bluuebunny/crossref_metadata_2025 huggingface dataset:
Cost-effectiveness analysis of surgical proximal femur fracture prevention in elderly: a Markov cohort simulation model
Authors: Alnemer Momin S. , Kotliar Konstantin E. , Neuhaus Valentin , Pape Hans-Christoph , Ciritsis Bernhard D.
Published: October 2023

Background

Hip fractures are a common and costly health problem, resulting in significant morbidity and mortality, as well as high costs for healthcare systems, especially for the elderly. Implementing surgical preventive strategies has the potential to improve the quality of life and reduce the burden on healthcare resources, particularly in the long term. However, there are currently limited guidelines for standardizing hip fracture prophylaxis practices.

Methods

This study used a cost-effectiveness analysis with a finite-state Markov model and cohort simulation to evaluate the primary and secondary surgical prevention of hip fractures in the elderly. Patients aged 60 to 90 years were simulated in two different models (A and B) to assess prevention at different levels. Model A assumed prophylaxis was performed during the fracture operation on the contralateral side, while Model B included individuals with high fracture risk factors. Costs were obtained from the Centers for Medicare & Medicaid Services, and transition probabilities and health state utilities were derived from available literature. The baseline assumption was a 10% reduction in fracture risk after prophylaxis. A sensitivity analysis was also conducted to assess the reliability and variability of the results.

Results

With a 10% fracture risk reduction, model A costs between $8,850 and $46,940 per quality-adjusted life-year ($/QALY). Additionally, it proved most cost-effective in the age range between 61 and 81 years. The sensitivity analysis established that a reduction of ≥ 2.8% is needed for prophylaxis to be definitely cost-effective. The cost-effectiveness at the secondary prevention level was most sensitive to the cost of the contralateral side’s prophylaxis, the patient’s age, and fracture treatment cost. For high-risk patients with no fracture history, the cost-effectiveness of a preventive strategy depends on their risk profile. In the baseline analysis, the incremental cost-effectiveness ratio at the primary prevention level varied between $11,000/QALY and $74,000/QALY, which is below the defined willingness to pay threshold.

Conclusion

Due to the high cost of hip fracture treatment and its increased morbidity, surgical prophylaxis strategies have demonstrated that they can significantly relieve the healthcare system. Various key assumptions facilitated the modeling, allowing for adequate room for uncertainty. Further research is needed to evaluate health-state-associated risks.
Potential determinants of antibody responses after vaccination against SARS-CoV-2 in older persons: the Doetinchem Cohort Study
Authors: Kuijpers Yunus , Picavet H. Susan J. , de Rond Lia , de Zeeuw-Brouwer Mary-lène , Rutkens Ryanne , Gijsbers Esther , Slits Irene , Engelfriet Peter , Buisman Anne-Marie , Verschuren W. M. Monique
Published: October 2023

Background

Immune responses to vaccination vary widely between individuals. The aim of this study was to identify health-related variables potentially underlying the antibody responses to SARS-CoV-2 vaccination in older persons. We recruited participants in the long-running Doetinchem Cohort Study (DCS) who underwent vaccination as part of the national COVID-19 program, and measured antibody concentrations to SARS-CoV-2 Spike protein (S1) and Nucleoprotein (N) at baseline (T0), and a month after both the first vaccination (T1), and the second vaccination (T2). Associations between the antibody concentrations and demographic variables, including age, sex, socio-economic status (SES), comorbidities (cardiovascular diseases and immune mediated diseases), various health parameters (cardiometabolic markers, inflammation markers, kidney- and lung function) and a composite measure of frailty (‘frailty index’, ranging from 0 to 1) were tested using multivariate models.

Results

We included 1457 persons aged 50 to 92 years old. Of these persons 1257 were infection naïve after their primary vaccination series. The majority (N = 954) of these individuals were vaccinated with two doses of BNT162b2 (Pfizer) and their data were used for further analysis. A higher frailty index was associated with lower anti-S1 antibody responses at T1 and T2 for both men (RT1 = -0.095, PT1 = 0.05; RT2 = -0.11, PT2 = 0.02) and women (RT1 = -0.24, PT1 < 0.01; RT2 = -0.15, PT2 < 0.01). After correcting for age and sex the frailty index was also associated with the relative increase in anti-S1 IgG concentrations between the two vaccinations (β = 1.6, P < 0.01). Within the construct of frailty, history of a cardiac catheterization, diabetes, gastrointestinal disease, a cognitive speed in the lowest decile of the population distribution, and impaired lung function were associated with lower antibody responses after both vaccinations.

Conclusions

Components of frailty play a key role in the primary vaccination response to the BNT162b2 vaccine within an ageing population. Older persons with various comorbidities have a lowered immune response after their first vaccination, and while frail and sick older persons see a stronger increase after their second vaccination compared to healthy people, they still have a lower antibody response after their second vaccination.
Dehydroepiandrosterone-induced polycystic ovary syndrome mouse model requires continous treatments to maintain reproductive phenotypes
Authors: Wu Haowen , Zhao Bining , Yao Qiyang , Kang Jihong
Published: October 2023

Background

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy associated with infertility and metabolic disorder in women of reproductive age. Animal models have been developed and used as tools to unravel the pathogenesis of PCOS, among which most postnatal models employ continuing experimental manipulations. However, the persistence and stability of these animals after modeling is unknown. Dehydroepiandrosterone (DHEA)-induced PCOS mouse model is commonly used in PCOS studies. Thus the aim of the present study was to investigate the reproductive features of DHEA-induced PCOS mice fed a normal chow or an high-fat diet (HFD) with treatment withdrawal or consecutive treatments after PCOS mouse models were established.

Methods

Prepubertal C57BL/6 J mice (age 25 days) were injected (s.c.) daily with DHEA on a normal chow or a 60% HFD for 20 consecutive days to induce PCOS mouse models. Mice injected with the vehicle sesame oil were used as controls. After 20 days, mice were divided into 2 groups, namely “Continue dosing group” and “Stop dosing group”. The animals were consecutively treated with DHEA or DHEA + HFD, or housed without any treatment for 2 or 4 weeks. Estrous cycles were evaluated during this period. At the end of the experiment, serum testosterone (T) levels were measured and the morphology of ovaries was evaluated.

Results

The mice in Continue dosing groups maintained reproductive phenotypes of PCOS mouse models. In contrast, 2 or 4 weeks after PCOS models were established, the mice with treatment withdrawal in Stop dosing groups exhibited normal serum testosterone levels, regular estrous cycle, and relatively normal ovarian morphology. In addition, even with consecutive treatments, there was no marked difference in body weight between DHEA mice on the normal chow or an HFD in Continue dosing groups and the control animals 3 weeks after modeling.

Conclusions

After PCOS mice were induced with DHEA or DHEA + HFD, the mice still need consecutive treatments to maintain reproductive phenotypes to be regarded as PCOS mice that meet the diagnostic criteria of PCOS defined by the 2003 Rotterdam criteria.
Outcome of severely injured patients in a unique trauma system with 24/7 double trauma surgeon on-call service
Authors: van Wessem Karlijn J. P. , Leenen Luke P. H. , Houwert R. Marijn , Benders Kim E. M. , Simmermacher Roger K. J. , van Baal Mark C. P. M. , de Bruin Ivar G. J. M. , de Jong Mirjam B. , Nijs Stefaan J. B. , Hietbrink Falco
Published: October 2023

Background

The presence of in-house attending trauma surgeons has improved efficiency of processes in the treatment of polytrauma patients. However, literature remains equivocal regarding the influence of the presence of in-house attendings on mortality. In our hospital there is a double trauma surgeon on-call system. In this system an in-house trauma surgeon is 24/7 backed up by a second trauma surgeon to assist with urgent surgery or multiple casualties. The aim of this study was to evaluate outcome in severely injured patients in this unique trauma system.

Methods

From 2014 to 2021, a prospective population-based cohort consisting of consecutive polytrauma patients aged ≥ 15 years requiring both urgent surgery (≤ 24h) and admission to Intensive Care Unit (ICU) was investigated. Demographics, treatment, outcome parameters and pre- and in-hospital transfer times were analyzed.

Results

Three hundred thirteen patients with a median age of 44 years (71% male), and median Injury Severity Score (ISS) of 33 were included. Mortality rate was 19% (68% due to traumatic brain injury). All patients stayed ≤ 32 min in ED before transport to either CT or OR. Fifty-one percent of patients who needed damage control surgery (DCS) had a more deranged physiology, needed more blood products, were more quickly in OR with shorter time in OR, than patients with early definitive care (EDC). There was no difference in mortality rate between DCS and EDC patients. Fifty-six percent of patients had surgery during off-hours. There was no difference in outcome between patients who had surgery during daytime and during off-hours. Death could possibly have been prevented in 1 exsanguinating patient (1.7%).

Conclusion

In this cohort of severely injured patients in need of urgent surgery and ICU support it was demonstrated that surgical decision making was swift and accurate with low preventable death rates. 24/7 Physical presence of a dedicated trauma team has likely contributed to these good outcomes.
Causal relationships between breast cancer risk factors based on mammographic features
Authors: Ye Zhoufeng , Nguyen Tuong L. , Dite Gillian S. , MacInnis Robert J. , Schmidt Daniel F. , Makalic Enes , Al-Qershi Osamah M. , Bui Minh , Esser Vivienne F. C. , Dowty James G. , Trinh Ho N. , Evans Christopher F. , Tan Maxine , Sung Joohon , Jenkins Mark A. , Giles Graham G. , Southey Melissa C. , Hopper John L. , Li Shuai
Published: October 2023

Background

Mammogram risk scores based on texture and density defined by different brightness thresholds are associated with breast cancer risk differently and could reveal distinct information about breast cancer risk. We aimed to investigate causal relationships between these intercorrelated mammogram risk scores to determine their relevance to breast cancer aetiology.

Methods

We used digitised mammograms for 371 monozygotic twin pairs, aged 40–70 years without a prior diagnosis of breast cancer at the time of mammography, from the Australian Mammographic Density Twins and Sisters Study. We generated normalised, age-adjusted, and standardised risk scores based on textures using the Cirrus algorithm and on three spatially independent dense areas defined by increasing brightness threshold: light areas, bright areas, and brightest areas. Causal inference was made using the Inference about Causation from Examination of FAmilial CONfounding (ICE FALCON) method.

Results

The mammogram risk scores were correlated within twin pairs and with each other (r = 0.22–0.81; allP < 0.005). We estimated that 28–92% of the associations between the risk scores could be attributed to causal relationships between the scores, with the rest attributed to familial confounders shared by the scores. There was consistent evidence for positive causal effects: of Cirrus, light areas, and bright areas on the brightest areas (accounting for 34%, 55%, and 85% of the associations, respectively); and of light areas and bright areas on Cirrus (accounting for 37% and 28%, respectively).

Conclusions

In a mammogram, the lighter (less dense) areas have a causal effect on the brightest (highly dense) areas, including through a causal pathway via textural features. These causal relationships help us gain insight into the relative aetiological importance of different mammographic features in breast cancer. For example our findings are consistent with the brightest areas being more aetiologically important than lighter areas for screen-detected breast cancer; conversely, light areas being more aetiologically important for interval breast cancer. Additionally, specific textural features capture aetiologically independent breast cancer risk information from dense areas. These findings highlight the utility of ICE FALCON and family data in decomposing the associations between intercorrelated disease biomarkers into distinct biological pathways.
[1, 8]-Naphthyridine derivatives as dual inhibitor of alkaline phosphatase and carbonic anhydrase
Authors: Alrokayan Salman , Hussain Tajamul , Alamery Salman , Mohammed Arif Ahmed , Mahmood Abid , Ejaz Syeda Abida , Langer Peter , Iqbal Jamshed
Published: October 2023

[1,8]-Naphthyridine derivatives have been reported to possess important biological activities and may serve as attractive pharmacophores in the drug discovery process. [1,8]-Naphthyridine derivatives (1a-1l) were evaluated for inhibitory potential for isozymes of carbonic anhydrase (CA) and alkaline phosphatase (ALP). CAs have been reported to carry out reversible hydration of CO2 into HCO3−, secretion of electrolytes, acid–base regulation, bone resorption, calcification, and biosynthetic reactions. Whereas ALPs hydrolyze monophosphate esters with the release of inorganic phosphate and play an important role in bone mineralization. Both enzymes have been found to be over-expressed and raised functional activities in patients suffering from rheumatoid arthritis. The discovery of dual inhibitors of these enzymes may provide a synergistic effect to cure bone disorders such as rheumatoid arthritis and ankylosing spondylitis. Among the test compounds, the most potent inhibitors for CA-II, CA-IX, and CA-XII were 1e, 1g, and 1a with IC50 values of 0.44 ± 0.19, 0.11 ± 0.03 and 0.32 ± 0.07 µM, respectively. [1,8]-Naphthyridine derivatives (1a–1l) were approximately 4 folds more potent than standard CA inhibitor acetazolamide. While in the case of ALPs, the most potent compounds for b-TNAP and c-IAP were 1b and 1e with IC50 values of 0.122 ± 0.06 and 0.107 ± 0.02 µM, respectively. Thus, synthesized derivatives proved to be 100 to 800 times more potent as compared to standard inhibitors of b-TNAP and c-IAP (Levamisole and L-phenyl alanine, respectively). In addition, selectivity and dual inhibition of [1,8]-Naphthyridine derivatives confer precedence over known inhibitors. Molecular docking and molecular simulation studies were also conducted in the present studies to define the type of interactions between potential inhibitors and enzyme active sites.
Maternal pre-pregnancy obesity modifies the association between first-trimester thyroid hormone sensitivity and gestational Diabetes Mellitus: a retrospective study from Northern China
Authors: Sun Honglin , Zhou Yibo , Liu Jia , Wang Ying , Wang Guang
Published: October 2023

Background

Contradictory relationships have been observed between thyroid function and gestational diabetes mellitus (GDM). Previous studies have indicated that pre-pregnancy BMI (pBMI) could modify their relationships. Few studies have illustrated the role of thyroid hormone sensitivity on GDM. We aimed to explore the effect of pre-pregnancy obesity on the association between early pregnancy thyroid hormone sensitivity and GDM in euthyroid pregnant women.

Methods

This study included 1310 women with singleton gestation. Subjects were classified into pre-pregnancy obese and non-obese subgroups by pBMI levels with a cutoff of 25 kg/m2. Sensitivity to thyroid hormone was evaluated by Thyroid Feedback Quartile-Based Index (TFQI), Chinese-referenced parametric TFQI (PTFQI), TSH Index (TSHI) and Thyrotrophic T4 Resistance Index (TT4RI). The associations between these composite indices and GDM were analyzed using multivariate regression models in the two subgroups, respectively.

Results

In pre-pregnancy non-obese group, early pregnancy TFQI, PTFQI, TSHI and TT4RI levels were higher in subjects with incident GDM compared to those without GDM (all P < 0.05). By contrast, obese women with GDM exhibited lower levels of those indices (all P < 0.05). The occurrence of GDM were increased with rising TFQI, PTFQI, TSHI and TT4RI quartiles in non-obese women ( all P for trend < 0.05), while exhibited decreased trend across quartiles of those indices in obese women (all P for trend < 0.05). Further logistic analysis indicated contrary relationships between thyroid hormone sensitivity and the occurrence of GDM in the two groups, respectively. The OR of the fourth versus the first quartile of TFQI for GDM was 1.981 (95% CI 1.224, 3.207) in pre-pregnancy non-obese group, while was 0.131 (95% CI 0.036, 0.472) in pre-pregnancy obese group. PTFQI and TSHI yielded similar results.

Conclusions

The association between maternal sensitivity to thyroid hormones during early gestation and the occurrence of GDM was modified by pre-pregnancy obesity.
Regulatory mechanism of LncRNAs in gonadal differentiation of hermaphroditic fish, Monopterus albus
Authors: Hu Qiaomu , Xia Xueping , Lian Zitong , Tian Haifeng , Li Zhong
Published: October 2023

Background

Monopterusalbus is a hermaphroditic fish with sex reversal from ovaries to testes via the ovotestes in the process of gonadal development, but the molecular mechanism of the sex reversal was unknown.

Methods

We produced transcriptomes containing mRNAs and lncRNAs in the crucial stages of the gonad, including the ovary, ovotestis and testis. The expression of the crucial lncRNAs and their target genes was detected using qRT‒PCR and in situ hybridization. The methylation level and activity of the lncRNA promoter were analysed by applying bisulfite sequencing PCR and dual-luciferase reporter assays, respectively.

Results

This effort revealed that gonadal development was a dynamic expression change. Regulatory networks of lncRNAs and their target genes were constructed through integrated analysis of lncRNA and mRNA data. The expression and DNA methylation of the lncRNAs MSTRG.38036 and MSTRG.12998 and their target genes Psmβ8 and Ptk2β were detected in developing gonads and sex reversal gonads. The results showed that lncRNAs and their target genes exhibited consistent expression profiles and that the DNA methylation levels were negatively regulated lncRNA expression. Furthermore, we found that Ptk2β probably regulates cyp19a1 expression via the Ptk2β/EGFR/STAT3 pathway to reprogram sex differentiation.

Conclusions

This study provides novel insight from lncRNA to explore the potential molecular mechanism by which DNA methylation regulates lncRNA expression to facilitate target gene transcription to reprogram sex differentiation in M.albus, which will also enrich the sex differentiation mechanism of teleosts.
Peer support interventions in maternal and child healthcare delivery in sub-Saharan Africa: protocol for a realist review
Authors: Dugle Gordon , Antwi John , Quentin Wilm
Published: October 2023

Background

Peer support has been proposed as a promising policy intervention for addressing adverse maternal and child healthcare (MCH) outcomes in sub-Saharan Africa (SSA). Existing reviews on peer support largely draw on evidence from high-income countries or focus on single services like breastfeeding, nutrition or postnatal care. In contrast, this review aims to provide a comprehensive overview of the empirical literature on peer support interventions across various MCH services in sub-Saharan Africa. Specifically, we aim to understand how, why, for whom, and in what circumstances different forms of MCH peer support interventions contribute to improving healthcare outcomes in sub-Saharan Africa.

Methods

This review follows five iterative steps for undertaking realist reviews (1) defining the review scope; (2) developing initial programme theories; (3) searching for evidence; (4) selecting and appraising evidence; and (5) extracting, analysing and synthesising evidence. Four databases–Cochrane Library, PubMed, CINAHL, and EMBASE–were repeatedly searched between March and June 2021. From a large volume of records retrieved from the database and citation search, 61 papers have been selected for review. We will conduct a second search of the same database covering June 2021 to the present before the final extraction and synthesis. The final list of selected papers will be imported into NVivo 12 software and organised, extracted, analysed and synthesised iteratively to examine and illustrate the causal links between contexts, mechanisms and outcomes of MCH peer support interventions in SSA. We have drawn on the existing literature on peer support in healthcare generally to develop initial programme theories. We will then use the empirical literature on MCH peer support interventions in SSA, inputs from a stakeholders’ workshop in Ghana and a conference presentation to refine the initial programme theory.

Discussion

The review will develop an explicit theory of peer support intervention in healthcare delivery and provide insights for developing evidence-informed policy on the intervention. Drawing lessons from the different national contexts and diverse areas of MCH in SSA, the review will provide an analytically generalizable programme theory that can guide intervention design and implementation. While focusing on MCH peer support interventions in SSA, the review contributes to evolving conversations on the use of theory for health policy planning and complex intervention design and implementation globally.

Trial registration

PROSPERO registration ID: CRD42023427751.
Universal approximation property of a continuous neural network based on a nonlinear diffusion equation
Authors: Honda Hirotada
Published: October 2023

Recently, differential equation-based neural networks have been actively studied. This paper discusses the universal approximation property of a neural network that is based on a nonlinear partial differential equation (PDE) of the parabolic type.

Based on the assumption that the activation function is non-polynomial and Lipschitz continuous, and applying the theory of the difference method, we show that an arbitrary continuous function on any compact set can be approximated using the output of the network with arbitrary precision. Additionally, we present an estimate of the order of accuracy with respect to △t and △x.
Attachment insecurity and breadcrumbing engagement in young adults: a cross-sectional, cross-country study in India and Spain
Authors: Khattar Vivek , Huete Nuria , Navarro Raúl
Published: October 2023

Background

Breadcrumbing, defined as the act of sending out flirtatious, but non-committal text messages to lure a sexual/romantic partner without expending much effort, has gained attention in popular culture and the media due to its relevance to contemporary dating dynamics. However, there is lack of evidence of the association between attachment insecurity and breadcrumbing This study aims to uncover the potential relationship between breadcrumbing engagement and attachment insecurity among Indian and Spanish young adults.

Methods

Data were collected through an anonymous online survey answered by 334 adults in India and by 348 adults in Spain aged between 18 and 40 years old. A linear regression model in both countries was run to examine breadcrumbing engagement and its relationship with the set of sociodemographic variables included in the study (participants’ age and sex, sexual orientation, relationship status and educational level) and the two dimensions of attachment insecurity (anxious and avoidant).

Results

The results showed that insecure attachment, both anxious and avoidant, were associated with engaging in breadcrumbing in both the countries. However, there was a stronger association between anxious attachment and breadcrumbing in India compared to Spain, where the association was stronger between avoidant attachment and breadcrumbing.

Conclusions

Findings from this study offer insight into an under-studied practice in the context of interpersonal relationships (i.e., breadcrumbing behaviour) and show the importance of attachment theoretical framework to hypothesize and analyse expectations regarding strategies to negotiate intimate relationships and the breadcrumbing experience particularly.
The effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats treated with the ACE2 inhibitor MLN-4760
Authors: Cacanyiova Sona , Cebova Martina , Simko Fedor , Baka Tomas , Bernatova Iveta , Kluknavsky Michal , Zorad Stefan , Krskova Katarina , Shaman Ezgi , Zemancikova Anna , Barta Andrej , Aydemir Basak G. , Berenyiova Andrea
Published: October 2023

Background

Angiotensin converting enzyme 2 (ACE2) plays a crucial role in the infection cycle of SARS-CoV-2 responsible for formation of COVID-19 pandemic. In the cardiovascular system, the virus enters the cells by binding to the transmembrane form of ACE2 causing detrimental effects especially in individuals with developed hypertension or heart disease. Zofenopril, a H2S-releasing angiotensin-converting enzyme inhibitor (ACEI), has been shown to be effective in the treatment of patients with essential hypertension; however, in conditions of ACE2 inhibition its potential beneficial effect has not been investigated yet. Therefore, the aim of the study was to determine the effect of zofenopril on the cardiovascular system of spontaneously hypertensive rats, an animal model of human essential hypertension and heart failure, under conditions of ACE2 inhibition induced by the administration of the specific inhibitor MLN-4760 (MLN).

Results

Zofenopril reduced MLN-increased visceral fat to body weight ratio although no changes in systolic blood pressure were recorded. Zofenopril administration resulted in a favorable increase in left ventricle ejection fraction and improvement of diastolic function regardless of ACE2 inhibition, which was associated with increased H2S levels in plasma and heart tissue. Similarly, the acute hypotensive responses induced by acetylcholine, L-NAME (NOsynthase inhibitor) and captopril (ACEI) were comparable after zofenopril administration independently from ACE2 inhibition. Although simultaneous treatment with zofenopril and MLN led to increased thoracic aorta vasorelaxation, zofenopril increased the NO component equally regardless of MLN treatment, which was associated with increased NO-synthase activity in aorta and left ventricle. Moreover, unlike in control rats, the endogenous H2S participated in maintaining of aortic endothelial function in MLN-treated rats and the treatment with zofenopril had no impact on this effect.

Conclusions

Zofenopril treatment reduced MLN-induced adiposity and improved cardiac function regardless of ACE2 inhibition. Although the concomitant MLN and zofenopril treatment increased thoracic aorta vasorelaxation capacity, zofenopril increased the participation of H2S and NO in the maintenance of endothelial function independently from ACE2 inhibition. Our results confirmed that the beneficial effects of zofenopril were not affected by ACE2 inhibition, moreover, we assume that ACE2 inhibition itself can lead to the activation of cardiovascular compensatory mechanisms associated with Mas receptor, nitrous and sulfide signaling.
In silico analysis of missense SNPs in GABRA1, GABRB1, and GABRB3 genes associated with some diseases in neurodevelopmental disorders
Authors: Manaz Mehmet , Karasakal Ömer Faruk , Özkan Oktay Ebru , Karahan Mesut
Published: October 2023

Background

Neurodevelopmental disorders are disorders that are generally seen in the early developmental period of an individual's life and involve more than one disease that causes disruptions in the central nervous system. These disorders can be given as examples of diseases such as autism, mental retardation, some epileptic disorders, communication disorders, and mental retardation. The aim of this study is to determine the possible harmful effects of missense single nucleotide polymorphisms (SNPs) in the GABRA1, GABRB1, and GABRB3 genes, which are associated with neurodevelopmental disorders, on the structure and stabilization of the protein, using in silico methods. Software tools SIFT, PolyPhen-2 HumVar, PolyPhen-2 HumDiv, PROVEAN, SNAP2, PHD-SNP, SNP&GO, PANTHER, and Meta-SNP were used to predict harmful SNPs. I-Mutant and MUpro software tools were used to predict the effects of predicted harmful SNPs on protein stabilization. The STRING software tool was used for protein–protein interactions, the GeneMANIA software tool for gene–gene interactions, and the Project HOPE software tool for three-dimensional modeling examples.

Results

As a result of the bioinformatics analysis, rs121434579, rs139163545, and rs267600530 in the GABRA1 gene; rs74608570, rs75612351, rs78815529 in the GABRB1 gene, and rs7819600779, rs1719850690, rs7819600779, rs171985060690, rs7819600779, rs1719850600779, rs149963014 in the GABRB3 gene were predicted as harmful SNPs.

Conclusions

In this study, protein structure, function, and stabilization of SNPs known to cause amino acid substitutions in GABRA1, GABRB1, and GABRB3 genes associated with some diseases in neurodevelopmental disorders were investigated using bioinformatics tools. As a result of the results obtained in our study, it is thought that it will benefit experimental studies and bioinformatics studies.
Fabrication and characterization of multiphase bituminous materials for cold region pavements
Authors: Wang Di , Cannone Falchetto Augusto , Zhang Fan , Riccardi Chiara , Sun Yuxuan
Published: October 2023

In this study, the low temperature creep properties of multiphase bituminous materials (binder, mastic, Fine Aggregate Matrix—FAM, and mixture) were experimentally evaluated, and the impact of size effect on FAM and mixture specimen was also assessed. First, the mix design of mastic and FAM was performed based on the reference mixture Asphalt Concrete (AC) 22 TS. The mathematical adaptation to the boundary sieve method was applied to calculate FAM gradation and binder content. Next, a preparation method was proposed to produce Fine Aggregate Matrix (FAM) in a laboratory environment, and scale-up slab samples were also fabricated for FAM and mixture specimens to evaluate the size effect phenomenon. Finally, three-point bending (3 PB) creep tests were conducted on the multiphase bituminous specimens with different dimensions at -6 °C, -12 °C, and -18 °C with a modified Bending Beam Rheometer (BBR) device and a dynamic loading machine, depending on the sample size. Results indicate that the creep stiffness of the FAM was close to mixtures and much higher than the one observed in binder and mastic. The proposed fabrication approach provides a satisfactory method for preparing a representative FAM phase in the mixture, while the air voids can be easily adjusted during the slab compaction procedure. This study supports the idea of using FAM to discriminate asphalt mixtures for cold regions. The correlation between up-scaled FAM and mixture specimens should be further investigated, including different mixture types and corresponding FAM.
Transformative technologies in medicine: a primer for psychiatrists
Authors: Mayfield Neil , Ker Suzy , Steele Rachel , Wright Stephen
Published: October 2023

Across medicine, key scientific advances in the past couple of decades have deepened knowledge of fundamental mechanisms of disease, leading to new treatments and the possibility of increased personalisation of care. Some of the most important developments in fields as diverse as immunology, the microbiome, genetics, stem cells and artificial intelligence are summarised in this article to raise awareness among psychiatrists and to help understand the opportunities and challenges they may present for mental healthcare in the future.
Leptin Increase During Dexamethasone and Its Association With Hunger and Fat in Pediatric Acute Lymphoblastic Leukemia
Authors: van Hulst Annelienke M , Verwaaijen Emma J , van den Berg Sjoerd A A , van Litsenburg Raphaële R L , Grootenhuis Martha A , Fiocco Marta , Neggers Sebastian J C M M , van den Heuvel-Eibrink Marry M , van den Akker Erica L T
Published: October 2023

Context

During treatment, children with acute lymphoblastic leukemia (ALL) receive high doses dexamethasone, which induce acute side effects.

Objective

To determine the influence of a 5-day dexamethasone course on changes in leptin, fat mass, BMI, hunger, sleep, and fatigue and to explore associations between these changes.

Methods

Pediatric ALL patients were included during maintenance treatment. Data were collected before (T1) and after (T2) a 5-day dexamethasone course (6 mg/m2/day). At both time points, BMI, fat mass (bioelectrical impedance analysis), and leptin were assessed, as well as parent-reported questionnaires regarding hunger, fatigue, and sleep problems. Changes between T1 and T2 were assessed using paired tests. Correlation coefficients were calculated to assess associations between these changes (Delta scores: T2-T1). Univariable regression models were estimated to study associations between covariates and elevated leptin.

Results

We included 105 children, with median age 5.4 years (range, 3.0-18.8). Leptin and fat mass, as well as hunger scores, fatigue, and sleep deteriorated after 5 days of dexamethasone (P < .001), in contrast to BMI (P = .12). No correlations between delta leptin and delta fat mass, BMI, hunger, fatigue, or sleep were found. Elevated leptin on T1 was associated with older age (odds ratio [OR] 1.51; 95% CI, 1.28-1.77), higher fat mass (OR 1.19; 95% CI, 1.07-1.33), and earlier maintenance week (OR 0.96; 95% CI, 0.92-0.99).

Conclusion

Five days of high-dose dexamethasone treatment led to direct and significant changes in leptin, hunger scores, and fat mass. Since children with ALL are at increased risk for metabolic adverse events, understanding underlying mechanisms is important, and a dexamethasone-induced state of acute leptin resistance might play a role.
Association of Gestational Free and Total Triiodothyronine With Gestational Hypertension, Preeclampsia, Preterm Birth, and Birth Weight: An Individual Participant Data Meta-analysis
Authors: Derakhshan Arash , Männistö Tuija , Chen Liangmiao , Osinga Joris A J , Ashoor Ghalia , Lu Xuemian , Bliddal Sofie , Tao Fang-Biao , Brown Suzanne J , Vaidya Bijay , Hattersley Andrew T , Itoh Sachiko , Popova Polina V , Aminorroaya Ashraf , Kishi Reiko , Kianpour Maryam , Vasukova Elena A , López-Bermejo Abel , Oken Emily , Chatzi Leda , Vafeiadi Marina , Bramer Wichor M , Bassols Judit , Lertxundi Aitana , Fernández-Somoano Ana , Carrasco Paula , Auvinen Juha , Huang Kun , Feldt-Rasmussen Ulla , Grineva Elena N , Alexander Erik K , Pearce Elizabeth N , Chaker Layal , Walsh John P , Peeters Robin P , Guxens Mònica , Suvanto Eila , Nicolaides Kypros H , Korevaar Tim I M
Published: October 2023

Context

Triiodothyronine (T3) is the bioactive form of thyroid hormone. In contrast to thyroid-stimulating hormone and free thyroxine, we lack knowledge on the association of gestational T3 with adverse obstetric outcomes.

Objective

To investigate the associaiton of gestational free or total T3 (FT3 or TT3) with adverse obstetric outcomes.

Methods

We collected individual participant data from prospective cohort studies on gestational FT3 or TT3, adverse obstetric outcomes (preeclampsia, gestational hypertension, preterm birth and very preterm birth, small for gestational age [SGA], and large for gestational age [LGA]), and potential confounders. We used mixed-effects regression models adjusting for potential confounders.

Results

The final study population comprised 33 118 mother–child pairs of which 27 331 had data on FT3 and 16 164 on TT3. There was a U-shaped association of FT3 with preeclampsia (P = .0069) and a J-shaped association with the risk of gestational hypertension (P = .029). Higher TT3 was associated with a higher risk of gestational hypertension (OR per SD of TT3 1.20, 95% CI 1.08 to 1.33; P = .0007). A lower TT3 but not FT3 was associated with a higher risk of very preterm birth (OR 0.72, 95% CI 0.55 to 0.94; P = .018). TT3 but not FT3 was positively associated with birth weight (mean difference per 1 SD increase in TT3 12.8, 95% CI 6.5 to 19.1 g, P < .0001) but there was no association with SGA or LGA.

Conclusion

This study provides new insights on the association of gestational FT3 and TT3 with major adverse pregnancy outcomes that form the basis for future studies required to elucidate the effects of thyroid function on pregnancy outcomes. Based on the current study, routine FT3 or TT3 measurements for the assessment of thyroid function during pregnancy do not seem to be of added value in the risk assessment for adverse outcomes.
All the Feels
Authors: Silber Lauren
Published: October 2023

Must we avoid the subjective and the personal when we stick to the text as close readers? By examining a moment of affective disruption in an advanced seminar, this autoethnographic account suggests that students should engage with their feelings as they develop meaningful readings of cultural texts.
TheView of Venicein a Genealogy of City Views and Government Mapping
Authors: Barzman Karen-edis
Published: October 2023

Chapter 1 evaluates Jacopo de’ Barbari’s View of Venice in terms of earlier city views and a near-contemporary innovation in cartography—the Venetian state’s decision to systematically collect quantitative and qualitative geospatial data about its territorial holdings and visualize them in a classified collection of annotated “pictures.” This watershed in mapping and data management dates to 1460, when officials in Venice decreed that accurate knowledge of place for the entire empire should be handily available in drawings for those with decision-making authority in the metropole. The essay demonstrates the importance of contextualizing de’ Barbari’s View in terms of this contemporary cartographic production in Venice, which remains relatively unstudied compared to maps that circulated in print. It also ties Venice’s innovation in government mapping and information technology to a humanist culture peculiar to that city at the time and associates the View with the same mapping impulse.
A Perspectival Investigation of Jacopo de’ Barbari'sView of Venice
Authors: Monteleone Cosimo
Published: October 2023

Jacopo de’ Barbari’s View of Venice, also known as Venetie MD, established a turning point in the history of urban mapping, attesting to the great skill achieved by artists and printers of the lagoon at the beginning of the sixteenth century. Scholars have long deliberated about the nature of this work: Is it a topographic city map or a work of art? Chapter 3 reconciles these two interpretations by situating de’ Barbari’s masterpiece within the scientific and artistic context of Renaissance Venice. It delineates the few but significant clues that art, mathematical, and perspective treatises, as manuscripts that circulated among artists and/or were published in the early sixteenth century, to demonstrate that the View of Venice constitutes both a scientific survey and an artistic masterpiece, linked together by a great invention of its time: the perspectiva artificialis.
Vessels of Political Communication
Authors: O'Connell Monique
Published: October 2023

De’ Barbari’s woodcut highlights the city’s commercial prosperity and military might. The more than five hundred vessels in the image represent the maritime trade that was the backbone of medieval Venice’s power. This vision of peace and prosperity contrasts starkly with the tumultuous political and economic events of the time. Between 1497 and 1500, Venetian merchants were alarmed to learn that the Portuguese had circumnavigated the Cape of Good Hope, threatening Venice’s Mediterranean monopoly on the spice trade, and the Venetian economy was rocked by banking failures and changes in patrician galley patronage. While some have seen the View as a representation of a self-satisfied city at the peak of its prosperity, chapter 6 argues that it was a product of crisis. The print formed part of the propagandistic culture intended to disseminate ideas, showing that Venetian commercial strength would allow the city to persist in the face of adversity.
Navigating the Business of Print in Venice with Jacopo de’ Barbari
Authors: Wilson Bronwen
Published: October 2023

A heroic figure of Neptune appears astride a sea creature in the foreground of Jacopo de’ Barbari’s ambitious woodcut of Venice. The body of the Roman god directs us vertically, toward the commercial hub of the city, and to his collaborator, the mythological messenger god Mercury. With his trident, Neptune points toward the left, perhaps purposefully, since this is where the Frezzeria is located, the street where many printers’ shops were being established. Suspended from the trident is a tablet with an inscription informing us that he is smoothing the waters, a reference to the sea but also to printmaking, since the distinctive shape of the block is characteristic of weights used to press paper flat. Taking a cue from Neptune and the View, chapter 7 creates an itinerary of spaces connected with the business of print in Venice during the sixteenth century.
On the Collection History of theView's Matrices
Authors: Cafà Valeria
Published: October 2023

Chapter 8 traces the collection history of the six original matrices of the View preserved in the Correr Museum. After the first successful print run in Venice at the start of the sixteenth century, the six blocks of pearwood were passed to unknown and undocumented printers, resulting in two additional states. Given that the portrait of the city visibly changed over time, especially with select sixteenth-century sites, the matrices and their first-state prints became precious relics worthy of patrician Wunderkammer collections. The collected life of the wooden blocks, however, lacks certainty until 1720, when they are documented in the collection of Count Baron Leopoldo de Tassis. Most likely between late 1700 and early 1800, Teodoro Correr acquired the blocks due to their value as precious material objects of Venice. Correr’s varied collection was donated to the city as the founding nucleus of the Civic Museums of Venice in 1830.
The Graphic Inventions of Jacopo de’ Barbari
Authors: Huffman Kristin Love
Published: October 2023

Jacopo de’ Barbari (ca. 1460/70–1516) contributed to the advancement of graphic arts for artists and collectors at a pivotal, historical moment in the dissemination of artistic inventions. His contributions included engagement with scientific and mathematical discourses, the formulation of new subject matter (still life, astrological symbolism, all’antica narratives), unusual compositional strategies, and technical enhancements. Despite his innovations, especially noteworthy with printmaking, this artist’s body of works remains less studied than those of celebrated contemporaries, such as Andrea Mantegna, Albrecht Dürer, and the Bellini (Jacopo, Gentile, and Giovanni). Chapter 9 sheds light on inventions made by this relatively enigmatic artist to reframe his imaginative contributions and to position his novel imagery in dialogue with those of his contemporaries. It also considers his printed designs, notably his woodcut and engraved sets, within the context of works he produced in the years before and after the publication of the View of Venice.
Revisiting “lontani et altra fantaxia”
Authors: Pardo Mary
Published: October 2023

Chapter 10 revisits textual and visual evidence for the art critical connotations of the term lontani (distances), which in the years around 1500 was used as a supplement, and sometimes near-synonym, for paesi (countrysides)—a term we now translate as “landscapes.” In Isabella d’Este’s much-cited correspondences with her Venetian agents, lontani were associated with Giovanni Bellini’s special gifts as a painter. This essay considers lontani as a specifically “Eyckian” legacy and argues that the term’s use correlates with the survival of Jan van Eyck’s pictorial strategies and the memory of specific Eyckian novelties into the late fifteenth century. This is attested by works such as Jacopo de’ Barbari’s dazzling variation on the bird’s-eye city portrait. In this connection, the essay probes into the relationship between Bellini’s approach to lontani and the Eyckian prototypes that are usually cited as sources for Bellini’s topographical inventions.
Toward the Perfect City
Authors: Goy Richard
Published: October 2023

De’ Barbari’s legendary View represents the culmination of well over a century of urban development and refinement. During this period, Venice’s population grew, its fabric became ever denser, its palazzi ever more grandiose, refined, and imposing. The city also expanded physically by means of a number of substantial reclamation projects around its perimeter. Chapter 12 attempts to trace and summarize some of these key developments, together with an assessment of their achievement in terms of progress toward the “perfect city.” These new developments had an essentially practical value, providing more land for expansion in this extremely densely developed city, but they also all contributed toward the renovatio urbis and the creation of the “ideal” capital city. In addition, the period saw a series of measures intended to improve the urban experience; these included the paving of streets, the excavation of new wells, and the relocation of industrial activities.
Luxury Goods in Jacopo de’ Barbari's Venice
Authors: de Maria Blake
Published: October 2023

Jacopo de Barbari’s View of Venice is rightfully celebrated as one of the most comprehensive representations of an early modern European city, and perhaps the most comprehensive. Yet the View offers more than a record of Venice’s urban environment. Rather, it serves as both a key record of the city’s commercial activities and a luxury good in its own right. Chapter 20 examines Venetian trade during the era of the woodcut, at a time in which the Republic dominated trade in the Mediterranean region. Whether fine-tooled leather goods, gemstones, or fabrics, the import and export of luxury goods served as the lifeblood of the Venetian economy. However, as this essay demonstrates, shortly after the production of the View, the Republic’s economic primacy started to decline and in doing so rendered the record provided by the image all the more important.
Imagining Social and Political Relations in theView
Authors: van Gelder Maartje , de Larivière Claire Judde
Published: October 2023

Jacopo de’ Barbari’s View is a beautiful portrait of the city of Venice, yet almost no people appear. One’s imagination is required to envision the many inhabitants who would have maintained Venice as a dynamic political, economic, and cultural center. Chapter 22 discusses the View as a representation of Venetian society around 1500, considering buildings and spaces as embodiments of the population. It attempts to reconstruct the many social and economic interactions as well as the political relations and tensions that constituted the Venetian state. It also shows how the View highlights spaces where patricians and non-elite Venetians met and socialized and where power was negotiated. Moving across the city, from the San Marco area in the south to the island of Murano in the north, this contribution traces how the city’s inhabitants would have filled the View’s empty spaces and thus how Venetian society functioned.