bluuebunny/crossref_metadata_2025 huggingface dataset:
Influence of Early Life Factors, including breast milk Composition, on the Microbiome of Infants Born to Mothers with and without Inflammatory Bowel Disease
Authors: Sabino João , Tarassishin Leonid , Eisele Caroline , Hawkins Kelly , Barré Amelie , Nair Nile , Rendon Alexa , Debebe Anketse , Picker Mellissa , Agrawal Manasi , Stone Joanne , George James , Legnani Peter , Maser Elana , Chen Ching-Lynn , Thjømøe Anne , Mørk Einar , Dubinsky Marla , Hu Jianzhong , Colombel Jean-Frederic , Peter Inga , Torres Joanna
Published: June 2023

Background and Aims

Herein we analysed the influence of early life factors, including breast milk composition, on the development of the intestinal microbiota of infants born to mothers with and without IBD.

Methods

The MECONIUM [Exploring MEChanisms Of disease traNsmission In Utero through the Microbiome] study is a prospective cohort study consisting of pregnant women with or without IBD and their infants. Longitudinal stool samples were collected from babies and analysed using 16s rRNA sequencing and faecal calprotectin. Breast milk proteomics was profiled using Olink inflammation panel.

Results

We analysed gut microbiota of 1034 faecal samples from 294 infants [80 born to mothers with and 214 to mothers without IBD]. Alpha diversity was driven by maternal IBD status and time point. The major influencers of the overall composition of the microbiota were mode of delivery, feeding, and maternal IBD status. Specific taxa were associated with these exposures, and maternal IBD was associated with a reduction in Bifidobacterium. In 312 breast milk samples [91 from mothers with IBD], mothers with IBD displayed lower abundance of proteins involved in immune regulation, such as thymic stromal lymphopoietin, interleukin-12 subunit beta, tumour necrosis factor-beta, and C-C motif chemokine 20, as compared with control mothers [adjusted p = 0.0016, 0.049, 0.049, and 0.049, respectively], with negative correlations with baby´s calprotectin, and microbiome at different time points.

Conclusion

Maternal IBD diagnosis influences microbiota in their offspring during early life. The proteomic profile of breast milk of women with IBD differs from that of women without IBD, with distinct time-dependent associations with baby’s gut microbiome and feacal calprotectin.
Autoimmune Pancreatitis in Patients with Inflammatory Bowel Disease: A Real-World Multicentre Collaborative ECCO CONFER Study
Authors: Eder Piotr , Verstock Bram , Culver Emma , Dragoni Gabriele , Kredel Lea Isabell , Wypych Joanna , de Paredes Ana Garcia Garcia , Kaniewska Magdalena , Leibovitzh Haim , Lobaton Triana , Truyens Marie , Oracz Grzegorz , Ribaldone Davide Giuseppe , Starzyńska Teresa , Badaoui Abdenor , Rahier Jean-Francois , Bezzio Cristina , Bossuyt Peter , Falloon Katherine , Pugliese Daniela , Frakes Vozzo Catherine , Jess Tine , Larsen Lone , Olesen Søren Schou , Pal Partha , Chaparro María , Dror Dikla , Ellul Pierre , Gromny Iga , Janiak Maria , Maciejewska Katarzyna , Peleg Noam , Bar-Gil Shitrit Ariella , Szwed Łukasz , Talar-Wojnarowska Renata , Snir Yifat , Weisshof Roni , Zittan Eran , Miechowicz Izabela , Goren Idan
Published: June 2023

Background

Autoimmune pancreatitis [AIP] is rarely associated with inflammatory bowel disease [IBD]. The long-term outcomes of AIP and IBD in patients with coexisting AIP–IBD and predictors of complicated AIP course have rarely been reported.

Methods

An ECCO COllaborative Network For Exceptionally Rare case reports project [ECCO-CONFER] collected cases of AIP diagnosed in patients with IBD. Complicated AIP was defined as a composite of endocrine and/or exocrine pancreatic insufficiency, and/or pancreatic cancer. We explored factors associated with complicated AIP in IBD.

Results

We included 96 patients [53% males, 79% ulcerative colitis, 72% type 2 AIP, age at AIP diagnosis 35 ± 16 years]. The majority of Crohn’s disease [CD] cases [78%] had colonic/ileocolonic involvement. In 59%, IBD preceded AIP diagnosis, whereas 18% were diagnosed simultaneously. Advanced therapy to control IBD was used in 61% and 17% underwent IBD-related surgery. In total, 82% of patients were treated with steroids for AIP, the majority of whom [91%] responded to a single course of treatment. During a mean follow-up of 7 years, AIP complications occurred in 25/96 [26%] individuals. In a multivariate model, older age at AIP diagnosis was associated with a complicated AIP course (odds ratio [OR] = 1.05, p = 0.008), whereas family history of IBD [OR = 0.1, p = 0.03], and CD diagnosis [OR = 0.2, p = 0.04] decreased the risk of AIP complications. No IBD- or AIP-related deaths occurred.

Conclusions

In this large international cohort of patients with concomitant AIP–IBD, most patients have type 2 AIP and colonic IBD. AIP course is relatively benign and long-term outcomes are favourable, but one-quarter develop pancreatic complications. Age, familial history of IBD, and CD may predict uncomplicated AIP course.
Juxtaposition of urgent angioplasty results in spontaneous coronary artery dissection: a case report of fresh vs. organized intramural haematoma
Authors: McConkey Hannah Z R , De Maria Giovanni Luigi
Published: June 2023

Background

Coronary intramural haematoma from spontaneous coronary artery dissection (SCAD) presents as an acute coronary syndrome, usually in young or middle-aged female patients. Conservative management in the absence of ongoing symptoms is best practice, and the artery eventually heals fully.

Case summary

A 49-year-old female presented with a non-ST elevation myocardial infarction. Initial angiography and intravascular ultrasound (IVUS) demonstrated typical intramural haematoma of the ostial to mid left circumflex artery. Initial conservative management was selected, but the patient developed further chest pain 5 days later and with worsening electrocardiogram changes. Further angiography was carried out demonstrating near-occlusive disease with organized thrombus in the false lumen. The angioplasty result from this is juxtaposed with another acute SCAD case on the same day with fresh intramural haematoma.

Discussion

Reinfarction is a common occurrence in SCAD, and little is known about how to predict it. These cases demonstrate the appearance on IVUS of fresh vs. organized thrombus and the relative angioplasty result in each case. Follow-up IVUS due to ongoing symptoms in one patient demonstrated significant stent malapposition, not apparent at the index intervention, in all likeliness due to intramural haematoma regression.
Juvenile-onset multifocal atrial arrhythmias, atrial standstill and compound heterozygosity of genetic variants in TAF1A: sentinel event for evolving dilated cardiomyopathy—a case report
Authors: ter Bekke Rachel M A , de Schouwer Koen , Conti Sergio , Claes Godelieve R F , Vanoevelen Jo , Gommers Suzanne , Helderman-van den Enden Apollonia T J M , Brunner-LaRocca Hans-Peter
Published: June 2023

Background

Juvenile onset of extensive atrial electromechanical failure, including atrial standstill, is a rare disease entity that may precede ventricular cardiomyopathy. Genetic variants associated with early-onset atrioventricular (AV) cardiomyopathy are increasingly recognized.

Case summary

A 16-year-old patient presented with atrial brady- and tachyarrhythmias and concomitant impaired atrial electromechanical function (atrial standstill). The atrial phenotype preceded the development of a predominantly right-sided AV dilated cardiomyopathy with pronounced myocardial fibrosis. A His-bundle pacemaker was installed for high-degree AV conduction block and sinus arrest. Using familial-based whole-exome sequencing, a missense mutation and a copy number variant deletion (compound heterozygosity) of the TAF1A gene (involved in ribosomal RNA synthesis) were identified.

Discussion

Juvenile onset of severe atrial electromechanical failure with atrial arrhythmias should prompt deep pheno- and genotyping and calls for vigilance for downstream cardiomyopathic deterioration.
Incidence of 12 common cardiovascular diseases and subsequent mortality risk in the general population
Authors: Prugger Christof , Perier Marie-Cécile , Gonzalez-Izquierdo Arturo , Hemingway Harry , Denaxas Spiros , Empana Jean-Philippe
Published: June 2023

Background

Incident events of cardiovascular diseases (CVDs) are heterogenous and may result in different mortality risks. Such evidence may help inform patient and physician decisions in CVD prevention and risk factor management.

Aims

This study aimed to determine the extent to which incident events of common CVD show heterogeneous associations with subsequent mortality risk in the general population.

Methods and results

Based on England-wide linked electronic health records, we established a cohort of 1 310 518 people ≥30 years of age initially free of CVD and followed up for non-fatal events of 12 common CVD and cause-specific mortality. The 12 CVDs were considered as time-varying exposures in Cox’s proportional hazards models to estimate hazard rate ratios (HRRs) with 95% confidence intervals (CIs). Over the median follow-up of 4.2 years (2010–16), 81 516 non-fatal CVD, 10 906 cardiovascular deaths, and 40 843 non-cardiovascular deaths occurred. All 12 CVDs were associated with increased risk of cardiovascular mortality, with HRR (95% CI) ranging from 1.67 (1.47–1.89) for stable angina to 7.85 (6.62–9.31) for haemorrhagic stroke. All 12 CVDs were also associated with increased non-cardiovascular and all-cause mortality risk but to a lesser extent: HRR (95% CI) ranged from 1.10 (1.00–1.22) to 4.55 (4.03–5.13) and from 1.24 (1.13–1.35) to 4.92 (4.44–5.46) for transient ischaemic attack and sudden cardiac arrest, respectively.

Conclusion

Incident events of 12 common CVD show significant adverse and markedly differential associations with subsequent cardiovascular, non-cardiovascular, and all-cause mortality risk in the general population.
Disruption of the skin, gill, and gut mucosae microbiome of gilthead seabream fingerlings after bacterial infection and antibiotic treatment
Authors: Rosado Daniela , Canada Paula , Marques Silva Sofia , Ribeiro Nuno , Diniz Pedro , Xavier Raquel
Published: June 2023

The activity of the microbiome of fish mucosae provides functions related to immune response, digestion, or metabolism. Several biotic and abiotic factors help maintaining microbial homeostasis, with disruptions leading to dysbiosis. Diseases and antibiotic administration are known to cause dysbiosis in farmed fish. Pathogen infections greatly affect the production of gilthead seabream, and antibiotic treatment is still frequently required. Here, we employed a 16S rRNA high-throughput metataxonomics approach to characterize changes in the gut, skin, and gill microbiomes occurring due to infection with Photobacterium damselae subsp. piscicida and subsequent antibiotic treatment with oxytetracycline (OTC), as well as during recovery. Although microbiota response differed between studied tissues, overall changes in composition, diversity, structure, and predicted function were observed in all mucosae. The skin and gill microbiomes of diseased fish became largely dominated by taxa that have been frequently linked to secondary infections, whereas in the gut the genus Vibrio, known to include pathogenic bacteria, increased with OTC treatment. The study highlights the negative impacts of disease and antibiotic treatment on the microbiome of farmed fish. Our results also suggest that fish transportation operations may have profound effects on the fish microbiome, but further studies are needed to accurately evaluate their impact.
Education, Social Engagement, and Cognitive Function: A Cross-Lagged Panel Analysis
Authors: Du Chenguang , Miyazaki Yasuo , Dong XinQi , Li Mengting
Published: June 2023

Objectives

Although education and social engagement are considered cognitive reserves, the pathway of both reserves on cognitive function has been rarely studied. This study aimed to examine the underlying mechanism between education, social engagement, and cognitive function.

Methods

This study used 2-wave data (2010 and 2014) from Health and Retirement Study in the United States (N = 3,201). Education was measured by years of schooling. Social engagement was evaluated by 20 items including volunteering, physical activities, social activities, and cognitive activities. Cognitive function was assessed by a modified Telephone Interview for Cognitive Status. A cross-lagged panel model was fitted to test the mediating mechanism between education, social engagement, and cognitive function.

Results

Controlling for covariates, higher education in early life was associated with better cognitive function in old age (b = 0.211, 95% confidence interval [CI] = [0.163, 0.259], p < .01). Late-life social engagement partially mediated the association between education and cognitive function (indirect effect = 0.021, 95% CI = [0.010, 0.033], p < .01). The indirect path between education and social engagement via cognition also existed (b = 0.009, 95% CI = [0.005, 0.012], p < .001).

Discussion

Education in earlier life stage may exert a lifelong effect on cognitive function as well as an indirect effect via enhancing late-life cognitive reserve such as social engagement. The cross-lagged effect of social engagement on cognitive function is significant and vice versa. Future research may explore other cognitive reserves over the life course and its underlying mechanism to achieve healthy cognitive aging.
Multimorbidity and Quality of Life: The Mediating Role of ADL, IADL, Loneliness, and Depressive Symptoms
Authors: Sieber Stefan , Roquet Angélique , Lampraki Charikleia , Jopp Daniela S
Published: June 2023

Background and Objectives

The ubiquity of multimorbidity makes it crucial to examine the intermediary factors linking it with quality of life (QoL). The objective was to examine to what extent the association between multimorbidity and QoL was mediated by functional and emotional/mental health and how these mediation pathways differed by sociodemographic factors (age, gender, education, and financial strain).

Research Design and Methods

Data from Waves 4 to 8 of 36,908 individuals from the Survey of Health, Aging, and Retirement in Europe (SHARE) were included. Multimorbidity (exposure) was defined as having 2 or more chronic conditions. Mediators included limitations with (instrumental) activities of daily living (ADL and IADL), loneliness, and depressive symptoms. QoL (outcome) was assessed with the CASP-12 scale. Longitudinal model-based causal mediation analyses were performed to decompose the total association between multimorbidity and QoL into direct and indirect effects. Moderated mediation analyses tested for differences in mediation pathways by sociodemographic factors.

Results

Multimorbidity was significantly associated with lower QoL (direct effect: b = −0.66). This association was mediated by ADL limitations (percentage mediated 0.97%), IADL limitations (3.24%), and depressive symptoms (16.70%), but not by loneliness. The mediation pathways were moderated by age, education, financial strain, and gender.

Discussion and Implications

ADL, IADL, and depressive symptoms are crucial intermediary factors between multimorbidity and QoL in older European adults, with changing importance according to age, education, financial strain, and gender. The findings may help to increase the QoL of individuals with multimorbidity and redirect care efforts to these factors.
Direct antitumoral effects of sulfated fucans isolated from echinoderms: a possible role of neuropilin-1/β1 integrin endocytosis and focal adhesion kinase degradation
Authors: Lima Antonio G F , Mignone Viviane W , Vardiero Francisco , Kozlowski Eliene O , Fernandes Laila R , Motta Juliana M , Pavão Mauro S G , Figueiredo Camila C , Mourão Paulo A S , Morandi Verônica
Published: June 2023

Hypercoagulability, a major complication of metastatic cancers, has usually been treated with heparins from natural sources, or with their synthetic derivatives, which are under intense investigation in clinical oncology. However, the use of heparin has been challenging for patients with risk of severe bleeding. While the systemic administration of heparins, in preclinical models, has shown primarily attenuating effects on metastasis, their direct effect on established solid tumors has generated contradictory outcomes. We investigated the direct antitumoral properties of two sulfated fucans isolated from marine echinoderms, FucSulf1 and FucSulf2, which exhibit anticoagulant activity with mild hemorrhagic potential. Unlike heparin, sulfated fucans significantly inhibited tumor cell proliferation (by ~30–50%), and inhibited tumor migration and invasion in vitro. We found that FucSulf1 and FucSulf2 interacted with fibronectin as efficiently as heparin, leading to loss of prostate cancer and melanoma cell spreading. The sulfated fucans increased the endocytosis of β1 integrin and neuropilin-1 chains, two cell receptors implicated in fibronectin-dependent adhesion. The treatment of cancer cells with both sulfated fucans, but not with heparin, also triggered intracellular focal adhesion kinase (FAK) degradation, with a consequent overall decrease in activated focal adhesion kinase levels. Finally, only sulfated fucans inhibited the growth of B16-F10 melanoma cells implanted in the dermis of syngeneic C57/BL6 mice. FucSulf1 and FucSulf2 arise from this study as candidates for the design of possible alternatives to long-term treatments of cancer patients with heparins, with the advantage of also controlling local growth and invasion of malignant cells.
A Longitudinal Study Examining the Effects of COVID-19 on Refugees Four Years Postresettlement in the United States
Authors: Shaw Stacey A , Middleton Heather , Poulin Patrick , Rodgers Graeme , Leung Tara
Published: June 2023

During the COVID-19 pandemic, many refugee communities faced intensified economic and social challenges. This longitudinal study began three years prior to the COVID pandemic and examined the effects of COVID on refugee outcomes in the United States including employment, health insurance, safety, and discrimination. The study also examined participant perspectives on COVID-related challenges. Participants included 42 refugees who resettled approximately three years prior to the onset of the pandemic. Data were collected at six months, 12 months, two years, three years, and four years postarrival, with the pandemic beginning between years 3 and 4. Linear growth models examined how the pandemic impacted participant outcomes over time. Descriptive analyses examined perspectives regarding pandemic challenges. Results indicated that during the pandemic, employment and safety significantly decreased. Participant concerns regarding the pandemic centered on health, economic challenges, and isolation. Attention to refugee outcomes during the COVID pandemic highlight the need for social work practitioners to promote equitable access to information and social supports, particularly during times of uncertainty.
A Recombinant Vesicular Stomatitis Virus–Based Vaccine Provides Postexposure Protection Against Bundibugyo Ebolavirus Infection
Authors: Woolsey Courtney , Strampe Jamie , Fenton Karla A , Agans Krystle N , Martinez Jasmine , Borisevich Viktoriya , Dobias Natalie S , Deer Daniel J , Geisbert Joan B , Cross Robert W , Connor John H , Geisbert Thomas W
Published: June 2023

Background

The filovirus Bundibugyo virus (BDBV) causes severe disease with a mortality rate of approximately 20%–51%. The only licensed filovirus vaccine in the United States, Ervebo, consists of a recombinant vesicular stomatitis virus (rVSV) vector that expresses Ebola virus (EBOV) glycoprotein (GP). Ervebo was shown to rapidly protect against fatal Ebola disease in clinical trials; however, the vaccine is only indicated against EBOV. Recent outbreaks of other filoviruses underscore the need for additional vaccine candidates, particularly for BDBV infections.

Methods

To examine whether the rVSV vaccine candidate rVSVΔG/BDBV-GP could provide therapeutic protection against BDBV, we inoculated seven cynomolgus macaques with 1000 plaque-forming units of BDBV, administering rVSVΔG/BDBV-GP vaccine to 6 of them 20–23 minutes after infection.

Results

Five of the treated animals survived infection (83%) compared to an expected natural survival rate of 21% in this macaque model. All treated animals showed an early circulating immune response, while the untreated animal did not. Surviving animals showed evidence of both GP-specific IgM and IgG production, while animals that succumbed did not produce significant IgG.

Conclusions

This small, proof-of-concept study demonstrated early treatment with rVSVΔG/BDBV-GP provides a survival benefit in this nonhuman primate model of BDBV infection, perhaps through earlier initiation of adaptive immunity.
Use of Next-Generation Sequencing in a State-Wide Strategy of HIV-1 Surveillance: Impact of the SARS-COV-2 Pandemic on HIV-1 Diagnosis and Transmission
Authors: Zhou Shuntai , Long Nathan , Moeser Matt , Hill Collin S , Samoff Erika , Mobley Victoria , Frost Simon , Bayer Cara , Kelly Elizabeth , Greifinger Annalea , Shone Scott , Glover William , Clark Michael , Eron Joseph , Cohen Myron , Swanstrom Ronald , Dennis Ann M
Published: June 2023

Background

The ongoing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posed an unpreceded threat to the management of other pandemics such as human immunodeficiency virus-1 (HIV-1) in the United States. The full impact of the SARS-CoV-2 pandemic on the HIV-1 pandemic needs to be evaluated.

Methods

All individuals with newly reported HIV-1 diagnoses from NC State Laboratory of Public Health were enrolled in this prospective observational study, 2018–2021. We used a sequencing-based recency assay to identify recent HIV-1 infections and to determine the days postinfection (DPI) for each person at the time of diagnosis.

Results

Sequencing used diagnostic serum samples from 814 individuals with new HIV-1 diagnoses spanning this 4-year period. Characteristics of individuals diagnosed in 2020 differed from those in other years. People of color diagnosed in 2021 were on average 6 months delayed in their diagnosis compared to those diagnosed in 2020. There was a trend that genetic networks were more known for individuals diagnosed in 2021. We observed no major integrase resistance mutations over the course of the study.

Conclusions

SARS-CoV-2 pandemic may contribute to the spread of HIV-1. Public health resources need to focus on restoring HIV-1 testing and interrupting active, ongoing, transmission.
Half-life Estimation of Pertussis-Specific Maternal Antibodies in (Pre)Term Infants After In-Pregnancy Tetanus, Diphtheria, Acellular Pertussis Vaccination
Authors: Embacher Stefan , Maertens Kirsten , Herzog Sereina A
Published: June 2023

Background

To reduce the risk of pertussis-related morbidity and mortality in early life, an increasing number of countries recommend maternal pertussis vaccination. However, there is limited knowledge about half-lives of vaccine-induced pertussis-specific maternal antibodies, especially in preterm infants, and factors potentially influencing them.

Methods

We compared 2 different approaches to provide estimates of the half-lives of pertussis-specific maternal antibodies in infants and explored potential effects on the half-life in 2 studies. In the first approach, we estimated the half-lives per child and used these estimates as responses in linear models. In the second approach, we used linear mixed effect models on a log2 transformed scale of the longitudinal data to use the inverse of the time parameter as an estimate for the half-lives.

Results

Both approaches provided similar results. The identified covariates partly explain differences in half-life estimates. The strongest evidence we observed was a difference between term and preterm infants, with the preterm infants showing a longer half-life. Among others, a longer interval between vaccination and delivery increases the half-life.

Conclusions

Several variables influence the decay speed of maternal antibodies. Both approaches have advantages and disadvantages, while the choice is secondary when assessing the half-life of pertussis-specific antibodies.

Clinical Trials Registration

NCT02408926 and NCT02511327.
Cotreatment With Clofazimine and Rapamycin Eliminates Drug-Resistant Tuberculosis by Inducing Polyfunctional Central Memory T-Cell Responses
Authors: Singh Dhiraj Kumar , Bhaskar Ashima , Pahuja Isha , Shaji Aishwarya , Moitra Barnani , Shi Yufang , Dwivedi Ved Prakash , Das Gobardhan
Published: June 2023

Mycobacterium tuberculosis, the causative agent of tuberculosis, is acquiring drug resistance at a faster rate than the discovery of new antibiotics. Therefore, alternate therapies that can limit the drug resistance and disease recurrence are urgently needed. Emerging evidence indicates that combined treatment with antibiotics and an immunomodulator provides superior treatment efficacy. Clofazimine (CFZ) enhances the generation of T central memory (TCM) cells by blocking the Kv1.3+ potassium channels. Rapamycin (RAPA) facilitates M. tuberculosis clearance by inducing autophagy. In this study, we observed that cotreatment with CFZ and RAPA potently eliminates both multiple and extensively drug-resistant (MDR and XDR) clinical isolates of M. tuberculosis in a mouse model by inducing robust T-cell memory and polyfunctional TCM responses. Furthermore, cotreatment reduces the expression of latency-associated genes of M. tuberculosis in human macrophages. Therefore, CFZ and RAPA cotherapy holds promise for treating patients infected with MDR and XDR strains of M. tuberculosis.
Machine learning-based detection of transportation infrastructure internal defects using ground-penetrating radar: a state-of-the-art review
Authors: Sui Xin , Leng Zhen , Wang Siqi
Published: June 2023

Early detection of internal defects is crucial to ensure the long-term performance and stability of transportation infrastructure. Researchers and practitioners have developed various nondestructive testing (NDT) methods for this purpose. Among them, the ground-penetrating radar (GPR) technique has been widely implemented due to its advantages such as large coverage, traffic-speed survey, and rich subsurface information. In addition, machine learning (ML) algorithms have been frequently applied to achieve automatic GPR data interpretations, which are essential for field applications. However, the fundamental concepts, architectures, and appropriate application scenarios of these algorithms are often questionable to practitioners and researchers. This paper presents a state-of-the-art review of ML applications in the internal defect detection of transportation infrastructure using GPR. In particular, pavements and bridges are covered. The basic knowledge of GPR working principles and ML algorithms is documented. The critical features of the ML algorithms for each detection task are presented. The drawbacks that may hinder the application of ML algorithms using GPR are indicated, including the insufficiency of labeled GPR data, unavailability of GPR dataset, customized ML architecture, and field validation. Finally, possible transfer learning, integrated robotic platform, and data fusion with other NDT methods are discussed. This review paper is expected to serve as a reference for practitioners to choose appropriate ML algorithms to detect internal defects in transportation infrastructure using GPR.
Performative Activism Redeemed
Authors: Ventzislavov Rossen
Published: June 2023

Over the last century, performance art has troubled the worlds of art and of philosophical aesthetics, unleashing modes of creativity and criticality that spill outside the customary boundaries of either. One of these modes is that of political activism. Performance art is genetically related to activism due to the shared historical contexts their respective waves have emerged from and responded to. In my article, I make the claim that the relationship between performance art and activism also has much to do with certain significant structural and methodological overlaps between the two. I explore these overlaps against the backdrop of extant philosophical scholarship on performativity, a selection of art historical examples, and a critique of the charge of “performative activism” that has become popular in the last decade. I see the tension between the figurative meaning of the phrase “performative activism” and its literal application to politically charged performance art as a space of philosophical opportunity. A better understanding of performance art and its political import can not only help clear up laypeople’s misconceptions of performativity, but it can also strengthen philosophy’s own position on the subject.
Residue Lys219 of CpxR is critical in the regulation of the antibiotic resistance of Escherichia coli
Authors: Lei Dan , Cao Linlin , Zhong Tairan , He Qing-Yu , Sun Xuesong
Published: June 2023

Background

CpxR is a critical regulator in bacterial adaptation to various harmful stresses, and is known to regulate bacterial resistance to commonly used antibiotics, such as aminoglycosides, β-lactams and polypeptides. However, the detailed study of functional residues of CpxR remains insufficient.

Objectives

To investigate the contribution of Lys219 to CpxR’s function in regulating antibiotic resistance of Escherichia coli.

Methods

We performed sequence alignment and conservative analysis of the CpxR protein and constructed mutant strains. We then performed electrophoretic mobility shift assay, real-time quantitative PCR assay, determination of reactive oxygen species (ROS) levels, molecular dynamics simulation, conformational analysis and circular dichroism.

Results

All mutant proteins (K219Q, K219A and K219R) lost the cpxP DNA-binding ability. Additionally, the three complemented strains eK219A, eK219Q, and eK219R exhibited lower resistance to copper toxicity and alkaline pH toxicity than eWT. Molecular dynamics analysis revealed that mutation of Lys219 leads to looser and more unstable conformation of CpxR, leading to its decreased binding affinity with downstream genes. Moreover, the Lys219 mutation resulted in the down-regulation of efflux pump genes (acrD, tolC, mdtB and mdtA), leading to the accumulation of antibiotics inside the cells and an increase in ROS production, which significantly reduces antibiotic resistance.

Conclusions

The mutation of the key residue Lys219 causes a conformational change that results in the loss of regulatory ability of CpxR, which may potentially reduce to antibiotic resistance. Therefore, this study suggests that targeting the highly conserved sequence of CpxR could be a promising strategy for the development of new antibacterial drugs.
Utilization of Chemometric-Aided UV Spectrophotometric Methods for Concurrent Assessment of Emtricitabine, Tenofovir Disoproxil Fumarate, Elvitegravir, and Cobicistat in Tablet Formulation
Authors: Singh Veena Devi , Singh Vijay Kumar , Daharwal Sanjay J
Published: June 2023

Background

Emtricitabine (ETC), tenofovir disoproxil fumarate (TNF), elvitegravir (EVG), and cobicistat (CBS) are antiviral drugs used to treat human immunodeficiency virus (HIV) infections.

Objective

To develop chemometric-aided UV spectrophotometric methods for concurrent estimation of the aforementioned drugs used to treat HIV. This method can be used to reduce modification of the calibration model by assessing the absorbance at various points in the zero-order spectra within the selected wavelength range. Additionally, it eliminates interfering signals and provides sufficient resolution in multi-component systems.

Methods

Two chemometric-assisted UV spectrophotometric methods, namely, partial least-squares (PLS) and principal component regression (PCR) models, were established for the concurrent assessment of EVG, CBS, TNF, and ETC in tablet formulations. The proposed methods were applied to decrease complexity of overlapped spectra and to achieve maximum sensitivity and the lowest error. These approaches were performed in accordance with International Council on Harmonization (ICH) criteria and compared to the reported HPLC method.

Results

The proposed methods were used to assess EVG, CBS, TNF, and ETC in the ranges of 5–30, 5–30 , 5–50, and 5–50 µg/mL, respectively, with an excellent correlation coefficient (r2 ≥ 0.998). The accuracy and precision results were found to be within the acceptable limits. No statistical difference was observed between the proposed and reported studies.

Conclusion

The chemometric-aided UV spectrophotometric approaches could be considered as alternatives to chromatographic procedures in the pharmaceutical industry for routine analysis and testing of readily accessible commercial formulations.

Highlights

Novel chemometric-assisted UV spectrophotometric techniques were developed for assessment of multicomponent antiviral combinations in single-tablet formulations. The proposed methods were performed without using harmful solvents, tedious preparation, or expensive instruments. The proposed methods were compared statistically with a reported HPLC method. Assessment of EVG, CBS, TNF, and ETC was performed without interference from excipients in their multicomponent formulations.
Clinical perspectives of rare ovarian tumors: clear cell ovarian cancer
Authors: Fujiwara Satoe
Published: June 2023

Ovarian clear cell carcinoma (OCCC) is a rare and distinct histological type of epithelial ovarian carcinoma in terms of its histopathological, clinical and genetic features. Patients with OCCC are younger and diagnosed at earlier stages than those with the most common histological type—high-grade serous carcinoma. Endometriosis is considered a direct precursor of OCCC. Based on preclinical data, the most frequent gene alternations in OCCC are mutations of AT-rich interaction domain 1A and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha. The prognosis of patients with early-stage OCCC is favorable, whereas patients at an advanced stage or who have the recurrent disease have a dismal prognosis due to OCCC’s resistance to standard platinum-based chemotherapy. Despite a lower rate of response due to its resistance to standard platinum-based chemotherapy, the treatment strategy for OCCC resembles that of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and adjuvant platinum-based chemotherapy. Alternative treatment strategies, including biological agents based on molecular characteristics specific to OCCC, are urgently needed. Furthermore, due to its rarity, well-designed collaborative international clinical trials are needed to improve oncologic outcomes and the quality of life in patients with OCCC.
Merkel cell carcinoma: a review of clinical management with focus on Asian patients
Authors: Nakano Eiji , Ogata Dai , Namikawa Kenjiro , Yamazaki Naoya
Published: June 2023

Merkel cell carcinoma is a highly aggressive skin cancer characterized by neuroendocrine differentiation. This review aimed to present updates on the knowledge and current trends of clinical management of Merkel cell carcinoma. Additionally, we focused on Asian reports of Merkel cell carcinoma because most skin cancers differ substantially between Caucasians and Asians, and researchers have reported differences in Merkel cell carcinoma in racial and ethnic groups. Owing to its rarity, there is limited evidence for the epidemiology, pathogenesis, diagnosis and Merkel cell carcinoma treatment. The development of a nationwide survey or cancer registry, the identification of Merkel cell polyomavirus and the use of immune checkpoint inhibitors allowed a better understanding of its characteristics and biology and have revolutionized the clinical management of patients with Merkel cell carcinoma. Its incidence has gradually increased worldwide; however, it depends on the geographic location, race and ethnicity. No randomized prospective studies have evaluated the significance of sentinel lymph node biopsy, complete lymph node dissection and adjuvant radiation therapy; however, most patients with localized Merkel cell carcinoma are treated surgically or with post-operative radiation. Patients with distant Merkel cell carcinoma are administered immune checkpoint inhibitors as the first-line therapy; however, there is no established second-line therapy for refractory Merkel cell carcinoma. Furthermore, it is necessary to validate the favorable results of clinical studies performed in Western countries in the patients in Asia.
Ectogestation and the Good Samaritan Argument
Authors: Stratman Christopher
Published: June 2023

Philosophical discussions concerning ectogestation are trending. And given that the Supreme Court of the United States overturned Roe v. Wade (1973) and Casey v. Planned Parenthood (1992), questions regarding the moral and legal status of abortion in light of the advent of ectogestation will likely continue to be of central importance in the coming years. If ectogestation can intersect with or even determine abortion policy in the future, then a new philosophical analysis of the legal status of abortion is both warranted and urgently needed. I argue that, even if there is no ‘moral’ right to fetal destruction once ectogestation becomes a reality, societies ought not to implement legal prohibitions on a pregnant person’s ability to safely obtain an abortion that results in fetal death because such laws are systemically misogynistic.
Insights into the roles of IL-10–producing regulatory B cells in cardiovascular disorders: recent advances and future perspectives
Authors: Zheng Huiqin , Cao Pei , Su Zhaoliang , Xia Lin
Published: June 2023

Interleukin-10–producing regulatory B (B10) cells mediate the immunomodulatory functions of biosystems by secreting anti-inflammatory factors, thus playing vital roles in cardiovascular diseases such as viral myocarditis, myocardial infarction, and ischemia-reperfusion injury. However, several challenges hinder B10 cells from regulating the immunoreactivity of organisms in specific cardiovascular diseases, such as atherosclerotic disease. Regarding the regulatory mechanisms of B10 cells, the interplay between B10 cells and the cardiovascular and immune systems is complex and requires clarification. In this study, we summarize the roles of B10 cells in bacterial and aseptic heart injuries, address their regulatory functions in different stages of cardiovascular disorders, and discuss their challenges and opportunities in addressing cardiovascular diseases from bench to bedside.
Genetic variants, neurocognitive outcomes, and functional neuroimaging in survivors of childhood acute lymphoblastic leukemia
Authors: Gandy Kellen , Sapkota Yadav , Scoggins Matthew A , Jacola Lisa M , Koscik Timothy R , Hudson Melissa M , Pui Ching-Hon , Krull Kevin R , van der Plas Ellen
Published: June 2023

Background

Genetic predispositions may modulate risk for developing neurocognitive late effects in childhood acute lymphoblastic leukemia (ALL) survivors.

Methods

Long-term ALL survivors (n = 212; mean = 14.3 [SD = 4.77] years; 49% female) treated with chemotherapy completed neurocognitive testing and task-based functional neuroimaging. Based on previous work from our team, genetic variants related to the folate pathway, glucocorticoid regulation, drug metabolism, oxidative stress, and attention were included as predictors of neurocognitive performance, using multivariable models adjusted for age, race, and sex. Subsequent analyses evaluated the impact of these variants on task-based functional neuroimaging. Statistical tests were 2-sided.

Results

Survivors exhibited higher rates of impaired attention (20.8%), motor skills (42.2%), visuo-spatial memory (49.3%-58.3%), processing speed (20.1%), and executive function (24.3%-26.1%) relative to population norms (10%; P < .001). Genetic variants implicated in attention deficit phenotypes predicted impaired attention span (synaptosome associated protein 25, F(2,172) = 4.07, P = .019) and motor skills (monoamine oxidase A, F(2,125) = 5.25, P = .007). Visuo-spatial memory and processing speed varied as a function of genetic variants in the folate pathway (methylenetetrahydrofolate reductase [MTHFRrs1801133], F(2,165) = 3.48, P = .033; methylenetetrahydrofolate dehydrogenase 1 [MTHFD1rs2236225], F(2,135) = 3.8, P = .025; respectively). Executive function performance was modulated by genetic variants in the folate pathway (MTHFD1rs2236225, F(2,158) = 3.95, P = .021; MTHFD1rs1950902, F(2,154) = 5.55, P = .005) and glucocorticoid regulation (vitamin D receptor, F(2,158) = 3.29, P = .039; FKBP prolyl isomerase 5, F(2,154) = 5.6, P = .005). Additionally, MTHFD1rs2236225 and FKBP prolyl isomerase 5 were associated with altered brain function during attention and working memory (P < .05; family wise error corrected).

Conclusions

Results extend previous findings of genetic risk of neurocognitive impairment following ALL therapy and highlight the importance of examining genetic modulators in relation to neurocognitive deficits.
Media stereotypes, prejudice, and preference-based reinforcement: toward the dynamic of self-reinforcing effects by integrating audience selectivity
Authors: Arendt Florian
Published: June 2023

The media portray various social groups stereotypically, and studying the effects of these portrayals on prejudice is paramount. Yet, audience selectivity—inherent within today’s high-choice media environments—has largely been disregarded. Relatedly, the predominance of forced-exposure designs is a source of concern. This article proposes the integration of audience selectivity into media stereotype effects research. Study 1 (N = 1,166) indicated that prejudiced individuals tended to approach prejudice-consistent stereotypical news and avoid prejudice-challenging counter-stereotypical news. Using a forced-exposure experiment, study 2 (N = 380) showed detrimental effects of prejudice-consistent news and beneficial effects of prejudice-challenging news. Relying on a self-selected exposure paradigm, study 3 (N = 1,149) provided evidence for preference-based reinforcement. Study 4’s “net-effect perspective” (N = 937) indicated that operationalizing exposure as forced or self-selected can lead to different interpretations of actual societal effects. The findings emphasize the key role played by audience selectivity when studying media effects.
Parenting Interventions Targeting Behavior for Children Born Preterm or Low Birth Weight: A Systematic Review
Authors: Patronick Jamie , Glazer Sandra , Sidol Craig , Parikh Nehal A , Wade Shari L
Published: June 2023

Objective

To systematically review and summarize the outcomes of parenting interventions designed to improve child and/or parenting behavior for children born preterm and/or low birth weight (LBW).

Methods

We conducted systematic searches of Embase, Scopus, PubMed, PsycInfo, and CINAHL in September 2021. We identified articles published at any time that describe the outcomes of parenting interventions targeting the child and/or parenting behavior of children born preterm/LBW and their caregivers. Two independent raters assessed the risk of bias using the Revised Cochrane Risk-of-Bias Tool.

Results

Eight hundred sixteen titles and abstracts were screened, followed by 71 full-text articles, resulting in 24 eligible articles reporting on nine interventions with 1,676 participants. Eligible articles had an adequate risk of bias ratings. Sample characteristics, intervention components, and intervention effects were tabulated and described narratively by the intervention type. Preventative and treatment programs demonstrated positive intervention effects on externalizing behavior, parenting stress, and parenting behaviors, with mixed effects on internalizing behavior and emotion regulation. The few studies with longitudinal follow-up found little evidence of effects beyond 6 months postintervention.

Conclusion

Behavior problems in children born preterm/LBW may be modifiable, and interventions targeting parenting behavior are promising. However, existing interventions may not produce long-lasting changes and are not designed for children older than four. Existing treatment programs may require adaptation for the neurocognitive, medical, and family needs of children born preterm/LBW (e.g., processing speed deficits, post-traumatic stress). Interventions that account for theories of sustained change may promote long-term effectiveness and the developmental tailoring of parenting skills.
The role of miR-21 as a predictive biomarker and a potential target to improve the effects of chemoradiotherapy against head and neck squamous cell carcinoma
Authors: Ishinaga Hajime , Okugawa Yoshinaga , Hou Bo , He Feng , Yin Chengzeng , Murata Mariko , Toiyama Yuji , Takeuchi Kazuhiko
Published: June 2023

This study aimed to clarify whether circulating miR-21 represents a predictive biomarker in patients with head and neck squamous cell carcinoma (HNSCC) undergoing chemoradiotherapy, and to investigate the effect of miR-21 inhibitor for chemoradiation in human SCC cells. Plasma samples were obtained from 22 patients with HNSCC and 25 non-cancer volunteers. Plasma miR-21 expression was measured using real-time quantitative reverse transcription polymerase chain reaction. The effects of miR-21 inhibitor in human SCC cells were investigated by performing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, flow cytometry and western blot analysis. As a result, plasma miR-21 expression was higher in HNSCC patients than in control patients (P < 0.001). Seven patients with recurrence showed significantly higher plasma miR-21 than the 15 patients without recurrence. And high miR-21 expression group showed poor overall survival. Moreover, miR-21 inhibition significantly enhanced cisplatin- or radiation-induced apoptosis. Western blot analysis suggested the programmed cell death 4 protein as a potential target of miR-21 in relation to apoptosis. In conclusion, this study provides new insights into the role of miR-21 as a predictive biomarker for HNSCC treated with chemoradiotherapy and suggests a potential target to improve the effects of chemoradiotherapy against HNSCC.
Disraeli and the Bible
Authors: Dent Megan
Published: June 2023

Benjamin Disraeli has often been represented as a mercurial self-fashioner who adopted various expedient personae over the course of his public life. The biographical emphasis on his eccentric personality has caused many historians to distance Disraeli from his nineteenth-century intellectual contexts in their analysis of his thought. Disraeli wrote within a literary culture that remained invested in the Bible as an important narrative authority. The poetry and fiction of the period inflected, transformed, and challenged this authority, but it also remained in purposeful conversation with the Bible as it forged new moral and literary territory. Disraeli participated in this discourse throughout his fiction, especially in two of his works: Alroy (1833) and Tancred (1847). In these novels Disraeli drew considerably on biblical patterns of kingship and nationhood and often used language from the King James Bible. In surfacing his interest in Scripture, this article suggests that Disraeli represented the Bible’s ancient wisdom as an important bulwark against some of the fast-paced social and political changes of his time and particularly against the ‘Whiggish’ tendencies of his political opponents.