bluuebunny/crossref_metadata_2025 huggingface dataset:
Hepatitis E seroprevalence and risk factors in humans and pig in Ghana
Authors: Bagulo Husein , Majekodunmi Ayodele O. , Welburn Susan C. , Bimi Langbong
Published: February 2022

Background

Although Hepatitis E virus (HEV) infection has significant negative impact on the health and wellbeing of underprivileged populations, the burden of HEV in Ghana is still unclear, despite widespread water, sanitation, and hygiene (WASH) related conditions that predispose people to the risk of infection.

Methods

A cross-sectional study was conducted to explore rates of HEV seroprevalence and HEV prevalence, as well as risk factors in humans and domestic pigs in Ghana. These were determined using ELISAs manufactured by Wantai Beijing Biopharmaceuticals, China. The study involved 1365 community members, 105 pig farmers and 474 domestic pigs from four administrative regions of Ghana.

Results

Results showed overall seroprevalence and prevalence of 12.4% and 0.7% in community members and 15.2% and 2.9% in pig farmers respectively. There was no significant difference in the seroprevalence between the two groups (Z = 0.851; p = 0.3953). However, the prevalence in pig farmers was significantly higher than in community members (Z = 2.412; p = 0.016). Age (OR = 1.369, CI = 1.243 – 1.508; p = 0.0000), gender (OR = 1.419, CI = 1.101 – 1.991; p = 0.043), and the region of residence (OR = 1.569, CI = 1.348 – 1.827; p = 0.0000) were significant risk factors for HEV seroprevalence in a multivariate regression model.

In pigs, overall seroprevalence and prevalence of 62.4% and 5.5% were recorded respectively. A significant difference in seroprevalence was found between confined (6.7%) and free-range pigs (88.3%), (Z = 7.492; p < 0.00001) in the Volta Region. Multivariate logistic regression showed a significant association between seroprevalence and husbandry (OR = 7.051, CI = 3.558– 13.972; p = 0.0000) and region (OR = 4.602, CI = 2.300 – 9.205; p = 0.0000) in pigs in the Volta and Greater Accra Region.

Conclusion

From this study, HEV is endemic in Ghana with high seroprevalence in humans and pig populations. This underscores the need for awareness creation and action for prevention and control.
Correlative analysis of lung CT findings in patients with Birt–Hogg–Dubé Syndrome and the occurrence of spontaneous pneumothorax: a preliminary study
Authors: Yang Jinjing , Hu Xiaowen , Li Junjun , Zhang Guofeng , Ge Yaqiong , Wei Wei
Published: February 2022

Background

The diagnosis of patients with Birt–Hogg–Dubé (BHD) syndrome is always delayed (even for more than 10 years). Improving the understanding and diagnosis of this disease is vital for clinicians and radiologists. In this study we presented the chest computed tomography (CT) findings of BHD syndrome and offered suggestions for BHD cases with spontaneous pneumothorax.

Methods

Twenty-six BHD patients from 11 families (10 men, 16 women; mean age: 46 ± 12 years, 20–68 years) were included. The clinical features of the patients included pneumothorax, renal lesions, and skin lesions. Twenty-three patients underwent chest CT imaging. The cyst condition of each patient derived from reconstructed chest CT imaging was recorded, including the cyst number, size, volume, pattern, and distribution.

Results

Pneumothorax occurred in 54% (14/26) of patients. Among them, 43% (6/14) had pneumothorax more than twice. However, typical skin and renal lesions were absent. Four patients had renal hamartoma. CT showed that 23 (100%) patients had lung cysts. Pulmonary cysts were bilateral and multiple, round, irregular, or willow-like. And 93.6% of the large cysts (long-axis diameter ≥ 20 mm) were under the pleura, and near the mediastinum and spine. The long-axis diameter, short-axis diameter and volume of the largest cysts were associated with the occurrence of pneumothorax (all P < 0.05).

Conclusions

Chest CT imaging can reveal some characteristic features of BHD syndrome. The occurrence of pneumothorax in BHD patients is closely related to their pulmonary cystic lesions.
Fasting during Ramadan and acute kidney injury (AKI): a retrospective, propensity matched cohort study
Authors: AlAbdan Numan A. , Almohammed Omar A. , Altukhaim Maryam S. , Farooqui Mahfooz A. , Abdalla Mubarak I. , Al Otaibi Hazza Q. , Alshuraym Norah R. , Alghusun Shahad N. , Alotaibi Lama H. , Alsayyari Abdullah A.
Published: February 2022

Background

During the month of Ramadan, Muslims abstain from daytime consumption of fluids and foods, although some high-risk individuals are exempt. Because fasting's effects on the risk of acute kidney injury (AKI) have not been established, this study assesses the relationship between fasting and risk of AKI and identifies patients at high risk.

Methods

A single-center, retrospective, propensity-score matched, cohort study was conducted with data collected from adult patients admitted to the emergency room during Ramadan and the following month over two consecutive years (2016 and 2017). AKI was diagnosed based on the 2012 definition from the Kidney Disease: Improving Global Outcomes clinical practice guideline. Multivariable logistic regression analyses were used to examine the correlation and measure the effect of fasting on the incidence of AKI, and assess the effect of different variables on the incidence of AKI between the matching cohorts.

Results

A total of 1199 patients were included; after matching, each cohort had 499 patients. In the fasting cohort, the incidence of AKI and the risk of developing AKI were significantly lower (adjusted odds ratio (AOR) 0.65;95% confidence interval (CI) 0.44–0.98). The most indicative risk factors for AKI were hypertension (AOR 2.17; 95% CI 1.48–3.18), history of AKI (AOR 5.05; 95% CI 3.46–7.39), and liver cirrhosis (AOR 3.01; 95% CI 1.04–8.70). Patients with these factors or most other comorbidities in the fasting cohort had a lower risk of AKI as compared with their nonfasting counterparts.

Conclusion

The data show a strong reduction in the risk of developing AKI as a benefit of fasting, particularly in patients with comorbid conditions. Therefore, most patients with comorbid conditions are not harmed from fasting during Ramadan. However, larger prospective studies are needed to investigate the benefit of fasting in reducing the risk of developing AKI.
Clinical characteristics, pregnancy outcomes and ovarian function of pregnancy-associated breast cancer patients: a retrospective age-matched study
Authors: Liao Qiuyue , Deng Dongmei , Xie Qin , Gong Xiaoqin , Meng Xiaolin , Xia Yun , Ai Jihui , Li Kezhen
Published: February 2022

Background

Pregnancy-associated breast cancer (PABC) is a rare disease with increasing incidence. The prognosis, pregnancy outcomes and subsequent ovarian function of PABC patients are attracting attention.

Methods

Sixty-three PABC patients and 126 age-matched non-PABC patients were obtained in Tongji Hospital from January 2011 to September 2019. The clinical characteristics and ovarian function of PABC patients were compared with those of non-PABC patients. The pregnancy outcomes and neonatal outcomes of patients with breast cancer diagnosed during pregnancy (BCP) were described. Nonparametric tests, the χ2-test Kaplan–Meier, Cox regression and binomial logistic regression were used for analysis.

Results

PABC patients were diagnosed with a more advanced tumour stage (II: 47.6% vs. 45.2%, III: 33.3% vs. 19.8%, IV 3.2% vs. 0%, p = 0.003), which caused worse progression-free survival (PFS) (log-rank p = 0.0138) and breast cancer-specific survival (CSS) (log-rank p = 0.0076) than non-PABC patients. Tumour stage (III/IV vs. 0/I/II) (HR 16.017, 95% CI 5.830 ~ 44.006, p < 0.001) and endocrine therapy (HR 0.254, 95% CI 0.099 ~ 0.653, p = 0.004) were predictors of PFS. Tumour stage (III/IV vs. 0/I/II) (HR 30.875, 95% CI 7.232 ~ 131.820, p < 0.001), endocrine therapy (HR 0.200, 95% CI 0.049 ~ 0.818, p = 0.025) and targeted therapy (HR 0.143, 95% CI 0.028 ~ 0.743, p = 0.021) were predictors for breast CSS. Among the 15 BCP patients, 11 patients voluntarily continued their pregnancy, and the newborns had no obvious birth defects, either in 5 patients who received chemotherapy or in 6 patients who did not receive chemotherapy during pregnancy. Among the patients who received chemotherapy and did not receive endocrine therapy, 24 PABC patients and 48 non-PABC patients experienced chemotherapy-induced amenorrhea. There was no significant difference in resumption of menstruation between the two groups at 6 months and 12 months after the end of chemotherapy. No potential factors affecting resumption of menstruation were found.

Conclusion

Pregnancy at diagnosis or within 1 year after delivery was not a risk factor for a worse prognosis in PABC patients. Compared with non-PABC patients, patients with PABC presented more aggressive tumour characteristics, which could mostly explain the worse prognosis observed in PABC patients. Receiving the appropriate regimen of chemotherapy in the second and third trimesters did not affect the maternal outcomes or neonatal outcomes of BCP patients. The special physiological state during pregnancy and lactation did not interfere with the damage of chemotherapy to ovarian function.
Sodium hyaluronate combined with rhEGF contributes to alleviate clinical symptoms and Inflammation in patients with Xerophthalmia after cataract surgery
Authors: Gong Xuewu , Yao Hongbo , Wu Jing
Published: February 2022

Background

To determine the effect of sodium hyaluronate combined with recombinant human epidermal growth factor (rhEGF) on clinical symptoms and inflammation in patients with newly diagnosed xerophthalmia after cataract surgery.

Methods

A total of 106 patients who underwent cataract surgery and were newly diagnosed with xerophthalmia in our hospital between June 2018 and August 2019 were enrolled. Of these, 50 patients who were treated with sodium hyaluronate (0.1%) were assigned to the monotherapy group (MG) and the remaining 56 patients who were treated with sodium hyaluronate (0.1%) combined with rhEGF (20 μg/ml) were assigned to the combination group (CG). The 2 groups were compared based on ocular surface disease index (OSDI) score, break-up time (BUT), fluorescein corneal staining level, Schirmer I test (SI) level, clinical efficacy (disappearance of typical symptoms, including eyes drying, burning sensation, foreign body sensation, etc), and interleukin (IL)-1, IL-6, and tumor necrosis factor-α (TNF-α) levels. Spearman correlation analysis was conducted to analyze the relationship between IL-1, IL-6, TNF-α and clinical efficacy. In addition, receiver operating characteristic curves were drawn to analyze the predictive value of IL-1, IL-6, and TNF-α in efficacy on xerophthalmia. Results: After treatment, the CG showed reduced OSDI score compared with the MG. The CG showed increased BUT (s) and SI (mm) levels compared with MG. After treatment, the CG exhibited decreased levels of IL-1(ng/mL), IL-6 (ng/mL), and TNF-α (ng/mL) compared with the MG. Spearman correlation analysis revealed that IL-1, IL-6, and TNF-α were negatively correlated with clinical efficacy. The areas under the curves of IL-1, IL-6, and TNF-α were 0.801, 0.800, and 0.736 respectively.

Conclusions

Sodium hyaluronate combined with rhEGF is helpful to alleviate clinical symptoms and inflammation in patients with xerophthalmia undergoing cataract surgery.
The feasibility and ongoing use of electronic decision support to strengthen the implementation of IMCI in KwaZulu-Natal, South Africa
Authors: Jensen Cecilie , McKerrow Neil H.
Published: February 2022

Background

Continued efforts are required to reduce preventable child deaths. User-friendly Integrated Management of Childhood Illness (IMCI) implementation tools and supervision systems are needed to strengthen the quality of child health services in South Africa. A 2018 pilot implementation of electronic IMCI case management algorithms in KwaZulu-Natal demonstrated good uptake and acceptance at primary care clinics. We aimed to investigate whether ongoing electronic IMCI implementation is feasible within the existing Department of Health infrastructure and resources.

Methods

In a mixed methods descriptive study, the electronic IMCI (eIMCI) implementation was extended to 22 health facilities in uMgungundlovu district from November 2019 to February 2021. Training, mentoring, supervision and IT support were provided by a dedicated project team. Programme use was tracked, quarterly assessments of the service delivery platform were undertaken and in-depth interviews were conducted with facility managers.

Results

From December 2019 – January 2021, 9 684 eIMCI records were completed across 20 facilities, with a median uptake of 29 records per clinic per month and a mean (range) proportion of child consultations using eIMCI of 15% (1–46%). The local COVID-19-related movement restrictions and epidemic peaks coincided with declines in the monthly eIMCI uptake. Substantial inter- and intra-facility variations in use were observed, with the use being positively associated with the allocation of an eIMCI trained nurse (p < 0.001) and the clinician workload (p = 0.032).

Conclusion

The ongoing eIMCI uptake was sporadic and the implementation undermined by barriers such as low post-training deployment of nurses; poor capacity in the DoH for IT support; and COVID-19-related disruptions in service delivery. Scaling eIMCI in South Africa would rely on resolving these challenges.
Change in pre- and in-service early childhood educators’ knowledge, self-efficacy, and intentions following an e-learning course in physical activity and sedentary behaviour: a pilot study
Authors: Bruijns Brianne A. , Vanderloo Leigh M. , Johnson Andrew M. , Adamo Kristi B. , Burke Shauna M. , Carson Valerie , Heydon Rachel , Irwin Jennifer D. , Naylor Patti-Jean , Timmons Brian W. , Tucker Patricia
Published: February 2022

Background

Early childhood educators (ECEs) are the primary daytime role models for many young children, and are responsible for facilitating physical activity (PA) opportunities and minimizing sedentary behaviour (SB) in childcare. However, they have reportedly received little related education in their pre-service training. The purpose of the Training pre-service EArly CHildhood educators in physical activity (TEACH) pilot study was to explore changes in pre- and in-service ECEs’ knowledge, self-efficacy, behavioural intention, and perceived behavioural control following the TEACH e-Learning course in PA and SB.

Methods

Pre-service ECEs were purposefully recruited from three Canadian colleges, while in-service ECEs were recruited via social media. A pre-post study design was used. ECEs completed two online surveys; one prior to, and one immediately following the completion of the TEACH e-Learning course (~ 5 h). Descriptive statistics were reported, and McNemar Chi-Square tests and paired samplest-tests were used to examine changes in ECEs’ question-specific, and total knowledge scores, respectively. Wilcoxon Signed Ranks tests were employed to examine changes in self-efficacy, behavioural intention, and perceived behavioural control.

Results

Both pre- (n = 32) and in-service (n = 121) ECEs significantly increased their total knowledge scores from pre- to post-course completion (p < .05*). Significant positive changes in self-efficacy (p < .025*), behavioural intention (p < .007*), and perceived behavioural control (p < .007*) were demonstrated by in-service ECEs following course completion, while only select composite scores within these tools were significant among pre-service ECEs.

Conclusions

These findings provide preliminary evidence of the potential efficacy of the e-Learning course at improving ECEs’ knowledge, self-efficacy, behavioural intention, and perceived behavioural control to support PA and minimize SB in childcare. Following the success of the pilot study, testing the effectiveness of the TEACH e-Learning course on a larger scale, with a comparison group, is warranted prior to recommending broader dissemination of the training in pre-service ECE programs and for in-service ECE professional learning.
COVID-19 measures in Belgium: how perception and adherence of the general population differ between time periods
Authors: van Loenhout Joris Adriaan Frank , Vanderplanken Kirsten , Van den Broucke Stephan , Aujoulat Isabelle
Published: February 2022

Background

Since the onset of the COVID-19 pandemic, Belgium has been hit by a series of surges in the number of COVID-19 cases. Each of these resulted in more stringent measures being taken to curb the pandemic. This study compared perception of and adherence to COVID-19 measures of the Belgian population at two time periods: September 2020 (survey 1) and April/May 2021 (survey 2).

Methods

Two samples of approximately 2000 participants, representative for the Belgian population in terms of gender, age, province and socio-economic status, participated in an online survey. The survey questionnaire measured the perceived infection risk and severity, and the perception of and adherence to protective measures. Answers were compared between the time periods and risk factors for lower adherence were identified using multivariate linear regression.

Results

In survey 2, at which time the measures were more stringent, respondents assessed the risk of infection for themselves as lower, and for parents and grandparents as higher than in survey 1. Scores for understanding and usefulness of the measures were higher in survey 2 compared to survey 1, while reported past and future adherence were lower. Risk factors for a lower adherence were being male, being young, speaking French vs. Dutch, and having undergone a symptomatic infection.

Conclusions

It is important to consider the potential effect of fatigue among the population with regards to measures that are sustained for a long time, especially regarding measures related to social contacts. The identified risk factors for lower adherence offer insights to policy makers for future crisis communication regarding COVID-19.
Individual and community-level factors of perinatal mortality in the high mortality regions of Ethiopia: a multilevel mixed-effect analysis
Authors: Girma Desalegn , Abita Zinie , Fetene Gossa , Birie Bamlaku
Published: February 2022

Background

Even though perinatal mortality has declined globally; it is still the major public health concern in sub-Saharan Africa countries. Ethiopia is one of the sub-Saharan countries which contribute the highest-burden of perinatal mortality with a devastating rate in some of the regions. Therefore, this study aimed to identify the determinants of perinatal mortality in the high mortality regions of Ethiopia.

Method

A secondary data analysis was done using the 2016 Ethiopian Demographic and Health Survey data. The outcomes of 4120 pregnancies reaching ≥ 7 months of gestational age were considered for the analysis. A multilevel mixed logistic regression model was fitted to identify the predictors of perinatal mortality. Finally, a statistically significant association was declared at ap-value of ≤ 0.05.

Result

The study found that birth interval < 2 years (AOR = 3.71, 95%CI:2.27, 6.07),having no antenatal care (AOR = 2.43,95%CI:1.15,5.38), initiating breastfeeding after 1 h(AOR = 4.01,95%CI:2.49,6.51), being distant from health institutions (AOR = 1.99, 95%CI: 1.24, 3.22), having previous terminated pregnancy (AOR = 4.68, 95%CI:2.76,7.86), being mothers not autonomous(AOR = 1.96, 95%CI:1.19,3.20),being no media exposure (AOR = 2.78, 95%CI:1.48,5.59),being households ≤ 4 family sizes (AOR = 4.12, 95%CI:2.19,7.79), having ≥ 6 parity (AOR = 2.48, 95%CI:1.21, 5.22) were associated with a high odds of perinatal mortality.

Conclusion

The study concludes that birth interval, antenatal care, time for breastfeeding initiation, distance from health institutions, previous history of terminated pregnancy, maternal autonomy, media exposure, family size, and parity were predictors of prenatal mortality. Therefore, programmatic emphases to maternal waiting service utilization for mothers distant from health institutions and media advertising regarding the complications related to pregnancy, childbirth and on its respective direction that the mothers should follow could reduce perinatal mortality in high mortality regions of Ethiopia.
Surgical treatment of slipped capital femoral epiphysis (SCFE) by Dunn procedure modified by Ganz: a systematic review
Authors: Gorgolini Giulio , Caterini Alessandro , Efremov Kristian , Petrungaro Lidio , De Maio Fernando , Ippolito Ernesto , Farsetti Pasquale
Published: February 2022

Background

Treatment of SCFE is still controversial, especially in moderate and severe forms. Dunn osteotomy performed with the Ganz approach became very popular in the last decade, although it is a complicated and challenging surgical procedure with a risk of AVN. The aim of our study was to analyze the current literature verifying the effectiveness of this surgical procedure, with specific attention to the incidence of AVN and other complications.

Main body

A systematic review on the subject was performed according to the PRISMA guidelines. A literature search was performed by searching all published articles about the topic in the databases. The articles were screened for the presence of the following inclusion criteria: patients affected by slipped capital femoral epiphysis (SCFE) surgically treated by Dunn osteotomy using the Ganz surgical approach. All the patients affected by pathologies other than SCFE, treated without surgery or with procedures not including a surgical hip dislocation were excluded.

Based on inclusion and exclusion criteria, 23 studies were included in our systematic review. Selected articles were published from 2009 to 2021 and they included 636 overall hips. According to the selected articles, Dunn osteotomy modified by Ganz, performed by an experienced surgeon, allows for anatomical reduction of moderate or severe SCFE with a low incidence of AVN.

Conclusions

The few papers with long term follow-up, reported no progression of hip osteoarthritis, however, since the patients are adolescent at surgery, longer follow-up studies are needed to validate this statement. It is still debated if better results are obtained in stable or unstable SCFE. The indication of this procedure in mild SCFE remains controversial.

Level of evidence

3
Epstein–Barr virus infection is associated with the nuclear factor-kappa B p65 signaling pathway in renal cell carcinoma
Authors: Farhadi Ali , Namdari Sepide , Chong Pei Pei , Geramizadeh Bita , Behzad-Behbahani Abbas , Sekawi Zamberi , Sharifzadeh Sedigheh
Published: February 2022

Background

There have been few studies regarding viral involvement in the pathogenesis of renal cell carcinoma (RCC). The aim of this study was to examine the possible association of Epstein–Barr virus (EBV) infection with clinicopathological features and cellular biomarkers including p53, p16INK4a, Ki-67 and nuclear factor-kappa B (NF-κB) in RCC tumors.

Methods

In this prospective study, 122 histologically confirmed Formalin-fixed Paraffin-embedded RCC tissue specimens along with 96 specimens of their corresponding peritumoral tissues and 23 samples of blunt renal injuries were subjected to nested polymerase chain reaction (nPCR) in order to amplify EBV DNA sequences. The expression of p53, p16INK4a, Ki-67 and NF-κB was investigated by immunohistochemistry (IHC) assay. Statistical analysis was employed to demonstrate the possible associations.

Results

Infection with EBV was found to be significantly associated with RCC. Our results indicate that p65 NF-κB signaling pathway is probably involved in EBV-mediated RCC pathogenesis. Moreover, we found p53, Ki-67 and cytoplasmic NF-κB expression to be associated with tumor nuclear grade in RCC patients. The expression of p53 and Ki-67 was associated with primary tumor category as well. In addition, p53 overexpression was significantly more frequent among nonconventional RCC tumors than the conventional histologic type.

Conclusions

Infection with EBV is likely to play an important role in the development of RCC through the constitutive and permanent activation of NF-κB p65 signaling pathway. However, more experiments and supporting data are required to reach a decisive conclusion.
Health care burden and mortality of acute on chronic liver failure in Thailand: a nationwide population-based cohort study
Authors: Chirapongsathorn Sakkarin , Poovorawan Kittiyod , Soonthornworasiri Ngamphol , Pan-ngum Wirichada , Chaiprasert Amnart , Phaosawasdi Kamthorn , Treeprasertsuk Sombat
Published: February 2022

Background

Accurate population-based data are required concerning the rate, economic impact, and long-term outcome from acute on chronic liver failures (ACLF) in hospitalized patients with cirrhosis.

We aimed to discover time trends for the epidemiology, economic burden, and mortality of ACLF in Thailand.

Methods

We conducted a nationwide, population-based, cohort study which involved all hospitalized patients with cirrhosis in Thailand during the period between 2009 and 2013, with data from the National Health Security Office. ACLF was defined by two or more extrahepatic organ failures in patients with cirrhosis. Primary outcomes were trends in hospitalizations, hospital costs, together with inpatient mortality.

Results

The number of ACLF hospitalizations in Thailand doubled between 3185 in 2009 and 7666 in 2013. The average cost of each ACLF hospitalization was 3.5-fold higher than for cirrhosis ($ 1893 versus $ 519). The hospital is paid using a diagnosis-related group (DRG) payment system that is only 15% of the average treatment costs ($ 286 from $ 1893). The in-hospital fatality rate was 51% for ACLF while the additional fatality rate was 85% up to 1 year. The ACLF organ failure trends indicated sepsis with septic shock and renal failure as the majority proportion. Age, the number and types of organ failure and male sex were predictors of ACLF death.

Conclusions and relevance

Cirrhosis and ACLF both represent substantial and increasing health and economic burdens for Thailand. These data can assist national health care policy stakeholders to target high-risk patients with cirrhosis for care.
Mating behavior and reproductive morphology predict macroevolution of sex allocation in hermaphroditic flatworms
Authors: Brand Jeremias N. , Harmon Luke J. , Schärer Lukas
Published: February 2022

Background

Sex allocation is the distribution of resources to male or female reproduction. In hermaphrodites, this concerns an individual’s resource allocation to, for example, the production of male or female gametes. Macroevolutionary studies across hermaphroditic plants have revealed that the self-pollination rate and the pollination mode are strong predictors of sex allocation. Consequently, we expect similar factors such as the selfing rate and aspects of the reproductive biology, like the mating behaviour and the intensity of postcopulatory sexual selection, to predict sex allocation in hermaphroditic animals. However, comparative work on hermaphroditic animals is limited. Here, we study sex allocation in 120 species of the hermaphroditic free-living flatworm genusMacrostomum. We ask how hypodermic insemination, a convergently evolved mating behaviour where sperm are traumatically injected through the partner’s epidermis, affects the evolution of sex allocation. We also test the commonly-made assumption that investment into male and female reproduction should trade-off. Finally, we ask if morphological indicators of the intensity of postcopulatory sexual selection (female genital complexity, male copulatory organ length, and sperm length) can predict sex allocation.

Results

We find that the repeated evolution of hypodermic insemination predicts a more female-biased sex allocation (i.e., a relative shift towards female allocation). Moreover, transcriptome-based estimates of heterozygosity reveal reduced heterozygosity in hypodermically mating species, indicating that this mating behavior is linked to increased selfing or biparental inbreeding. Therefore, hypodermic insemination could represent a selfing syndrome. Furthermore, across the genus, allocation to male and female gametes is negatively related, and larger species have a more female-biased sex allocation. Finally, increased female genital complexity, longer sperm, and a longer male copulatory organ predict a more male-biased sex allocation.

Conclusions

Selfing syndromes have repeatedly originated in plants. Remarkably, this macroevolutionary pattern is replicated inMacrostomumflatworms and linked to repeated shifts in reproductive behavior. We also find a trade-off between male and female reproduction, a fundamental assumption of most theories of sex allocation. Beyond that, no theory predicts a more female-biased allocation in larger species, suggesting avenues for future work. Finally, morphological indicators of more intense postcopulatory sexual selection appear to predict more intense sperm competition.
Ionotropic receptors in the turnip moth Agrotis segetum respond to repellent medium-chain fatty acids
Authors: Hou Xiao-Qing , Zhang Dan-Dan , Powell Daniel , Wang Hong-Lei , Andersson Martin N. , Löfstedt Christer
Published: February 2022

Background

In insects, airborne chemical signals are mainly detected by two receptor families, odorant receptors (ORs) and ionotropic receptors (IRs). Functions of ORs have been intensively investigated in Diptera and Lepidoptera, while the functions and evolution of the more ancient IR family remain largely unexplored beyond Diptera.

Results

Here, we identified a repertoire of 26 IRs from transcriptomes of female and male antennae, and ovipositors in the moth Agrotis segetum. We observed that a large clade formed by IR75p and IR75q expansions is closely related to the acid-sensing IRs identified in Diptera. We functionally assayed each of the five AsegIRs from this clade using Xenopus oocytes and found that two receptors responded to the tested ligands. AsegIR75p.1 responded to several compounds but hexanoic acid was revealed to be the primary ligand, and AsegIR75q.1 responded primarily to octanoic acid, and less so to nonanoic acid. It has been reported that the C6-C10 medium-chain fatty acids repel various insects including many drosophilids and mosquitos. We show that the C6-C10 medium-chain fatty acids elicited antennal responses of both sexes of A. segetum, while only octanoic acid had repellent effect to the moths in a behavioral assay. In addition, using fluorescence in situ hybridization, we demonstrated that the five IRs and their co-receptor AsegIR8a are not located in coeloconic sensilla as found in Drosophila, but in basiconic or trichoid sensilla.

Conclusions

Our results significantly expand the current knowledge of the insect IR family. Based on the functional data in combination with phylogenetic analysis, we propose that subfunctionalization after gene duplication plays an important role in the evolution of ligand specificities of the acid-sensing IRs in Lepidoptera.
Systematic review and meta-analysis of the diagnostic accuracy of prostate-specific antigen (PSA) for the detection of prostate cancer in symptomatic patients
Authors: Merriel Samuel W. D. , Pocock Lucy , Gilbert Emma , Creavin Sam , Walter Fiona M. , Spencer Anne , Hamilton Willie
Published: February 2022

Background

Prostate-specific antigen (PSA) is a commonly used test to detect prostate cancer. Attention has mostly focused on the use of PSA in screening asymptomatic patients, but the diagnostic accuracy of PSA for prostate cancer in patients with symptoms is less well understood.

Methods

A systematic database search was conducted of Medline, EMBASE, Web of Science, and the Cochrane library. Studies reporting the diagnostic accuracy of PSA for prostate cancer in patients with symptoms were included. Two investigators independently assessed the titles and abstracts of all database search hits and full texts of potentially relevant studies against the inclusion criteria, and data extracted into a proforma. Study quality was assessed using the QUADAS-2 tool by two investigators independently. Summary estimates of diagnostic accuracy were calculated with meta-analysis using bivariate mixed effects regression.

Results

Five hundred sixty-three search hits were assessed by title and abstract after de-duplication, with 75 full text papers reviewed. Nineteen studies met the inclusion criteria, 18 of which were conducted in secondary care settings with one from a screening study cohort. All studies used histology obtained by transrectal ultrasound-guided biopsy (TRUS) as a reference test; usually only for patients with elevated PSA or abnormal prostate examination. Pooled data from 14,489 patients found estimated sensitivity of PSA for prostate cancer was 0.93 (95% CI 0.88, 0.96) and specificity was 0.20 (95% CI 0.12, 0.33). The area under the hierarchical summary receiver operator characteristic curve was 0.72 (95% CI 0.68, 0.76). All studies were assessed as having a high risk of bias in at least one QUADAS-2 domain.

Conclusions

Currently available evidence suggests PSA is highly sensitive but poorly specific for prostate cancer detection in symptomatic patients. However, significant limitations in study design and reference test reduces the certainty of this estimate. There is very limited evidence for the performance of PSA in primary care, the healthcare setting where most PSA testing is performed.
Estimating the effect of non-pharmaceutical interventions to mitigate COVID-19 spread in Saudi Arabia
Authors: Bisanzio Donal , Reithinger Richard , Alqunaibet Ada , Almudarra Sami , Alsukait Reem F. , Dong Di , Zhang Yi , El-Saharty Sameh , Herbst Christopher H.
Published: February 2022

Background

The Kingdom of Saudi Arabia (KSA) quickly controlled the spread of SARS-CoV-2 by implementing several non-pharmaceutical interventions (NPIs), including suspension of international and national travel, local curfews, closing public spaces (i.e., schools and universities, malls and shops), and limiting religious gatherings. The KSA also mandated all citizens to respect physical distancing and to wear face masks. However, after relaxing some restrictions during June 2020, the KSA is now planning a strategy that could allow resuming in-person education and international travel. The aim of our study was to evaluate the effect of NPIs on the spread of the COVID-19 and test strategies to open schools and resume international travel.

Methods

We built a spatial-explicit individual-based model to represent the whole KSA population (IBM-KSA). The IBM-KSA was parameterized using country demographic, remote sensing, and epidemiological data. A social network was created to represent contact heterogeneity and interaction among age groups of the population. The IBM-KSA also simulated the movement of people across the country based on a gravity model. We used the IBM-KSA to evaluate the effect of different NPIs adopted by the KSA (physical distancing, mask-wearing, and contact tracing) and to forecast the impact of strategies to open schools and resume international travels.

Results

The IBM-KSA results scenarios showed the high effectiveness of mask-wearing, physical distancing, and contact tracing in controlling the spread of the disease. Without NPIs, the KSA could have reported 4,824,065 (95% CI: 3,673,775–6,335,423) cases by June 2021. The IBM-KSA showed that mandatory mask-wearing and physical distancing saved 39,452 lives (95% CI: 26,641–44,494). In-person education without personal protection during teaching would have resulted in a high surge of COVID-19 cases. Compared to scenarios with no personal protection, enforcing mask-wearing and physical distancing in schools reduced cases, hospitalizations, and deaths by 25% and 50%, when adherence to these NPIs was set to 50% and 70%, respectively. The IBM-KSA also showed that a quarantine imposed on international travelers reduced the probability of outbreaks in the country.

Conclusions

This study showed that the interventions adopted by the KSA were able to control the spread of SARS-CoV-2 in the absence of a vaccine. In-person education should be resumed only if NPIs could be applied in schools and universities. International travel can be resumed but with strict quarantine rules. The KSA needs to keep strict NPIs in place until a high fraction of the population is vaccinated in order to reduce hospitalizations and deaths.
Identification of targetable kinases in idiopathic pulmonary fibrosis
Authors: Higo Hisao , Ohashi Kadoaki , Tomida Shuta , Okawa Sachi , Yamamoto Hiromasa , Sugimoto Seiichiro , Senoo Satoru , Makimoto Go , Ninomiya Kiichiro , Nakasuka Takamasa , Nishii Kazuya , Taniguchi Akihiko , Kubo Toshio , Ichihara Eiki , Hotta Katsuyuki , Miyahara Nobuaki , Maeda Yoshinobu , Toyooka Shinichi , Kiura Katsuyuki
Published: February 2022

Background

Tyrosine kinase activation plays an important role in the progression of pulmonary fibrosis. In this study, we analyzed the expression of 612 kinase-coding and cancer-related genes using next-generation sequencing to identify potential therapeutic targets for idiopathic pulmonary fibrosis (IPF).

Methods

Thirteen samples from five patients with IPF (Cases 1–5) and eight samples from four patients without IPF (control) were included in this study. Six of the thirteen samples were obtained from different lung segments of a single patient who underwent bilateral pneumonectomy. Gene expression analysis of IPF lung tissue samples (n = 13) and control samples (n = 8) was performed using SureSelect RNA Human Kinome Kit. The expression of the selected genes was further confirmed at the protein level by immunohistochemistry (IHC).

Results

Gene expression analysis revealed a correlation between the gene expression signatures and the degree of fibrosis, as assessed by Ashcroft score. In addition, the expression analysis indicated a stronger heterogeneity among the IPF lung samples than among the control lung samples. In the integrated analysis of the 21 samples, DCLK1 and STK33 were found to be upregulated in IPF lung samples compared to control lung samples. However, the top most upregulated genes were distinct in individual cases. DCLK1, PDK4, and ERBB4 were upregulated in IPF case 1, whereas STK33, PIM2, and SYK were upregulated in IPF case 2. IHC revealed that these proteins were expressed in the epithelial layer of the fibrotic lesions.

Conclusions

We performed a comprehensive kinase expression analysis to explore the potential therapeutic targets for IPF. We found that DCLK1 and STK33 may serve as potential candidate targets for molecular targeted therapy of IPF. In addition, PDK4, ERBB4, PIM2, and SYK might also serve as personalized therapeutic targets of IPF. Additional large-scale studies are warranted to develop personalized therapies for patients with IPF.
Plasma apolipoprotein concentrations and incident diabetes in subjects with prediabetes
Authors: Croyal Mikaël , Wargny Matthieu , Chemello Kevin , Chevalier Chloé , Blanchard Valentin , Bigot-Corbel Edith , Lambert Gilles , Le May Cédric , Hadjadj Samy , Cariou Bertrand
Published: February 2022

Background

The identification of circulating biomarkers associated with the risk of type 2 diabetes (T2D) is useful for improving the current prevention strategies in the most at-risk patients. Here, we aimed to investigate the association of plasma apolipoprotein concentrations in prediabetes subjects with the incidence of new-onset T2D during follow-up.

Methods

In the IT-DIAB prospective study, 307 participants with impaired fasting glucose levels (fasting plasma glucose [FPG]: 110–125 mg/dL) were followed yearly for 5 years. The onset of T2D was defined as a first FPG value ≥ 126 mg/dL during follow-up. Apolipoprotein (apo)A-I, A-II, A-IV, B100, C-I, C-II, C-III, C-IV, D, E, F, H, J, L1, M, and (a) plasma concentrations were determined by mass spectrometry. Correlations between apolipoproteins and metabolic parameters at baseline were assessed by Spearman’s coefficients. Kaplan–Meier curves were drawn using a ternary approach based on terciles and incident T2D. The association between plasma apolipoproteins concentrations and the incidence of T2D was determined using Cox proportional-hazards models.

Results

During a median follow-up of 5-year, 115 participants (37.5%) developed T2D. After adjustment for age, sex, body mass index, FPG, HbA1c, and statin use, the plasma levels of apoC-I, apoC-II, apoC-III, apoE, apoF, apoH, apoJ, and apoL1 were positively associated with a high risk for T2D. After further adjustment for plasma triglycerides, only apoE (1 SD natural-log-transformed hazard ratio: 1.28 [95% confidence interval: 1.06; 1.54]; p = 0.010), apoF (1.22 [1.01; 1.48]; p = 0.037), apoJ (1.24 [1.03; 1.49]; p = 0.024), and apoL1 (1.26 [1.05; 1.52]; p = 0.014) remained significantly associated with the onset of T2D. Kaplan–Meier survival curves also showed that the lower third of plasma apoE levels (< 5.97 mg/dL) was significantly associated with a lower risk of conversion to T2D (log-rank test, p = 0.002) compared to the middle and upper thirds.

Conclusions

The plasma apoE levels are positively associated with the risk of T2D in prediabetes subjects, independently of traditional risk factors. The possible associations of apoF, apoJ, and apoL1 with T2D risk also pave the way for further investigations.

Trial registration This trial was registered at clinicaltrials.gov as NCT01218061 and NCT01432509
Dual CRISPR interference and activation for targeted reactivation of X-linked endogenous FOXP3 in human breast cancer cells
Authors: Cui Xuelian , Zhang Chao , Xu Zhifang , Wang Shuaibin , Li Xin , Stringer-Reasor Erica , Bae Sejong , Zeng Leiping , Zhao Dehua , Liu Runhua , Qi Lei S. , Wang Lizhong
Published: February 2022

Background

Unlike autosomal tumor suppressors, X-linked tumor suppressors can be inactivated by a single hit due to X-chromosome inactivation (XCI). Here, we argue that targeted reactivation of the non-mutated allele from XCI offers a potential therapy for female breast cancers.

Methods

Towards this goal, we developed a dual CRISPR interference and activation (CRISPRi/a) approach for simultaneously silencing and reactivating multiple X-linked genes using two orthogonal, nuclease-deficient CRISPR/Cas9 (dCas9) proteins.

Results

Using Streptococcus pyogenes dCas9-KRAB for silencing XIST and Staphylococcus aureus dCas9-VPR for activating FOXP3, we achieved CRISPR activation of FOXP3 in various cell lines of human female breast cancers. In human breast cancer HCC202 cells, which express a synonymous heterozygous mutation in the coding region of FOXP3, simultaneous silencing of XIST from XCI led to enhanced and prolonged FOXP3 activation. Also, reactivation of endogenous FOXP3 in breast cancer cells by CRISPRi/a inhibited tumor growth in vitro and in vivo. We further optimized CRISPRa by fusing dCas9 to the demethylase TET1 and observed enhanced FOXP3 activation. Analysis of the conserved CpG-rich region of FOXP3 intron 1 confirmed that CRISPRi/a-mediated simultaneous FOXP3 activation and XIST silencing were accompanied by elevated H4 acetylation, including H4K5ac, H4K8ac, and H4K16ac, and H3K4me3 and lower DNA methylation. This indicates that CRISPRi/a targeting to XIST and FOXP3 loci alters their transcription and their nearby epigenetic modifications.

Conclusions

The simultaneous activation and repression of the X-linked, endogenous FOXP3 and XIST from XCI offers a useful research tool and a potential therapeutic for female breast cancers.
Pregnancy, perinatal and childhood outcomes in women with and without polycystic ovary syndrome and metformin during pregnancy: a nationwide population-based study
Authors: Fornes Romina , Simin Johanna , Nguyen Minh Hanh , Cruz Gonzalo , Crisosto Nicolás , van der Schaaf Maartje , Engstrand Lars , Brusselaers Nele
Published: February 2022

Background

Polycystic Ovary Syndrome (PCOS) is an endocrine disorder that affects women in reproductive age and represents an unfavourable risk factor for several pregnancy and perinatal outcomes. Despite, no guidelines or pharmaceutical strategies for treating PCOS during pregnancy are available. The aim of this study is to determine the association between polycystic ovary syndrome with or without metformin and the pregnancy, perinatal outcomes as well as the risk of obesity in children born to these mothers.

Methods

In this nationwide population-based cohort study based in Swedish population, all singleton births (n = 1,016,805) from 686,847 women since 2006 up to 2016 were included. Multivariable logistic and Cox regression modelling with odds ratios (OR) and hazard ratios (HR) and 95% confidence intervals were used to study the association between the exposure of maternal PCOS, metformin during pregnancy (or the combination of both) and: 1) Pregnancy outcomes: preeclampsia, gestational diabetes, caesarean section, and acute caesarean section, 2) Perinatal outcomes: preterm birth, stillbirth, low birth weight, macrosomia, Apgar < 7 at 5 min, small for gestational age and large for gestational age, and 3) Childhood Obesity.

Results

PCOS in women without metformin use during pregnancy was associated with higher risks of preeclampsia (OR = 1.09, 1.02–1.17), gestational diabetes (OR = 1.71, 1.53–1.91) and caesarean section (OR = 1.08, 1.04–1.12), preterm birth (OR = 1.30, 1.23–1.38), low birth weight (OR = 1.29, 1.20–1.38), low Apgar scores (OR = 1.17, 1.05–1.31) and large for gestational age (OR = 1.11, 1.03–1.20). Metformin use during pregnancy (in women without PCOS) was associated with a 29% lower risks of preeclampsia (OR = 0.71, 0.51–0.97), macrosomia and large for gestational age. Obesity was more common among children born to mothers with PCOS without metformin (HR = 1.61, 1.44–1.81); and those with metformin without PCOS (HR = 1.67, 1.05–2.65). PCOS with metformin was not associated with any adverse outcome.

Conclusion

PCOS was associated with increased risks of adverse pregnancy and perinatal outcomes and childhood obesity. Metformin appears to reduce these risks in mothers with polycystic ovary syndrome and their children; but may increase the risk of childhood-obesity in children form women without PCOS.
On-the-job vocational training of nonprofessional ethnic health workers of a primary health care team improves their sense of coherence
Authors: Katona Cintia , Bíró Éva , Vincze Szilvia , Kósa Karolina
Published: February 2022

Objectives

A Primary Care Model Programme had been implemented in Hungary between 2013 and 2017 in which group practices were established that employed—among others—nonprofessional health workers (health mediators, similar to community health workers) to facilitate access for the most disadvantaged population groups. The health of mediators, themselves mostly disadvantaged ethnic Roma, was monitored every odd year of the Programme.

Methods

A repeated cross-sectional health interview survey had been implemented inviting all health mediators who were employed at the time of the survey. The same questionnaire was used in all 3 surveys with items from the European Health Interview Survey 2009 and validated versions of other scales.

Results

Positive changes occurred in the health status of mediators during 5 years of follow-up. Significant improvement in mental health occurred among those who completed on-the-job vocational training. By 2017, significant increase in sense of coherence was observed among those who obtained vocational qualification as opposed to those who did not. The proportion of highly stressed mediators showed a significant increase among those with no vocational training. Improvement was detected in all mediators in health awareness, dysfunctional attitudes, psychological stress and smoking prevalence.

Conclusions

Significant improvement in mental status among those who obtained on-the-job vocational qualification were observed during follow-up of ethnic Roma health mediators in the programme in which they were equal members of the primary health care team. Employment of health mediators in primary care teams not only contributed to improving access to care for disadvantaged groups, but also improved the mental health of mediators themselves.