bluuebunny/crossref_metadata_2025 huggingface dataset:
Evolution of nuptial gifts and its coevolutionary dynamics with male-like persistence traits of females for multiple mating
Authors: Kamimura Yoshitaka , Yoshizawa Kazunori , Lienhard Charles , Ferreira Rodrigo L. , Abe Jun
Published: September 2021

Background

Many male animals donate nutritive materials during courtship or mating to their female mates. Donation of large-sized gifts, though costly to prepare, can result in increased sperm transfer during mating and delayed remating of the females, resulting in higher paternity. Nuptial gifting sometimes causes severe female-female competition for obtaining gifts (i.e., sex-role reversal in mate competition) and selection on females to increase their mating rate, changing the intensity of sperm competition and the resultant paternity gains. We built a theoretical model to simulate such coevolutionary feedbacks between nuptial gift size (male trait) and propensity for multiple mating (female trait). Donation of nuptial gifts sometimes causes development of female persistence trait for gift acquisition. We also analyzed the causes and consequences of this type of traits, taking double receptacles for nutritious seminal gifts, which are known to occur in an insect group with a “female penis” (Neotrogla spp.), as an illustrative example.

Results

Our individual-based simulations demonstrated that female-female competition for male-derived nutrients always occur when the environment is oligotrophic and mating costs are low for females. However, a positive correlation between donated gift size and the resultant paternity gain was a requisite for the co-occurrence of large gifts and females’ competitive multiple mating for the gifts. When gift donation satisfied female demands and thus resulted in monandry, exaggeration of nuptial gift size also occurred under the assumption that the last male monopolizes paternity. The evolution of double slots for gift acquisition and digestion (female persistence trait) always occurred when males could not satisfy the demands of females for gifts. However, through coevolutionary reduction in male gift size, fixation of this trait in a population drastically reduced the average female fitness.

Conclusion

Sperm usage patterns, which have rarely been examined for animals with nuptial gifts, can be a critical factor for determining the extent of exaggeration in nuptial gifting. Sex-role reversals in mate competition, as a result of donation of nuptial gifts from males to females, can involve the evolution of male-like, persistent traits in females that reduce population productivity, as is the case with persistence traits in males.
DNA methylation changes in African American women with a history of preterm birth from the InterGEN study
Authors: Barcelona Veronica , Montalvo-Ortiz Janitza L. , Wright Michelle L. , Nagamatsu Sheila T. , Dreisbach Caitlin , Crusto Cindy A. , Sun Yan V. , Taylor Jacquelyn Y.
Published: September 2021

Background

Preterm birth (< 37 weeks’ gestation) is a common outcome of pregnancy that has been associated with increased risk of cardiovascular disease for women later in life. Little is known about the physiologic mechanisms underlying this risk. To date, no studies have evaluated if differences in DNA methylation (DNAm) among women who experience preterm birth are short-term or if they persist and are associated with subsequent cardiovascular sequelae or other health disorders. The purpose of this study was to examine long-term epigenetic effects of preterm birth in African American mothers (n = 182) from the InterGEN Study (2014–2019). In this study, we determine if differences in DNAm exist between women who reported a preterm birth in the last 3–5 years compared to those who had full-term births by using two different approaches: epigenome-wide association study (EWAS) and genome-wide co-methylation analyses.

Results

Though no significant CpG sites were identified using the EWAS approach, we did identify significant modules of co-methylation associated with preterm birth. Co-methylation analyses showed correlations with preterm birth in gene ontology and KEGG pathways. Functional annotation analysis revealed enrichment for pathways related to central nervous system and sensory perception. No association was observed between DNAm age and preterm birth, though larger samples are needed to confirm this further.

Conclusions

We identified differentially methylated gene networks associated with preterm birth in African American women 3–5 years after birth, including pathways related to neurogenesis and sensory processing. More research is needed to understand better these associations and replicate them in an independent cohort. Further study should be done in this area to elucidate mechanisms linking preterm birth and later epigenomic changes that may contribute to the development of health disorders and maternal mood and well-being.
C-terminal domain phosphatase-like 1 (CPL1) is involved in floral transition in Arabidopsis
Authors: Yuan Chen , Xu Jingya , Chen Qianqian , Liu Qinggang , Hu Yikai , Jin Yicheng , Qin Cheng
Published: September 2021

Background

RNA polymerase II plays critical roles in transcription in eukaryotic organisms. C-terminal Domain Phosphatase-like 1 (CPL1) regulates the phosphorylation state of the C-terminal domain of RNA polymerase II subunit B1, which is critical in determining RNA polymerase II activity. CPL1 plays an important role in miRNA biogenesis, plant growth and stress responses. Although cpl1 mutant showes delayed-flowering phenotype, the molecular mechanism behind CPL1’s role in floral transition is still unknown.

Results

To study the role of CPL1 during the floral transition, we first tested phenotypes of cpl1-3 mutant, which harbors a point-mutation. The cpl1-3 mutant contains a G-to-A transition in the second exon, which results in an amino acid substitution from Glu to Lys (E116K). Further analyses found that the mutated amino acid (Glu) was conserved in these species. As a result, we found that the cpl1-3 mutant experienced delayed flowering under both long- and short-day conditions, and CPL1 is involved in the vernalization pathway. Transcriptome analysis identified 109 genes differentially expressed in the cpl1 mutant, with 2 being involved in floral transition. Differential expression of the two flowering-related DEGs was further validated by qRT-PCR.

Conclusions

Flowering genetic pathways analysis coupled with transciptomic analysis provides potential genes related to floral transition in the cpl1-3 mutant, and a framework for future studies of the molecular mechanisms behind CPL1’s role in floral transition.
Predicting the 10-year risk of cardiovascular diseases and its relation to healthy diet indicator in Iranian military personnel
Authors: Parastouei Karim , Sepandi Mojtaba , Eskandari Eslam
Published: September 2021

Background

Epidemiological studies indicate increased prevalence of cardiovascular disease (CVD) among military personnel. Accordingly, identification of at-risk individuals and lifestyle modification such as improving diet quality can potentially inhibits the increasing trend of CVD mortality. The aim of this study was predicting the 10-year risk of CVD and its association with healthy diet indicator (HDI) among military personnel.

Methods

In this cross-sectional study, 400 male military personnel within the age range of 30–75 years were included. HDI score was calculated based on food frequency questionnaire, and the 10-year risk of CVD was evaluated using Framingham risk score (FRS). The FRS items include age, gender, total cholesterol, high density lipoprotein cholesterol (HDL-C), systolic blood pressure, status of diabetes and smoking. Partial correlation test was employed to investigate the relationship between Framingham risk score and HDI score.

Results

The mean age and body mass index (BMI) of participants were 38.67 ± 5.3 year and 25.28 ± 3.22 kg/m2, respectively. Prediction of FRS was as follows: 96.5% were low risk, 2% were moderate risk, and 1.5% were high risk. The mean HDI score of participants in this study was 5.98 ± 1.36. While HDI score did not show a significant correlation with FRS (r: − 0.009, p:0.860), increased dietary sodium intake had a significant positive correlation with FRS (r: 0.114, p:0.026).

Conclusion

The most of participants (96.5%) had in low risk of CVD development in the next 10 years. Meanwhile, the FRS showed no significant relationship with HDI score. Further researches are required to confirm the results of the present study.
Continuum of maternity care in Zambia: a national representative survey
Authors: Sserwanja Quraish , Musaba Milton W. , Mutisya Linet M. , Olal Emmanuel , Mukunya David
Published: September 2021

Background

Globally, over half of maternal deaths are related to pregnancy-related complications. Provision of a continuum of care during pregnancy, childbirth and the postnatal period results in reduced maternal and neonatal morbidity and mortality. Hence this study determined the prevalence of the continuum of care and its determinants among women in Zambia.

Methods

We used weighted data from the Zambian Demographic and Health Survey (ZDHS) of 2018 for 7325 women aged 15 to 49 years. Multistage stratified sampling was used to select study participants. Complete continuum of care was considered when a woman had; at least four antenatal care (ANC) contacts, utilized a health facility for childbirth and had at least one postnatal check-up within six weeks. We conducted multivariable logistic regression to explore continuum of care in Zambia. All our analyses were done using SPSS version 25.

Results

Of the 7,325 women, 38.0% (2787/7325) (95% confidence interval (CI): 36.9-39.1) had complete continuum of maternal healthcare. Women who had attained tertiary level of education (adjusted odds ratio (AOR): 1.93, 95% CI: 1.09-3.42) and whose partners had also attained tertiary level of education (AOR: 2.58, 95% CI: 1.54-4.32) were more likely to utilize the whole continuum of care compared to those who had no education. Women who initiated ANC after the first trimester (AOR: 0.46, 95% CI: 0.39-0.53) were less likely to utilize the whole continuum of care compared to those who initiated in the first semester. Women with exposure to radio (AOR: 1.58, 95% CI: 1.27-1.96) were more likely to utilize the whole continuum of care compared to those who were not exposed to radio. Women residing in the Western province were less likely to utilize the entire continuum of care compared to those in the other nine provinces.

Conclusion

Level of education of the women and of their partners, early timing of ANC initiation, residing in other provinces other than the Western province, and exposure to information through radio were positively associated with utilization of the entire continuum of care. Improving literacy levels and promoting maternity services through radio may improve the level of utilization of maternity services.
Contrast in utilization of maternal and child health services between Himalayan region and rest of India: Evidence from National Family Health Survey (2015–16)
Authors: Mustafa Akif , Shekhar Chander
Published: September 2021

Background

Maternal and child health services, like antenatal care, skilled birth attendance and postnatal care, are crucial to improve maternal and neonatal health outcomes. Numerous studies have been conducted on the distribution of utilization of maternal and child healthcare (MCH) services in India with respect to socioeconomic and demographic characteristics. But no study has analyzed the utilization of MCH services with a focus on the topography of a given region (hilly/plain). The present study analyzes the utilization of MCH services in the hilly-Himalayan region of India in comparison to the rest of the country.

Methods

Data from India’s National Family Health Survey-4 (2015–16), on 190,898 women, was utilized for analysis in the present study. The association between the utilization of MCH services and the topography of the region of residence (hilly/plain) was analyzed by calculating adjusted odds ratios (AOR) with 95% confidence interval (95%CI) and predicted probabilities using a two-level random intercept logistic regression model.

Results

It was found that the utilization of MCH services was significantly lower in the hilly regions compared to the plain regions. Women living in hilly areas (AOR: 0.42, 95%CI: 0.39–0.45) had 58% lower odds of receiving skilled birth attendance (SBA) than those living in plain areas. Similarly, the odds of receiving PNC, ANC, and full immunization were also lower in the hilly regions compared to the plain regions. The utilization of MCH services was alarmingly low in the rural-hilly regions. The odds of receiving two tetanus injections before birth were 71% lower for women in the rural-hilly areas (AOR: 0.39, 95% CI: 0.36–43) than those in the rural-plain areas. Predicted probabilities also showed that women in the hilly regions were less likely to receive MCH services compared to their counterparts in the plain regions.

Conclusion

Except for the consumption of Iron Folic Acid (IFA) and the utilization of AWC services/ICDS (Integrated Child and Development Services), all other MCH services were significantly underutilized in the hilly regions compared to the plain regions. This calls for the attention of and concentrated efforts by policy makers and stakeholders, with a special focus on the rural-hilly regions. We firmly believe that the results of the present study have important policy implications.
The association of antenatal D-dimer and fibrinogen with postpartum hemorrhage and intrauterine growth restriction in preeclampsia
Authors: Shao Hailing , Gao Shichu , Dai Dongru , Zhao Xiaomin , Hua Ying , Yu Huijun
Published: September 2021

Background

D-dimer and fibrinogen were verified to be altered in preeclampsia. This study was to evaluate the associations of D-dimer and fibrinogen plasma levels with postpartum hemorrhage or intrauterine growth restriction in preeclamptic women.

Methods

This was a retrospective study that recruited 278 preeclamptic women with singleton pregnancy from January 2016 to December 2019. Patients were allocated into five groups: mild preeclampsia (mPE) (n=68), mild preeclampsia with postpartum hemorrhage (mPE+PPH) (n=13), severe preeclampsia (sPE) (n=112), severe preeclampsia with postpartum hemorrhage (sPE+PPH) (n=17) and severe preeclampsia with intrauterine growth restriction (sPE+IUGR) (n=68). The antenatal D-dimer and fibrinogen plasma levels were analyzed among the groups. Logistic regression was used to determine the correlation between serum indexes and PPH or IUGR in preeclampsia.

Results

The antenatal D-dimer plasma levels were significantly higher in the sPE+PPH group than that in the sPE group (2.02 μg/ml versus 1.37 μg/ml, P = 0.001), but there was no difference in fibrinogen. Elevated D-dimer was associated with PPH among severe preeclamptic women (adjusted odds ratio (aOR) [95% CI]: 3.093 [1.527-6.264], P = 0.002). No differences in D-dimer and fibrinogen were found between the mPE and mPE+PPH groups or between the sPE and sPE+IUGR groups.

Conclusions

Elevated antenatal plasma D-dimer level may be associated with postpartum hemorrhage in severe preeclampsia, but not with intrauterine growth restriction. Future prospective clinical trials are needed to investigate the predictive value of D-dimer in postpartum hemorrhage in severe preeclampsia.
Clinical-radiological predictive model in differential diagnosis of small (≤ 20 mm) solitary pulmonary nodules
Authors: Zhao Hai-Cheng , Xu Qing-Song , Shi Yi-Bing , Ma Xi-Juan
Published: September 2021

Background

There is a lack of clinical-radiological predictive models for the small (≤ 20 mm) solitary pulmonary nodules (SPNs). We aim to establish a clinical-radiological predictive model for differentiating malignant and benign small SPNs.

Materials and methods

Between January 2013 and December 2018, a retrospective cohort of 250 patients with small SPNs was used to construct the predictive model. A second retrospective cohort of 101 patients treated between January 2019 and December 2020 was used to independently test the model. The model was also compared to two other models that had previously been identified.

Results

In the training group, 250 patients with small SPNs including 156 (62.4%) malignant SPNs and 94 (37.6%) benign SPNs patients were included. Multivariate logistic regression analysis indicated that older age, pleural retraction sign, CT bronchus sign, and higher CEA level were the risk factors of malignant small SPNs. The predictive model was established as: X = − 10.111 + [0.129 × age (y)] + [1.214 × pleural retraction sign (present = 1; no present = 0)] + [0.985 × CT bronchus sign (present = 1; no present = 0)] + [0.21 × CEA level (ug/L)]. Our model had a significantly higher region under the receiver operating characteristic (ROC) curve (0.870; 50% CI: 0.828–0.913) than the other two models.

Conclusions

We established and validated a predictive model for estimating the pre-test probability of malignant small SPNs, that can help physicians to choose and interpret the outcomes of subsequent diagnostic tests.
Roles of N-linked and O-linked glycosylation sites in the activity of equine chorionic gonadotropin in cells expressing rat luteinizing hormone/chorionic gonadotropin receptor and follicle-stimulating hormone receptor
Authors: Lee So-Yun , Byambaragchaa Munkhzaya , Choi Seung-Hee , Kang Han-Ju , Kang Myung-Hwa , Min Kwan-Sik
Published: September 2021

Background

Equine chorionic gonadotropin (eCG), which comprises highly glycosylated α-subunit and β-subunit, is a unique member of the glycoprotein hormone family as it elicits both follicle-stimulating hormone (FSH)-like and luteinizing hormone (LH)-like responses in non-equid species. To examine the biological function of glycosylated sites in eCG, the following glycosylation site mutants were constructed: eCGβ/αΔ56, substitution of Asn56 of α-subunit with Gln; eCGβ-D/α, deletion of the O-linked glycosylation site at the carboxyl-terminal peptide (CTP) region of the β-subunit; eCGβ-D/αΔ56, double mutant. The recombinant eCG (rec-eCG) mutants were expressed in Chinese hamster ovary suspension (CHO-S) cells. The FSH-like and LH-like activities of the mutants were examined using CHO-K1 cells expressing rat lutropin/CG receptor (rLH/CGR) and rat FSH receptor (rFSHR).

Results

Both rec-eCGβ/α and rec-eCGβ/αΔ56 were efficiently secreted into the CHO-S cell culture medium on day 1 post-transfection. However, the secretion of eCGβ-D/α and eCGβ-D/αΔ56, which lack approximately 12 O-linked glycosylation sites, was slightly delayed. The expression levels of all mutants were similar (200–250 mIU/mL) from days 3 to 7 post-transfection. The molecular weight of rec-eCGβ/α, rec-eCGβ/αΔ56 and rec-eCG β-D/α were in the ranges of 40–45, 37–42, and 34–36 kDa, respectively. Treatment with peptide-N-glycanase F markedly decreased the molecular weight to approximately 5–10 kDa. Rec-eCGβ/αΔ56 exhibited markedly downregulated LH-like activity. The signal transduction activity of both double mutants was completely impaired. This indicated that the glycosylation site at Asn56 of the α-subunit plays a pivotal role in the LH-like activity of eCG. Similarly, the FSH-like activity of the mutants was markedly downregulated. eCGβ-D/α exhibited markedly downregulated LH-like and FSH-like activities.

Conclusions

Rec-eCGβ/α exhibits potent biological activity in cells expressing rLH/CGR and rFSHR. The findings of this study suggest that the LH-like and FSH-like activities of eCG are regulated by the N-linked glycosylation site at Asn56 of the eCG α-subunit and/or by the O-linked glycosylation sites of the eCG β-subunit. These findings improved our understanding of the mechanisms underlying both LH-like and FSH-like activities of eCG.
Evaluating the presence of IAN injury in patients with juxta-apical radiolucency after third molar surgery: a retrospective cohort study
Authors: Hasani Mahvash , Razavi Nasim , Haghnegahdar Abdolaziz , Zarifi Motahhareh
Published: September 2021

Background

Juxta-apical radiolucency (JAR) has been presented as a radiographic sign, suggestive of the IAN injury through third molar surgery. This study aimed to evaluate the relation of JAR with IAN injury in cone-beam computed tomography (CBCT) images and to determine whether the presence of JAR is related to tooth angulation, proximity to the mandibular canal, position to the IAN, and thinning of the cortical plates.

Methods

Of an initial sample of 545 mandibular third molars, a total of 75 JAR+ and 75 JAR− teeth were evaluated by CBCT. We assessed the relationship between the presence of JAR in cone-beam computed tomography (CBCT) images and the presence of IAN injury after mandibular third molar surgeries. Moreover, we investigated whether the presence of IAN injury is related to tooth angulation, proximity to the mandibular canal, position to the IAN, and thinning of the cortical plates. Descriptive statistics, Chi-square test, and Fisher’s exact test were performed for statistical analysis.

Results

A significant relationship was found between JAR and temporary IAN injury (P = 0.036). However, there was no case of permanent IAN injury. IAN injury showed no significant relationship with the tooth angulation, position to IAN and proximity to the mandibular canal, lingual cortical plate thinning, sex, and age.

Conclusions

JAR is generally in contact with the mandibular canal, and some degree of cortical thinning can be found in most cases. In this study, JAR was significantly related to temporary IAN injury. JAR may increase the risk of nerve injury during the surgical removal of third molars.
A new comprehensive oral health literacy scale: development and psychometric evaluation
Authors: Sun Yue , Sun Jing , Zhao Yan , Cheng Aixiao , Zhou Junhong
Published: September 2021

Background

It has been widely accepted that oral health status is related to oral health literacy. The need to measure oral health literacy has led to the development of measurement instruments. This study aimed to develop a comprehensive instrument for adults and to examine its reliability and validity in China.

Methods

A three-step design process was used. First, a literature review and expert panel discussion were used to draw up a 37-item pool covering oral health knowledge, belief, practice, skill, and functional oral health literacy. The Delphi method was used to delete and modify questions in the item pool. The draft instrument was evaluated by nine experts and the consensus among them was calculated using the content validity index. The scale was then used to conduct a psychometric study among 370 participants from community health centers in Beijing. Construct validity, discriminant validity and concurrent validity were examined. The Cronbach’s alpha coefficient, and test–retest methods were used to assess reliability.

Results

The final scale included 30 items across four dimensions. The item–level content validity index was 0.90. Exploratory factor analysis extracted four fixed factors, and the result of the Kaiser–Meyer–Olkin and Bartlett’s tests was 0.752, with the model explaining 35.21% of the total variance. The four dimensions were associated with oral health knowledge, perceptions of oral health issues, oral health practice and skills, and functional oral health literacy. The mean score of the lowest 27% was significantly lower than the highest 27% (P < 0.01), suggesting adequate discriminant validity. The associations between comprehensive oral health literacy scores and educational level, income and self-reported literacy level were significant (P < 0.001), showing adequate overall concurrent validity. Internal consistency and test–retest reliability were acceptable, with a Cronbach’s alpha of 0.72 and a total test–retest reliability coefficient of 0.979.

Conclusions

Initial testing of the comprehensive oral health literacy instrument suggested that it is a valid and reliable instrument to evaluate individuals’ oral health literacy, with four dimensions for evaluating knowledge, belief, skills, and functional oral health literacy.
The prevalence of educational burnout, depression, anxiety, and stress among medical students of the Islamic Azad University in Tehran, Iran
Authors: Aghajani Liasi Ghazal , Mahdi Nejad Sanaz , Sami Nafiseh , Khakpour Shahrzad , Ghorbani Yekta Batool
Published: September 2021

Background

Psychological disorders have negative consequences on students’ learning and academic performance. In addition, academic burnout is one of the common challenges that affects students’ motivation and academic eagerness; however, the determinant is not clear. Medical students, meanwhile, demand special attention due to their professional responsibilities. In this regard, this study is conducted to investigate the academic burnout, rate of depression, anxiety and stress as well as related factors among undergraduate medical students at the Tehran Medical Sciences Islamic Azad University.

Methods

This cross-sectional and descriptive study was performed on medical students of Islamic Azad University of Tehran in 2017. In phase I, conducted on all stager students, Maslach Burnout questionnaire was used. In phase II, the DASS-42 questionnaire was provided for 123 students, 120 of whom met the inclusion criteria. In addition, another questionnaire including gender, age, lifestyle, marital and financial status, nutrition style, vitamin D deficiency, smoking, study hours per week, work efficiency and distance from the place of residence to the teaching hospital was used. Finally, the data extracted by SPSS version 23 was analyzed at the significance level of 0.05.

Results

In phase I of the study, 17 subjects showed academic burnout (16.3%). Out of all, 76.5% of students with academic burnout did not focus on the study and students’ academic burnout was associated with a decrease in their focus (P < 0.05). However, the relationship between academic burnout and other factors was not significant.

In phase II, the prevalence of depression, anxiety and stress was 37.5, 41.1 and 30.3%, respectively. The prevalence of severe and very severe degrees that required psychiatric follow-up were 10.5, 10.5 and 7% for depression, anxiety and stress, respectively. According to statistical analyzes, there is a significant direct relationship between anxiety and the distance from the place of residence to the teaching hospital (P = 0.040).

Conclusion

The present study estimated the prevalence of academic burnout to be between 9.2 and 23.4%, considering the 5% error in the calculation, and the level of anxiety was related to the distance from the place of residence to the hospital.
Pharmacy-based screening to detect persons at elevated risk of type 2 diabetes: a cost-utility analysis
Authors: Jalkanen Kari , Aarnio Emma , Lavikainen Piia , Lindström Jaana , Peltonen Markku , Laatikainen Tiina , Martikainen Janne
Published: September 2021

Background

Early identification of people at elevated risk of type 2 diabetes (T2D) is an important step in preventing or delaying its onset. Pharmacies can serve as a significant channel to reach these people. This study aimed to assess the potential health economic impact of screening and recruitment services in pharmacies in referring people to preventive interventions.

Methods

A decision analytic model was constructed to perform a cost-utility analysis of the expected national health economic consequences (in terms of costs and quality-adjusted life years, QALYs) of a hypothetical pharmacy-based service where people screened and recruited through pharmacies would participate in a digital lifestyle program. Cost-effectiveness was considered in terms of net monetary benefit (NMB). In addition, social return on investment (SROI) was calculated as the ratio of the intervention and recruitment costs and the net present value of expected savings. Payback time was the time taken to reach the break-even point in savings. In the base scenario, a 20-year time horizon was applied. Probabilistic and deterministic sensitivity analyses were applied to study robustness of the results.

Results

In the base scenario, the expected savings from the pharmacy-based screening and recruitment among the reached target cohort were 255.3 m€ (95% CI − 185.2 m€ to 717.2 m€) in pharmacy visiting population meaning 1412€ (95% CI − 1024€ to 3967€) expected savings per person. Additionally, 7032 QALYs (95% CI − 1344 to 16,143) were gained on the population level. The intervention had an NMB of 3358€ (95% CI − 1397€ to 8431€) using a cost-effectiveness threshold of 50,000 €/QALY. The initial costs were 122.2 m€ with an SROI of 2.09€ (95% CI − 1.52€ to 5.88€). The expected payback time was 10 and 8 years for women and men, respectively. Results were most sensitive for changes in effectiveness of the intervention and selected discount rate.

Conclusions

T2D screening and recruitment to prevention programs conducted via pharmacies was a dominant option providing both cost savings and QALY gains. The highest savings can be potentially reached by targeting recruitment at men at elevated risk of T2D.
The association between first-time accreditation and the delivery of recommended care: a before and after study in the Faroe Islands
Authors: Bergholt Maria Daniella , Falstie-Jensen Anne Mette , Hibbert Peter , Eysturoy Barbara Joensen , Guttesen Gunnvá , Róin Tóra , Valentin Jan Brink , Braithwaite Jeffrey , von Plessen Christian , Johnsen Søren Paaske
Published: September 2021

Background

Significant resources are spent on hospital accreditation worldwide. However, documentation of the effects of accreditation on processes, quality of care and outcomes in healthcare remain scarce. This study aimed to examine changes in the delivery of patient care in accordance with clinical guidelines (recommended care) after first-time accreditation in a care setting not previously exposed to systematic quality improvement initiatives.

Methods

We conducted a before and after study based on medical record reviews in connection with introducing first-time accreditation. We included patients with stroke/transient ischemic attack, bleeding gastric ulcer, diabetes, chronic obstructive pulmonary disease (COPD), childbirth, heart failure and hip fracture treated at public, non-psychiatric Faroese hospitals during 2012–2013 (before accreditation) or 2017–2018 (after accreditation). The intervention was the implementation of a modified second version of The Danish Healthcare Quality Program (DDKM) from 2014 to 2016 including an on-site accreditation survey in the Faroese hospitals. Recommended care was assessed using 63 disease specific patient level process performance measures in seven clinical conditions. We calculated the fulfillment and changes in the opportunity-based composite score and the all-or-none score.

Results

We included 867 patient pathways (536 before and 331 after). After accreditation, the total opportunity-based composite score was marginally higher though the change did not reach statistical significance (adjusted percentage point difference (%): 4.4%; 95% CI: − 0.7 to 9.6). At disease level, patients with stroke/transient ischemic attack, bleeding gastric ulcer, COPD and childbirth received a higher proportion of recommended care after accreditation. No difference was found for heart failure and diabetes. Hip fracture received less recommended care after accreditation. The total all-or-none score, which is the probability of a patient receiving all recommended care, was significantly higher after accreditation (adjusted relative risk (RR): 2.32; 95% CI: 2.03 to 2.67). The improvement was particularly strong for patients with COPD (RR: 16.22; 95% CI: 14.54 to 18.10).

Conclusion

Hospitals were in general more likely to provide recommended care after first-time accreditation.
Case report: hepatitis in a child infected with SARS-CoV-2 presenting toll-like receptor 7 Gln11Leu single nucleotide polymorphism
Authors: Pessoa Natália Lima , Bentes Aline Almeida , de Carvalho Andrea Lucchesi , de Souza Silva Thaís Bárbara , Alves Pedro Augusto , de Sousa Reis Erik Vinicius , Rodrigues Tayse Andrade , Kroon Erna Geessien , Campos Marco Antônio
Published: September 2021

Background

Covid-19 has the respiratory tract as the main target of infection, and patients present mainly dyspnea, pneumonia, dry cough, and fever. Nevertheless, organs outside the respiratory tract had been reported in recent studies, including the gastrointestinal tract and liver. The host innate immune system recognizes pathogen-associated molecular patterns (PAMPs) through their pattern recognition receptor (PRRs). Toll-like receptor 7 (TLR-7) is a pattern recognition receptor recognizing ssRNA (SARS-CoV-2 is an ssRNA). Polymorphisms are characterized by two or more alternative forms of a distinct phenotype in the same population. Polymorphisms in tlrs genes can negatively influence the immune response to infectious diseases. There are several references in the literature to non-synonymous single nucleotide (rs) polymorphisms related to several genes. Some of them are important for the innate immunity, as rs 179008 (tlr-7), rs3775291 (tlr3), rs8177374 (tir domain-containing adaptor protein, tirap), rs1024611 (monocyte chemoattractant protein-1, mcp-1) and rs61942233 (2′-5′-oligoadenylate synthase-3, oas-3).

Case presentation

We identified a 5-year-old-male child with gastrointestinal symptoms and fever presenting acholic stool and jaundice, who was positive for SARS-CoV-2 IgM, IgA, and IgG and presenting the Gln11Leu rs 179008 in tlr-7. The child presented high levels of aspartate aminotransferase, alanine aminotransferase, bilirubin, C-reactive protein, D-dimer, gamma-glutamyl transferase, alkaline phosphatase, and was negative for serological tests for hepatitis A, B, C, E, HIV 1 and 2, herpes virus, cytomegalovirus, Epstein–Barr virus, and negative for RTqPCR for Influenza A and B, RSV and SARS-CoV-2. We also investigated other SNPs in the tlr-3 (rs3775291), tirap (rs8177374), mcp-1 (rs1024611), and oas-3 (rs61942233) genes, and no mutation was detected. After an interview with the child's caregivers, any possible accidental ingestion of drugs or hepatotoxic substances was ruled out.

Conclusion

To our knowledge, this is the first report of a SARS-CoV-2 caused hepatitis in a male child that has the tlr-7 Gln11Leu rs 179008, which could impair an efficient initial immune response. The knowledge of the patient's immune deficiency could improve the treatment to correct this deficiency with specific medications.
Quality of life and treatment-related burden during ocular proton therapy: a prospective trial of 131 patients with uveal melanoma
Authors: Gollrad Johannes , Rabsahl Christopher , Riechardt Aline-Isabel , Heufelder Jens , Stroux Andrea , Goerling Ute , Joussen Antonia , Budach Volker , Boehmer Dirk
Published: September 2021

Background

Proton beam therapy is a well-established treatment option for patients with uveal melanoma (UM). The treatment procedure, in general, includes placing radiopaque clips to ensure exact eye-positioning during radiotherapy, followed by the delivery of proton irradiation.

The short-term burden associated with proton therapy in patients with UM has rarely been addressed. In this prospective study, we investigated the physiological and psychological aspects of proton therapy that might affect the well-being of patients during the different stages of treatment.

Methods

During the treatment procedure, we conducted longitudinal assessments of the Quality of life (QOL), organ-specific symptoms, and psychological aspects in patients with UM with three questionnaires (EORTC QLQ-C30, EORTC QLQ-OPT30, and GAD-7). Patients completed questionnaires before clip surgery (T0), before proton therapy (T1), after completing treatment (T2), and three months after treatment completion (T3). We also collected data on tumor characteristics and socio-demographics to identify potential risk factors associated with high treatment burdens.

Results

We prospectively included 131 consecutive patients. Questionnaire data showed a significant, temporary decline in global QOL and an increase in eye-related symptoms, as a result of the clip surgery (T0–T1). After treatment completion (T2), global QOL improved gradually, and none of the eye-related symptoms significantly deteriorated over the course of proton therapy. The global QOL returned to baseline levels three months after treatment (T3). We identified baseline anxiety as an independent risk factor for experiencing an acute treatment-related burden. Furthermore, we found interactions between GAD7 and patient sex showing that anxiety had a more pronounced effect on QOL outcome in female patients.

Conclusion

The short-term treatment-related burden of ocular proton therapy appeared to be largely associated with the preceding clip surgery, rather than the irradiation procedure. We found that anxiety was strongly associated with experiencing QOL issues during the treatment procedure. Our findings could contribute to the development of future strategies for improving the treatment process and psycho-oncologic patient care.
Anthropometric measurements of non-arthritic knees in an Egyptian population: an MRI-based study
Authors: Abdelnasser Mohammad Kamal , Khalifa Ahmed A. , Bassem Micheal , Abdelhameed Mohammed Anter , Adam Mahmoud Faisal , Bakr Hatem M. , Khalifa Yaser E.
Published: September 2021

Background

Knee anthropometric characteristics were evaluated for different ethnicities; however, data from North African populations are deficient. The primary aim was to investigate the Egyptian knees’ anthropometric characteristics as a representative of North African populations. Secondary aims are as follows: (1) to study the anthropometric gender difference, (2) to compare results with other ethnic groups, and (3) to study the mismatch in comparison to geometric characteristics of modern TKA implant designs.

Methods

Two hundred normal knee MRI scans (100 females and 100 males, aging from 18 to 60) were obtained for analysis. Linear measurements (anteroposterior (AP), mediolateral (ML), and aspect ratio (AR)) of the planned cut surface of the distal femur (f) and the proximal tibia (t) were evaluated.

Results

A significant difference between both sexes was found, males had larger measurements in anteroposterior [fAP: 60.97 ± 3.1 vs 54.78 ± 3.3 (P < 0.001), tAP: 46.89 ± 3.0 vs 41.35 ± 2.9 (P < 0.001)] and mediolateral [fML: 74.89 ± 3.2 vs 67.29 ± 3.7 (P < 0.001), tML: 76.01 ± 3.0 vs 67.26 ± 3.2 (P < 0.001)], the mean femoral and tibial AP and ML measurements were different from other ethnic groups. None of the seven studied TKA systems matched the largest ML or the smallest AP dimensions of the distal femur in the current study population.

Conclusion

A significant difference was found between males’ and females’ knee anthropometric characteristics. Some of the commonly used TKA implants in our area could not provide a perfect fit and coverage.

Trial registration

ClinicalTrials.gov identifier: NCT03622034, registered on July 28, 2018.
Histological regional analysis of the aortic root and thoracic ascending aorta: a complete analysis of aneurysms from root to arch
Authors: Surman Timothy Luke , Abrahams John Matthew , Manavis Jim , Finnie John , O’Rourke Dermot , Reynolds Karen Jane , Edwards James , Worthington Michael George , Beltrame John
Published: September 2021

Background

Although aortic root and ascending aortic aneurysms are treated the same, they differ in embryological development and pathological processes. This study examines the microscopic structural differences between aortic root and ascending aortic aneurysms, correlating these features to the macroscopic pathophysiological processes.

Methods

We obtained surgical samples from ascending aortic aneurysms (n = 11), aortic root aneurysms (n = 3), and non-aneurysmal patients (n = 7), Aortic collagen and elastin content were examined via histological analysis, and immunohistochemistry techniques used to determine collagen I, III, and IV subtypes. Analysis was via observational features, and colour deconvolution quantification techniques.

Results

Elastin fiber disruption and fragmentation was the most extensive in the proximal aneurysmal regions. Medial fibrosis and collagen density increased in proximal aneurysmal regions and aortic root aneurysms (p < 0.005). Collagen I was seen in highest quantity in aortic root aneurysms. Collagen I content was greatest in the sinus tissue regions compared to the valvular and ostial regions (p < 0.005) Collagen III and IV quantification did not vary greatly. The most susceptible regions to ultrastructural changes in disease are the proximal ascending aorta and aortic root.

Conclusions

The aortic root differs histologically from the ascending aorta confirming its unique composition in aneurysm pathology. These findings should prompt further evaluation on the influence of this altered structure on function which could potentially guide clinical management.
Methylphenidate for attention-deficit/hyperactivity disorder in patients with Smith–Magenis syndrome: protocol for a series of N-of-1 trials
Authors: Müller A. R. , Zinkstok J. R. , Rommelse N. N. J. , van de Ven P. M. , Roes K. C. B. , Wijburg F. A. , de Rooij-Askes E. , Linders C. , Boot E. , van Eeghen A. M.
Published: September 2021

Background

Smith–Magenis syndrome (SMS) is a rare genetic neurodevelopmental disorder characterized by intellectual disability and severe behavioural and sleep disturbances. Often, patients with SMS are diagnosed with attention-deficit/hyperactivity disorder (ADHD). However, the effectiveness of methylphenidate (MPH), the first-line pharmacological treatment for ADHD, in patients with SMS is unclear. Our objective is to examine the effectiveness of MPH for ADHD symptoms in individuals with SMS, proposing an alternative trial design as traditional randomized controlled trials are complex in these rare and heterogeneous patient populations.

Methods and analysis

We will initiate an N-of-1 series of double-blind randomized and placebo-controlled multiple crossover trials in six patients aged ≥ 6 years with a genetically confirmed SMS diagnosis and a multidisciplinary established ADHD diagnosis, according to a power analysis based on a summary measures analysis of the treatment effect. Each N-of-1 trial consists of a baseline period, dose titration phase, three cycles each including randomized intervention, placebo and washout periods, and follow-up. The intervention includes twice daily MPH (doses based on age and body weight). The primary outcome measure will be the subscale hyperactivity/inattention of the Strengths and Difficulties Questionnaire (SDQ), rated daily. Secondary outcome measures are the shortened version of the Emotion Dysregulation Inventory (EDI) reactivity index, Goal Attainment Scaling (GAS), and the personal questionnaire (PQ). Statistical analysis will include a mixed model analysis. All subjects will receive an assessment of their individual treatment effect and data will be aggregated to investigate the effectiveness of MPH for ADHD in SMS at a population level.

Conclusions

This study will provide information on the effectiveness of MPH for ADHD in SMS, incorporating personalized outcome measures. This protocol presents the first properly powered N-of-1 study in a rare genetic neurodevelopmental disorder, providing a much-needed bridge between science and practice to optimize evidence-based and personalized care.

Trial registration

This study is registered in the Netherlands Trial Register (NTR9125).
Minhee Analysis Package: an integrated software package for detection and management of spontaneous synaptic events
Authors: Kim Yong Gyu , Shin Jae Jin , Kim Sang Jeong
Published: September 2021

To understand the information encoded in a connection between the neurons, postsynaptic current (PSC) has been widely measured as a primary index of synaptic strength in the field of neurophysiology. Although several automatic detection methods for PSCs have been proposed to simplify a workflow in the analysis, repetitive steps such as quantification and management of PSC data should be still performed with much effort. Here, we present Minhee Analysis Package, an integrated standalone software package that is capable of detecting, sorting, and quantifying PSC data. First, we developed a stepwise exploratory algorithm to detect PSC and validated our detection algorithm using the simulated and experimental data. We also described all the features and examples of the package so that users can use and follow them properly. In conclusion, our software package is expected to improve the convenience and efficiency of neurophysiologists to analyze PSC data by simplifying the workflow from detection to quantification. Minhee Analysis Package is freely available to download from http://www.github.com/parkgilbong/Minhee_Analysis_Pack.
Matching-adjusted indirect treatment comparison of liso-cel versus axi-cel in relapsed or refractory large B cell lymphoma
Authors: Maloney David G. , Kuruvilla John , Liu Fei Fei , Kostic Ana , Kim Yeonhee , Bonner Ashley , Zhang Yixie , Fox Christopher P. , Cartron Guillaume
Published: September 2021

Background

In the absence of randomized studies directly comparing chimeric antigen receptor T cell therapies, this study used matching-adjusted indirect comparisons (MAIC) to evaluate the comparative efficacy and safety of lisocabtagene maraleucel (liso-cel) versus axicabtagene ciloleucel (axi-cel) in patients with relapsed or refractory large B cell lymphoma (LBCL).

Methods

Primary data sources included individual patient data from the TRANSCEND NHL 001 study (TRANSCEND [NCT02631044]; N = 256 for efficacy set, N = 269 for safety set) for liso-cel and summary-level data from the ZUMA-1 study (NCT02348216; N = 101 for efficacy set, N = 108 for safety set) for axi-cel. Inter-study differences in design, eligibility criteria, baseline characteristics, and outcomes were assessed and aligned to the extent feasible. Clinically relevant prognostic factors were adjusted in a stepwise fashion by ranked order. Since bridging therapy was allowed in TRANSCEND but not ZUMA-1, the initial efficacy and safety analyses included bridging therapy use as a matching factor (TRANSCEND patients who received bridging therapy were removed). Subsequent sensitivity analyses excluded this matching factor.

Results

The initial analysis showed similar MAIC-weighted efficacy outcomes between TRANSCEND and ZUMA-1 for overall and complete response rates (odds ratio [95% confidence interval (CI)], 1.40 [0.56–3.49] and 1.21 [0.56–2.64], respectively) and for overall survival and progression-free survival (hazard ratio [95% CI], 0.81 [0.44–1.49] and 0.95 [0.58–1.57], respectively). MAIC-weighted safety outcomes favored liso-cel, with significantly lower odds of all-grade and grade ≥ 3 cytokine release syndrome (odds ratio [95% CI], 0.03 [0.01–0.07] and 0.08 [0.01–0.67], respectively) and study-specific neurological events (0.16 [0.08–0.33] and 0.05 [0.02–0.15], respectively). Efficacy and safety outcomes remained similar in sensitivity analyses, which did not include use of bridging therapy as a matching factor.

Conclusions

After matching and adjusting for clinically relevant prognostic factors, liso-cel demonstrated comparable efficacy and a more favorable safety profile compared with axi-cel in patients with third- or later-line relapsed or refractory LBCL.

Trial registration: NCT02631044 and NCT02348216