bluuebunny/crossref_metadata_2025 huggingface dataset:
Validating left atrial fractionation and low-voltage substrate during atrial fibrillation and sinus rhythm—A high-density mapping study in persistent atrial fibrillation
Authors: Huang Taiyuan , Chen Juan , Müller-Edenborn Björn , Mayer Louisa , Eichenlaub Martin , Moreno Weidmann Zoraida , Allgeier Juergen , Bohnen Marius , Lehrmann Heiko , Trenk Dietmar , Schoechlin Simon , Westermann Dirk , Arentz Thomas , Jadidi Amir
Published: October 2022

Background

Low-voltage-substrate (LVS)-guided ablation for persistent atrial fibrillation (AF) has been described either in sinus rhythm (SR) or AF. Prolonged fractionated potentials (PFPs) may represent arrhythmogenic slow conduction substrate and potentially co-localize with LVS. We assess the spatial correlation of PFP identified in AF (PFP-AF) to those mapped in SR (PFP-SR). We further report the relationship between LVS and PFPs when mapped in AF or SR.

Materials and methods

Thirty-eight patients with ablation naïve persistent AF underwent left atrial (LA) high—density mapping in AF and SR prior to catheter ablation. Areas presenting PFP-AF and PFP-SR were annotated during mapping on the LA geometry. Low-voltage areas (LVA) were quantified using a bipolar threshold of 0.5 mV during both AF and SR mapping. Concordance of fractionated potentials (CFP) (defined as the presence of PFPs in both rhythms within a radius of 6 mm) was quantified. Spatial distribution and correlation of PFP and CFP with LVA were assessed. The predictors for CFP were determined.

Results

PFPs displayed low voltages both during AF (median 0.30 mV (Q1–Q3: 0.20–0.50 mV) and SR (median 0.35 mV (Q1–Q3: 0.20–0.56 mV). The duration of PFP-SR was measured at 61 ms (Q1–Q3: 51–76 ms). During SR, most PFP-SRs (89.4 and 97.2%) were located within LVA (<0.5 mV and <1.0 mV, respectively). Areas presenting PFP occurred more frequently in AF than in SR (median: 9.5 vs. 8.0, p = 0.005). Both PFP-AF and PFP-SR were predominantly located at anterior LA (>40%), followed by posterior LA (>20%) and septal LA (>15%). The extent of LVA < 0.5 mV was more extensive in AF (median: 25.2% of LA surface, Q1–Q3:16.6–50.5%) than in SR (median: 12.3%, Q1–Q3: 4.7–29.4%, p = 0.001). CFP in both rhythms occurred in 80% of PFP-SR and 59% of PFP-AF (p = 0.008). Notably, CFP was positively correlated to the extent of LVA in SR (p = 0.004), but not with LVA in AF (p = 0.226). Additionally, the extent of LVA < 0.5 mV in SR was the only significant predictor for CFP, with an optimal threshold of 16% predicting high (>80%) fractionation concordance in AF and SR.

Conclusion

Substrate mapping in SR vs. AF reveals smaller areas of low voltage and fewer sites with PFP. PFP-SR are located within low-voltage areas in SR. There is a high degree of spatial agreement (80%) between PFP-AF and PFP-SR in patients with moderate LVA in SR (>16% of LA surface). These findings should be considered when substrate-based ablation strategies are applied in patients with the left atrial low-voltage substrate with recurrent persistent AF.
Clinical outcomes of subcutaneous vs. transvenous implantable defibrillator therapy in a polymorbid patient cohort
Authors: Kattih Badder , Operhalski Felix , Boeckling Felicitas , Hecker Florian , Michael Felix , Vamos Mate , Hohnloser Stefan H. , Erath Julia W.
Published: October 2022

Background

The subcutaneous implantable cardioverter-defibrillator (S-ICD) has been designed to overcome lead-related complications and device endocarditis. Lacking the ability for pacing or resynchronization therapy its usage is limited to selected patients at risk for sudden cardiac death (SCD).

Objective

The aim of this single-center study was to assess clinical outcomes of S-ICD and single-chamber transvenous (TV)-ICD in an all-comers population.

Methods

The study cohort comprised a total of 119 ICD patients who underwent either S-ICD (n = 35) or TV-ICD (n = 84) implantation at the University Hospital Frankfurt from 2009 to 2017. By applying an inverse probability-weighting (IPW) analysis based on the propensity score including the Charlson Comorbidity Index (CCI) to adjust for potential extracardiac comorbidities, we aimed for head-to-head comparison on the study composite endpoint: overall survival, hospitalization, and device-associated events (including appropriate and inappropriate shocks or system-related complications).

Results

The median age of the study population was 66.0 years, 22.7% of the patients were female. The underlying heart disease was ischemic cardiomyopathy (61.4%) with a median LVEF of 30%. Only 52.9% had received an ICD for primary prevention, most of the patients (67.3%) had advanced heart failure (NYHA class II–III) and 16.8% were in atrial fibrillation. CCI was 5 points in TV-ICD patients vs. 4 points for patients with S-ICD (p = 0.209) indicating increased morbidity. The composite endpoint occurred in 38 patients (31.9 %), revealing no significant difference between patients implanted with an S-ICD or TV-ICD (unweighted HR 1.50, 95 % confidence interval (CI) 0.78–2.90; p = 0.229, weighted HR 0.94, 95% CI, 0.61–1.50, p = 0.777). Furthermore, we observed no difference in any single clinical endpoint or device-associated outcome, neither in the unweighted cohort nor following inverse probability-weighting.

Conclusion

Clinical outcomes of the S-ICD and TV-ICD revealed no differences in the composite endpoint including survival, freedom of hospitalization and device-associated events, even after careful adjustment for potential confounders. Moreover, the CCI was evaluated in a S-ICD cohort demonstrating higher survival rates than predicted by the CCI in young, polymorbid (S-)ICD patients.
Improving predictive performance in incident heart failure using machine learning and multi-center data
Authors: Sabovčik František , Ntalianis Evangelos , Cauwenberghs Nicholas , Kuznetsova Tatiana
Published: October 2022

Objective

To mitigate the burden associated with heart failure (HF), primary prevention is of the utmost importance. To improve early risk stratification, advanced computational methods such as machine learning (ML) capturing complex individual patterns in large data might be necessary. Therefore, we compared the predictive performance of incident HF risk models in terms of (a) flexible ML models and linear models and (b) models trained on a single cohort (single-center) and on multiple heterogeneous cohorts (multi-center).

Design and methods

In our analysis, we used the meta-data consisting of 30,354 individuals from 6 cohorts. During a median follow-up of 5.40 years, 1,068 individuals experienced a non-fatal HF event. We evaluated the predictive performance of survival gradient boosting (SGB), CoxNet, the PCP-HF risk score, and a stacking method. Predictions were obtained iteratively, in each iteration one cohort serving as an external test set and either one or all remaining cohorts as a training set (single- or multi-center, respectively).

Results

Overall, multi-center models systematically outperformed single-center models. Further, c-index in the pooled population was higher in SGB (0.735) than in CoxNet (0.694). In the precision-recall (PR) analysis for predicting 10-year HF risk, the stacking method, combining the SGB, CoxNet, Gaussian mixture and PCP-HF models, outperformed other models with PR/AUC 0.804, while PCP-HF achieved only 0.551.

Conclusion

With a greater number and variety of training cohorts, the model learns a wider range of specific individual health characteristics. Flexible ML algorithms can be used to capture these diverse distributions and produce more precise prediction models.
Sex-based considerations for implementation of ventricular assist device therapy
Authors: Jones-Ungerleider K. Candis , Rose Angela , Knott Kevin , Comstock Sarah , Haft Jonathan W. , Pagani Francis D. , Tang Paul C.
Published: October 2022

Women with advanced heart failure receive advanced surgical therapies such as durable left ventricular assist device (LVAD) implantation or heart transplantation at a rate much lower compared to males. Reasons for this discrepancy remain largely unknown. Much of what is understood reflects outcomes of those patients who ultimately receive device implant or heart transplantation. Females have been shown to have a higher mortality following LVAD implantation and experience higher rates of bleeding and clotting phenomena and right ventricular failure. Beyond outcomes, the literature is limited in the identification of pre-operative factors that drive lower than expected LVAD implant rates in this population. More focused research is needed to define the disparities in advance heart failure therapy delivery in women and other underserved populations.
The projections of global and regional rheumatic heart disease burden from 2020 to 2030
Authors: Hu Yingying , Tong Zijia , Huang Xuewei , Qin Juan-Juan , Lin Lijin , Lei Fang , Wang Wenxin , Liu Weifang , Sun Tao , Cai Jingjing , She Zhi-Gang , Li Hongliang
Published: October 2022

Background

Rheumatic heart disease (RHD) remains the leading cause of preventable death and disability in children and young adults, killing an estimated 320,000 individuals worldwide yearly.

Materials and methods

We utilized the Bayesian age-period cohort (BAPC) model to project the change in disease burden from 2020 to 2030 using the data from the Global Burden of Disease (GBD) Study 2019. Then we described the projected epidemiological characteristics of RHD by region, sex, and age.

Results

The global age-standardized prevalence rate (ASPR) and age-standardized incidence rate (ASIR) of RHD increased from 1990 to 2019, and ASPR will increase to 559.88 per 100,000 population by 2030. The global age-standardized mortality rate (ASMR) of RHD will continue declining, while the projected death cases will increase. Furthermore, ASPR and cases of RHD-associated HF will continue rising, and there will be 2,922,840 heart failure (HF) cases in 2030 globally. Female subjects will still be the dominant population compared to male subjects, and the ASPR of RHD and the ASPR of RHD-associated HF in female subjects will continue to increase from 2020 to 2030. Young people will have the highest ASPR of RHD among all age groups globally, while the elderly will bear a greater death and HF burden.

Conclusion

In the following decade, the RHD burden will remain severe. There are large variations in the trend of RHD burden by region, sex, and age. Targeted and effective strategies are needed for the management of RHD, particularly in female subjects and young people in developing regions.
Plasma brain injury markers are associated with volume status but not muscle health in heart failure patients
Authors: Lahiri Shouri , Mastali Mitra , Van Eyk Jennifer E. , Hitzeman Tara C. , Bresee Catherine , Raedschelders Koen , Lyden Patrick D. , Gottlieb Roberta A. , Fang James C. , Shaw Robin M. , Hong Ting Ting
Published: October 2022

Background: Neurofilament light chain protein (NfL) and tau are plasma biomarkers of neuronal injury which can be elevated in patients with neurodegenerative diseases. N-terminal pro-brain natriuretic peptide (NT-proBNP) is an established marker of volume status in patients with heart failure (HF) and plasma cBIN1 score (CS) is an emerging biomarker of cardiac muscle health. It is not known if, in HF patients, there is a correlation between cardiac markers and brain injury markers.

Methods: We studied ambulatory HF patients with either preserved and reduced ejection fraction (N = 50 with 25 HFrEF and 25 HFpEF) and age and sex matched healthy controls (N = 50). Plasma NT-proBNP and CS were determined using commercial kits. A bead-based ELISA assay was used to quantify femtomolar concentrations of plasma neuronal markers NfL and total tau.

Results: Plasma levels of NT-proBNP and CS in heart failure patients were significantly higher than those from healthy controls. In both patients with HFrEF and HFpEF, we found independent and direct correlations between the volume status marker NT-proBNP, but not the cardiomyocyte origin muscle health marker CS, with NfL (r = 0.461, p = 0.0007) and tau (r = 0.333, p = 0.0183).

Conclusion: In patients with HF with or without preserved ejection fraction, plasma levels of NfL and tau correlate with volume status rather than muscle health, indicating volume overload-associated neuronal injury.
Integration analysis identifies the role of metallothionein in the progression from hepatic steatosis to steatohepatitis
Authors: Li Xiaoya , Zhong Shaoping , Sun Yifan , Huang Xinmei , Li Yue , Wang Lihong , Wu Yueyue , Yang Min , Yuan Hai-Xin , Liu Jun , Zang Shufei
Published: October 2022

Background

Non-alcoholic fatty liver disease (NAFLD), a metabolic disorder that develops from non-alcoholic fatty liver (NAFL) to non-alcoholic steatohepatitis (NASH), has become an epidemic of chronic liver dysfunction worldwide. However, mechanisms that govern the transition from NAFL to NASH have not been fully elucidated.

Methods

Gene expression profile data of NAFLD liver tissues were obtained from Gene Expression Omnibus (GEO), including three microarray datasets with 60 NAFL and 44 NASH patients. Integrative differentially expressed genes (DEGs) between NAFL and NASH patients were identified using robust rank aggregation (RRA) analysis. Hub genes were identified combined with gene ontology functional annotation and protein–protein interaction network construction and validated using a sequencing dataset. Huh-7 cells with palmitate-induced lipid overload and NAFLD-diet mouse model of different stages were used to verify our findings.

Results

RRA analysis determined 70 robust DEGs between NAFL and NASH. The most robustly upregulated genes were SPP1, AKR1B10, CHST9, and ANXA2, while the most robustly downregulated DEGs were SNORD94, SCARNA10, SNORA20, and MT1M. Cellular response to zinc ion (GO: 0071294) ranked first in GO analysis of downregulated genes, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment showed that mineral absorption (hsa04978) was significantly enriched. The involvement of the metallothionein pathway was further validated by the decrease of Mt1 expression during NAFL to NASH progression in NAFLD mice and the protection from lipotoxicity in liver cells by overexpressing MT1M.

Conclusions

Our integrated analysis identified novel gene signatures and provided comprehensive molecular mechanisms underlying the transition from NAFL to NASH. Metallothionein might be a potential intervention target for NAFLD progression.
Are environmental regulation tools effective? An analysis based on financial investment of entity enterprises
Authors: Niu Dengyun , Wang Zhihua , Yang Songling
Published: October 2022

Environmental regulation and economic development are consistent in the long run, but there are certain contradictions in the short term. Examining the characteristics of available environmental regulation tools and using them in a way that will align the interests of local governments and enterprises can improve environmental regulation and enhance green transformation and development. This study considers two general types of environmental regulation tools: negative punishment types and positive incentive types. Applying an intermediary effect model and the two-stage least squares method, a sample of Chinese A-share listed companies from 2007 to 2019 is used to test the impact of these different types of environmental regulation tools on the financial investment levels of entity enterprises. The mechanism through which these macro-environmental regulation tools function and the micro-enterprise heterogeneity factors that influence their impact are systematically studied. The results show that negative punishment type environmental regulation tools have a positive impact on the financial investment levels of entity enterprises, while positive incentive type environmental regulation tools inhibit financial investment levels. This impact is formed through managerial incentive mechanisms referred to as “whipping the fast ox” and “heavy rewards and light punishments.” Factors such as financing constraints, relocation costs, pollution levels, and enterprise scale have heterogeneous effects on these paths. Policy suggestions are offered based on the findings. This study makes a significant contribution to the literature by clarifying the channel through which environmental regulation influences micro-enterprise decision-making. It provides a theoretical basis and policy reference for local government officials as they address the conflict between economic growth and environmental protection in the short term. Moreover, the results offer long-term development decision-making ideas for shareholders and managers in the process of green transformation and upgrading of enterprises.
Complexity of daily precipitation and its change in China during 1961–2015 based on approximate entropy
Authors: Zhao Shanshan , Mei Ying , Jiang Yundi , Wan Shiquan , He Wenping
Published: October 2022

Approximate entropy (ApEn) can measure the regularity and complexity of a nonlinear system. We find that the results of ApEn are relatively stable when the sample size of a time series exceeds 100, which indicates that the estimation results of the ApEn algorithm are robust to small sample data. In this study, the complexity of the daily precipitation records in China from 1961 to 2015 was first analyzed by using ApEn, and then we further investigated the spatial and temporal variability of the dynamical characteristics of precipitation. The results show that the ApEn values of daily precipitation in China during 1961–2015 present the following characteristics: larger in southern and eastern China and smaller in northern and western China. In addition, ApEn in Northwest China and the Tibetan Plateau has been increasing since 1961. However, since the 1970s, ApEn in the south of the middle and lower reaches of the Yangtze River shows a gradual decrease. The temporal instances of abrupt ApEn changes in daily precipitation occur from region to region. The number of stations with an abrupt ApEn shift has a statistically significant increase since 1984 at a significant level of α = 0.01, which means the complexity characteristic of daily precipitation in China has been more prone to abrupt shifts since 1984 than in the previous period.
Vulnerability evaluation and prediction of the water-energy-food-ecology nexus in the Yangtze River Economic Belt based on TOPSIS, neighborhood rough set and support vector machine
Authors: Pan Yue , Chen Yan , Liu Yue
Published: October 2022

With the intensification of human activities, the vulnerability of water, energy, food and ecology systems has become more and more prominent, and the research on the vulnerability of the water-energy-food-ecology (WEFE) nexus is significant to realizing regional sustainable development. This study aims to make a comprehensive measurement of the vulnerability of the WEFE nexus in the Yangtze River Economic Belt (YREB) from 2008 to 2019, clarify the evolutionary trend of its vulnerability, and predict the vulnerability of each province (municipality) in the future, to formulate policies to reduce vulnerability. This study firstly constructs a vulnerability evaluation index system of the WEFE nexus based on the VSD framework and uses the neighborhood rough set (NRS) to reduce the attributes. Then, the TOPSIS model is used to evaluate the vulnerability of the WEFE nexus. Finally, by comparing the training accuracy of the random forest, decision tree and support vector machine (SVM) model, the SVM model is selected to predict the vulnerability of the WEFE nexus under different scenarios in 2025. The results show that the vulnerability of the WEFE nexus in the YREB showed a fluctuating downward trend from 2008 to 2019. The decline is faster in the middle and upper reaches, and slower in the lower reaches. In 2025, under a strong resource management scenario, the vulnerability of the provinces (municipalities) in the YREB will decrease significantly, while the weak and moderate resource management scenarios are not conducive to reducing vulnerability and even worsening. Therefore, in the future, the provinces (municipalities) in the upper, middle and lower reaches should make reasonable use of the resource endowments, take measurements actively according to local conditions, and continuously strengthen the management of water, energy, food and ecological resources, thus promoting the continuous improvement of the vulnerability of the WEFE nexus.
Towards REDD+ implementation: Deforestation and forest degradation drivers, REDD+ financing, and readiness activities in participant countries
Authors: Andoh Jewel , Oduro Kwame Antwi , Park Joowon , Lee Yohan
Published: October 2022

This study provides an assessment of dominant drivers of deforestation and forest degradation across 29 REDD+ participant countries and total funds disbursed from the Forest Carbon Partnership Facility to 15 participant countries since they signed their respective Readiness Preparation Proposals (R-PPs), as well as what they spent the grants on. This study aims to provide information for policymakers and donors on the need to invest in REDD+, as well as the need for participant countries to channel funds to key activities for effectively and efficiently implementing REDD+. The assessment is based on participant countries’ R-PPs and FCPF readiness fund progress reports, using a content analysis approach. The expansion of agriculture, which includes both commercial and subsistence agriculture, was the predominant driver of deforestation, while logging, such as industrial and small-scale exploitation, was the main driver of forest degradation in most participating countries. In addition, we observed that the 15 participant countries received a total of USD 702.36 million for REDD+ readiness preparation. However, most countries have received less than USD 10 million for their readiness-related activities. We observed a huge disparity regarding the funds received between countries from sub-Saharan Africa and their Asian and Latin American counterparts, particularly Indonesia and Peru, respectively. Furthermore, almost all countries have spent their funds on policy and strategy development, stakeholder and consultation events, and public awareness creation. Relatively small amounts have been spent on capacity building and training. Thus, international donors need to focus on strengthening institutional capacities and building effective forest governance structures in countries participating in REDD+, and they should also provide platforms to engage with participant countries to tackle the main deforestation and forest degradation drivers. We suggest further studies to identify high-performing countries that have received lower-than-average funding, consider their deforestation pressures, the size of forests, and the emission reduction potential.
Role of NK cells in cord blood transplantation and their enhancement by the missing ligand effect of the killer-immunoglobulin like receptor
Authors: Yokoyama Hisayuki
Published: October 2022

Natural killer (NK) cells are the first lymphocytes reconstituted after allogenic hematopoietic stem cell transplantation (HSCT). Especially, in cord blood transplantation (CBT), the increase in the number of NK cells is sustained for a long period. Although there are conflicting results, many studies show that early reconstitution of NK cells is associated with favorable CBT outcomes, suggesting that maximizing NK cell functions could improve the CBT outcome. Killer immunoglobulin-like receptors (KIRs) include inhibitory and stimulatory receptors, which can regulate NK-cell activity. Because some of the KIRs have HLA class I as their ligand, the KIR—ligand interaction on NK cells can be lost in some cases of CBT, which results in the activation of NK cells and alters HSCT outcome. Thus, effects of KIR–ligand mismatch under various conditions have been widely examined; however, the results have been controversial. Among such studies, those using the largest number of CBTs showed that HLA—C2 (KIR2DL1—ligand) mismatches have a favorable effect on the relapse rate and overall survival only when the CBT used methotrexate for graft-versus-host disease prophylaxis. Another study suggested that KIR—ligand mismatch is involved in reducing the relapse of acute myeloid leukemia, mediated by reactivation of cytomegalovirus. These results indicate that activation of NK cells by KIR—ligand mismatch may have favorable effects on CBT outcomes and could help enhance the NK-cell function.
Prolonged hematological toxicity in patients receiving BCMA/CD19 CAR-T-cell therapy for relapsed or refractory multiple myeloma
Authors: Li Hujun , Zhao Lina , Sun Zengtian , Yao Yue , Li Li , Wang Jiaojiao , Hua Tian , Ji Shengwei , Wang Shiyuan , Cheng Hai , Shi Ming , Li Zhenyu , Zeng Lingyu , Wu Qingyun , Qiao Jianlin , Chen Chong , Zheng Junnian , Cao Jiang , Xu Kailin
Published: October 2022

Although chimeric antigen receptor T (CAR-T) cell therapy has been indicated to be effective in treating relapsed or refractory multiple myeloma (R/R MM), severe hematological toxicity (HT) remains an intractable issue. This study enrolled 54 patients with R/R MM following combined infusion of anti-CD19 and anti-BCMA CAR-T cells. The results showed that the rates of severe cytopenia were high, including severe neutropenia (28/54, 52%), severe anemia (15/54, 28%), and severe thrombocytopenia (18/54, 33%). Moreover, the incidence of prolonged HT (PHT) on Day 28 post-infusion was 52% (28/54), including 46% for severe neutropenia, 30% for severe anemia, and 31% for severe thrombocytopenia. Patients with PHT had a poorer median progression-free survival (PFS) and overall survival (OS) than patients without PHT (P=0.011; P=0.007). Furthermore, Cox regression analyses showed that PHT was an independent risk factor for PFS and OS. Univariate analyses showed that IFNγ (OR: 1.046; 95% CI: 1.002-1.093, P=0.042) and severe HT after lymphodepletion chemotherapy (OR: 0.082; 95% CI: 0.017-0.404; P=0.002) were independent risk factors for PHT. In conclusion, these results indicated that PHT was associated with poor outcomes following CAR-T-cell therapy in MM patients. Early detection and management of PHT would be beneficial for the prevention of life-threatening complications and improvement in the survival of patients after CAR-T-cell therapy.

Clinical trial registration

This trial was registered on 1 May 2017 at http://www.chictr.org.cn as ChiCTR-OIC-17011272.
The state of the art in cost-benefit of HTS methods for stock assessment: An overview
Authors: Rodríguez-Rodríguez Gonzalo , Ballesteros Hugo M. , Sánchez-Llamas Eduardo , Bande Roberto , Otero Rosa Fernández
Published: October 2022

Over the past two decades, enormous progresses have been made in high-throughput sequencing (HTS) method development. This fact unveiled the potential usefulness of HTS methods in a wide range of fields such as fishery assessment and management, for which their application has been extensively discussed. As a consequence of the rapid development, sequencing costs have continuously declined, leading to a general claim that HTS methods are cost-efficient compared with traditional ones. Within this context, the underlying research objective is to assess the cost-effectiveness of genomic techniques through a review of the state of the art (SoA) on three HTS methods: i) environmental DNA (eDNA); ii) epigenetics method for age determination through DNA methylation (DNAm), and; iii) close-kin mark-recapture (CKMR) applied on marine ecosystems and fisheries and for stock assessment purposes. The SoA review of the literature on HTS methods was performed through the snow-balling systematic reviewing approach. The analysis has considered the set of processes and variables necessary to perform the stock assessment and compared the capacity of current and HTS methods for providing the required data. Research reveals that HTS methods constitute a promising tool for fishery research and, particularly, for improving scientific advice. Nevertheless, up to now, only one research, on a non-commercial species, has been conducted on the application of HTS methods for stock assessment purposes. Although some partial data are present in the literature, no systematic analysis on costs has been found. This paper suggests that the future research agenda should attempt to straddle both the scenarios for the transition process, considering complementary implementation and substitution possibilities and their cost-efficiency. Clarifying these questions is likely to pave the way for the effective and step-wise implementation of these methods in fishery management; thus, further research is recommended to encompass the transition process.
High temperature induced metabolic reprogramming and lipid remodeling in a high-altitude fish species, Triplophysa bleekeri
Authors: Yuan Dengyue , Wang Haoyu , Liu Xiaoqin , Wang Siya , Shi Jinfeng , Cheng Xinkai , Gu Haoran , Xiao Shijun , Wang Zhijian
Published: October 2022

The effect of thermal changes on the physiology and behavior of fish is a major research focus in the face of ongoing global warming. There is little information about the effects of temperature increase on fish in the wild. However, the consequences of temperature increase on fish in controlled laboratory conditions can provide insights into what can be expected in the wild. Triplophysa bleekeri, a high-plateau fish, exhibits high sensitivity to high temperatures, suggesting it to be a good model to investigate the impact of temperature increase on fish. In this study, we analyzed the effect of gradual temperature increase on transcriptional and metabolic levels of T. bleekeri subjected to a gradual temperature change of 0.5°C/day until temperatures of 10°C, 13°C, 16°C, and 19°C were reached. Transcriptomics results of the liver, gut, spleen, and trunk kidney showed that metabolic pathways are widely involved in the response to increased temperatures in T. bleekeri. Lipidomics results further indicated that the lipid composition was altered by increased temperatures, and three lipids (PC 14:0e/22:1, PC 18:0e/22:5, and TAG 14:3-21:2-21:2) were identified as potential biomarkers of heat stress in T. bleekeri. Moreover, a decline in unsaturated fatty acid levels was observed in T. bleekeri under high temperatures. These results suggest that high temperatures modify the metabolomic pathways. Overall, our results help improve the understanding of physiological responses in fish to increased temperatures, and provide valuable information predicting the consequences of global warming on fish.
Assessment and validation of the TREAT-B score to assess the treatment eligibility of patients with chronic hepatitis B virus infection
Authors: Thanapirom Kessarin , Suksawatamnuay Sirinporn , Thaimai Panarat , Treeprasertsuk Sombat , Komolmit Piyawat , Tangkijvanich Pisit
Published: October 2022

Background and aims

Access to Hepatitis B virus (HBV) DNA testing to determine treatment eligibility is limited in low-income countries. Therefore, this study aimed to assess and validate the TREAT-B score proposed as the treatment threshold in an Asian cohort in determining the HBV treatment eligibility.

Methods

A retrospective analysis was conducted on consecutive patients with treatment-naïve chronic HBV mono-infection who visited the liver clinic at Chulalongkorn University Hospital, Bangkok, Thailand, from 2016 to 2020. The 2018 American Association for the Study of Liver Diseases guideline was the reference standard.

Results

Overall, 825 patients with chronic HBV infection were enrolled, comprising 409 (50.4%) males, with a median age of 50 (38–58) years. Of these, 216 (26.2%), 565 (68.5%), and 377 (45.7%) were eligible for treatment based on the AASLD, TREAT-B score, and simplified WHO criteria, respectively. The area under the receiver operating characteristics curve (AUROC) of the TREAT-B ≥ 2 was better than the simplified WHO criteria (0.69 vs. 0.62, p = 0.006) for selecting patients eligible for antiviral therapy. The sensitivity and specificity of the TREAT-B ≥ 2 were 96.3% and 41.4%, respectively. Applying the TREAT-B ≥ 3 improved the specificity (89.0%) and AUROC (0.80, 95% CI 0.76–0.84, but reduced the sensitivity (70.8%) for selecting eligible patients for HBV therapy.

Conclusions

In resource-constrained countries where HBV DNA is unavailable, the TREAT-B score is an alternative criteria for indicating treatment eligibility. The TREAT-B score of ≥3 is highly accurate and may minimize the number of patients unnecessarily treated in Asian HBV patients.
Decision making under uncertainty in the diagnosis and management of Alzheimer's Disease in primary care: A study protocol applying concepts from neuroeconomics
Authors: Saposnik Gustavo , Ismail Zahinoor , Rivard Anne-Marie , Knifton Debbie , Bromfield Gillian , Terzaghi Maria , Montoya Alonso , Menard Marie-Chantal
Published: October 2022

Background

The current management of patients with Dementia, primarily with Alzheimer's Disease (AD) is rapidly evolving. However, limited information is available about the current gaps and decision-making in primary care.

Objectives

To evaluate factors associated with gaps, risk preferences regarding diagnostic and therapeutic choices in the management of patients with AD by primary care physicians (PCP) from across Canada.

Methods

We propose a non-interventional, cross-sectional pilot study involving 120 primary care physicians referred from the College of Family Physicians of Canada to assess diagnostic and therapeutic decisions in the management of ten simulated AD-related case-scenarios commonly encountered in clinical practice. We initially describe the current landscape and gaps regarding diagnostic and therapeutic challenges in the management of patients with AD in primary care. Then, we provide concepts from behavioral economics and neuroeconomics applied to medical decision-making. Specifically, we include standardized tests to measure risk aversion, physicians' reactions to uncertainty, and questions related to risk preferences in different domains. Finally, we summarize the protocol to be implemented to address our goals. The primary study outcome is the proportion of participants that elect to defer initial investigations to the specialist and the associated factors. Secondary outcomes include the proportion of PCP willing to order cerebral spinal fluid studies, PET scans, or initiate treatment according to the simulated case-scenarios. The study will be conducted in English and French.

Conclusions

The study findings will contribute a better understanding of relevant factors associated with diagnostic and therapeutic decisions of PCP in the management of AD, identifying participant's preferences and evaluating the role of behavioral aspects such tolerance to uncertainty, aversion to ambiguity, and therapeutic inertia.
It’s all in the numbers: Cohesin stoichiometry
Authors: Matityahu Avi , Onn Itay
Published: October 2022

Cohesin, a structural maintenance of chromosome (SMC) complex, organizes chromatin into three-dimensional structures by threading chromatin into loops and stabilizing long-range chromatin interactions. Four subunits in a 1:1:1:1 ratio compose the cohesin core, which is regulated by auxiliary factors that interact with or modify the core subunits. An ongoing debate about cohesin’s mechanism of action regards its stoichiometry. Namely, is cohesin activity mediated by a single complex or cooperation between several complexes that organize into dimers or oligomers? Several investigations that used various experimental approaches have tried to resolve this dispute. Some have convincingly demonstrated that the cohesin monomer is the active unit. However, others have revealed the formation of cohesin dimers and higher-order clusters on and off chromosomes. Elucidating the biological function of cohesin clusters and determining what regulates their formation are just two of the many new questions raised by these findings. We briefly review the history of the argument about cohesin stoichiometry and the central evidence for cohesin activity as a monomer vs. an oligomer. Finally, we discuss the possible biological significance of cohesin oligomerization and present open questions that remain to be answered.
Personalized nutrition, microbiota, and metabolism: A triad for eudaimonia
Authors: Sarfraz Muhammad Hassan , Shahid Aqsa , Asghar Samra , Aslam Bilal , Ashfaq Usman Ali , Raza Hammad , Prieto Miguel A. , Simal-Gandara Jesus , Barba Francisco J. , Rajoka Muhammad Shahid Riaz , Khurshid Mohsin , Nashwan Abdulqadir J.
Published: October 2022

During the previous few years, the relationship between the gut microbiota, metabolic disorders, and diet has come to light, especially due to the understanding of the mechanisms that particularly link the gut microbiota with obesity in animal models and clinical trials. Research has led to the understanding that the responses of individuals to dietary inputs vary remarkably therefore no single diet can be suggested to every individual. The variations are attributed to differences in the microbiome and host characteristics. In general, it is believed that the immanent nature of host-derived factors makes them difficult to modulate. However, diet can more easily shape the microbiome, potentially influencing human physiology through modulation of digestion, absorption, mucosal immune response, and the availability of bioactive compounds. Thus, diet could be useful to influence the physiology of the host, as well as to ameliorate various disorders. In the present study, we have described recent developments in understanding the disparities of gut microbiota populations between individuals and the primary role of diet-microbiota interactions in modulating human physiology. A deeper understanding of these relationships can be useful for proposing personalized nutrition strategies and nutrition-based therapeutic interventions to improve human health.
Bibliometric analysis of research on Alzheimer’s disease and non-coding RNAs: Opportunities and challenges
Authors: Fei Xinxing , Wang Shiqi , Li Jiyang , Zeng Qiu , Gao Yaqian , Hu Yue
Published: October 2022

Background

Non-coding RNAs (ncRNA) are a kind of RNA that does not encode protein, which play an important role in Alzheimer’s disease (AD). However, there is a lack of bibliometric analysis and visualization analysis of the research related to AD and ncRNAs.

Materials and methods

Literature related to AD and ncRNAs in the last decade were searched through the Web of Science Core Collection (WOSCC). The relevant information from all the searched articles was collected. The bibliometric visualization website, CiteSpace, and VOSviewer were used for visualization analysis of countries/regions, institutions, authors, and keywords.

Results

In total, 1,613 kinds of literature were published in the field. Literature in this field were published in 494 journals. The Journal of Alzheimer’s Disease was the most popular journal. China, Louisiana State University System, and Lukiw WJ were the countries/regions, institutions, and authors with the highest scientific productivity, respectively. The research hotspots in this field focused on the role and mechanism of ncRNAs, especially microRNAs, in AD. The level of research was mainly based on basic research, focusing on animal and cellular levels, and related to proteomics. “Circular RNAs,” “regulation of neuroinflammation,” and “tau protein” were the future research directions.

Conclusion

Taken together, the field of AD and ncRNAs is developing well. The research hotspots and frontiers in this field can provide a reference for researchers to choose their research direction.
Up-regulation of CB1 cannabinoid receptors located at glutamatergic terminals in the medial prefrontal cortex of the obese Zucker rat
Authors: Echeazarra Leyre , Barrondo Sergio , García del Caño Gontzal , Bonilla-Del Río Itziar , Egaña-Huguet Jon , Puente Nagore , Aretxabala Xabier , Montaña Mario , López de Jesús Maider , González-Burguera Imanol , Saumell-Esnaola Miquel , Goicolea María Aránzazu , Grandes Pedro , Sallés Joan
Published: October 2022

The present study describes a detailed neuroanatomical distribution map of the cannabinoid type 1 (CB1) receptor, along with the biochemical characterization of the expression and functional coupling to their cognate Gi/o proteins in the medial prefrontal cortex (mPCx) of the obese Zucker rats. The CB1 receptor density was higher in the prelimbic (PL) and infralimbic (IL) subregions of the mPCx of obese Zucker rats relative to their lean littermates which was associated with a higher percentage of CB1 receptor immunopositive excitatory presynaptic terminals in PL and IL. Also, a higher expression of CB1 receptors and WIN55,212-2-stimulated [35S]GTPγS binding was observed in the mPCx but not in the neocortex (NCx) and hippocampus of obese rats. Low-frequency stimulation in layers II/III of the mPCx induced CB1 receptor-dependent long-term synaptic plasticity in IL of area obese Zucker but not lean rats. Overall, the elevated 2-AG levels, up-regulation of CB1 receptors, and increased agonist-stimulated [35S]GTPγS binding strongly suggest that hyperactivity of the endocannabinoid signaling takes place at the glutamatergic terminals of the mPCx in the obese Zucker rat. These findings could endorse the importance of the CB1 receptors located in the mPCx in the development of obesity in Zucker rats.
GNE myopathy: History, etiology, and treatment trials
Authors: Mullen Jeffrey , Alrasheed Khalid , Mozaffar Tahseen
Published: October 2022

GNE myopathy is an ultrarare muscle disease characterized by slowly progressive muscle weakness. Symptoms typically start in early adulthood, with weakness and atrophy in the tibialis anterior muscles and with slow progression over time, which largely spares the quadriceps muscles. Muscle biopsy shows atrophic fibers and rimmed vacuoles without inflammation. Inherited in an autosomal recessive manner, patients with GNE myopathy carry mutations in the GNE gene which affect the sialic acid synthesis pathway. Here, we look at the history and clinical aspects of GNE myopathy, as well as focus on prior treatment trials and challenges and unmet needs related to this disorder.
MXene catalytic amplification-fluorescence/absorption dimode aptamer sensor for the detection of trace Pb2+ in milk
Authors: Zhi Shengfu , Wei Qi , Zhang Chi , Yi Chenguang , Li Chongning , Jiang Zhiliang
Published: October 2022

Lead ion (Pb2+) is a toxic heavy metal, which is very harmful to organisms. Therefore, the establishment of a rapid, simple, and sensitive method is of great significance to food safety and human health. It was found that MXeneTi3C2 nanosheet (NS) has a strong catalytic effect on the oxidation of 3,3,5,5-tetramethylbenzidine (TMB) via H2O2 to form the oxidized product (TMBOX); it has a strong fluorescence peak at 415 nm and an absorption (Abs) peak at 295 nm. The aptamer of Pb2+ (Aptpb) can be adsorbed on the surface of an NS to form MXene-Apt conjugates, which reduces its catalytic active sites and inhibits its catalytic activity. When the target Pb2+ is added, it specifically binds with Aptpb to release MXene NSs to enhance the dimode signals. Therefore, a new MXene catalytic fluorescence/absorption dimode aptamer biosenering platform was fabricated for the determination of trace Pb2+ in milk and water samples, with the fluorescence assay linear range (LR) of 5.0 × 10−2-2.0 nmol/L.
Impact of respiratory motion on lung dose during total marrow irradiation
Authors: Kavak Ayse Gulbin , Surucu Murat , Ahn Kang-Hyun , Pearson Erik , Aydogan Bulent
Published: October 2022

We evaluated the impact of respiratory motion on the lung dose during linac-based intensity-modulated total marrow irradiation (IMTMI) using two different approaches: (1) measurement of doses within the lungs of an anthropomorphic phantom using thermoluminescent detectors (TLDs) and (2) treatment delivery measurements using ArcCHECK where gamma passing rates (GPRs) and the mean lung doses were calculated and compared with and without motion. In the first approach, respiratory motions were simulated using a programmable motion platform by using typical published peak-to-peak motion amplitudes of 5, 8, and 12 mm in the craniocaudal (CC) direction, denoted here as M1, M2, and M3, respectively, with 2 mm in both anteroposterior (AP) and lateral (LAT) directions. TLDs were placed in five selected locations in the lungs of a RANDO phantom. Average TLD measurements obtained with motion were normalized to those obtained with static phantom delivery. The mean dose ratios were 1.01 (0.98–1.03), 1.04 (1.01–1.09), and 1.08 (1.04–1.12) for respiratory motions M1, M2, and M3, respectively. To determine the impact of directional respiratory motion, we repeated the experiment with 5-, 8-, and 12-mm motion in the CC direction only. The differences in average TLD doses were less than 1% when compared with the M1, M2, and M3 motions indicating a minimal impact from CC motion on lung dose during IMTMI. In the second experimental approach, we evaluated extreme respiratory motion 15 mm excursion in only the CC direction. We placed an ArcCHECK device on a commercial motion platform and delivered the clinical IMTMI plans of five patients. We compared, with and without motion, the dose volume histograms (DVHs) and mean lung dose calculated with the ArcCHECK-3DVH tool as well as GPR with 3%, 5%, and 10% dose agreements and a 3-mm constant distance to agreement (DTA). GPR differed by 11.1 ± 2.1%, 3.8 ± 1.5%, and 0.1 ± 0.2% with dose agreement criteria of 3%, 5%, and 10%, respectively. This indicates that respiratory motion impacts dose distribution in small and isolated parts of the lungs. More importantly, the impact of respiratory motion on the mean lung dose, a critical indicator for toxicity in IMTMI, was not statistically significant (p > 0.05) based on the Student’s t-test. We conclude that most patients treated with IMTMI will have negligible dose uncertainty due to respiratory motion. This is particularly reassuring as lung toxicity is the main concern for future IMTMI dose escalation studies.
Host and immunosuppression-related factors influencing fibrosis occurrence post liver transplantation
Authors: Iacob Speranta , Iacob Razvan , Manea Ioana , Uta Mihaela , Chiosa Andrei , Dumbrava Mona , Becheanu Gabriel , Stoica Luminita , Popa Codruta , Brasoveanu Vlad , Hrehoret Doina , Gheorghe Cristian , Gheorghe Liana , Dima Simona , Popescu Irinel
Published: October 2022

Post liver transplantation (LT) fibrosis has a negative impact on graft function. Cytokine production in the host immune response after LT may contribute to the variable CYP3A-dependent immunosuppressive drug disposition, with subsequent impact on liver fibrogenesis, together with host-related factors. We aimed to investigate whether the cytochrome P4503A5*3 (CYP3A5*3) or TBX21 genotypes impact post-LT liver fibrogenesis. Furthermore, the impact of immunosuppressants on cellular apoptosis has been evaluated using human hepatocytes harvested from cirrhotic explanted livers. We have enrolled 98 LT recipients that were followed for occurrence of liver fibrosis for at least 12 months. There was a statistically significant higher trough level of TAC in patients with homozygous CC-TBX21 genotype (7.83 ± 2.84 ng/ml) vs. 5.66 ± 2.16 ng/ml in patients without this genotype (p = 0.009). The following variables were identified as risk factors for fibrosis ≥2: donor age (p = 0.02), neutrophil to lymphocyte ratio (p = 0.04) and TBX21 genotype CC (p = 0.009). In the cell culture model cytometry analysis has indicated the lowest apoptotic cells percentage in human cirrhotic hepatocytes cultures treated with mycophenolate mofetil (MMF) (5%) and TAC + MMF (2%) whereas the highest apoptosis percentage was registered for the TAC alone (11%). The gene expression results are concordant to cytometry study results, indicating the lowest apoptotic effect for MMF and MMF + TAC immunosuppressive regimens. The allele 1993C of the SNP rs4794067 may predispose to the development of late significant fibrosis of the liver graft. MMF-based regimens have a favourable anti-apoptotic profile in vitro, supporting its use in case of LT recipients at high risk for liver graft fibrosis.