bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms behind changes of neurodegeneration biomarkers in plasma induced by sleep deprivation
Authors: Eide Per Kristian , Lashkarivand Aslan , Pripp Are Hugo , Valnes Lars Magnus , Hovd Markus , Ringstad Geir , Blennow Kaj , Zetterberg Henrik
Published: December 2023

Acute sleep deprivation has been shown to affect cerebrospinal fluid and plasma concentrations of biomarkers associated with neurodegeneration, though the mechanistic underpinnings remain unknown. This study compared individuals who, for one night, were either subject to total sleep deprivation or free sleep, (i) examining plasma concentrations of neurodegeneration biomarkers the morning after sleep deprivation or free sleep and (ii) determining how overnight changes in biomarkers plasma concentrations correlate with indices of meningeal lymphatic and glymphatic clearance functions. Plasma concentrations of amyloid-β 40 and 42, phosphorylated tau peptide 181, glial fibrillary acid protein and neurofilament light were measured longitudinally in subjects who from Day 1 to Day 2 either underwent total sleep deprivation (n = 7) or were allowed free sleep (n = 21). The magnetic resonance imaging contrast agent gadobutrol was injected intrathecally, serving as a cerebrospinal fluid tracer. Population pharmacokinetic model parameters of gadobutrol cerebrospinal fluid-to-blood clearance were utilized as a proxy of meningeal lymphatic clearance capacity and intrathecal contrast-enhanced magnetic resonance imaging as a proxy of glymphatic function. After one night of acute sleep deprivation, the plasma concentrations of amyloid-β 40 and 42 were reduced, but not the ratio, and concentrations of the other biomarkers were unchanged. The overnight change in amyloid-β 40 and 42 plasma concentrations in the sleep group correlated significantly with indices of meningeal lymphatic clearance capacity, while this was not seen for the other neurodegeneration biomarkers. However, overnight change in plasma concentrations of amyloid-β 40 and 42 did not correlate with the glymphatic marker. On the other hand, the overnight change in plasma concentration of phosphorylated tau peptide 181 correlated significantly with the marker of glymphatic function in the sleep deprivation group but not in the sleep group. The present data add to the evidence of the role of sleep and sleep deprivation on plasma neurodegeneration concentrations; however, the various neurodegeneration biomarkers respond differently with different mechanisms behind sleep-induced alterations in amyloid-β and tau plasma concentrations. Clearance capacity of meningeal lymphatics seems more important for sleep-induced changes in amyloid-β 40 and 42 plasma concentrations, while glymphatic function seems most important for change in plasma concentration of phosphorylated tau peptide 181 during sleep deprivation. Altogether, the present data highlight diverse mechanisms behind sleep-induced effects on concentrations of plasma neurodegeneration biomarkers.
Gut-immune axis and cardiovascular risk in chronic kidney disease
Authors: Behrens Felix , Bartolomaeus Hendrik , Wilck Nicola , Holle Johannes
Published: December 2023

Patients with chronic kidney disease (CKD) suffer from marked cardiovascular morbidity and mortality, so lowering the cardiovascular risk is paramount to improve quality of life and survival in CKD. Manifold mechanisms are hold accountable for the development of cardiovascular disease (CVD), and recently inflammation arose as novel risk factor significantly contributing to progression of CVD. While the gut microbiome was identified as key regulator of immunity and inflammation in several disease, CKD-related microbiome-immune interaction gains increasing importance. Here, we summarize the latest knowledge on microbiome dysbiosis in CKD, subsequent changes in bacterial and host metabolism and how this drives inflammation and CVD in CKD. Moreover, we outline potential therapeutic targets along the gut-immune-cardiovascular axis that could aid the combat of CVD development and high mortality in CKD.
Automating the Detection of IV Fluid Contamination Using Unsupervised Machine Learning
Authors: Spies Nicholas C , Hubler Zita , Azimi Vahid , Zhang Ray , Jackups Ronald , Gronowski Ann M , Farnsworth Christopher W , Zaydman Mark A
Published: December 2023

Background

Intravenous (IV) fluid contamination is a common cause of preanalytical error that can delay or misguide treatment decisions, leading to patient harm. Current approaches for detecting contamination rely on delta checks, which require a prior result, or manual technologist intervention, which is inefficient and vulnerable to human error. Supervised machine learning may provide a means to detect contamination, but its implementation is hindered by its reliance on expert-labeled training data. An automated approach that is accurate, reproducible, and practical is needed.

Methods

A total of 25 747 291 basic metabolic panel (BMP) results from 312 721 patients were obtained from the laboratory information system (LIS). A Uniform Manifold Approximation and Projection (UMAP) model was trained and tested using a combination of real patient data and simulated IV fluid contamination. To provide an objective metric for classification, an “enrichment score” was derived and its performance assessed. Our current workflow was compared to UMAP predictions using expert chart review.

Results

UMAP embeddings from real patient results demonstrated outliers suspicious for IV fluid contamination when compared with the simulated contamination's embeddings. At a flag rate of 3 per 1000 results, the positive predictive value (PPV) was adjudicated to be 0.78 from 100 consecutive positive predictions. Of these, 58 were previously undetected by our current clinical workflows, with 49 BMPs displaying a total of 56 critical results.

Conclusions

Accurate and automatable detection of IV fluid contamination in BMP results is achievable without curating expertly labeled training data.
Linguistic identity in multigenerational ethnic minority/ethnically heterogeneous deaf families
Authors: Belenyi Emese , Flora Gavril
Published: December 2023

This paper discusses language use and identity patterns in ethnic minority/ethnically heterogeneous multigenerational deaf families in Romania, where at least one of the family members belongs to the ethnic Hungarian minority. Early childhood and school linguistic socialization, language use within the family, and cross-generational transmission of identity to children are explored. The research is based on five ethnic minority/ethnically heterogeneous multigenerational deaf family case studies. The research results show that within ethnic-national minority/ethnically heterogeneous multigenerational deaf families, complex identity patterns may develop and multifaceted linguistic communication models may prevail, including the use of national oral languages and national sign languages of the parties involved. At the same time, a kind of special linguistic and cultural enrichment, a striving for cultural-linguistic balance, may occur.
Sex differences in outcomes after acute coronary syndrome vary with age: a New Zealand national study
Authors: Earle Nikki J , Doughty Robert N , Devlin Gerry , White Harvey , Riddell Craig , Choi Yeunhyang , Kerr Andrew J , Poppe Katrina K
Published: December 2023

Aims

This study investigated age-specific sex differences in short- and long-term clinical outcomes following hospitalization for a first-time acute coronary syndrome (ACS) in New Zealand (NZ).

Methods and results

Using linked national health datasets, people admitted to hospital for a first-time ACS between January 2010 and December 2016 were included. Analyses were stratified by sex and 10-year age groups. Logistic and Cox regression were used to assess in-hospital death and from discharge the primary outcome of time to first cardiovascular (CV) readmission or death and other secondary outcomes at 30 days and 2 years. Among 63 245 people (mean age 69 years, 40% women), women were older than men at the time of the ACS admission (mean age 73 vs. 66 years), with a higher comorbidity burden. Overall compared with men, women experienced higher rates of unadjusted in-hospital death (10% vs. 7%), 30-day (16% vs. 12%) and 2-year (44% vs. 34%) death, or CV readmission (all P < 0.001). Age group-specific analyses showed sex differences in outcomes varied with age, with younger women (<65 years) at higher risk than men and older women (≥85 years) at lower risk than men: unadjusted hazard ratio of 2-year death or CV readmission for women aged 18–44 years = 1.51 [95% confidence interval (CI) 1.21–1.84] and aged ≥85 years = 0.88 (95% CI 0.83–0.93). The increased risk for younger women was no longer significant after multivariable adjustment whereas the increased risk for older men remained.

Conclusion

Men and women admitted with first-time ACS have differing age and comorbidity profiles, resulting in contrasting age-specific sex differences in the risk of adverse outcomes between the youngest and oldest age groups.
Prognostic value of a novel artificial intelligence-based coronary computed tomography angiography-derived ischaemia algorithm for patients with suspected coronary artery disease
Authors: Bär Sarah , Nabeta Takeru , Maaniitty Teemu , Saraste Antti , Bax Jeroen J , Earls James P , Min James K , Knuuti Juhani
Published: December 2023

Aims

Coronary computed tomography angiography (CTA) imaging is used to diagnose patients with suspected coronary artery disease (CAD). A novel artificial intelligence-guided quantitative computed tomography ischaemia algorithm (AI-QCTischaemia) aims to identify myocardial ischaemia directly from CTA images and may be helpful to improve risk stratification. The aims were to investigate (i) the prognostic value of AI-QCTischaemia amongst symptomatic patients with suspected CAD entering diagnostic imaging with coronary CTA and (ii) the prognostic value of AI-QCTischaemia separately amongst patients with no/non-obstructive CAD (≤50% visual diameter stenosis) and obstructive CAD (>50% visual diameter stenosis).

Methods and results

For this cohort study, AI-QCTischaemia was calculated by blinded analysts amongst patients with suspected CAD undergoing coronary CTA. The primary endpoint was the composite of death, myocardial infarction (MI), or unstable angina pectoris (uAP) (median follow-up 6.9 years). A total of 1880/2271 (83%) patients had conclusive AI-QCTischaemia result. Patients with an abnormal AI-QCTischaemia result (n = 509/1880) vs. patients with a normal AI-QCTischaemia result (n = 1371/1880) had significantly higher crude and adjusted rates of the primary endpoint [adjusted hazard ratio (HRadj) 1.96, 95% confidence interval (CI) 1.46–2.63, P < 0.001; covariates: age/sex/hypertension/diabetes/smoking/typical angina]. An abnormal AI-QCTischaemia result was associated with significantly higher crude and adjusted rates of the primary endpoint amongst patients with no/non-obstructive CAD (n = 1373/1847) (HRadj 1.81, 95% CI 1.09–3.00, P = 0.022), but not amongst those with obstructive CAD (n = 474/1847) (HRadj 1.26, 95% CI 0.75–2.12, P = 0.386) (P-interaction = 0.032).

Conclusion

Amongst patients with suspected CAD, an abnormal AI-QCTischaemia result was associated with a two-fold increased adjusted rate of long-term death, MI, or uAP. AI-QCTischaemia may be useful to improve risk stratification, especially amongst patients with no/non-obstructive CAD on coronary CTA.
Antidromic snare technique for re-implantation of a coronary sinus lead into the same cardiac vein after transvenous lead extraction: a case report
Authors: Kim Juwon , Chung Tae-Wan , Park Seung-Jung
Published: December 2023

Background

After coronary sinus (CS) lead extraction in patients with cardiac resynchronization therapy (CRT), occlusion of the branch vessel from which CS lead was extracted is a major obstacle to re-implantation, particularly if that vessel is the only optimal vessel for resynchronization.

Case summary

A 75-year-old female who underwent CRT implantation 11 years prior presented with worsening dyspnoea, right ventricle-only pacing rhythm, and increased CS lead pacing threshold. Because she was a CRT responder, we decided to replace the malfunctioning CS lead. After successful extraction, the vessel from which CS lead was extracted was not visualized, and guidewire re-insertion attempts failed. No other branch vessels suitable for re-implantation were observed. Fortunately, distal portion of the target vessel was viewed by a retrograde flow of contrast. A guidewire was advanced retrograde into the target vein via a connecting vessel, and the distal end of the guidewire was snared around CS ostium and then pulled out of the sheath. A new CS lead was inserted through the distal end of the guidewire and successfully implanted antegrade into the same target vein using a veno-venous loop of the guidewire (‘anti-dromic snare technique’). The patient was discharged 2 days after the procedure without complications.

Discussion

Antegrade re-implantation of CS lead may not be possible after extracting CS leads with long dwell times, possibly due to extraction-induced vessel occlusion. If the occluded vessel is the only proper vessel for CS lead re-implantation, the anti-dromic snare technique could be a safe and effective bail-out strategy.
The potential benefit of statin prescription based on prediction of treatment responsiveness in older individuals: an application to the PROSPER randomized controlled trial
Authors: Nguyen Tri-Long , Trompet Stella , Brodersen John B , Hoogland Jeroen , Debray Thomas P A , Sattar Naveed , Jukema J Wouter , Westendorp Rudi G J
Published: December 2023

Aims

Clinical guidelines often recommend treating individuals based on their cardiovascular risk. We revisit this paradigm and quantify the efficacy of three treatment strategies: (i) overall prescription, i.e. treatment to all individuals sharing the eligibility criteria of a trial; (ii) risk-stratified prescription, i.e. treatment only to those at an elevated outcome risk; and (iii) prescription based on predicted treatment responsiveness.

Methods and results

We reanalysed the PROSPER randomized controlled trial, which included individuals aged 70–82 years with a history of, or risk factors for, vascular diseases. We conducted the derivation and internal–external validation of a model predicting treatment responsiveness. We compared with placebo (n = 2913): (i) pravastatin (n = 2891); (ii) pravastatin in the presence of previous vascular diseases and placebo in the absence thereof (n = 2925); and (iii) pravastatin in the presence of a favourable prediction of treatment response and placebo in the absence thereof (n = 2890). We found an absolute difference in primary outcome events composed of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke, per 10 000 person-years equal to: −78 events (95% CI, −144 to −12) when prescribing pravastatin to all participants; −66 events (95% CI, −114 to −18) when treating only individuals with an elevated vascular risk; and −103 events (95% CI, −162 to −44) when restricting pravastatin to individuals with a favourable prediction of treatment response.

Conclusion

Pravastatin prescription based on predicted responsiveness may have an encouraging potential for cardiovascular prevention. Further external validation of our results and clinical experiments are needed.

Trial registration

ISRCTN40976937.
An analysis of COVID-19 vaccination campaign in Ukraine
Authors: Mamontova Tetiana Vasylivna
Published: December 2023

Background

The Coronavirus disease (COVID-19) pandemic is still an important problem of concern in Ukraine. The rapid deployment of the vaccination program is a key event for the formation of herd immunity and helps to prevent negative outcomes, overloading the public health system.

Methods

The object of the retrospective-archival study was a depersonalized database of open panels on the management of the COVID-19 situation from the Ministry of Health of Ukraine.

Results

The total number of COVID-19 cases in Ukraine as of 25 December 2022 amounted to 5 314 388 individuals (12.83% of the population), and COVID-19-related deaths reached 110 029 individuals (0.26% of the population). The overall number of COVID-19 vaccinated persons in Ukraine as of 16 January 2022, with one dose was 36 198 per 100 000 persons (36% of the population), and with two doses, it was 34 703 per 100 000 persons (35% of the population). It was shown a decrease in the number of COVID-19 vaccinated persons among men and persons over the age of 70. In the dynamics of COVID-19 vaccination with one and two doses, an increase in the number of persons vaccinated with Pfizer/BioNTech and CoronaVac was noted.

Conclusions

Despite the significant increase in the morbidity and mortality rates of COVID-19, the coverage of vaccination among the population remained insufficient in Ukraine. The effective COVID-19 vaccination strategy should include appropriate management and ensuring the public health system capacity, implementation of information technologies to address logistics issues, and clear communication strategies to maintain public trust.
Associations between neighbourhood characteristics, physical activity and depressive symptoms: the Northern Finland Birth Cohort 1966 Study
Authors: Rautio Nina , Seppänen Marjo , Timonen Markku , Puhakka Soile , Kärmeniemi Mikko , Miettunen Jouko , Lankila Tiina , Farrahi Vahid , Niemelä Maisa , Korpelainen Raija
Published: December 2023

Background

Due to rapid urbanization, there is a need to better understand the relative roles of residential environment and physical activity in depression. We aimed to investigate whether neighbourhood characteristics are related to the presence of depressive symptoms and whether the association is modified by physical activity.

Methods

This cross-sectional study used the 46-year-old follow-up data (n = 5489) from the Northern Finland Birth Cohort 1966. Data on depressive symptoms, measured by Beck Depression Inventory-II, and self-reported and accelerometer-measured physical activity were included. Neighbourhood characteristics, population density, distance to the closest grocery store, bus stops and cycle/pedestrian paths, distance to the nearest parks and forests, residential greenness and level of urbanicity were calculated using Geographic Information System methods based on participants’ home coordinates.

Results

According to ordinal logistic regression analyses adjusted for physical activity at different intensities and individual covariates, living in a neighbourhood with higher population density and urbanicity level were associated with a higher risk of experiencing more severe depressive symptoms. Higher residential greenness was associated with a lower risk of experiencing more severe depressive symptoms after adjustment for self-reported light and moderate-to-vigorous physical activity, accelerometer-measured moderate-to-vigorous physical activity and individual covariates. Both higher self-reported and accelerometer-measured physical activity were independently associated with a lower risk of more severe depressive symptoms.

Conclusions

Both residential environment and physical activity behaviour play an important role in depressive symptoms; however, further research among populations of different ages is required. Our findings can be utilized when designing interventions for the prevention of depression.
A marker weighting approach for enhancing within-family accuracy in genomic prediction
Authors: Montesinos-López Osval A , Crespo-Herrera Leonardo , Xavier Alencar , Godwa Manje , Beyene Yoseph , Pierre Carolina Saint , de la Rosa-Santamaria Roberto , Salinas-Ruiz Josafhat , Gerard Guillermo , Vitale Paolo , Dreisigacker Susanne , Lillemo Morten , Grignola Fernando , Sarinelli Martin , Pozzo Ezequiel , Quiroga Marco , Montesinos-López Abelardo , Crossa José
Published: December 2023

Genomic selection is revolutionizing plant breeding. However, its practical implementation is still very challenging, since predicted values do not necessarily have high correspondence to the observed phenotypic values. When the goal is to predict within-family, it is not always possible to obtain reasonable accuracies, which is of paramount importance to improve the selection process. For this reason, in this research, we propose the Adversaria-Boruta (AB) method, which combines the virtues of the adversarial validation (AV) method and the Boruta feature selection method. The AB method operates primarily by minimizing the disparity between training and testing distributions. This is accomplished by reducing the weight assigned to markers that display the most significant differences between the training and testing sets. Therefore, the AB method built a weighted genomic relationship matrix that is implemented with the genomic best linear unbiased predictor (GBLUP) model. The proposed AB method is compared using 12 real data sets with the GBLUP model that uses a nonweighted genomic relationship matrix. Our results show that the proposed AB method outperforms the GBLUP by 8.6, 19.7, and 9.8% in terms of Pearson’s correlation, mean square error, and normalized root mean square error, respectively. Our results support that the proposed AB method is a useful tool to improve the prediction accuracy of a complete family, however, we encourage other investigators to evaluate the AB method to increase the empirical evidence of its potential.
Genome assemblies of two species of porcelain crab, Petrolisthes cinctipes and Petrolisthes manimaculis (Anomura: Porcellanidae)
Authors: Angst Pascal , Dexter Eric , Stillman Jonathon H
Published: December 2023

Crabs are a large subtaxon of the Arthropoda, the most diverse and species-rich metazoan group. Several outstanding questions remain regarding crab diversification, including about the genomic capacitors of physiological and morphological adaptation, that cannot be answered with available genomic resources. Physiologically and ecologically diverse Anomuran porcelain crabs offer a valuable model for investigating these questions and hence genomic resources of these crabs would be particularly useful. Here, we present the first two genome assemblies of congeneric and sympatric Anomuran porcelain crabs, Petrolisthes cinctipes and Petrolisthes manimaculis from different microhabitats. Pacific Biosciences high-fidelity sequencing led to genome assemblies of 1.5 and 0.9 Gb, with N50s of 706.7 and 218.9 Kb, respectively. Their assembly length difference can largely be attributed to the different levels of interspersed repeats in their assemblies: The larger genome of P. cinctipes has more repeats (1.12 Gb) than the smaller genome of P. manimaculis (0.54 Gb). For obtaining high-quality annotations of 44,543 and 40,315 protein-coding genes in P. cinctipes and P. manimaculis, respectively, we used RNA-seq as part of a larger annotation pipeline. Contrarily to the large-scale differences in repeat content, divergence levels between the two species as estimated from orthologous protein-coding genes are moderate. These two high-quality genome assemblies allow future studies to examine the role of environmental regulation of gene expression in the two focal species to better understand physiological response to climate change, and provide the foundation for studies in fine-scale genome evolution and diversification of crabs.
Genetic Affinities and Adaptation of the South-West Coast Populations of India
Authors: Kumar Lomous , Chowdhari Anuhya , Sequeira Jaison J , Mustak Mohammed S , Banerjee Moinak , Thangaraj Kumarasamy
Published: December 2023

Evolutionary event has not only altered the genetic structure of human populations but also associated with social and cultural transformation. South Asian populations were the result of migration and admixture of genetically and culturally diverse groups. Most of the genetic studies pointed to large-scale admixture events between Ancestral North Indian (ANI) and Ancestral South Indian (ASI) groups, also additional layers of recent admixture. In the present study, we have analyzed 213 individuals inhabited in South-west coast India with traditional warriors and feudal lord status and historically associated with migratory events from North/North West India and possible admixture with West Eurasian populations, whose genetic links are still missing. Analysis of autosomal Single Nucleotide Polymorphism (SNP) markers suggests that these groups possibly derived their ancestry from some groups of North West India having additional Middle Eastern genetic components. Higher distribution of West Eurasian mitochondrial haplogroups also points to female-mediated admixture. Estimation of Effective Migration Surface (EEMS) analysis indicates Central India and Godavari basin as a crucial transition zone for population migration from North and North West India to South-west coastal India. Selection screen using 3 distinct outlier-based approaches revealed genetic signatures related to Immunity and protection from Viral infections. Thus, our study suggests that the South-west coastal groups with traditional warriors and feudal lords’ status are of a distinct lineage compared to Dravidian and Gangetic plain Indo-Europeans and are remnants of very early migrations from North West India following the Godavari basin to Karnataka and Kerala.
Leukocyte Telomere Length and the Risk of Prostate Cancer and Benign Prostatic Hyperplasia: Insights From UK Biobank and Mendelian Randomization Study
Authors: Lv Kaikai , Wu Yangyang , Yang Guorong , Hao Xiaowei , Huang Shuai , Song Tao , Yuan Qing
Published: December 2023

Background

Previous observational studies have been controversial regarding the association of leukocyte telomere length (LTL) with prostate cancer (PCa) and benign prostatic hyperplasia (BPH).

Methods

First, we conducted an observational study utilizing UK Biobank data. The correlation between LTL and the risk of PCa and BPH was evaluated via multivariate-adjusted logistic regression. Then, we conducted a 2-sample Mendelian randomization to examine causal links between LTL (472 174 individuals) and PCa as well as BPH. To verify the reliability of the primary analysis, we conducted a second analysis and sensitivity analyses.

Results

In the UK Biobank study, individuals in the longer quartiles of LTL were observed to have a higher risk of PCa (1.155-fold to 1.349-fold, all p < .001) and BPH (1.119-fold to 1.212-fold, all p < .001) compared to those in the lowest quartile in multivariate-adjusted logistic regression. We observed that genetically predicted longer LTL resulted in a 1.427-fold risk of PCa (odds ratio [OR] = 1.427, 95% confidence interval [CI] = 1.197–1.702, p < .001) and 1.539-fold risk of BPH (OR = 1.539, 95% CI = 1.387–1.707, p < .001) in the primary analysis. In the second analysis, the results also indicated that longer LTL increased the genetic liability to both PCa (OR = 1.338, 95% CI = 1.189–1.507, p < .001) and BPH (OR = 1.006, 95% CI = 1.003–1.008, p < .001). Sensitivity analyses also supported the reliability of the results.

Conclusions

Our study provides convincing evidence supporting that longer LTL increases the risk of PCa and BPH in European individuals. Large-scale studies are needed to elucidate the potential mechanisms of LTL in PCa and BPH occurrence.
The Botrytis cinerea effector BcXYG1 suppresses immunity in Fragaria vesca by targeting FvBPL4 and FvACD11
Authors: Su Liyao , Zhang Tian , Yang Bin , Bai Yibo , Fang Wanping , Xiong Jingsong , Cheng Zong-Ming (Max)
Published: December 2023

Botrytis cinerea is one of the most destructive pathogens in strawberry cultivation. Successful infection by B. cinerea requires releasing a large number of effectors that interfere with the plant’s immune system. One of the effectors required by B. cinerea for optimal virulence is the secreted protein BcXYG1, which is thought to associate with proteins near the plasma membrane of the host plant to induce necrosis. However, the host proteins that associate with BcXYG1 at the plasma membrane are currently unknown. We found that BcXYG1 binds to FvBPL4 and FvACD11 at the plasma membrane. Both FvBPL4 and FvACD11 are negative regulators of plant immunity in strawberry. Our results demonstrate that degradation of FvBPL4 by BcXYG1 promotes disease resistance while stabilization of FvACD11 by BcXYG1 suppresses the immune response. These findings suggest that BcXYG1 suppresses plant immunity and promotes B. cinerea infection by regulating FvBPL4 and FvACD11 protein levels.
Predicting 1-year non-cancer-related adverse events after lung resection
Authors: Eguchi Takashi , Ide Shogo , Matsuoka Shunichiro , Iijima Yasuhiro , Mishima Shuji , Hara Daisuke , Kumeda Hirotaka , Miura Kentaro , Hamanaka Kazutoshi , Shimizu Kimihiro
Published: December 2023

OBJECTIVES

Assessing the risk for non-cancer-related outcomes following lung cancer surgery is crucial for high-risk patients. This study examined non-cancer-related adverse events within 1 year after lung resection, emphasizing the role of resected lung volume and postoperative atrial fibrillation (POAF).

METHODS

We conducted a retrospective analysis of 460 patients who underwent anatomical lung resection for malignant lung tumours. We assessed perioperative factors, such as the number of resected subsegments and POAF, as potential predictors of 1-year non-cancer-related adverse events. Additionally, we validated a previously published nomogram for predicting POAF.

RESULTS

One-year non-cancer-related adverse events occurred in 20% of patients. Multivariable analysis identified higher age, lower percentage-predicted forced expiratory volume in 1 second, greater number of resected subsegments and POAF as independent predictors of these adverse events. The incidence of POAF was 8.5%, with higher age, history of atrial fibrillation, and open thoracotomy as independent predictors. A temporal link between POAF and other severe postoperative complications was observed, as 71% of POAF cases preceded other complications. The nomogram's predicted risk for POAF was associated well with the actual incidence.

CONCLUSIONS

Resected lung volume and POAF are statistically significant factors associated with non-cancer-related outcomes after lung resection. Minimizing resected lung volume when oncologically and technically feasible, along with identifying patients at risk for POAF, may contribute to improved postoperative outcomes. Our results have implications for risk stratification and preoperative decision-making in lung cancer surgery.
Making Data Visualizations, Contesting Security: Digital Humanities Meet International Relations
Authors: Aradau Claudia , Blanke Tobias , Hussain Ibtehal
Published: December 2023

This article brings debates about data visualization in digital humanities in conversation with critical security studies and international relations. Building on feminist approaches in digital humanities, we explore the potential and limitations of data visualization as a critical method for research on (in)security. We unpack three aspects of making data visualizations by specifying “making” in this context as working, orienting, and critiquing. Making data visualizations as a methodological device is oriented by questions about the contestation of security and orients research by provoking new questions about practices of critique. Empirically, we situate data visualizations within British parliamentary debates about the Government Communications Headquarters (GCHQ), the UK's signals intelligence agency, which has garnered much public attention in the wake of the Snowden disclosures of transnational mass surveillance. We argue that data visualization in the parliamentary archive can destabilize dominant understandings of security, problematize narratives of security actors and oversight, and attend to the uneven presence of critique and contestation within and beyond parliamentary debates.
Antimicrobial resistance expansion in pathogens: a review of current mitigation strategies and advances towards innovative therapy
Authors: Adefisoye Martins A , Olaniran Ademola O
Published: December 2023

The escalating problem of antimicrobial resistance (AMR) proliferation in clinically important pathogens has become one of the biggest threats to human health and the global economy. Previous studies have estimated AMR-associated deaths and disability-adjusted life-years (DALYs) in many countries with a view to presenting a clearer picture of the global burden of AMR-related diseases. Recently, several novel strategies have been advanced to combat resistance spread. These include efflux activity inhibition, closing of mutant selection window (MSW), biofilm disruption, lytic bacteriophage particles, nanoantibiotics, engineered antimicrobial peptides, and the CRISPR-Cas9 gene-editing technique. The single or integrated deployment of these strategies has shown potentialities towards mitigating resistance and contributing to valuable therapeutic outcomes. Correspondingly, the new paradigm of personalized medicine demands innovative interventions such as improved and accurate point-of-care diagnosis and treatment to curtail AMR. The CRISPR-Cas system is a novel and highly promising nucleic acid detection and manipulating technology with the potential for application in the control of AMR. This review thus considers the specifics of some of the AMR-mitigating strategies, while noting their drawbacks, and discusses the advances in the CRISPR-based technology as an important point-of-care tool for tracking and curbing AMR in our fight against a looming ‘post-antibiotic’ era.
Gamification as an educational tool to address antimicrobial resistance: a systematic review
Authors: Nowbuth Avis A , Asombang Akwi W , Alaboud Khuder , Souque Célia , Dahu Butros M , Pather Kyrtania , Mwanza Monica M , Lotfi Sameen , Parmar Vikram S
Published: December 2023

Background

Antimicrobial resistance (AMR) poses a serious threat to global healthcare, and inadequate education has been identified as a major challenge by the WHO. The human , animal and agricultural sectors contribute to the emergence of AMR. Gamification has emerged as an innovative tool to improve knowledge and change behaviours. Our study provides an overview of the literature on existing games in prescribers’ education across the One Health sectors, with a particular focus on the impact of gamification on learning.

Methods

Using the PRISMA guidelines, we searched Cochrane, PubMed, Scopus and Google Scholar for articles related to gamification for future prescribers of antimicrobials from inception until 28 March 2023. Retrieval and screening of articles was done using a structured search protocol with strict inclusion/exclusion criteria.

Results

A total of 120 articles were retrieved, of which 6 articles met the inclusion criteria for final analysis. High-income countries had the most studies, with one global study incorporating low- to middle-income countries. All games were evaluated in the human sector. Board and card games, featuring scoring and point systems, were the most prevalent game types. Most games focused on improving knowledge and prescribing behaviours of medical students, with bacteria or antibiotics as the only content. All studies highlighted the significant potential of gamification in mitigating AMR, promoting antimicrobial stewardship, and improving retention of information compared with conventional lectures.

Conclusions

Our review found an absence of studies in the animal and environmental sectors, disproportionately focused on medical students with questionable sample size, inadequate assessment of game content and effectiveness, and opportunities for game developers.
Improving antibiotic prescribing quality in out-of-hours primary care: a mixed-methods study using participatory action research
Authors: Colliers Annelies , Coenen Samuel , Teughels Stefan , Boogaerts Yentry , Vandeput Olivia , Tans Anouk , Vermeulen Helene , Remmen Roy , Philips Hilde , Anthierens Sibyl
Published: December 2023

Background

During out-of-hours (OOH) primary care, GPs overprescribe antibiotics for respiratory tract infections (RTIs). Many interventions have been shown to improve antibiotic prescribing quality, but their implementation in practice remains difficult. Participatory action research (PAR) aims to explore, implement and evaluate change in practice with an active involvement of local stakeholders, while generating knowledge through experience.

Objectives

To evaluate whether PAR improves antibiotic prescribing quality for RTIs during OOH primary care and simultaneously identify the pivotal lessons learned.

Methods

A mixed-methods study with a PAR approach in three OOH GP cooperatives (GPCs). Each GPC co-created a multifaceted intervention focusing on improving antibiotic use for RTIs through plan-do-study-act cycles. We quantified antibiotic prescribing quality indicators and formulated the lessons learned from a qualitative process analysis.

Results

Interventions were chosen with the GPs and adapted to be context-relevant. The willingness to work on quality and engagement of local stakeholders led to ownership of the project, but was time-consuming. In one GPC, antibiotic prescribing significantly decreased for tonsillitis, bronchitis, otitis media and acute upper RTI. In all three GPCs, use of guideline-recommended antibiotics for otitis media significantly increased.

Conclusions

Implementing multifaceted interventions through PAR can lower total and increase guideline-recommended antibiotic prescribing for RTIs in OOH primary care. Co-creating interventions with GPs to suit local needs is feasible, but reaching all GPs targeted is challenging.
Ninety Sixth-Hour Impact of Scalding Burns on End Organ Damage, Systemic Oxidative Stress, and Wound Healing in Rats Treated With Three Different Types of Dressings
Authors: Aslan Mehmet , Gül Mehmet , Üremiş Nuray , Akbulut Sami , Gürünlüoğlu Semra , Nur Özsoy Eda , Türköz Yusuf , Ateş Hasan , Akpinar Necmettin , Gül Semir , Gürünlüoğlu Kubilay , Demircan Mehmet
Published: December 2023

In this study, we investigated the effects of 3 different burn dressing treatments, including experimental, silver, and modern dressing materials, on systemic oxidative stress in rats with severe scald burns within the first 96 h. The rats were divided into five groups: a burn group (n = 10), a polylactic membrane group (n = 10), a silver sulfadiazine group (n = 10), a curcumin group (n = 10), and a control group (n = 10), consisting of equal numbers of female and male rats. In the first 4 groups, 30% of the rats’ total body surface area was scalded at 95°C. The burn group was not treated. Each group was treated with group-name dressing material. The control group was neither treated nor burned. The rats were sacrificed, and blood and tissue samples were obtained at the 96th hour when severe effects of oxidative stress developed postburns. Systemic inflammatory biomarkers and oxidative stress parameters were examined. In addition, apoptosis and organ damage in liver, kidney, lung, and skin tissues were evaluated biochemically and histopathologically. When the parameters were statistically analyzed, we found that the systemic levels of oxidative stress and inflammatory damage to liver, kidney, and lung tissues were lower in the 3 treated groups than in the burn group. We believe that the dressing material’s efficacy in the treatment of severe burns may be dependent on its ability to combat oxidative stress and inflammation.
ISDS 2.0: time for a doctrine of precedent?
Authors: Jarrett Martin
Published: December 2023

The reform process for ISDS at UNCITRAL is reaching its climax. Within the next few years, a treaty for ‘ISDS 2.0’ should emerge from this process. A key feature of ISDS 2.0 will be a new international court for resolving investor–state disputes. This court should include an appellate tribunal. A core function of this appellate tribunal will be to produce consistent case law, noting a common complaint about ‘ISDS 1.0’ is that it has produced inconsistent case law. There is good reason to believe that the appellate tribunal of ISDS 2.0 can deliver consistent case law, but the promoters behind ISDS 2.0 need to be careful what they wish for. The WTO dispute settlement system produced consistent case law, yet that achievement turned out to be a reason for its subsequent breakdown. Consistent case law apparently sounds good in theory, but it is not welcome in practice. Is there a way out of this conundrum? This article proposes that a formal doctrine of precedent is the solution. This proposal might initially provoke some surprise—a softer system of precedent is apparently the best compromise. But a doctrine of precedent can be crafted to limit adjudicative law-making power, while emphasizing states’ control over their investment–treaty obligations. This article puts forward the broad outline of this conception of a doctrine of precedent, explains why it gives effect to states’ interests, and examines the methods by which a doctrine of precedent could be adopted.
Clinicopathologic features of a novel star-shaped transactive response DNA-binding protein 43 (TDP-43) pathology in the oldest old
Authors: Carlos Arenn F , Sekiya Hiroaki , Koga Shunsuke , Gatto Rodolfo G , Casey Monica Castanedes , Pham Nha Trang Thu , Sintini Irene , Machulda Mary M , Jack Clifford R , Lowe Val J , Whitwell Jennifer L , Petrucelli Leonard , Reichard R Ross , Petersen Ronald C , Dickson Dennis W , Josephs Keith A
Published: December 2023

Transactive response DNA-binding protein 43 (TDP-43) pathology is categorized as type A-E in frontotemporal lobar degeneration and as type α-β in Alzheimer disease (AD) based on inclusion type. We screened amygdala slides of 131 cases with varying ages at death, clinical/neuroimaging findings, and AD neuropathologic changes for TDP-43 pathology using anti-phospho-TDP-43 antibodies. Seven cases (5%) only showed atypical TDP-43 inclusions that could not be typed. Immunohistochemistry and immunofluorescence assessed the atypical star-shaped TDP-43 pathology including its distribution, species, cellular localization, and colocalization with tau. All 7 had died at an extremely old age (median: 100 years [IQR: 94–101]) from nonneurological causes and none had dementia (4 cognitively unimpaired, 3 with amnestic mild cognitive impairment). Neuroimaging showed mild medial temporal involvement. Pathologically, the star-shaped TDP-43-positive inclusions were found in medial (subpial) amygdala and, occasionally, in basolateral regions. Hippocampus only showed TDP-43-positive neurites in the fimbria and subiculum while the frontal lobe was free of TDP-43 inclusions. The star-shaped inclusions were better detected with antibodies against N-terminal than C-terminal TDP-43. Double-labeling studies confirmed deposition of TDP-43 within astrocytes and colocalization with tau. We have identified a novel TDP-43 pathology with star-shaped morphology associated with superaging, with a homogeneous clinicopathologic picture, possibly representing a novel, true aging-related TDP-43 pathology.
A study on rose-window instability in a dielectric droplet exposed to corona discharge
Authors: Chiou Yi-Jen , Fu Chiang , Liao Ying-Hao
Published: December 2023

The rose-window instability (RWI) is an electrohydrodynamic instability occurring in a dielectric liquid subjected to an electric field. This instability leads to variations in the shape of the liquid and its spreading. Despite the significance of the RWI, there have been limited studies, especially concerning dielectric droplets. Thus, the aim of this study is to investigate the characteristic of rose-window instability in silicone oil droplets exposed to corona discharge. The study examines the effects of electrode gap, applied voltage, and viscosity on the formation of RWI. Increasing the electrode gap results in an enlarged rose-window lattice, accompanied by a decrease in the number of lattices. This can be attributed to a more diffusive ionic flow and a more pronounced inhomogeneity of charge distribution across the droplet surface. On the other hand, higher voltages, which enhances the ionic flow, accelerate the formation of RWI and lead to a larger inner diameter. Viscosity has little influence on the geometry of the lattice. However, droplets with low viscosity exhibit a more rapid development of instability. The observation suggests that the small Ohnesorge number (Oh), influenced by factors such as viscosity and surface tension, may play a role in the development of the rose-window instability. The influence of surface tension, although not the main focus of the study, cannot be completely disregarded as it is interconnected with the Oh and may contribute to the observed results.
Differential effects of dietary polyphenols on oral pharmacokinetics of cyclin-dependent kinase inhibitors in rats: a mechanistic framework for in vitro–in vivo extrapolation
Authors: Patil Prajakta Harish , Desai Mrunal Pradeep , Birangal Sumit , Gautham Shenoy G , Channabasavaiah Jagadish Puralae
Published: December 2023

Objectives

Cyclin-dependent kinase inhibitors are subject to rapid first-pass metabolism, and their oral absorption is hindered by intestinal CYP3A4 and P-gp. The present study investigates the impact of dietary polyphenols on the oral pharmacokinetics of palbociclib and ribociclib, considering their potential as modulators of CYP3A4 and P-gp.

Methods

Therefore, potential inhibitory effects of dietary polyphenols on drug metabolism and efflux of these drugs were investigated using molecular docking; in vitro preclinical assay using rat liver microsomes and Caco-2 cell monolayers; in vivo, pharmacokinetic parameters were determined in rats pretreated with dietary polyphenols.

Key findings

Curcumin and quercetin have the highest binding affinities to the PXR’s AF-2 region cluster. Curcumin and quercetin significantly inhibited both intestinal efflux and CYP3A4-mediated metabolism of palbociclib and ribociclib (P < .05). In rats pretreated with curcumin, Cmax of palbociclib exhibited a 5.13% increase, while the AUC0-24h of ribociclib showed a significant increase of 18.83% (P < .05). Quercetin administration, notably, impedes the pharmacokinetics of palbociclib. However, the pharmacokinetics of ribociclib remains unaffected by quercetin.

Conclusions

In conclusion, the utilization of curcumin as a bioenhancer can enhance the bioavailability of dual substrates of P-gp and CYP3A4.
Agency’s Moral Universe
Authors: Black Monica
Published: December 2023

Agency belongs to a distinctly moral understanding of the cosmos, buttressed by faith in an ultimately just and knowable universe. On some deep level, historians believe that the good will out. But looking at those moments when the agency concept creates cognitive dissonance—when, for example, Holocaust perpetrators’ “agency” was placed in the service of evil—reveals things about the moral universe historians think we inhabit. Using the example of post-1945 West Germany, the essay asks whether a shift toward increasingly diffuse forms of agency across various fields may be part of a larger historical, and not merely historiographical, pattern. In the “post-truth” early twenty-first century, will historians’ accounts of the past continue to be shaped by the idea of a benevolent and graspable universe, or will chaos make agency seem like an unrecognizable relic from a lost world?
Meanings of Agency, Agency of Meaning: On Synthesis and Entanglement
Authors: Burke Timothy
Published: December 2023

Two decades later, the conceptual problems of the term “agency” identified by Walter Johnson remain largely unresolved, in particular the analytic inhibitions that follow from what the historian Lynn Thomas has described as agency-as-argument. Taking the case of the colonial Zimbabwean chief Munhuwepayi Mangwende as a reference point, this essay argues that the microhistorical tracing of agency as meaning rather than causality is what may permit us to move past the “safe harbor” of agency-as-argument and begin to understand the full range of what people have chosen to do in the past—and to interact more effectively with what they might yet choose to do in the present.