful in women than in men. For adenocarcinoma, women showed excess risk higher than men, contrary to squamous cell carcinoma; after adjusting for all factors, 47% ([1.30–1.16]/[1.30–1]) and 4% ([7.02–6.75]/[7.02–1])) of the excess risk was explainable in adenocarcinoma and squamous cell carcinoma. The main causes of gender differences in lung cancer risk were lifestyle factors, baseline comorbidity, and family history.

Conclusions:
Significant gender differences in the risk of lung cancer were discovered in China non-smokers. Existing risk factors did not explain the excess lung cancer risk of all non-smoking men, and the internal causes for the excess risk still need to be explored; most known risk factors were more harmful to non-smoking women; further exploring the causes of the sex difference would help to improve the prevention and screening programs and protect the non-smoking males from lung cancers.