bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a high-affinity anti-bovine PD-1 rabbit–bovine chimeric antibody using an efficient selection and large production system
Authors: Okagawa Tomohiro , Konnai Satoru , Goto Shinya , Sajiki Yamato , Ganbaatar Otgontuya , Watari Kei , Nakamura Hayato , Wang Cai-Xia , Tachibana Taro , Kato Yukinari , Kameda Yayoi , Kohara Junko , Terasaki Nobuhiro , Kubota Manabu , Takeda Akira , Takahashi Hirofumi , Suzuki Yasuhiko , Maekawa Naoya , Murata Shiro , Ohashi Kazuhiko
Published: September 2023

Immune checkpoint molecules PD-1/PD-L1 cause T-cell exhaustion and contribute to disease progression in chronic infections of cattle. We established monoclonal antibodies (mAbs) that specifically inhibit the binding of bovine PD-1/PD-L1; however, conventional anti-PD-1 mAbs are not suitable as therapeutic agents because of their low binding affinity to antigen. In addition, their sensitivity for the detection of bovine PD-1 is low and their use for immunostaining PD-1 is limited. To address these issues, we established two anti-bovine PD-1 rabbit mAbs (1F10F1 and 4F5F2) and its chimeric form using bovine IgG1 (Boch1D10F1), which exhibit high binding affinity. One of the rabbit mAb 1D10F1 binds more strongly to bovine PD-1 compared with a conventional anti-PD-1 mAb (5D2) and exhibits marked inhibitory activity on the PD-1/PD-L1 interaction. In addition, PD-1 expression in bovine T cells could be detected with higher sensitivity by flow cytometry using 1D10F1. Furthermore, we established higher-producing cells of Boch1D10F1 and succeeded in the mass production of Boch1D10F1. Boch1D10F1 exhibited a similar binding affinity to bovine PD-1 and the inhibitory activity on PD-1/PD-L1 binding compared with 1D10F1. The immune activation by Boch1D10F1 was also confirmed by the enhancement of IFN-γ production. Finally, Boch1D10F1 was administered to bovine leukemia virus-infected cows to determine its antiviral effect. In conclusion, the high-affinity anti-PD-1 antibody developed in this study represents a powerful tool for detecting and inhibiting bovine PD-1 and is a candidate for PD-1-targeted immunotherapy in cattle.
Quantitative analysis of viremia and viral shedding in pigs infected experimentally with classical swine fever virus isolates obtained from recent outbreaks in Japan
Authors: Fukai Katsuhiko , Nishi Tatsuya , Masujin Kentaro , Yamada Manabu , Ikezawa Mitsutaka
Published: September 2023

Although classical swine fever occurred in September 2018 for the first time in 26 years, its virulence is thought to be moderate based on field observations by veterinary authorities and our previous experimental infections. We quantified viremia and viral shedding in pigs infected with recent Japanese classical swine fever virus isolates, as well as a highly virulent strain. The results show that pigs infected with the Japanese strains exhibited lower viremia and viral shedding than those infected with the highly virulent strain. However, horizontal transmission occurred in pigs infected with the Japanese strains, similar to those infected with the highly virulent strain. Additionally, viremia and neuralization antibodies coexisted in pigs infected with the Japanese strains, presenting challenges for control measures.
Study on disinfection effect of a 222-nm UVC excimer lamp on object surface
Authors: Ning Peiyong , Han Yanzhen , Liu Yang , Liu Shengchun , Sun Zhili , Wang Xinru , Wang Baiqi , Gao Feng , Wang Ying , Wang Yuan , Gao Xin , Chen Guanyi , Li Xiaoyan
Published: September 2023

Effective disinfection of contaminated surfaces is essential for preventing the transmission of pathogens. In this study, we investigated the UV irradiance and wavelength distribution of a 222-nm ultraviolet C (UVC) excimer lamp and its disinfection efficacy against microorganisms in laboratory conditions. By using a carrier quantitative germicidal test with stainless steel sheets as carriers, we examined the disinfection effect of the 222-nm UVC lamp on three standard strains-Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. We tested the disinfection efficacy under different conditions by adjusting irradiation time, as well as the state and temperature of the stainless steel carriers. Our results indicated that a bacterial suspension in PBS and not-dried stainless steel carriers yielded better disinfection than in TSB and dried carriers. Additionally, carrier temperature had no significant impact on disinfection efficacy. When utilizing a bacterial suspension in PBS and non-dried carriers at a temperature of 20 °C, the three bacteria were eliminated by 222-nm UVC excimer lamp irradiation in just 15 s. In contrast, when using a bacterial suspension in TSB and dried carriers at temperatures of 20 °C, 4 °C, or − 20 °C, the three bacteria were eradicated by 222-nm UVC excimer lamp irradiation in 60 s. Comparatively, the LPM lamp required more than 10 min to achieve the same disinfection effect. Our data demonstrate that the 222-nm UVC excimer lamp has higher irradiance and a more potent microbial disinfection effect than the LPM lamp, requiring significantly less irradiation time to achieve the same disinfection effect under identical conditions. Furthermore, the 222-nm UVC excimer lamp exhibited a substantial disinfection effect on bacterial propagules at low temperatures. Our findings support the optimization of “tunnel-type” cold-chain goods disinfection devices, providing an alternative, highly efficient, and practical tool to combat the spread of SARS-CoV-2 through cold-chain systems.

Graphical Abstract
Impact of renal complications on outcome in adult patients with acute fulminant myocarditis receiving venoarterial extracorporeal membrane oxygenation: an analysis of nationwide CSECLS database in China
Authors: Hao Tong , Chen Lei , Wu Changde , Xie Jianfeng , Li Chenglong , Xie Haixiu , Du Zhongtao , Liu Ling , Yang Yi , Liu Songqiao , Hou Xiaotong , Qiu Haibo
Published: September 2023

Background

Limited data are available on renal complications in patients with acute fulminant myocarditis (AFM) receiving venoarterial extracorporeal membrane oxygenation (VA-ECMO) support in China. To evaluate the impact of renal complications on outcomes in adult patients with AFM supported with VA-ECMO.

Methods

Data were extracted from Chinese Society of ExtraCorporeal Life Support (CSECLS) Registry database. Adult patients who were diagnosed with AFM receiving VA-ECMO support in the database were included. The primary outcome was 30-day mortality in patients with AFM supported with VA-ECMO. Logistic regression model was used to examine the impact of renal complications on 30-day mortality by adjusting confounders.

Results

A total of 202 patients were included. The median age was 38 years (IQR 29–48) and males (n = 103) represented 51.0% of the total accounted patients. The median ECMO duration was 142.9 h (IQR 112.1–188.8 h). 178 (88.1%) patients weaned from ECMO and 156 (71.9%) patients survived. 94(46.5%) patients developed renal complications while on ECMO course. Patients with renal complications had higher 30-day mortality (40.7% (37 of 94) vs 8.3% (9 of 108), P < 0.001) compared with those without. The development of renal complications was related to a 3.12-fold increase risk of 30-day mortality (adjusted OR 3.120, 95%CI 1.002–6.577, P = 0.049). Increasing age (adjusted OR1.025, 95% CI 1.008–1.298, P = 0.040) and higher SOFA score (adjusted OR 1.162, 95%CI 1.012–1.334, P = 0.034) were independent risk factors of renal complications.

Conclusions

Our findings demonstrated that patients with AFM receiving VA-ECMO at high risk of developing renal complications. Advancing age and higher SOFA score was associated with increased risk of developing renal complications. The onset of renal complications was significantly associated with 30-day mortality.
Interventions for Indigenous Peoples making health decisions: a systematic review
Authors: Jull Janet , Fairman Kimberly , Oliver Sandy , Hesmer Brittany , Pullattayil Abdul Kareem ,   Not Deciding Alone Team
Published: September 2023

Background

Shared decision-making facilitates collaboration between patients and health care providers for informed health decisions. Our review identified interventions to support Indigenous Peoples making health decisions. The objectives were to synthesize evidence and identify factors that impact the use of shared decision making interventions.

Methods

An Inuit and non-Inuit team of service providers and academic researchers used an integrated knowledge translation approach with framework synthesis to coproduce a systematic review. We developed a conceptual framework to organize and describe the shared decision making processes and guide identification of studies that describe interventions to support Indigenous Peoples making health decisions. We conducted a comprehensive search of electronic databases from September 2012 to March 2022, with a grey literature search. Two independent team members screened and quality appraised included studies for strengths and relevance of studies’ contributions to shared decision making and Indigenous self-determination. Findings were analyzed descriptively in relation to the conceptual framework and reported using guidelines to ensure transparency and completeness in reporting and for equity-oriented systematic reviews.

Results

Of 5068 citations screened, nine studies reported in ten publications were eligible for inclusion. We categorized the studies into clusters identified as: those inclusive of Indigenous knowledges and governance (“Indigenous-oriented”)(n = 6); and those based on Western academic knowledge and governance (“Western-oriented”)(n = 3). The studies were found to be of variable quality for contributions to shared decision making and self-determination, with Indigenous-oriented studies of higher quality overall than Western-oriented studies. Four themes are reflected in an updated conceptual framework: 1) where shared decision making takes place impacts decision making opportunities, 2) little is known about the characteristics of health care providers who engage in shared decision making processes, 3) community is a partner in shared decision making, 4) the shared decision making process involves trust-building.

Conclusions

There are few studies that report on and evaluate shared decision making interventions with Indigenous Peoples. Overall, Indigenous-oriented studies sought to make health care systems more amenable to shared decision making for Indigenous Peoples, while Western-oriented studies distanced shared decision making from the health care settings. Further studies that are solutions-focused and support Indigenous self-determination are needed.
Multiple high-risk fertility behaviours and children under five mortality survivors among ever-married women of reproductive age in Nigeria
Authors: Bolarinwa Obasanjo Afolabi , Hajjar Julia Marie , Alawode Oluwatobi Abel , Ajayi Kobi V. , Roberts Adedoyin Tinuoya , Yaya Sanni
Published: September 2023

Background

Multiple high-risk fertility behaviours (MHRFBs), including maternal age < 18 or > 34 years old, a birth order 4+, and birth spacing < 24 months, can directly or indirectly affect survival outcomes among under-five children. There is a dearth of available information and data about these two phenomena in Nigeria. Thus, this study evaluates the prevalence of MHRFBs and examines the association between MHRFBs and under-five mortality survival (U5M) outcomes among ever-married women of reproductive age in Nigeria.

Methods

This study used the recent secondary datasets from the Nigerian Demographic Health Surveys conducted in 2018, with a total sample size of 10,304 women of reproductive age. The outcome variable was MHRFBs. Multivariable logistic regression analysis was employed to examine the association between U5M and MHRFBs. Odds ratios with a p-value of less than 0.05 were considered significant.

Results

It was found that among women who had MHRFBs, U5M was prevalent, particularly in young maternal age (< 18 years) and within short birth intervals (< 24 months). The adjusted odds ratio of the association between MHRFBs and U5M shows the experience of MHRFBs, in addition to other factors such as household wealth index, type of marriage, and sex of child, to be significant predictors for U5M. The odds were higher for U5M to occur among women who had experienced MHRFBs compared to those who have not had an experience of MHRFBs [aOR = 1.48; 95%CI: 1.02–2.17 ]. Similarly, the odds of U5M occurrence among women in polygamous marriages are higher compared to those in monogamous unions [aOR = 1.35; 95% CI: 1.10–1.65]. While under-five children born in the richest households (wealth quintiles) are less likely to die compared to those born in the poorest households [aOR = 0.64; 95% CI: 0.41–1.01].

Conclusion

This study concludes that women in Nigeria who engaged in MHRFBs, particularly maternal ages < 18 years and short birth intervals (< 24 months), were more likely to experience U5M. Furthermore, children born to women who received post-natal care after delivery were more likely to survive U5M, as were children born to women with educated partners. We recommend strengthening educational opportunities and creating adaptive reproductive health education programs for ever-married women of reproductive age in Nigeria.
Exploring dog ownership in the lives of people with substance use disorder: a qualitative study
Authors: Kerr-Little Andi , Bramness Jørgen G. , Newberry Ruth C. , Biong Stian
Published: September 2023

Background

Recovery from substance use is commonly seen as a process of integrating social relationships and creating a sense of meaning in one’s life. Dog owners describe a close relationship with their dog that impacts many aspects of their everyday life. Yet for individuals with substance use disorder (SUD), little is known about how dog ownership could affect their lives. The aim of this study was to explore how people living with SUD experience and describe their everyday life when owning a dog.

Method

Eight semi-structured in-depth individual interviews were conducted with people having personal experience of living with SUD and owning a dog. Data were gathered and analysed using qualitative content analysis.

Results

The analysis yielded four categories, reflecting different aspects of dog ownership. Living with SUD and owning a dog was primarily something positive in their life. People increased their social connections personally and within society. They felt a belonging which gave a sense of agency and purpose, and they developed structure in their day and boundaries to their environment. Dog ownership, however, could hinder access to services which was found to be challenging for some participants.

Conclusions

The owning of a dog can lead to changes that parallel those of a recovery process. This finding adds to the research on the connection that dogs can provide and shows how pertinent this can be particularly for vulnerable persons such as those with SUD.
Association between CYP3A4/CYP3A5 genetic polymorphisms and treatment outcomes of atorvastatin worldwide: is there enough research on the Egyptian population?
Authors: Maslub Mohammed G. , Radwan Mahasen A. , Daud Nur Aizati Athirah , Sha’aban Abubakar
Published: September 2023

Introduction

Atorvastatin is regarded as the most frequently prescribed statin worldwide for dyslipidemia. However, clinical response and risk of adverse effects to statin therapy are associated with genetic variations. Numerous research linked statins pharmacokinetics (PK) variations to genetic polymorphisms in cytochromes P450 (CYPs) metabolic enzymes.

Objective

This article reviews the association between CYP3A4/5 genetic variations and response to atorvastatin therapy globally, which includes atorvastatin PK, and the risk for adverse reactions, with a hint to the Egyptians.

Methods

Up to March 30, 2022, electronic medical databases like PubMed, Web of Science, MEDLINE, and Egyptian Knowledge Bank (EKB) were searched. All articles that highlighted the relationship between CYP3A4/5 genetic polymorphisms and atorvastatin efficacy/safety profile were included in this review.

Results

Initially, 492 articles were retrieved after an exhaustive search. There were 24 articles included according to the inclusion criteria. Findings of association studies of CYP3A4/5 genetic polymorphisms with response to atorvastatin varied among different ethnicities. CYP3A4*1B was associated with better therapeutic outcomes after atorvastatin therapy in Chileans and vice versa in Americans. Caucasians with myalgia while using atorvastatin were at significant risk of suffering severe muscle damage if they were carriers of CYP3A5*3/*3. As far as we can report for the Egyptian population, the impact of CYP3A4/5 genetic variations on the response to atorvastatin therapy was understudied.

Conclusion

More pharmacogenetic studies amongst diverse populations worldwide, like the Egyptian population, are necessary to detect further atorvastatin-gene interactions.

Graphical Abstract
The risk factors of the 72-h unscheduled return visit admission to emergency department in adults below 50 years old
Authors: Kao Chia-Lung , Chuang Chia-Chang , Hwang Chi-Yuan , Lee Chung-Hsun , Huang Po-Chang , Hong Ming-Yuan , Chi Chih-Hsien
Published: September 2023

Background

An unscheduled return visit (URV) to the emergency department (ED) within 72-h is an indicator of ED performance. An unscheduled return revisit (URV) within 72-h was used to monitor adverse events and medical errors in a hospital quality improvement program. The study explores the potential factors that contribute to URV to the ED within 72-h and the unscheduled return revisit admission (URVA) in adults below 50 years old.

Methods

The case–control study enrolled 9483 URV patients during 2015–2020 in National Cheng-Kung University Hospital. URVA and URV non-admission (URVNA) patients were analyzed. The Gini impurity index was calculated by decision tree (DT) to split the variables capable of partitioning the groups into URVA and URVNA. Logistic regression is applied to calculate the odds ratio (OR) of candidate variables. The α level was set at 0.05.

Results

Among patients under the age of 50, the percentage of females in URVNA was 55.05%, while in URVA it was 53.25%. Furthermore, the average age of URVA patients was 38.20 ± 8.10, which is higher than the average age of 35.19 ± 8.65 observed in URVNA. The Charlson Comorbidity Index (CCI) of the URVA patients (1.59 ± 1.00) was significantly higher than that of the URVNA patients (1.22 ± 0.64). The diastolic blood pressure (DBP) of the URVA patients was 85.29 ± 16.22, which was lower than that of the URVNA (82.89 ± 17.29). Severe triage of URVA patients is 21.1%, which is higher than the 9.7% of URVNA patients. The decision tree suggests that the factors associated with URVA are “severe triage,” “CCI higher than 2,” “DBP less than 86.5 mmHg,” and “age older than 34 years”. These risk factors were verified by logistic regression and the OR of CCI was 2.42 (1.50–3.90), the OR of age was 1.84 (1.50–2.27), the OR of DBP less than 86.5 was 0.71 (0.58–0.86), and the OR of severe triage was 2.35 (1.83–3.03).

Conclusions

The results provide physicians with a reference for discharging patients and could help ED physicians reduce the cognitive burden associated with the diagnostic errors and stress.
Identifying pyroptosis- and inflammation-related genes in intracranial aneurysms based on bioinformatics analysis
Authors: Zhou Donglin , Zhu Yimin , Jiang Peng , Zhang Tongfu , Zhuang Jianfeng , Li Tao , Qi Linzeng , Wang Yunyan
Published: September 2023

Background

Intracranial aneurysm (IA) is the most common cerebrovascular disease, and subarachnoid hemorrhage caused by its rupture can seriously impede nerve function. Pyroptosis is an inflammatory mode of cell death whose underlying mechanisms involving the occurrence and rupture of IAs remain unclear. In this study, using bioinformatics analysis, we identified the potential pyroptosis-related genes (PRGs) and performed their inflammatory response mechanisms in IAs.

Methods

The mRNA expression matrix of the IA tissue was obtained from the Gene Expression Omnibus database, and 51 PRGs were obtained from previous articles collected from PubMed. The differentially expressed PRGs (DEPRGs) were performed using R software. Subsequently, we performed enrichment analysis, constructed a protein–protein interaction network, performed weighted gene coexpression network analysis (WGCNA) and external validation using another dataset, and identified a correlation between hub genes and immune cell infiltration. Finally, the expression and tissue distribution of these hub genes in IA tissues were detected using Western blotting and immunohistochemical (IHC) staining.

Results

In total, 12 DEPRGs associated with IA were identified in our analysis, which included 11 up-regulated and one down-regulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses revealed that the DEPRGs were mostly enriched in the NOD-like receptor signaling pathway, interleukin-1 beta production, and the inflammasome complex. Three hub genes, NLRP3, IL1B and IL18, were identified using Cytoscape software and the WGCNA correlation module, and external validation revealed statistically significant differences between the expression of these hub genes in the ruptured and unruptured aneurysm groups (p < 0.05). Furthermore, all AUC values were > 0.75. Immune cell infiltration analysis suggested that the hub genes are related to CD8 T cell, macrophages and mast cells. Finally, IHC staining revealed that the protein levels of these hub genes were higher in ruptured and unruptured IA tissues than in normal tissues (p < 0.05).

Conclusion

The results of bioinformatics analysis showed that pyroptosis is closely related to the formation and rupture of IA, and identified three potential hub genes involved in the pyroptosis and infiltration ofcells. Our findings may improve the understanding of the mechanisms underlying pyroptosis in IA.
Development of an item pool for a patient reported outcome measure of resilience for people living with dementia
Authors: Roberts Jennifer Rhiannon , MacLeod Catherine Anne , Hoare Zoe , Sullivan Mary Pat , Brotherhood Emilie , Stott Joshua , Windle Gill
Published: September 2023

Background and objectives

Policies to support people living with dementia increasingly focus on strengths-based approaches, highlighting the importance of building resilience. This research responds to the lack of a suitable resilience measure for people with dementia. It develops a pool of items to inform a new measure of resilience for this population.

Methods

A conceptual model and associated data informed the item generation of the draft resilience measure. Regular meetings with professionals (n = 7) discussed response-scale formatting, content and face validity, leading to refinement and item reduction. Cognitive interviews with people living with dementia (n = 11) then examined the face and content validity of items and the suitability of response-scale formatting. These two phases informed subsequent revision and further item reduction of the resilience measure.

Results

The first item generation exercise led to 140 items. These were independently assessed by the professionals and this refinement reduced the measure to 63 items across 7 domains of the conceptual model (psychological strengths; practical approaches for adapting to life with dementia; continuing with hobbies, interests and activities; strong relationships with family and friends; peer support and education; participating in community activities; the role of professional support services). Cognitive interviews explored the 63 items with people living with dementia. Detailed feedback led to items removed due to difficulty with (a) understanding (N = 7); (b) answering (n = 11); (c) low preference for that item (n = 6); and (d) presence of a preferred item within a cluster of similar questions (n = 4). Items were amended to enhance clarity/conciseness (n = 19) leading to a final 37-item pool.

Conclusion

Established methods for measurement development included the expertise of people with dementia and led to the generation of a set of items for a new resilience measure that were understandable and acceptable to this target population. This 37-item pool reflects the conceptual understanding of resilience in dementia as being derived across individual, community and societal level resources.
Comprehensive evaluation of the Infinium human MethylationEPIC v2 BeadChip
Authors: Kaur Diljeet , Lee Sol Moe , Goldberg David , Spix Nathan J. , Hinoue Toshinori , Li Hong-Tao , Dwaraka Varun B. , Smith Ryan , Shen Hui , Liang Gangning , Renke Nicole , Laird Peter W. , Zhou Wanding
Published: September 2023

Infinium Methylation BeadChips are widely used to profile DNA cytosine modifications in large cohort studies for reasons of cost-effectiveness, accurate quantification, and user-friendly data analysis in characterizing these canonical epigenetic marks. In this work, we conducted a comprehensive evaluation of the updated Infinium MethylationEPIC v2 BeadChip (EPICv2). Our evaluation revealed that EPICv2 offers significant improvements over its predecessors, including expanded enhancer coverage, applicability to diverse ancestry groups, support for low-input DNA down to one nanogram, coverage of existing epigenetic clocks, cell type deconvolution panels, and human trait associations, while maintaining accuracy and reproducibility. Using EPICv2, we were able to identify epigenome and sequence signatures in cell line models of DNMT and SETD2 loss and/or hypomorphism. Furthermore, we provided probe-wise evaluation and annotation to facilitate the use of new features on this array for studying the interplay between somatic mutations and epigenetic landscape in cancer genomics. In conclusion, EPICv2 provides researchers with a valuable tool for studying epigenetic modifications and their role in development and disease.
Quantum computing for fluids: Where do we stand?
Authors: Succi Sauro , Itani W. , Sreenivasan K. , Steijl R.
Published: September 2023

We present a pedagogical introduction to the current state of quantum computing algorithms for the simulation of classical fluids. Different strategies, along with their potential merits and liabilities, are discussed and commented on.
Coherence dynamics in Simon's quantum algorithm
Authors: Ye Linlin , Wu Zhaoqi , Fei Shao-Ming
Published: September 2023

Quantum coherence plays a pivotal role in quantum algorithms. We study the coherence dynamics of the evolved states in Simon's quantum algorithm based on Tsallis relative α entropy and

norm. We prove that the coherence of the first register and the second register both rely on the dimension N of the state spaces of the n qubit systems, and increase with the increase of N. We show that the oracle operator O does not change the coherence. Moreover, we study the coherence dynamics in Simon's quantum algorithm and prove that overall the coherence is in production when

and in depletion when

.
Community detection from fuzzy and higher-order perspectives
Authors: Xiao Jing , Xu Xiao-Ke
Published: September 2023

Our ability to observe the mesoscale topology of complex networks through community detection has significantly advanced in the past decades. This progress has opened up new frontiers in discovering more sophisticated and meaningful community structures that possess fuzzy and higher-order characteristics. This review provides an overview of two emerging research directions, which are fuzzy and higher-order community detection. It includes related concepts and practical scenarios, mathematical descriptions and latest advancements, as well as current challenges and future directions. Therefore, it will facilitate researchers in swiftly grasping the two emerging fields, offering valuable insights for future development of community detection studies.
SIRT1 and miR-34a-5p Expression in PBMCs as Potential Biomarkers for Patients With Type 2 Diabetes With Cognitive Impairments
Authors: Liu Xiaofeng , Zhao Zhipei , Chen Dengbin , Zhang Zeqin , Lin Xiaozhen , Shen Zhanbo , Lin Qingwen , Fan Kengna , Wang Qi , Zhang Weiqing , Ou Qishui
Published: September 2023

Context

Patients with type 2 diabetes mellitus (T2DM) are at significantly increased risk of Alzheimer disease (AD). However, no biomarkers are available for early identification of patients with T2DM with cognitive impairment (T2DM-CI). Mitochondrial dysfunction is linked to AD. Silent Information Regulator 1 (SIRT1), which is responsible for regulating mitochondrial biogenesis, and its related miRNAs were also altered in AD.

Objective

This study aimed to determine whether mitochondrial function in peripheral blood mononuclear cells (PBMCs) of patients with T2DM-CI was altered and if these alterations could be used as biomarkers.

Methods

A total of 374 subjects were enrolled, including AD, T2DM-CI, T2DM-nCI (T2DM without cognitive impairment), and healthy controls. The mitochondrial function was determined using a commercial assay kit. The mitochondrial DNA (mtDNA) content, the expression of SIRT1, and selected miRNAs in PBMCs were measured by quantitative polymerase chain reaction. The correlations and diagnostic accuracy were assessed using the Spearman correlation coefficient or receiver operating characteristics analysis, respectively.

Results

We found significant changes in mitochondrial function in PBMCs of patients with AD compared with controls (all P < .05), which were not found in T2DM-CI. However, mtDNA content and SIRT1 mRNA expression were lower in PBMCs of patients with T2DM-CI, while miR-34a-5p expression was higher than in patients with T2DM-nCI (all P < .05). A combination of SIRT1 and miR-34a-5p demonstrated excellent discrimination between T2DM-CI and T2DM-nCI (area under the curve = 0.793; sensitivity: 80.01%; specificity: 78.46%). Furthermore, correlation analysis revealed a link between miR-34a-5p expression and hyperglycemia in T2DM-CI.

Conclusion

Our findings revealed that there was an alteration of mitochondria at the peripheral level in patients with T2DM-CI. SIRT1 combined with miR-34a-5p in PBMCs performed well in identifying patients with T2DM-CI and may be a promising biomarker.
New Treatments for Acromegaly in Development
Authors: Gadelha Mônica R , Gadelha Ana Carolina , Kasuki Leandro
Published: September 2023

Acromegaly treatment has greatly evolved in recent decades, but there are still patients whose acromegaly is not controlled with currently available treatments, and there is a need to improve the treatment burden. Fortunately, there are new treatments under development that may increase treatment efficacy and convenience.
The Frequency of Differentiated Thyroid Cancer Recurrence in 2302 Patients With Excellent Response to Primary Therapy
Authors: Pałyga Iwona , Rumian Maciej , Kosel Alicja , Albrzykowski Maciej , Krawczyk Paulina , Kalwat Agata , Gąsior-Perczak Danuta , Walczyk Agnieszka , Kuchareczko Artur , Kopczyński Janusz , Chrapek Magdalena , Góźdź Stanisław , Kowalska Aldona
Published: September 2023

Context

Discrepant data on the recurrence rate of differentiated thyroid cancer (DTC) are reported.

Objective

To evaluate the frequency and risk factors of true recurrence in DTC patients with excellent responses (ExR) to initial therapy.

Methods

A retrospective analysis of the 2302 consecutive DTC patients with ExR to primary therapy, treated during 24 years at single center. The percentage of recurrence and cumulative recurrence rate (CRR) were analyzed. Risk factors for recurrence for patients with papillary thyroid cancer (PTC) were investigated and methods for establishing a diagnosis of recurrence were evaluated.

Results

Of DTC patients, 32 (1.4%) experienced recurrence. PTC patients with recurrence were more likely to have younger age (P = .0182), larger tumor size (P = .0013), lymph node metastases (P = .0013), incomplete resection (P = .0446), higher ATA risk (P = .0002), and had more frequently been treated with 131I (P = .0203). CRRs at 5, 10, 15, 20, and 24 years after surgery were 1.2%, 1.9%, 2.5%, 2.9%, and 2.9%, respectively. The CRRs according to histological type were highest for poorly differentiated thyroid cancer (PDTC), lower for oncocytic (OTC) and follicular thyroid cancer (FTC), and lowest for PTC. Most recurrences occurred within the first 5 years of observation. The most effective method for detecting local recurrence was ultrasonography with fine needle aspiration cytology, and for distant metastases, 18F-FDG PET.

Conclusion

True recurrence is rare in DTC patients. PTC patients with ExR to primary therapy and N0/Nx can be dismissed from oncological follow-up. Despite ExR to primary therapy, DTC patients with N1, and PDTC, OTC, FTC should remain under oncological follow-up.
Spectrum of Adrenal Dysfunction in Hemoglobin E/Beta Thalassemia
Authors: Singha Arijit , Mukhopadhyay Pradip , Ghosh Sujoy
Published: September 2023

Background

Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied.

Aims and Objectives

In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements.

Methods

In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated. Among them, 57 and 47 were transfusion dependent and non-transfusion dependent. According to Mahidol criteria, patients were classified into mild (n = 39), moderate (n = 39), and severe (n = 26) disease. Early morning (8 Am) serum cortisol, plasma ACTH, and plasma aldosterone, renin were measured. Patients with baseline cortisol of 5 to 18 μg/dL underwent both 1 μg and 250 μg short Synacthen test. According to these results, patients were classified as having either normal, subclinical, or overt (primary/secondary) adrenal dysfunction.

Results

Adrenal insufficiency was found in 41% (n = 43). Among them 83.7% (n = 34) had primary AI and 16.3% (n = 9) had secondary AI. Thirty-three patients (31%) with normal or elevated ACTH and with low or normal aldosterone with high renin were diagnosed as having subclinical AI. There was no difference in prevalence of AI between transfusion dependent and non-transfusion dependent (P = .56) nor was there was any difference in prevalence of AI according to disease severity (P = .52).

Conclusion

Adrenal insufficiency is common in HbE/beta thalassemia and is independent of transfusion dependency and disease severity.
Multiple Fractures in an Infant With Hepatoblastoma and Beckwith-Wiedemann Syndrome
Authors: Eimicke Toni , Swartz Jonathan
Published: September 2023

Children with hepatoblastoma have an increased incidence of fractures, but data are limited. Previous reports document an average of 4 fractures per child with hepatoblastoma. We present a severe case of a premature 4-month-old with multiple fractures in the setting of Beckwith-Wiedemann syndrome and hepatoblastoma. Although prematurity is a known risk for metabolic bone disease, it did not entirely explain the severity. Our patient underwent chemotherapy and surgical resection of his hepatoblastoma. Once deemed stable, he received a dose of zoledronic acid (ZA). One month post treatment with ZA, a skeletal survey revealed healing of the rib and femoral fractures and no new fractures. Five months post ZA, the skeletal survey revealed no new fractures and motor development was appropriate. An extensive search revealed scant literature on the rate or cause of pathologic fractures in patients with newly diagnosed hepatoblastoma. A better understanding of fracture risk in this population may guide prevention strategies, screening, and treatment. In our case, prematurity and substantial chronic illness may have compounded the known fracture risk associated with hepatoblastoma and may provide insight into the pathophysiology and prevention of fractures in this setting.
The Physician Anesthesia Workforce in Canada From 1996 to 2018: A Longitudinal Analysis of Health Administrative Data
Authors: Simkin Sarah , Orser Beverley A. , Wilson C. Ruth , McVicar Jason A. , Crozier Mitchell , Bourgeault Ivy Lynn
Published: September 2023

BACKGROUND:

A robust anesthesia workforce is essential to the provision of safe surgical, obstetrical, and critical care but information describing the physician anesthesia workforce and volume of clinical services delivered in Canada is limited. This study examines the Canadian physician anesthesia workforce, exploring trends in physician characteristics and activity levels over time. Practice patterns of specialist anesthesiologists and family physician anesthetists (FPAs) working in urban and rural communities were of particular interest.

METHODS:

Physicians who provided anesthesia care between 1996 and 2018 were identified using health administrative data from the Canadian Institute of Health Information (CIHI). In addition, data from the Canadian Post-MD Education Registry (CAPER) were used to characterize physicians pursuing postgraduate anesthesia training (1996–2019). Descriptive analyses of physician demographics, training, location, specialty designations, and volume of clinical services were undertaken.

RESULTS:

Between 1996 and 2018, the anesthesia workforce grew 1.8-fold to 3681 physicians, including 536 FPAs. Over the same time, nerve block services increased 7-fold, and payments for other anesthesia services increased 5-fold. The average age of the anesthesiology workforce increased by 2.3 years and the annual retirement rate was 3%. The workforce has become more gender balanced but remains predominantly male (73% in 2018). The proportion of physicians who were trained internationally (about 30%; 38% in rural areas) remained stable (and higher than that in the overall physician workforce). FPAs provided most anesthesia care in rural Canada and their attrition rate was generally 2- to 3-fold higher than specialists. Physicians in the rural anesthesia workforce provided anesthesia services more intensively over time. Relatively few FPAs who left the anesthesia workforce entered full retirement and they instead contributed other medical services to their communities.

CONCLUSIONS:

This study provides foundational information regarding anesthesia workforce capacity over a 22-year period, including insights into demographics, locations of practice, and clinical volumes. The results do not quantify the gap between service capacity and need; however, they support the need for a national workforce strategy to achieve equitable access to sustainable anesthesia services in Canada, particularly for rural communities.
The Influence of Electromyographic on Electroencephalogram-Based Monitoring: Putting the Forearm on the Forehead
Authors: Lichtenfeld Felicitas , Kratzer Stephan , Hinzmann Dominik , García Paul S. , Schneider Gerhard , Kreuzer Matthias
Published: September 2023

BACKGROUND:

Monitoring the electroencephalogram (EEG) during general anesthesia can help to safely navigate the patient through the procedure by avoiding too deep or light anesthetic levels. In daily clinical practice, the EEG is recorded from the forehead and available neuromonitoring systems translate the EEG information into an index inversely correlating with the anesthetic level. Electrode placement on the forehead can lead to an influence of electromyographic (EMG) activity on the recorded signal in patients without neuromuscular blockade (NMB). A separation of EEG and EMG in the clinical setting is difficult because both signals share an overlapping frequency range. Previous research showed that indices decreased when EMG was absent in awake volunteers with NMB. Here, we investigated to what extent the indices changed, when EEG recorded during surgery with NMB agents was superimposed with EMG.

METHODS:

We recorded EMG from the flexor muscles of the forearm of 18 healthy volunteers with a CONOX monitor during different activity settings, that is, during contraction using a grip strengthener and during active diversion (relaxed arm). Both the forehead and forearm muscles are striated muscles. The recorded EMG was normalized by z-scoring and added to the EEG in different amplification steps. The EEG was recorded during anesthesia with NMB. We replayed these combined EEG and EMG signals to different neuromonitoring systems, that is, bispectral index (BIS), CONOX with qCON and qNOX, and entropy module with state entropy (SE) and response entropy (RE). We used the Friedman test and a Tukey-Kramer post hoc correction for statistical analysis.

RESULTS:

The indices of all neuromonitoring systems significantly increased when the EEG was superimposed with the contraction EMG and with high EMG amplitudes, the monitors returned invalid values, representative of artifact contamination. When replaying the EEG being superimposed with “relaxed” EMG, the qCON and BIS showed significant increases, but not SE and RE. For SE and RE, we observed an increased number of invalid values.

CONCLUSIONS:

With our approach, we could show that EMG activity during contraction and resting state can influence the neuromonitoring systems. This knowledge may help to improve EEG-based patient monitoring in the future and help the anesthesiologist to use the neuromonitoring systems with more knowledge regarding their function.
Six Decades of Economic Research at the Bank of England
Authors: Acosta Juan , Cherrier Beatrice , Claveau François , Fontan Clément , Goutsmedt Aurélien , Sergi Francesco
Published: September 2023

This paper discusses the transformation of the content, role, and status of economic research at the Bank of England in the past sixty years. We show how three factors (the policy functions and missions of the Bank, the attitude of its executives toward economics, and its organizational structure) shaped the evolution of in-house economic research at the Bank during three distinctive periods (1960–91; 1992–2007; 2007–14). Our account relies on a broad set of sources and methods (the Bank's publications, archives, interviews with current and former Bank economists, citation analysis, prosopography, and topic modeling).
Cournot on the Communication of Markets: The Principle of Compensation of Demands and the Effects of International Trade on Social Income
Authors: Béraud Alain , Numa Guy
Published: September 2023

Cournot's views on the effects of international trade on social income have received little attention. Drawing upon a comprehensive analysis of Cournot's writings, this article shows that Cournot distinguished between variations in nominal income and variations in real income. He introduced the principle of compensation of demands: if the price of a commodity changes, the value of the total demand for other commodities remains unchanged. He relied on this principle to demonstrate that a unilateral removal of trade restrictions can cause real income to fall. Under specific circumstances, protective tariffs may be warranted. Cournot thus endorsed the infant-industry argument without being a die-hard protectionist. The article discusses the arguments of his critics and concludes that many commentators have misrepresented his thinking.
Thomas Edward Cliffe Leslie's Enthralling Journeys and His Critique of Ricardianism: From Inductive Political Economy to the Emergence of British Historical Economics
Authors: Manioudis Manolis
Published: September 2023

Thomas Edward Cliffe Leslie was one of the founders of British historical economics. He was an important figure in the history of economic thought of the nineteenth century, as he contributed to the critique of Ricardian political economy while at the same time being one of the founders of the British historical school. Cliffe Leslie was influenced by classical economists, such as Adam Smith and J. S. Mill, in calling for a historically and institutionally informed political economy. This article attempts to delineate the evolution of his economic thought by presenting the first phase of his intellectual development, which is marked by his frequent journeys in continental Europe. This phase, which is characterized by his applied political economy, is of considerable importance for understanding the emergence of British historical economics.
Writing Castelessly
Authors: Costa Dia Da
Published: September 2023

This article combines historical and life-writing approaches to demonstrate how caste is made invisible in histories and structures of education, canonical knowledge, and research. As a dominant-caste (savarna) Bengali academic, the author follows caste-oppressed feminists to offer a methodological intervention that challenges several ways in which castelessness is reproduced in feminist scholarship. The author asks why savarna write castelessly. “Writing castelessly,” wherein caste reflexivity is absented from analysis, solidarity, and teaching, is one manifestation of savarna feminists’ historical-material relation to caste. Narrating regional caste histories of savarna Bengalis, the author shows that her practice of writing castelessly is founded on material structures of power—historically claimed monopolies over culture and education, land, labor, and political representation. Relatedly, another reason savarna write castelessly is that disciplinary training in social sciences in higher education taught the author to think, feel, read, and write castelessly. Finally, the author traces the reproduction of these disciplinary structures in her scholarship. Ultimately, this self-critique grounded in historical and material relations of caste seeks a feminist readership invested in public accountability and denaturalizing Brahminical merit in academia.
The Tbx20-TLE interaction is essential for the maintenance of the second heart field
Authors: Edwards Whitney , Bussey Olivia K. , Conlon Frank L.
Published: September 2023

T-box transcription factor 20 (Tbx20) plays a multifaceted role in cardiac morphogenesis and controls a broad gene regulatory network. However, the mechanism by which Tbx20 activates and represses target genes in a tissue-specific and temporal manner remains unclear. Studies show that Tbx20 directly interacts with the Transducin-like Enhancer of Split (TLE) family of proteins to mediate transcriptional repression. However, a function for the Tbx20-TLE transcriptional repression complex during heart development has yet to be established. We created a mouse model with a two amino acid substitution in the Tbx20 EH1 domain, thereby disrupting the Tbx20-TLE interaction. Disruption of this interaction impaired crucial morphogenic events, including cardiac looping and chamber formation. Transcriptional profiling of Tbx20EH1Mut hearts and analysis of putative direct targets revealed misexpression of the retinoic acid pathway and cardiac progenitor genes. Further, we show that altered cardiac progenitor development and function contribute to the severe cardiac defects in our model. Our studies indicate that TLE-mediated repression is a primary mechanism by which Tbx20 controls gene expression.