bluuebunny/crossref_metadata_2025 huggingface dataset:
UGDR: a generic pipeline to detect recombined regions in polyploid and complex hybrid yeast genomes
Authors: Bedrat Amina
Published: December 2022

Motivation

In eukaryotes, homologous recombination between the parental genomes frequently occurs during the evolutionary conserved process of meiosis, generating the genetic diversity transmitted by the gametes. The genome-wide determination of the frequency and location of the recombination events can now be efficiently performed by genotyping the offspring’s polymorphic markers. However, genotyping recombination in complex hybrid genomes with existing methods remains challenging because of their strain and ploidy specificity and the degree of diversity and complexity of the parental genomes, especially in $$>2n$$

>
2
n

polyploids.

Results

We present UGDR, a pipeline to genotype the polymorphisms of complex hybrid yeast genomes. It is based on optimal mapping strategies of NGS reads, comparative analyses of the allelic ratio variation and read depth coverage. We tested the UGDR pipeline with sequencing reads from recombined hybrid diploid yeast strains and various clinical strains exhibiting different degrees of ploidy. UGDR allows to plot the markers distribution and recombination profile per chromosome.

Conclusion

UGDR detects and plots recombination events in haploids and polyploid yeasts, which facilitates the discovery and understanding of the yeast genetic recombination map and identify new out-performing recombinants.
Alterations of the vaginal microbiome in healthy pregnant women positive for group B Streptococcus colonization during the third trimester
Authors: Shabayek Sarah , Abdellah Asmaa M. , Salah Mohammed , Ramadan Mohammed , Fahmy Nora
Published: December 2022

Background

Streptococcus agalactiaeor group B Streptococcus (GBS) asymptomatically colonizes the genitourinary tracts of up to 30% of pregnant women. Globally, GBS is an important cause of neonatal morbidity and mortality. GBS has recently been linked to adverse pregnancy outcomes. The potential interactions between GBS and the vaginal microbiome composition remain poorly understood. In addition, little is known about the vaginal microbiota of pregnant Egyptian women.

Results

Using V3-V4 16S rRNA next-generation sequencing, we examined the vaginal microbiome in GBS culture-positive pregnant women (22) and GBS culture-negative pregnant women (22) during the third trimester in Ismailia, Egypt. According to the alpha-diversity indices, the vaginal microbiome of pregnant GBS culture-positive women was significantly more diverse and less homogenous. The composition of the vaginal microbiome differed significantly based on beta-diversity between GBS culture-positive and culture-negative women. The phylumFirmicutesand the familyLactobacillaceaewere significantly more abundant in GBS-negative colonizers. In contrast, the phylaActinobacteria,Tenericutes, andProteobacteriaand the familiesBifidobacteriaceae,Mycoplasmataceae,Streptococcaceae,Corynebacteriaceae,Staphylococcaceae, andPeptostreptococcaceaewere significantly more abundant in GBS culture-positive colonizers. On the genus and species levels,Lactobacilluswas the only genus detected with significantly higher relative abundance in GBS culture-negative status (88%), andL. inerswas the significantly most abundant species. Conversely, GBS-positive carriers exhibited a significant decrease inLactobacillusabundance (56%). In GBS-positive colonizers, the relative abundance of the generaUreaplasma,Gardnerella,Streptococcus,Corynebacterium,Staphylococcus, andPeptostreptococcusand the speciesPeptostreptococcus anaerobiuswas significantly higher. The Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways related to the metabolism of cofactors and vitamins, phosphatidylinositol signaling system, peroxisome, host immune system pathways, and host endocrine system were exclusively enriched among GBS culture-positive microbial communities. However, lipid metabolism KEGG pathways, nucleotide metabolism, xenobiotics biodegradation and metabolism, genetic information processing pathways associated with translation, replication, and repair, and human diseases (Staphylococcus aureusinfection) were exclusively enriched in GBS culture-negative communities.

Conclusions

Understanding how perturbations of the vaginal microbiome contribute to pregnancy complications may result in the development of alternative, targeted prevention strategies to prevent maternal GBS colonization. We hypothesized associations between inferred microbial function and GBS status that would need to be confirmed in larger cohorts.
Cortical thickness analysis in temporal lobe epilepsy using fully Bayesian spectral method in magnetic resonance imaging
Authors: Sarbisheh Iman , Tapak Leili , Fallahi Alireza , Fardmal Javad , Sadeghifar Majid , Nazemzadeh MohammadReza , Mehvari Habibabadi Jafar
Published: December 2022

Background

Temporal lobe epilepsy (TLE) is the most common type of epilepsy associated with changes in the cerebral cortex throughout the brain. Magnetic resonance imaging (MRI) is widely used for detecting such anomalies; nevertheless, it produces spatially correlated data that cannot be considered by the usual statistical models. This study aimed to compare cortical thicknesses between patients with TLE and healthy controls by considering the spatial dependencies across different regions of the cerebral cortex in MRI.

Methods

In this study, T1-weighted MRI was performed on 20 healthy controls and 33 TLE patients. Nineteen patients had a left TLE and 14 had a right TLE. Cortical thickness was measured for all individuals in 68 regions of the cerebral cortex based on images. Fully Bayesian spectral method was utilized to compare the cortical thickness of different brain regions between groups. Neural networks model was used to classify the patients using the identified regions.

Results

For the left TLE patients, cortical thinning was observed in bilateral caudal anterior cingulate, lateral orbitofrontal (ipsilateral), the bilateral rostral anterior cingulate, frontal pole and temporal pole (ipsilateral), caudal middle frontal and rostral middle frontal (contralateral side). For the right TLE patients, cortical thinning was only observed in the entorhinal area (ipsilateral). The AUCs of the neural networks for classification of left and right TLE patients versus healthy controls were 0.939 and 1.000, respectively.

Conclusion

Alteration of cortical gray matter thickness was evidenced as common effect of epileptogenicity, as manifested by the patients in this study using the fully Bayesian spectral method by taking into account the complex structure of the data.
HERPUD1 promotes ovarian cancer cell survival by sustaining autophagy and inhibit apoptosis via PI3K/AKT/mTOR and p38 MAPK signaling pathways
Authors: Nie Xin , Liu Dawo , Zheng Mingjun , Li Xiao , Liu Ouxuan , Guo Qian , Zhu Liancheng , Lin Bei
Published: December 2022

HERPUD1 is an important early marker of endoplasmic reticulum stress (ERS) and is involved in the ubiquitination and degradation of several unfolded proteins. However, its role in tumorigenesis is seldom studied, and its role in ovarian cancer is unclear. Lewis y antigen is a tumor-associated sugar antigen that acts as an ‘antenna’ on the cell surface to receive signals from both inside and outside the cell. We previously reported that Lewis y can promote ovarian cancer by promoting autophagy and inhibiting apoptosis. In this study, we detect the expression of HERPUD1 and Lewis y antigens in 119 different ovarian cancer tissues, determine their relationship with clinicopathological parameters, analyze the correlation between these two proteins, and explore the related cancer-promoting mechanisms through MTT, flow cytometry, western blotting, and bioinformatics. HERPUD1 is highly expressed in ovarian cancer, especially in the early stage, and the expression of HERPUD1 and Lewis y antigen was positively correlated. After overexpression of Lewis y antigen, the expression level of HERPUD1 increased. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathways (KEGG) analysis showed that HERPUD1 and its related genes are enriched in regulating immunity, endoplasmic reticulum stress, ubiquitin-dependent degradation, ERS-induced apoptosis, and other key signaling pathways. We also clarified the HERPUD1 network of kinases, microRNA and transcription factor targets, and the impact of HERPUD1 mutations on prognosis. In addition, HERPUD1 promotes the proliferation of ovarian cancer cells, inhibits apoptosis, affects the cell cycle, promotes the occurrence of autophagy, and inhibits EMT and PI3K/AKT/mTOR and p38MAPK pathways. Overall, HERPUD1, regulated by the expression of tumor-associated protein Lewis y, promotes cell survival in the early stages of tumors, suggesting that HERPUD1 may play an important role in the development of ovarian cancer.
Drivers of young adults’ voluntary compliance with COVID-19 protective measures: results from a multi-method study
Authors: Reinhardt Anne , Weber Winja , Rossmann Constanze
Published: December 2022

Background

With the easing of governmental COVID-19 restrictions, promoting voluntary public compliance with protective measures becomes essential for the pandemic evolution. A highly relevant target group for such health promotion are adolescents and young adults since they showed a strong decline in compliance throughout the pandemic. Building on an extended version of the Theory of Planned Behavior, this article investigates drivers of young people’s intentions to engage in voluntary COVID-19 measures in phases of re-opening.

Methods

We conducted a sequential multi-method study among 14- to 29-year-olds in Germany: (1) a semi-standardized online survey (N = 88) to examine underlying beliefs and (2) a standardized online survey (N = 979) to identify influencing factors of compliance. The pre-study addressed the respondents’ perceptions about wearing a mask, social distancing, and avoiding crowded locations (open-ended questions). Responses for all protective measures were aggregated to identify general behavioral, normative, and control beliefs about COVID-19 protective measures. In order to gain generalizable insights into the factors determining voluntary compliance intentions in younger adults, we conceptualized the model constructs in the subsequent standardized online survey as formative measures based on their underlying beliefs. PLS-SEM was used to examine the effects of attitudes, subjective norms, perceived behavioral control, risk perceptions, and knowledge on young people’s intentions to comply (main study). Furthermore, a multi-group analysis was conducted to investigate differences between compliers and non-compliers.

Results

The pre-study revealed that young people’s instrumental attitudes not only cover reasons of protection but also aspects of self-presentation (e.g., being a role model). The main study showed that besides knowledge and perceived severity of illness, instrumental attitude is the strongest predictor of intention to comply. The influence is even stronger in the group of non-compliers.

Conclusion

This article highlights the importance of theory-based campaign planning and provides practical guidance to health communicators on how to increase voluntary compliance with COVID-19 protective measures in adolescents and young adults. The findings demonstrate the great potential of combining the Theory of Planned Behavior with risk perception and knowledge to gain deeper insights into the feelings and thoughts of younger target groups during a health crisis.
Does fragmented cancer care affect survival? Analysis of gastric cancer patients using national insurance claim data
Authors: Choi Dong-Woo , Kim Sun Jung , Kim Dong Jun , Chang Yoon-Jung , Kim Dong Wook , Han Kyu-Tae
Published: December 2022

Background

We aimed to investigate the association between fragmented cancer care in the early phase after cancer diagnosis and patient outcomes using national insurance claim data.

Methods

From a nationwide sampled cohort database, we identified National Health Insurance beneficiaries diagnosed with gastric cancer (ICD-10: C16) in South Korea during 2005–2013. We analyzed the results of a multiple logistic regression analysis using the generalized estimated equation model to investigate which patient and institution characteristics affected fragmented cancer care during the first year after diagnosis. Then, survival analysis using the Cox proportional hazard model was conducted to investigate the association between fragmented cancer care and five-year mortality.

Results

Of 2879 gastric cancer patients, 11.9% received fragmented cancer care by changing their most visited medical institution during the first year after diagnosis. We found that patients with fragmented cancer care had a higher risk of five-year mortality (HR: 1.310, 95% CI: 1.023–1.677). This association was evident among patients who only received chemotherapy or radiotherapy (HR: 1.633, 95% CI: 1.005–2.654).

Conclusions

Fragmented cancer care was associated with increased risk of five-year mortality. Additionally, changes in the most visited medical institution occurred more frequently in either patients with severe conditions or patients who mainly visited smaller medical institutions. Further study is warranted to confirm these findings and examine a causal relationship between fragmented cancer care and survival.
Shifting the narrative: equity, evidence, effectiveness, and innovation in the era of Ending the HIV Epidemic
Authors: Perez Alexander , Galván  Rosy , Morejon Milanes
Published: December 2022

Background

The use of evidence-based (EB) and evidence-informed (EI) criteria in determining the effectiveness of health interventions has been widely adopted by national and international agencies in their attempt to address health gaps, particularly around Ending the HIV Epidemic (EHE) initiatives. Utilization of these rigorous standards has proven critical in making progress towards achieving EHE goals, yet many communities remain unreached and underserved despite widespread adoption of EB/EI standards in public health research and practice. Although a crucial tool for innovative healthcare delivery, emphasis on the use of EB/EI parameters has created bias within the cycle of knowledge creation that favors well-resourced institutions given their capacity to meet the rigorous evaluation standards required of EB/EI science. This bias can systematically exclude institutions more aligned with community needs, such as community-based organizations and other grass-roots initiatives, which may have long-standing interventions that more effectively engage marginalized groups but do not have the capacity to meet EB/EI standards.

Main body

This paper will explore the manifestation of systematic bias and research inequity in the process of identifying and assessing EB/EI HIV care interventions through the lens of a Health Resources and Services Administration funded initiative, coined the Center for Innovation and Engagement, which supports people living with HIV in the United States. An overview of the initiative is provided along with examples of how promising interventions with positive outcomes for members of marginalized communities are excluded in place of interventions that meet traditional standards of scientific rigor but are not novel or particularly innovative. Themes around academic imperialism and power hierarchies will be considered along with key barriers, lessons learned, and recommendations for promoting more equitable EB/EI research practice.

Conclusions

It is crucial for entities supporting public health interventions to prioritize equity and inclusion in all stages of funding, design, and implementation. This is particularly true for conditions, such as HIV, that disproportionally impact the most marginalized. This will require approaching EB/EI research with a critical lens towards power and a willingness to dismantle historical dynamics that perpetuate inequities as a way of encouraging truly innovative solutions to support those who need it most.
Exposure to family planning messages and teenage pregnancy: results from the 2017 Philippine National Demographic and Health Survey
Authors: Pepito Veincent Christian F. , Amit Arianna Maever L. , Tang Clinton S. , Co Luis Miguel B. , Aliazas Neil Andrew K. , De Los Reyes Sarah J. , Baquiran Raymundo S. , Tanchanco Lourdes Bernadette S.
Published: December 2022

Background

Teenage pregnancy is known to have physical, emotional, and psychosocial effects. Because of these risks, family planning and contraception messages have been disseminated in various forms of media, but their association with teenage pregnancy has not been studied previously in the Philippines. This study aims to examine the association between exposure to various family planning and contraception messages disseminated in various media channels and pregnancy among Filipino women aged 15–19. The study also intended to examine interactions between the different media channels where these family planning and contraception messages are being disseminated on their effect on teenage pregnancy.

Methods

We used data from the individual recode of the 2017 Philippine National Demographic and Health Survey. We used logistic regression for survey data to  study the association between exposure to family planning and contraception messages and teenage pregnancy.

Results

Out of 5120 respondents, 44% of respondents have accessed information on contraception from the internet, 25% have heard information about contraception through the radio, 55% of respondents have heard about contraception via television, 15% have read about contraception in the newspapers and magazines, and only 6% have received information on contraception via short messaging service (SMS). There were 420 (8.56%) who have ever been pregnant. After adjusting for confounding variables, those who were exposed to family planning/contraceptive messages via the internet (aOR: 0.90; 95% CI: 0.59, 1.35) and newspapers/magazines (aOR: 0.78; 95% CI: 0.44, 1.41) have lower odds of teenage pregnancy, but no strong evidence of their effectiveness. On the other hand, exposure to family planning messages through the radio (aOR: 1.06; 95% CI: 0.71, 1.59), television (aOR: 1.09; 95% CI: 0.72, 1.65), and short messaging service (aOR: 1.29; 95% CI: 0.51, 3.22) marginally increase the risk of teenage pregnancy. We did not find any pairwise interactions between the different exposure variables.

Conclusions

Our results highlight the need to improve the content and key messages of contraceptive and family planning messages in the Philippines, especially those that are broadcasted online and in print media. There is also a need to increase the reach of these different family planning and contraception messages, especially by utilizing social media and other print and online media platforms commonly used by the youth.
Thirty-five years (1986–2021) of HIV/AIDS in Nigeria: bibliometric and scoping analysis
Authors: Okoroiwu Henshaw Uchechi , Umoh Ekementeabasi Aniebo , Asanga Edet Effiong , Edet Uwem Okon , Atim-Ebim Michael Raymond , Tangban Edum Abang , Mbim Elizabeth Nkagafel , Odoemena Cynthia Amarachi , Uno Victor Kanu , Asuquo Joseph Okon , Effiom-Ekaha Otu Otu , Dozie-Nwakile Ogechukwu C. , Uchendu Ikenna K. , Echieh Chidiebere Peter , Emmanuel Kingsley John , Ejemot-Nwadiaro Regina Idu , Nja Glory Mbe Egom , Oreh Adaeze , Uchenwa Mercy Ogechi , Ufornwa Emmanuel Chukwuma , Nwaiwu Ndidi Patience , Ogar Ogar Christopher , Nkang Ani , Kabiri Obinna Justice , Povedano-Montero F. Javier
Published: December 2022

Background

Acquired immunodeficiency syndrome (AIDS) is an acquired defect of the cellular immunity associated with the infection by the human immunodeficiency virus (HIV). The disease has reached pandemic proportion and has been considered a public health concern. This study is aimed at analyzing the trend of HIV/AIDS research in Nigeria.

Method

We used the PUBMED database to a conduct bibliometric analysis of HIV/AIDS-related research in Nigeria from 1986 to 2021 employing “HIV”, “AIDS”, “acquired immunodeficiency syndrome”, “Human immunodeficiency virus”, and “Nigeria” as search description. The most common bibliometric indicators were applied for the selected publications.

Result

The number of scientific research articles retrieved for HIV/AIDS-related research in Nigeria was 2796. Original research was the predominant article type. Articles authored by 4 authors consisted majority of the papers. The University of Ibadan was found to be the most productive institution. Institutions in the United States dominated external production with the University of Maryland at the top. The most utilized journal was PLoS ONE. While Iliyasu Z. was the most productive principal author, Crowel TA. was the overall most productive author with the highest collaborative strength. The keyword analysis using overlay visualization showed a gradual shift from disease characteristics to diagnosis, treatment and prevention. Trend in HIV/AIDS research in Nigeria is increasing yet evolving. Four articles were retracted while two had an expression of concern.

Conclusion

The growth of scientific literature in HIV/AIDS-related research in Nigeria was found to be high and increasing. However, the hotspot analysis still shows more unexplored grey areas in future.
Normality in medicine: an empirical elucidation
Authors: Rost Michael , Favaretto Maddalena , De Clercq Eva
Published: December 2022

Background

Normality is both a descriptive and a normative concept. Undoubtedly, the normal often operates normatively as an exclusionary tool of cultural authority. While it has prominently found its way into the field of medicine, it remains rather unclear in what sense it is used. Thus, our study sought to elucidate people’s understanding of normality in medicine and to identify concepts that are linked to it.

Methods

Using convenient sampling, we carried out a cross-sectional survey. Since the survey was advertised through social media, we employed an online survey. We performed descriptive and inferential analyses. Predictors were chosen in a theory-driven manner.

Results

In total, 323 persons from 21 countries completed the survey. Analysis revealed that the overall acceptance of normality in medicine was associated with notions of injustice, authority, discrimination, and with having a medical profession. More precisely, for the field of mental health, injustice insensitivity, genderism and transphobia, and authority were positively associated with a person’s acceptance of normality; and, for the field of physical health, injustice insensitivity and having a medical profession were positively associated with a person’s acceptance of normality. Finally, participants’ acceptance of the use of normality in the area of mental health was lower than in the area of physical health.

Conclusions

What is considered normal has implications for clinical practice, both at an individual and at a policy-level. Acknowledging its normalistic condition, the discipline of medicine has to confront itself with its own contribution to the augmentation of social inequalities through the excessive reliance on the concept of normality. Research that centers the lived experiences of those who are being systematically marginalized because they are deemed abnormal is needed. By empirically elucidating the conceptual relationships between normality in medicine and other variables, we provide points of leverage to deprive normality of its normative power. For medicine, this is needed to first do no harm.
Expert opinion of an Italian working group on the assessment of cognitive, psychological, and neurological outcomes in pediatric, adolescent, and adult patients with phenylketonuria
Authors: Manti Filippo , Caviglia Stefania , Cazzorla Chiara , Dicintio Annamaria , Pilotto Andrea , Burlina Alessandro P.
Published: December 2022

Phenylketonuria (PKU) is an inherited metabolic disease characterized by a defective conversion of phenylalanine (Phe) to tyrosine, potentially leading to Phe accumulation in the brain. Dietary restriction since birth has led to normal cognitive development. However, PKU patients can still develop cognitive or behavioral abnormalities and subtle neurological deficits. Despite the increasing evidence in the field, the assessment of neurocognitive, psychopathological, and neurological follow-up of PKU patients at different ages is still debated. The high interindividual variability in the cognitive outcome of PKU patients makes the specificity of the neurocognitive and behavioral assessment extremely challenging. In the present paper, a multidisciplinary panel of Italian PKU experts discussed different tools available for cognitive, psychopathological, and neurological assessment at different ages based on the existing literature and daily clinical practice. This study aims to provide evidence and a real-life-based framework for a specific clinical assessment of pediatric, adolescent, and adult patients affected by PKU.
Patient centered guidelines for the laboratory diagnosis of Gaucher disease type 1
Authors: Dardis A. , Michelakakis H. , Rozenfeld P. , Fumic K. , Wagner J. , Pavan E. , Fuller M. , Revel-Vilk S. , Hughes D. , Cox T. , Aerts J. ,   the International Working Group of Gaucher Disease (IWGGD)
Published: December 2022

Gaucher disease (GD) is an autosomal recessive lysosomal storage disorder due to the deficient activity of the acid beta-glucosidase (GCase) enzyme, resulting in the progressive lysosomal accumulation of glucosylceramide (GlcCer) and its deacylated derivate, glucosylsphingosine (GlcSph). GCase is encoded by the GBA1 gene, located on chromosome 1q21 16 kb upstream from a highly homologous pseudogene. To date, more than 400 GBA1 pathogenic variants have been reported, many of them derived from recombination events between the gene and the pseudogene. In the last years, the increased access to new technologies has led to an exponential growth in the number of diagnostic laboratories offering GD testing. However, both biochemical and genetic diagnosis of GD are challenging and to date no specific evidence-based guidelines for the laboratory diagnosis of GD have been published. The objective of the guidelines presented here is to provide evidence-based recommendations for the technical implementation and interpretation of biochemical and genetic testing for the diagnosis of GD to ensure a timely and accurate diagnosis for patients with GD worldwide. The guidelines have been developed by members of the Diagnostic Working group of the International Working Group of Gaucher Disease (IWGGD), a non-profit network established to promote clinical and basic research into GD for the ultimate purpose of improving the lives of patients with this disease. One of the goals of the IWGGD is to support equitable access to diagnosis of GD and to standardize procedures to ensure an accurate diagnosis. Therefore, a guideline development group consisting of biochemists and geneticists working in the field of GD diagnosis was established and a list of topics to be discussed was selected. In these guidelines, twenty recommendations are provided based on information gathered through a systematic review of the literature and two different diagnostic algorithms are presented, considering the geographical differences in the access to diagnostic services. Besides, several gaps in the current diagnostic workflow were identified and actions to fulfill them were taken within the IWGGD. We believe that the implementation of recommendations provided in these guidelines will promote an equitable, timely and accurate diagnosis for patients with GD worldwide.
Trajectories of stressful life events and long-term changes in mental health outcomes, moderated by family functioning? the TRAILS study
Authors: Wijbenga Lisette , Reijneveld Sijmen A. , Almansa Josue , Korevaar Eliza L. , Hofstra Jacomijn , de Winter Andrea F.
Published: December 2022

Purpose

We assessed the association between trajectories of stressful life events (SLEs) throughout adolescence and changes in mental health from childhood to young adulthood. Further, we assessed whether family functioning moderated this association.

Methods

Data of the first six waves of the TRAILS study (2001-2016; n = 2229) were used, a cohort followed from approximately age 11 to 23. We measured SLEs (death of a family member or other beloved one, delinquency, moving, victim of violence, parental divorce, and sexual harassment) at ages 14, 16 and 19. Family functioning was measured at all six time points using the Family Assessment Device (FAD), and mental health was measured through the Youth/Adult Self-Report at ages 11 and 23. Latent class growth analyses (LCGA) were used to examine longitudinal trajectories and associations.

Results

We identified three SLE trajectories (low, middle, high) throughout adolescence, and found no significant associations between these trajectories and changes in mental health from childhood to young adulthood. Family functioning and SLE trajectories were significantly associated, however, the association of SLE trajectories and changes in mental health was not modified by family functioning. Mental health problems at age 11 increased the likelihood of high SLE trajectories during adolescence, and of experiencing negative family functioning.

Conclusion

Experiencing SLEs throughout adolescence does not have a direct impact on changes in mental health from childhood to young adulthood, but early adolescence mental health problems increase the likelihood of experiencing SLEs.
Fabricating a robust POSS-PCL nanofiber scaffold for nesting of mesenchymal stem cells: potential application in bone tissue regeneration
Authors: bagheri Leyla , Valizadeh Hasan , Dindar-safa Kazem , Zarghami Nosratollah
Published: December 2022

Background

According to recent studies, electrospun Poly (Ɛ-caprolactone) (PCL) is an absorbing candidate for the formulation of biocompatible scaffolds used in tissue engineering. Tissue engineering is a set of techniques for producing or reconstructing tissue, whose primary purpose is to restore or improve the function of tissues in the human body. Tissue engineering combines the principles of materials and cell transplantation to develop alternative tissues or promote endogenous regeneration. However, this electrospun scaffold, consisting of PCL, has disadvantages such as low cell adhesion, inactivity of the surface, osteoinduction, and acidic destruction of the scaffold that causes inflammation at the implant site, often making it unsuitable implant. This study aimed to improve PCL base cellular scaffolds with the formulation of polyhedral oligomeric silsesquioxane – Polycaprolactone (POSS-PCL) nanofiber scaffolds. The present research focuses on the synthesis of nanofibers for their cell interaction features, and application in bone tissue engineering and regeneration.

Results

POSS/ PCL Nanocomposites with 2, 5, and 10 wt.% of POSS were synthesized in the Trichloromethane, then POSS – PCL Nanofibers were prepared by the electrospinning technique. In this study, the structures of nanohybrids and nanofibers have been evaluated by FTIR, HNMR, XRD, SEM, EDX, and DSC. The biocompatibility of formulated POSS-PCL scaffolds was detected using mesenchymal stem cells (MSCs). Then several parameters were examined, involving DCFH ROS detection system, gene expression (cell viability/apoptosis, osteogenesis potentiality, and redox molecular homeostasis.

Conclusions

Based on our results, POSS-PCL nano-scaffolds in comparison with PCL have shown a robust potentiality in homing, growth, and differentiation of stem cells.

Graphical Abstract

Synthesis of POSS-PCL Nanofibers and their potential application in Bone Regeneration.
CBL0137 impairs homologous recombination repair and sensitizes high-grade serous ovarian carcinoma to PARP inhibitors
Authors: Lu Xue , He Yaowu , Johnston Rebecca L. , Nanayakarra Devathri , Sankarasubramanian Sivanandhini , Lopez J. Alejandro , Friedlander Michael , Kalimutho Murugan , Hooper John D. , Raninga Prahlad V. , Khanna Kum Kum
Published: December 2022

Background

High-grade serous ovarian carcinomas (HGSCs) are a heterogeneous subtype of epithelial ovarian cancers and include serous cancers arising in the fallopian tube and peritoneum. These cancers are now subdivided into homologous recombination repair (HR)-deficient and proficient subgroups as this classification impacts on management and prognosis. PARP inhibitors (PARPi) have shown significant clinical efficacy, particularly as maintenance therapy following response to platinum-based chemotherapy in BRCA-mutant or homologous recombination (HR)-deficient HGSCs in both the 1st and 2nd line settings. However, PARPi have limited clinical benefit in HR-proficient HGSCs which make up almost 50% of HGSC and improving outcomes in these patients is now a high priority due to the poor prognosis with ineffectiveness of the current standard of care. There are a number of potential lines of investigation including efforts in sensitizing HR-proficient tumors to PARPi. Herein, we aimed to develop a novel combination therapy by targeting SSRP1 using a small molecule inhibitor CBL0137 with PARPi in HR-proficient HGSCs.

Experimental design

We tested anti-cancer activity of CBL0137 monotherapy using a panel of HGSC cell lines and patient-derived tumor cells in vitro. RNA sequencing was used to map global transcriptomic changes in CBL0137-treated patient-derived HR-proficient HGSC cells. We tested efficacy of CBL0137 in combination with PARPi using HGSC cell lines and patient-derived tumor cells in vitro and in vivo.

Results

We show that SSRP1 inhibition using a small molecule, CBL0137, that traps SSRP1 onto chromatin, exerts a significant anti-growth activity in vitro against HGSC cell lines and patient-derived tumor cells, and also reduces tumor burden in vivo. CBL0137 induced DNA repair deficiency via inhibition of the HR repair pathway and sensitized SSRP1-high HR-proficient HGSC cell lines and patient-derived tumor cells/xenografts to the PARPi, Olaparib in vitro and in vivo. CBL0137 also enhanced the efficacy of DNA damaging platinum-based chemotherapy in HGSC patient-derived xenografts.

Conclusion

Our findings strongly suggest that combination of CBL0137 and PARP inhibition represents a novel therapeutic strategy for HR-proficient HGSCs that express high levels of SSRP1 and should be investigated in the clinic.
Assessment of selected interleukins (IL-6, IL-17A, IL-18, IL-23) and chemokines (RANTES, IP-10) in children with acute and chronic urticaria
Authors: Góra Anna , Przybył Maciej , Świętochowska Elżbieta , Machura Edyta
Published: December 2022

Background

Urticarial lesions develop as a result of the activation of mast cells which, through the release of mediators, influence the formation of local inflammatory infiltrates. Changes in the expression of many cytokines and chemokines are observed in the course of urticaria.

The aim of the study was to evaluate serum levels of interleukin (IL)-6, IL-17A, IL-18, IL-23, regulated on activation, normal T cell expressed and secreted (RANTES) and interferon (IFN)-γ-inducible protein-10 (IP-10) in children with acute urticaria and exacerbation of chronic urticaria in comparison to healthy volunteers. Moreover, we made an attempt to identify factors associated with the acute phase of urticaria and factors predicting the course of the disease among the studied parameters.

Methods

We retrospectively analyzed 32 children with acute urticaria and 32 children with chronic urticaria. The control group consisted of 40 healthy children. Each patient was clinically evaluated. Serum concentrations of selected cytokines and chemokines were determined by using enzyme-linked immunosorbent assay.

Results

Patients with acute and chronic urticaria had higher concentrations of IL-6 and IL-17A (p < 0.001) and lower concentrations of IL-18, IL-23, RANTES and IP-10 (p < 0.001) as compared to the control group. A significant association between IL-6 and IP-10 with the acute phase of urticaria has been demonstrated. There was no correlation of the studied cytokines and chemokines with disease activity.

Conclusions

In children with acute phase of urticaria, the cytokine serum concentration differs compared to healthy subjects. IL-6 and IP-10 seem to be useful in differentiating children with acute phase of urticaria and healthy ones. The search for factors predicting the course of the disease requires further studies.
Poisoning-related emergency department visits in children with autism spectrum disorder
Authors: Cornell Emma , Blanchard Ashley , Chihuri Stanford , DiGuiseppi Carolyn G. , Li Guohua
Published: December 2022

Background

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition, and its prevalence has increased markedly in the past two decades. Research indicates that people with ASD are at increased risk for premature mortality from injuries. Often, children with ASD are prescribed multiple medications, increasing their risk for intentional and unintentional poisonings. We examined the epidemiologic patterns of emergency department (ED)-treated poisonings in children with ASD and the association of ED-treated poisonings with ASD according to common co-occurring conditions.

Methods

We analyzed data from the Nationwide Emergency Department Sample for 2016–2018 to estimate the frequencies of ED-treated poisonings among autistic children aged 1–20 years and adjusted odds ratios of ED-treated poisoning associated with ASD in the presence or absence of co-occurring attention-deficit hyperactivity disorder (ADHD) or intellectual disability (ID). The ICD-10-CM external cause-of-injury matrix was utilized to identify poisoning cases.

Results

During 2016–2018, there were an estimated 523,232 ED visits in children with ASD aged 1–20 years, including 12,152 (2.3%) visits for poisoning. Of ED-treated poisonings in children with ASD, 73.6% were related to pharmaceutical drugs, such as psychotropic medications and prescription opioids, 16.6% were intentional, 36.5% were unintentional, and 47.0% were undetermined. Among children with ASD, those aged 5–9 had the highest odds of poisoning-related ED visits compared to all other age-groups (adjusted OR = 3.41; 95% CI 3.15, 3.68). The odds of poisoning for children with ASD were 59.0% greater than for their peers (adjusted OR = 1.59; 95% CI 1.53, 1.66) and varied significantly with age and co-occurring ADHD or ID.

Conclusions

Children with ASD are at a significantly increased risk of poisoning, particularly among those aged 5–9 years. Co-occurring ADHD or ID with ASD further increases the risk of poisoning. Interventions to reduce poisoning in children with ASD should prioritize the safety of prescription medications.
Open-access tools for the modelling and simulation of electricity markets
Authors: Carvalho Rui , Santos Gabriel , Vale Zita
Published: December 2022

Globally, the amount of renewable energy generation is increasing, which raises the complexity of operating electrical grids to maintain stability and balance and boosts the need for developing new electricity market (EM) models fitting this new reality. To test, study, and validate the possible effects of novel EM designs, simulation techniques are frequently employed. This work proposes the use of two open-access tools for the modeling and simulation of complex EMs. These are the Electricity Markets Service (EMS) and the Spine Toolbox. EMS enables the simulation of two commonly used auction-based algorithms and the execution of three European wholesale EMs. Being published as a web service facilitates its integration with other services, systems, or software agents, such as the Spine Toolbox. The Spine Toolbox, in turn, is an open-source software for complex energy systems modeling. Combining them allows the modeling and simulation of complex EMs from the wholesale to local markets, as well as testing and validating new market designs. This work’s case study demonstrates how to use these tools to simulate the operation of the Iberian EM – MIBEL – for a month, using public data available from the market operator’s website. The results are analyzed from the perspective of the market operator and two players, i.e., a selected buyer and seller, for a specific day and the whole month.
Automatic optimal multi-energy management of smart homes
Authors: Fiorini Laura , Aiello Marco
Published: December 2022

Residential and commercial buildings are responsible for approximately 35% of carbon emissions in industrialized countries. Making buildings more efficient and sustainable is, therefore, a fundamental step toward a low-carbon energy society. A key to achieving sustainability is by leveraging on energy storage systems and smart technologies to switch between energy carriers in order to optimize environmental impact. However, the research on energy management in buildings has mostly focused on its economic aspect, overlooking the environmental dimension. Additionally, the concept of energy system flexibility has been mostly proposed as the ability to shift demand over time or, at most, to curtail it, aiming at reducing the system’s operating costs. We propose a multi-energy multi-objective scheduling model to optimally manage the supply, demand, and interchange of multiple energy carriers, based on dynamic price and carbon emission signals. Our holistic and integrated approach is applied to a group of 200 smart homes with varying thermal and electric loads, and equipped with different types of smart technologies. The effectiveness of the approach in reducing the home carbon footprint, while remunerating the users, is evaluated using historical and statistical data of three European countries.
Heart rate variability among gym-goers and age-matched sedentary individuals
Authors: Ashok C. , Anandhi D. , Jayakumar B. , Jawahar V.
Published: December 2022

Background

The physiological phenomenon of variation in relation to the time interval between two consecutive heartbeats is described as heart rate variability (HRV). Any increase in HRV is associated with good fitness and health and vice versa. The aim of this study is to find and compare the HRV, sympathetic and parasympathetic nervous system dominance in gym-goers, and sedentary individuals.

Methodology

A cross-sectional study was conducted among 10 gym-goers and 10 sedentary individuals, aged 18–22 years. The HRV was determined by the elite HRV (mobile application) and Kubios software.

Outcome measure

HRV

Result

The median values of HRV
and LF/HF(Low Frequency/High Frequency) ratio for Gym goers is 57.5 & 1.85
whereas for a sedentary individual is 54.5 & 2.6.

Conclusion

This study concluded that age-matched sedentary individuals have more SNS dominance than in gym-goers. Likewise, PNS dominance is higher in gym-goers than sedentary individuals, but it is not statistically significant (p > 0.05).
Genetic-evolutionary adaptive moment estimation-based semisupervised deep sequential convolution network for seismic impedance inversion: Application and uncertainty analysis
Authors: Dixit Anjali , Mandal Animesh , Ganguli Shib Sankar , Sanyal Subhajit
Published: December 2022

Recent developments in deep learning have shown significant improvement in the accuracy of acoustic impedance inversion results. However, the conventional gradient-based optimizers such as the root-mean-square propagation, the momentum, the adaptive moment estimation (ADAM), etc., used in the deep learning framework, inherently tend to converge at the nearest optimum point, thereby compromising the solution by not attaining the global minimum. We apply a hybrid global optimizer, genetic-evolutionary ADAM (GADAM) to address the issue of convergence at a local optimum in a semisupervised deep sequential convolution network-based learning framework to solve the nonconvex seismic impedance inversion problem. GADAM combines the advantages of adaptive learning of ADAM and genetic evolution of genetic algorithm, which facilitates faster convergence, and avoids sinking into the local minima. The efficacy of GADAM is tested on synthetic benchmark data and field examples. The results are compared with that obtained from a widely used ADAM optimizer and conventional least-squares method. In addition, uncertainty analysis is performed to check the implication of the optimizer’s choice in obtaining efficient and accurate seismic impedance values. Results find that the level of uncertainty and minima of loss function attained using the GADAM optimizer are comparatively lower than that for ADAM. Thus, we demonstrate that the hybrid optimizer, i.e., GADAM is more efficient than the extensively used ADAM optimizer in impedance estimation from seismic data in a deep learning framework.
Circulating Tumor DNA Profiling for Detection, Risk Stratification, and Classification of Brain Lymphomas
Authors: Mutter Jurik A. , Alig Stefan K. , Esfahani Mohammad S. , Lauer Eliza M. , Mitschke Jan , Kurtz David M. , Kühn Julia , Bleul Sabine , Olsen Mari , Liu Chih Long , Jin Michael C. , Macaulay Charles W. , Neidert Nicolas , Volk Timo , Eisenblaetter Michel , Rauer Sebastian , Heiland Dieter H. , Finke Jürgen , Duyster Justus , Wehrle Julius , Prinz Marco , Illerhaus Gerald , Reinacher Peter C. , Schorb Elisabeth , Diehn Maximilian , Alizadeh Ash A. , Scherer Florian
Published: December 2022

PURPOSE

Clinical outcomes of patients with CNS lymphomas (CNSLs) are remarkably heterogeneous, yet identification of patients at high risk for treatment failure is challenging. Furthermore, CNSL diagnosis often remains unconfirmed because of contraindications for invasive stereotactic biopsies. Therefore, improved biomarkers are needed to better stratify patients into risk groups, predict treatment response, and noninvasively identify CNSL.

PATIENTS AND METHODS

We explored the value of circulating tumor DNA (ctDNA) for early outcome prediction, measurable residual disease monitoring, and surgery-free CNSL identification by applying ultrasensitive targeted next-generation sequencing to a total of 306 tumor, plasma, and CSF specimens from 136 patients with brain cancers, including 92 patients with CNSL.

RESULTS

Before therapy, ctDNA was detectable in 78% of plasma and 100% of CSF samples. Patients with positive ctDNA in pretreatment plasma had significantly shorter progression-free survival (PFS, P < .0001, log-rank test) and overall survival (OS, P = .0001, log-rank test). In multivariate analyses including established clinical and radiographic risk factors, pretreatment plasma ctDNA concentrations were independently prognostic of clinical outcomes (PFS HR, 1.4; 95% CI, 1.0 to 1.9; P = .03; OS HR, 1.6; 95% CI, 1.1 to 2.2; P = .006). Moreover, measurable residual disease detection by plasma ctDNA monitoring during treatment identified patients with particularly poor prognosis following curative-intent immunochemotherapy (PFS, P = .0002; OS, P = .004, log-rank test). Finally, we developed a proof-of-principle machine learning approach for biopsy-free CNSL identification from ctDNA, showing sensitivities of 59% (CSF) and 25% (plasma) with high positive predictive value.

CONCLUSION

We demonstrate robust and ultrasensitive detection of ctDNA at various disease milestones in CNSL. Our findings highlight the role of ctDNA as a noninvasive biomarker and its potential value for personalized risk stratification and treatment guidance in patients with CNSL.

[Media: see text]
Dynamical vertex correction to the generalized Kadanoff-Baym Ansatz
Authors: Kalvová A. , Špička V. , Velický B. , Lipavský P.
Published: December 2022

The generalized Kadanoff-Baym Ansatz, used to simplify the non-equilibrium Green's functions to the kinetic equation for the density matrix, leads to an incorrect dynamics of a system if the self-energy has a rich energy spectrum. We propose an approximation of the vertex correction which dynamically changes with the density matrix while it benefits from simplicity of stationary propagators. On the molecular bridge between ferromagnetic leads, we demonstrate that this simple vertex fixes the failure of the kinetic equation on a negligible computational cost.
Erratum: Stochastic theory of gravitational relaxation and Lévy-fractional Klein-Kramers equation
Authors: Milovanov A. V.
Published: December 2022

Original article:
EPL, 140 (2022) 59001.