bluuebunny/crossref_metadata_2025 huggingface dataset:
Coronary artery disease as an independent predictor of short-term and long-term outcomes in patients with type-B aortic dissection undergoing thoracic endovascular repair
Authors: Li Wei , Luo Songyuan , Lin Wenhui , Su Sheng , Xu Wenmin , Hu Xiaolu , Liu Yuan , Huang Wenhui , Luo Jianfang , Zhou Yingling
Published: December 2022

Background and aims

Previous studies reported a high prevalence of concomitant coronary artery disease (CAD) in patients with Type B aortic dissection (TBAD). However, there is too limited data on the impact of CAD on prognosis in patients with TBAD. The present study aimed to assess the short-term and long-term impact of CAD on patients with acute or subacute TBAD undergoing thoracic endovascular aortic repair (TEVAR).

Methods

We retrospectively evaluated 463 patients with acute or subacute TBAD undergoing TEVAR from a prospectively maintained database from 2010 to 2017. CAD was defined before TEVAR by coronary angiography. Multivariable logistic and cox regression analyses were performed to evaluate the relationship between CAD and the short-term as well as long-term outcomes.

Results

According to the results of coronary angiography, the 463 patients were divided into the following two groups: CAD group (N = 148), non-CAD group (N = 315). In total, 12 (2.6%) in-hospital deaths and 54 (12%) all-cause deaths following a median follow-up of 48.1 months were recorded. Multivariable analysis revealed that CAD was an independent predictor of in-hospital major adverse clinical events (MACE) (odd ratio [OR], 2.33; 95% confidence interval [CI], 1.07–5.08; p = 0.033), long-term mortality [hazard ratio (HR), 2.11, 95% CI, 1.19–3.74, P = 0.011] and long-term MACE (HR, 1.95, 95% CI, 1.26–3.02, P = 0.003). To further clarify the relationship between the severity of CAD and long-term outcomes, we categorized patients into three groups: zero-vessel disease, single-vessel disease and multi-vessel disease. The long-term mortality (9.7 vs. 14.4 vs. 21.2%, P = 0.045), and long-term MACE (16.8 vs. 22.2 vs. 40.4%, P = 0.001) increased with the number of identified stenosed coronary vessels. Multivariable analysis indicated that, multi-vessel disease was independently associated with long-term mortality (HR, 2.38, 95% CI, 1.16–4.89, P = 0.018) and long-term MACE (HR, 2.79, 95% CI, 1.65–4.73, P = 0.001), compared with zero-vessel disease.

Conclusions

CAD was associated with short-term and long-term worse outcomes in patients with acute or subacute TBAD undergoing TEVAR. Furthermore, the severity of CAD was also associated with worse long-term prognosis. Therefore, CAD could be considered as a useful independent predictor for pre-TEVAR risk stratification in patients with TBAD.
Concomitant intramyocardial and hepatic hydatid cysts diagnosed by multi-modality imaging: A rare case report
Authors: Nguyen Hoai Thi Thu , Pham Viet Tuan , Duong Hung Duc , Kirkpatrick James N. , Taylor Walter Robert , Pham Hung Manh
Published: December 2022

Cardiac echinococcosis is a potentially fatal form of hydatid disease; yet, its diagnosis and treatment are challenging due to the variability in its clinical manifestations and due to its various unpredictable preoperative complications. Multi-modality imaging is shown to provide important guidance for the treatment and decision-making. We report a rare case of a 50-year-old woman who had concomitant cardiac and hepatic hydatid cysts. She presented with abdominal pain and elevated eosinophilic white blood cells. The initial abdominal ultrasound and computerized tomography revealed a large cyst in the liver. An intramyocardial cyst was detected by two-dimensional echocardiography. Three-dimensional echocardiography increased the confidence level of two-dimensional echocardiography by displaying the three-dimensional volume of the cyst and allowing visualization of its spatial characteristics and the relationships with adjacent cardiac structures, which was subsequently confirmed at surgery. Multi-detector computed tomography and magnetic resonance imaging helped localize and define the typical morphological features of the cyst. Serology and antigen detection were used for diagnosis. This rare case underlines the integration of clinical, multi-modality imaging, and pathological data in the diagnosis of concomitant intramyocardial and hepatic hydatid cysts. Surgical resection of cysts and anthelmintic medication were successful in the management of this patient.
Long-term monitoring of pesticide residues on public sites: A regional approach to survey and reduce spray drift
Authors: Prechsl Ulrich E. , Bonadio Martina , Wegher Lino , Oberhuber Michael
Published: December 2022

Plant protection strongly increased food safety and agricultural productivity, but with societal and environmental costs as the downside. Especially the contamination of non-target areas via spray drift represents an adverse side-effect. Residential zones and playgrounds are so-called “sensitive zones”, where spray drift is considered to have an increased potential for human health risk. To study the residue profile potentially associated with spray drift we analyzed data of a residue monitoring program in South Tyrol (Northern Italy). From 2018 to 2021, 39 playgrounds were analyzed multiple times per year for the presence and concentration of pesticide residues on grass samples. In a total of 399 samples, we identified 39 different residues deriving primarily from agricultural production. Mean concentration (0.0645 mg kg−1, SD: ± 0.1013 mg kg−1) and comparison to Maximum Residue Levels (MRLs) of food, revealed that 98.2% of the residues were in the range of MRLs and close to the analytical limit of quantification. We found that 6 out of 334 residues had relatively elevated concentrations clearly above the MRLs. Finally, a time series analysis of the study period revealed a significant decrease in the number of detected residues and their concentration by 72% and 78%, respectively. In the last year of this study, playgrounds showed on average 1.46 residues (SD: ± 1.252) with a mean concentration of 0.012 mg kg−1 (SD: ± 0.025), which is almost equal to the limit of detection (0.01 mg kg−1). The presented results demonstrate that 1) spray drift decreased significantly within 4-year and that 2) the introduced measures to decrease spray drift have been effective. Consequently, these results imply 3) that improved farming practice represents an important leverage point of further spray drift reduction.
Non-viviparous pre-dispersal seed germination in Amaranthaceae in the cold deserts of Central Asia
Authors: Lu Juanjuan , Liu Wenya , Han Jincai , Tan Dunyan , Baskin Carol C. , Baskin Jerry M.
Published: December 2022

In the broad context of understanding the relationship between timing of seed germination and adaptation of a plant species to its habitat, the purpose of this study was to purse an observation of pre-dispersal seed germination of Salsola brachiata (Amaranthaceae) in late winter 2021 in the Amaranthaceae species-rich cold deserts in northwest China (Central Asia). We searched for pre-dispersal germination in species of Amaranthaceae growing in sand dunes (S), salt deserts (SD) and gravel deserts (GD). We examined 69 species in 155 populations in autumn 2021 and 52 species in 12 populations in early spring 2022. No seeds of any of the 69 species germinated on the mother plants in autumn 2021, while 30 of 52 species (57.7%) did so during snowmelt in early spring 2022. The rank order of species with few to many seeds germinated on the mother plants was annuals (66.7%) > small shrubs (23.3%) > small trees (6.7%) > shrubs (3.3%). The number of species in S, SD, and GD with pre-dispersal germinated seeds was 16 of 27 (59.3%), 15 of 31 (48.4%), and 15 of 30 (50.0%), respectively. The high species occurrence of pre-dispersal germination in early spring suggested that it might be adaptive in the unpredictable-rainfall growing-season environment of the cold deserts of Central Asia, a center of diversity of Amaranthaceae. However, preliminary studies on seedling/juvenile survival of S. brachiata showed that those from post-dispersal soil-germinated seeds had the best survival, suggesting that pre-dispersal seed germination may be maladaptive.
Cutting the long branches: Consilience as a path to unearth the evolutionary history of Gnetales
Authors: Coiro Mario , Roberts Emily A. , Hofmann Christa-Ch. , Seyfullah Leyla J.
Published: December 2022

The Gnetales are one of the most fascinating groups within seed plants. Although the advent of molecular phylogenetics has generated some confidence in their phylogenetic placement of Gnetales within seed plants, their macroevolutionary history still presents many unknowns. Here, we review the reasons for such unknowns, and we focus the discussion on the presence of “long branches” both in their molecular and morphological history. The increased rate of molecular evolution and genome instability as well as the numerous unique traits (both reproductive and vegetative) in the Gnetales have been obstacles to a better understanding of their evolution. Moreover, the fossil record of the Gnetales, though relatively rich, has not yet been properly reviewed and investigated using a phylogenetic framework. Despite these apparent blocks to progress we identify new avenues to enable us to move forward. We suggest that a consilience approach, involving different disciplines such as developmental genetics, paleobotany, molecular phylogenetics, and traditional anatomy and morphology might help to “break” these long branches, leading to a deeper understanding of this mysterious group of plants.
Phenotypic plasticity enables considerable acclimation to heat and drought in a cold-adapted boreal forest tree species
Authors: Ravn Jacob , D’Orangeville Loïc , Lavigne Michael B. , Taylor Anthony R.
Published: December 2022

Increasing frequencies of severe heat waves and drought are expected to influence the composition and functioning of ecosystems globally. Our ability to predict and mitigate these impacts depends on our understanding of species- and age-specific responses to these stressors. To assess the adaptive capacity of balsam fir to climate change, a cold-adapted boreal tree species, we conducted a climate-controlled greenhouse experiment with four provenances originating from across the species biogeographic range, 12 temperature treatments ensuring a minimum of +11°C warming, and five drought treatment intensities. We found considerable acclimation to temperature and drought treatments across all provenances, with steady gains in biomass under temperatures well-beyond the “worst-case” (RCP 8.5) climate forcing scenario within the species natural range. Acclimation was supported by high phenotypic plasticity in root:shoot ratio (RSR) and photosynthesis, which were greatly increased with warming, but were not affected by drought. Our results suggest that regardless of the observed provenance variation, drought and heat are not limiting factors of the current-year balsam fir seedling growth, instead, these factors may be more impactful on later stages of regeneration or previously stressed individuals, thus highlighting the necessity of incorporating the factors of ontogeny and provenance origin in future research regarding plant and climate interactions.
Predicting gene expression from histone modifications with self-attention based neural networks and transfer learning
Authors: Chen Yuchi , Xie Minzhu , Wen Jie
Published: December 2022

It is well known that histone modifications play an important part in various chromatin-dependent processes such as DNA replication, repair, and transcription. Using computational models to predict gene expression based on histone modifications has been intensively studied. However, the accuracy of the proposed models still has room for improvement, especially in cross-cell lines gene expression prediction. In the work, we proposed a new model TransferChrome to predict gene expression from histone modifications based on deep learning. The model uses a densely connected convolutional network to capture the features of histone modifications data and uses self-attention layers to aggregate global features of the data. For cross-cell lines gene expression prediction, TransferChrome adopts transfer learning to improve prediction accuracy. We trained and tested our model on 56 different cell lines from the REMC database. The experimental results show that our model achieved an average Area Under the Curve (AUC) score of 84.79%. Compared to three state-of-the-art models, TransferChrome improves the prediction performance on most cell lines. The experiments of cross-cell lines gene expression prediction show that TransferChrome performs best and is an efficient model for predicting cross-cell lines gene expression.
Expression of TRX1 optimizes the antitumor functions of human CAR T cells and confers resistance to a pro-oxidative tumor microenvironment
Authors: Balta Emre , Janzen Nina , Kirchgessner Henning , Toufaki Vasiliki , Orlik Christian , Liang Jie , Lairikyengbam Divya , Abken Hinrich , Niesler Beate , Müller-Decker Karin , Ruppert Thomas , Samstag Yvonne
Published: December 2022

Use of chimeric antigen receptor (CAR) T cells to treat B cell lymphoma and leukemia has been remarkably successful. Unfortunately, the therapeutic efficacy of CAR T cells against solid tumors is very limited, with immunosuppression by the pro-oxidative tumor microenvironment (TME) a major contributing factor. High levels of reactive oxygen species are well-tolerated by tumor cells due to their elevated expression of antioxidant proteins; however, this is not the case for T cells, which consequently become hypo-responsive. The aim of this study was to improve CAR T cell efficacy in solid tumors by empowering the antioxidant capacity of CAR T cells against the pro-oxidative TME. To this end, HER2-specific human CAR T cells stably expressing two antioxidant systems: thioredoxin-1 (TRX1), and glutaredoxin-1 (GRX1) were generated and characterized. Thereafter, antitumor functions of CAR T cells were evaluated under control or pro-oxidative conditions. To provide insights into the role of antioxidant systems, gene expression profiles as well as global protein oxidation were analyzed. Our results highlight that TRX1 is pivotal for T cell redox homeostasis. TRX1 expression allows CAR T cells to retain their cytolytic immune synapse formation, cytokine release, proliferation, and tumor cell-killing properties under pro-oxidative conditions. Evaluation of differentially expressed genes and the first comprehensive redoxosome analysis of T cells by mass spectrometry further clarified the underlying mechanisms. Taken together, enhancement of the key antioxidant TRX1 in human T cells opens possibilities to increase the efficacy of CAR T cell treatment against solid tumors.
Mesangial cell: A hub in lupus nephritis
Authors: Liu Mengdi , Zhang Lei , Wang Yixin , Hu Weijie , Wang Chunhong , Wen Zhenke
Published: December 2022

Lupus nephritis (LN) is a severe renal disease caused by the massive deposition of the immune complexes (ICs) in renal tissue, acting as one of the significant organ manifestations of systemic lupus erythematosus (SLE) and a substantial cause of death in clinical patients. As mesangium is one of the primary sites for IC deposition, mesangial cells (MCs) constantly undergo severe damage, resulting in excessive proliferation and increased extracellular matrix (ECM) production. In addition to playing a role in organizational structure, MCs are closely related toin situimmunomodulation by phagocytosis, antigen-presenting function, and inflammatory effects, aberrantly participating in the tissue-resident immune responses and leading to immune-mediated renal lesions. Notably, such renal-resident immune responses drive a second wave of MC damage, accelerating the development of LN. This review summarized the damage mechanisms and thein situimmune regulation of MCs in LN, facilitating the current drug research for exploring clinical treatment strategies.
Case report: Eculizumab plus obinutuzumab induction in a deceased donor kidney transplant recipient with DEAP-HUS
Authors: Favi Evaldo , Molinari Paolo , Alfieri Carlo , Castellano Giuseppe , Ferraresso Mariano , Cresseri Donata
Published: December 2022

The wide-spread use of the anti-complement component 5 monoclonal antibody (moAb) eculizumab has greatly reduced the incidence of relapsing atypical hemolytic uremic syndrome (aHUS) after kidney transplantation (KT). However, the optimal management of aHUS transplant candidates with anti-Complement Factor H (CFH) antibodies remains debated. In these patients, the benefits of chronic eculizumab administration should be weighed against the risk of fatal infections, repeated hospital admissions, and excessive costs. We report the case of a 45-year-old female patient with CFHR1/CFHR3 homozygous deletion-associated aHUS who underwent deceased-donor KT despite persistently elevated anti-CFH antibody titers. As induction and aHUS prophylaxis, she received a combination of eculizumab and obinutuzumab, a humanized type 2 anti-CD20 moAb. The post-operative course was uneventful. After 1-year of follow-up, she is doing well with excellent allograft function, undetectable anti-CFH antibodies, sustained B-cell depletion, and no signs of aHUS activity. A brief review summarizing current literature on the topic is also included. Although anecdotal, our experience suggests that peri-operative obinutuzumab administration can block anti-CFH antibodies production safely and effectively, thus ensuring long-lasting protection from post-transplant aHUS relapse, at a reasonable cost. For the first time, we have demonstrated in vivo that obinutuzumab B-cell depleting properties are not significantly affected by eculizumab-induced complement inhibition.
Association between lactate-to-albumin ratio and 28-days all-cause mortality in patients with acute pancreatitis: A retrospective analysis of the MIMIC-IV database
Authors: Liu Qiang , Zheng Hai-Lun , Wu Man-Man , Wang Qi-Zhi , Yan Shan-Jun , Wang Meng , Yu Jiao-Jiao , Li Da-Peng
Published: December 2022

Objective

The Lactate-to-Albumin Ratio (LAR) has been applied as a new predictor in sepsis, heart failure, and acute respiratory failure. However, the role of LAR in predicting all-cause mortality in patients with acute pancreatitis has not been evaluated. Therefore, this study aimed to elucidate the correlation between LAR and 28-d all-cause mortality in patients with Acute Pancreatitis (AP).

Methods

This study is a retrospective cohort study with the data from the MIMIC-IV (v1.0) database. We included adult patients with acute pancreatitis who were admitted to the intensive care unit in the study. The primary outcome was to evaluate the ability of LAR to predict death at 28-d of hospital admission in patients with AP.

Results

A total of 539 patients with acute pancreatitis were included in this study. They were divided into a survival group (486 patients) and a death group (53 patients) according to whether they survived within 28-d of admission, and the mortality rate of patients within 28-d of admission was 9.8%. LAR was shown to be an independent predictor of all-cause mortality within 28-d of admission in patients with AP by multivariate COX regression analysis (HR, 1.59; 95% CI, 1.23 - 2.05; P < 0.001). the Area Under the Curve (AUC) value for LAR was 74.26% (95% CI: 67.02% - 81.50%), which was higher than that for arterial blood lactate (AUC = 71.25%) and serum albumin (AUC = 65.92%) alone. It was not inferior even when compared to SOFA (AUC = 75.15%). The optimal cutoff value for separating the survival and death groups according to Receiver Operating Characteristic (ROC) was found to be 1.1124. plotting Kaplan-Meier analysis with this cutoff value showed that patients with LAR ≥ 1.1124 had significantly higher all-cause mortality within 28-d of admission than those with LAR < 1.1124 (P < 0.001). The final subgroup analysis showed no significant interaction of LAR with each subgroup (P for interaction: 0.06 - 0.974).

Conclusion

LAR can be used as an independent predictor of all-cause mortality in AP patients within 28-d of admission, with superior prognostic performance than arterial blood lactate or serum albumin alone.
Risk of liver dysfunction and non-alcoholic fatty liver diseases in people with hidradenitis suppurativa: A systematic review and meta-analysis of real-world evidences
Authors: Gau Shuo-Yan , Hsiao Yu-Ping , Liao Wen-Chieh , Ma Kevin Sheng-Kai , Wu Meng-Che
Published: December 2022

Background

To date, evidences with high evidence-level evaluating the association between liver diseases and hidradenitis suppurativa was lacking. Given that inconsistency exists in some of the previous observational studies, evaluating the prevalence of liver diseases in HS patients could potentially serve as a reference of future guidelines for HS comorbidity screening. The aim of the current study was to evaluate potential association between hidradenitis suppurativa and liver diseases and provide integrated evidences.

Methods

A search in PubMed, Web of Science and Embase based on the syntaxes ‘‘hidradenitis suppurativa’’ or ‘‘acne inversa’’ with “comorbidities”, “liver diseases”, “fatty liver” or “hepatitis” was performed. Observational studies evaluating epidemiological association between hidradenitis suppurativa and the risk of all liver diseases, including specific diseases as non-alcoholic fatty liver disease, hepatitis B, hepatitis C were targeted to be extracted in this systematic review and meta-analysis.

Results

Within the initial 702 records, there were finally 8 real-world observational studies extracted. Results suggest that patients with HS are associated with all liver diseases (OR= 1.50; 95% CI, 1.27, 1.76), non-alcoholic fatty liver disease (OR= 1.78; 95% CI, 1.28, 2.48) and hepatitis B (OR=1.48; 95% CI, 1.12, 1.94), but not hepatitis C (OR= 1.27; 95% CI, 0.78, 2.07). HS patients were associated with significantly increased risk of liver diseases, especially the risk of non-alcoholic fatty liver disease and hepatitis B.

Conclusions

Clinicians should be alert to the clinical relationship while caring people with hidradenitis suppurativa and the screening of liver function should be recommended to HS patients.

Systematic review registration

https://www.crd.york.ac.uk/prospero/, identifier CRD42022296034.
Increased CEACAM1 expression on peripheral blood neutrophils in patients with rheumatoid arthritis
Authors: Matsumoto Haruki , Fujita Yuya , Onizawa Michio , Saito Kenji , Sumichika Yuya , Yoshida Shuhei , Temmoku Jumpei , Matsuoka Naoki , Yashiro-Furuya Makiko , Asano Tomoyuki , Sato Shuzo , Suzuki Eiji , Machida Takeshi , Watanabe Hiroshi , Migita Kiyoshi
Published: December 2022

Altered expression of adhesion molecules in immune cells has been demonstrated in rheumatoid arthritis (RA). Carcinoembryonic–antigen–related cell–adhesion molecule 1 (CEACAM1) is an adhesion molecule that acts as a coinhibitory receptor in the immune system. We investigated the role of CEACAM1 in immune cell subsets of patients with RA. Peripheral blood was obtained from 37 patients with RA and 20 healthy controls (HC). The expression of CEACAM1 and T–cell immunoglobulin mucin domain molecule (TIM) –3 on peripheral blood mononuclear cells and neutrophils was analyzed by flow cytometry. Intracellular TIM–3 expression was analyzed using cellular lysates by Western blot analysis. Serum levels of soluble CEACAM1 (sCEACAM1) were estimated by an enzyme-linked immunosorbent assay. CEACAM1 expression was not detected in peripheral blood mononuclear cells, including in CD14(+) monocytes and CD3(+) lymphocytes isolated from patients with RA or HC. However, substantial cell–surface expression of CEACAM1 was detected in peripheral blood neutrophils, and it was significantly elevated in samples from patients with RA without remission compared to those in remission. There was no significant difference in serum levels of sCEACAM1 between patients with RA and HC. Cell-surface expression of TIM-3 was not detected in peripheral blood neutrophils from patients with RA or HC but was seen in CD14(+) monocytes. However, there was no significant difference in TIM–3 expression on monocytes between patients with RA and HC. Our data indicate that cell-surface expression of CEACAM1 on peripheral blood neutrophils are higher in patients with RA and that it is associated with rheumatoid inflammation. Further studies are needed to explore the potential role of CEACAM1 in rheumatoid inflammatory pathways.
Biomarkers of mitochondrial dysfunction in acute respiratory distress syndrome: A systematic review and meta-analysis
Authors: McClintock Catherine R. , Mulholland Niamh , Krasnodembskaya Anna D.
Published: December 2022

Introduction

Acute respiratory distress syndrome (ARDS) is one of the main causes of Intensive Care Unit morbidity and mortality. Metabolic biomarkers of mitochondrial dysfunction are correlated with disease development and high mortality in many respiratory conditions, however it is not known if they can be used to assess risk of mortality in patients with ARDS.

Objectives

The aim of this systematic review was to examine the link between recorded biomarkers of mitochondrial dysfunction in ARDS and mortality.

Methods

A systematic review of CINAHL, EMBASE, MEDLINE, and Cochrane databases was performed. Studies had to include critically ill ARDS patients with reported biomarkers of mitochondrial dysfunction and mortality. Information on the levels of biomarkers reflective of energy metabolism and mitochondrial respiratory function, mitochondrial metabolites, coenzymes, and mitochondrial deoxyribonucleic acid (mtDNA) copy number was recorded. RevMan5.4 was used for meta-analysis. Biomarkers measured in the samples representative of systemic circulation were analyzed separately from the biomarkers measured in the samples representative of lung compartment. Cochrane risk of bias tool and Newcastle-Ottawa scale were used to evaluate publication bias (Prospero protocol: CRD42022288262).

Results

Twenty-five studies were included in the systematic review and nine had raw data available for follow up meta-analysis. Biomarkers of mitochondrial dysfunction included mtDNA, glutathione coupled mediators, lactate, malondialdehyde, mitochondrial genetic defects, oxidative stress associated markers. Biomarkers that were eligible for meta-analysis inclusion were: xanthine, hypoxanthine, acetone, N-pentane, isoprene and mtDNA. Levels of mitochondrial biomarkers were significantly higher in ARDS than in non-ARDS controls (P = 0.0008) in the blood-based samples, whereas in the BAL the difference did not reach statistical significance (P = 0.14). mtDNA was the most frequently measured biomarker, its levels in the blood-based samples were significantly higher in ARDS compared to non-ARDS controls (P = 0.04). Difference between mtDNA levels in ARDS non-survivors compared to ARDS survivors did not reach statistical significance (P = 0.05).

Conclusion

Increased levels of biomarkers of mitochondrial dysfunction in the blood-based samples are positively associated with ARDS. Circulating mtDNA is the most frequently measured biomarker of mitochondrial dysfunction, with significantly elevated levels in ARDS patients compared to non-ARDS controls. Its potential to predict risk of ARDS mortality requires further investigation.

Systematic review registration

[https://www.crd.york.ac.uk/prospero], identifier [CRD42022288262].
Use of complementary and alternative medicine by patients with hypermobile Ehlers–Danlos Syndrome: A qualitative study
Authors: Doyle Tom A. , Halverson Colin M. E.
Published: December 2022

Background

Patients with hypermobile Ehlers–Danlos Syndrome (hEDS) often make use of complementary and alternative medical (CAM) techniques to manage their chronic pain and other symptoms. Nevertheless, how they use CAM, which techniques they favor, and how CAM use affects their allopathic care remain unclear. The purpose of this qualitative study was to understand patients’ personal experiences with CAM and its role in their symptom management.

Materials and methods

Thirty individuals living with hEDS completed a brief online survey related to their CAM use. Thereafter, in-depth interviews were conducted with 24 of the survey respondents, qualitatively investigating their experiences with CAM. Data were analyzed using thematic analysis.

Results

Participants described massage therapy (N = 21), medical cannabis (N = 12), and mindfulness (N = 13) as some of the most useful CAM modalities for managing symptoms related to hEDS, but they expressed a general interest in pursuing any treatment that could potentially reduce their chronic pain. They suggested an overall trust in CAM modalities and practitioners and ascribed greater empathy to CAM practitioners than to conventional medical providers. However, they also described a critical skepticism of CAM (and conventional) therapies and recounted instances of injury from such treatments.

Conclusion

Participants made extensive use of CAM therapies. They described both critical benefits as well as harms from the use of these non-conventional modalities. These results underscore the importance of clinicians maintaining communicative and compassionate relationships with their patients, and of an openness to the discussion and use of CAM treatments.
Immune mechanism of gut microbiota and its metabolites in the occurrence and development of cardiovascular diseases
Authors: Lu Jing , Jin Xiao , Yang Shengjie , Li Yujuan , Wang Xinyue , Wu Min
Published: December 2022

The risk of cardiovascular disease (CVD) is associated with unusual changes in the human gut microbiota, most commonly coronary atherosclerotic heart disease, hypertension, and heart failure. Immune mechanisms maintain a dynamic balance between the gut microbiota and the host immune system. When one side changes and the balance is disrupted, different degrees of damage are inflicted on the host and a diseased state gradually develops over time. This review summarizes the immune mechanism of the gut microbiota and its metabolites in the occurrence of common CVDs, discusses the relationship between gut-heart axis dysfunction and the progression of CVD, and lists the currently effective methods of regulating the gut microbiota for the treatment of CVDs.
The role of microbial ecology in improving the performance of anaerobic digestion of sewage sludge
Authors: Krohn Christian , Khudur Leadin , Dias Daniel Anthony , van den Akker Ben , Rees Catherine A. , Crosbie Nicholas D. , Surapaneni Aravind , O'Carroll Denis M. , Stuetz Richard M. , Batstone Damien J. , Ball Andrew S.
Published: December 2022

The use of next-generation diagnostic tools to optimise the anaerobic digestion of municipal sewage sludge has the potential to increase renewable natural gas recovery, improve the reuse of biosolid fertilisers and help operators expand circular economies globally. This review aims to provide perspectives on the role of microbial ecology in improving digester performance in wastewater treatment plants, highlighting that a systems biology approach is fundamental for monitoring mesophilic anaerobic sewage sludge in continuously stirred reactor tanks. We further highlight the potential applications arising from investigations into sludge ecology. The principal limitation for improvements in methane recoveries or in process stability of anaerobic digestion, especially after pre-treatment or during co-digestion, are ecological knowledge gaps related to the front-end metabolism (hydrolysis and fermentation). Operational problems such as stable biological foaming are a key problem, for which ecological markers are a suitable approach. However, no biomarkers exist yet to assist in monitoring and management of clade-specific foaming potentials along with other risks, such as pollutants and pathogens. Fundamental ecological principles apply to anaerobic digestion, which presents opportunities to predict and manipulate reactor functions. The path ahead for mapping ecological markers on process endpoints and risk factors of anaerobic digestion will involve numerical ecology, an expanding field that employs metrics derived from alpha, beta, phylogenetic, taxonomic, and functional diversity, as well as from phenotypes or life strategies derived from genetic potentials. In contrast to addressing operational issues (as noted above), which are effectively addressed by whole population or individual biomarkers, broad improvement and optimisation of function will require enhancement of hydrolysis and acidogenic processes. This will require a discovery-based approach, which will involve integrative research involving the proteome and metabolome. This will utilise, but overcome current limitations of DNA-centric approaches, and likely have broad application outside the specific field of anaerobic digestion.
Blind detection of circular image rotation angle based on ensemble transfer regression and fused HOG
Authors: Dong Wenxin , Zhang Jianxun , Zhou Yuechuan , Gao Linfeng , Zhang Xinyue
Published: December 2022

Introduction

Aiming at the problems of low accuracy in estimating the rotation angle after the rotation of circular image data within a wide range (0°–360°) and difficulty in blind detection without a reference image, a method based on ensemble transfer regression network, fused HOG, and Rotate Loss is adopted to solve such problems.

Methods

The proposed Rotate Loss was combined to solve the angle prediction error, especially the huge error when near 0°. Fused HOG was mainly used to extract directional features. Then, the feature learning was conducted by the ensemble transfer regression model combined with the feature extractor and the ensemble regressors to estimate an exact rotation angle. Based on miniImageNet and Minist, we made the circular random rotation dataset Circular-ImageNet and random rotation dataset Rot-Minist, respectively.

Results

Experiments showed that for the proposed evaluation index MSE_Rotate, the best single regressor could be as low as 28.79 on the training set of Circular-ImageNet and 2686.09 on the validation set. For MSE_Rotate, MSE, MAE, and RMSE on the test set were 1,702.4325, 0.0263, 0.0881, and 0.1621, respectively. And under the ensemble transfer regression network, it could continue to decrease by 15%. The mean error rate on Rot-Minist could be just 0.59%, significantly working easier in a wide range than other networks in recent years. Based on the ensemble transfer regression model, we also completed the application of image righting blindly.
Complications of rabbit anti-thymocyte globulin induction immunosuppression in HIV-infected kidney transplant recipients
Authors: Al Jurdi Ayman , Liu Esther C. , Salinas Thalia , Aull Meredith J. , Lubetzky Michelle , Drelick Alexander L. , Small Catherine B. , Kapur Sandip , Hartono Choli , Muthukumar Thangamani
Published: December 2022

Background

Kidney transplantation in HIV-infected individuals with end-stage kidney disease is associated with improved survival compared to dialysis. Rabbit anti-thymocyte globulin (rATG) induction in HIV-infected kidney transplant recipients has been associated with a lower risk of acute rejection, but data on the rates of de novo malignancy and BK viremia in these patients is lacking.

Methods

We performed a single-center retrospective cohort study of adult HIV-infected individuals who underwent kidney transplantation with rATG induction between January 2006 and December 2016. The primary outcome was the development of de novo malignancy. Secondary outcomes included the development of BK viremia, infections requiring hospitalization, HIV progression, biopsy-proven acute rejection, and patient and allograft survival.

Results

Twenty-seven HIV-infected individuals with end-stage kidney disease received deceased (n=23) or living (n=4) donor kidney transplants. The cumulative rate of malignancy at five years was 29%, of whom 29% died because of advanced malignancy. BK viremia was detected in six participants (22%), of whom one had biopsy-proven BK virus-associated nephropathy and all of whom cleared the BK viremia. Five-year acute rejection rates, patient survival and death-censored allograft survival were 17%, 85% and 80% respectively.

Conclusion

rATG induction in HIV-infected kidney transplant recipients was associated with a low risk of acute rejection, but a potentially higher risk of de novo malignancies and BK viremia in this cohort. Screening strategies to closely monitor for BK virus infection and malignancy post-transplantation may improve outcomes in HIV-infected kidney transplant recipients receiving rATG induction.
Progressive multifocal leukoencephalopathy genetic risk variants for pharmacovigilance of immunosuppressant therapies
Authors: Hatchwell Eli , Smith Edward B. , Jalilzadeh Shapour , Bruno Christopher D. , Taoufik Yassine , Hendel-Chavez Houria , Liblau Roland , Brassat David , Martin-Blondel Guillaume , Wiendl Heinz , Schwab Nicholas , Cortese Irene , Monaco Maria Chiara , Imberti Luisa , Capra Ruggero , Oksenberg Jorge R. , Gasnault Jacques , Stankoff Bruno , Richmond Todd A. , Rancour David M. , Koralnik Igor J. , Hanson Barbara A. , Major Eugene O. , Chow Christina R. , Eis Peggy S.
Published: December 2022

Background

Progressive multifocal leukoencephalopathy (PML) is a rare and often lethal brain disorder caused by the common, typically benign polyomavirus 2, also known as JC virus (JCV). In a small percentage of immunosuppressed individuals, JCV is reactivated and infects the brain, causing devastating neurological defects. A wide range of immunosuppressed groups can develop PML, such as patients with: HIV/AIDS, hematological malignancies (e.g., leukemias, lymphomas, and multiple myeloma), autoimmune disorders (e.g., psoriasis, rheumatoid arthritis, and systemic lupus erythematosus), and organ transplants. In some patients, iatrogenic (i.e., drug-induced) PML occurs as a serious adverse event from exposure to immunosuppressant therapies used to treat their disease (e.g., hematological malignancies and multiple sclerosis). While JCV infection and immunosuppression are necessary, they are not sufficient to cause PML.

Methods

We hypothesized that patients may also have a genetic susceptibility from the presence of rare deleterious genetic variants in immune-relevant genes (e.g., those that cause inborn errors of immunity). In our prior genetic study of 184 PML cases, we discovered 19 candidate PML risk variants. In the current study of another 152 cases, we validated 4 of 19 variants in both population controls (gnomAD 3.1) and matched controls (JCV+ multiple sclerosis patients on a PML-linked drug ≥ 2 years).

Results

The four variants, found in immune system genes with strong biological links, are: C8B, 1-57409459-C-A, rs139498867; LY9 (alias SLAMF3), 1-160769595-AG-A, rs763811636; FCN2, 9-137779251-G-A, rs76267164; STXBP2, 19-7712287-G-C, rs35490401. Carriers of any one of these variants are shown to be at high risk of PML when drug-exposed PML cases are compared to drug-exposed matched controls: P value = 3.50E-06, OR = 8.7 [3.7–20.6]. Measures of clinical validity and utility compare favorably to other genetic risk tests, such as BRCA1 and BRCA2 screening for breast cancer risk and HLA-B*15:02 pharmacogenetic screening for pharmacovigilance of carbamazepine to prevent Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis.

Conclusion

For the first time, a PML genetic risk test can be implemented for screening patients taking or considering treatment with a PML-linked drug in order to decrease the incidence of PML and enable safer use of highly effective therapies used to treat their underlying disease.
Sleep deficiency promotes Alzheimer's disease development and progression
Authors: Lv Ya-Nan , Cui Yu , Zhang Bo , Huang Shu-Ming
Published: December 2022

Sleep disorders are a common health problem in modern society. Long-term sleep deficiency increases the risk for Alzheimer's disease. However, the exact mechanisms by which sleep deficiency affects Alzheimer's disease remain unclear. Therefore, we reviewed the relevant studies and investigated the role of sleep deprivation in Alzheimer's disease pathogenesis. Sleep deficiency was found to be associated with oxidative stress, β-amyloid protein deposition, tau hyperphosphorylation, and neuroinflammation, which are known to increase the risk for Alzheimer's disease. In addition, insufficient sleep also increases glucocorticoid levels, decreases brain-derived neurotrophic factor levels, and reduces the number of synapses in the central nervous system. These factors also promote Alzheimer's disease development and progression. The present study showed that a growing body of evidence supports an association between sleep disturbances and Alzheimer's disease. It discusses the role of sleep insufficiency in Alzheimer's disease pathogenesis, which may provide a theoretical basis for effective treatment and prevention strategies.
Case report: Pain in anti-DPPX encephalitis
Authors: Bjerknes Tale L. , Steihaug Ole Martin , Haugen Mette , Hjelland Ina Elen , Vedeler Christian Alexander
Published: December 2022

Encephalitis due to antibodies targeting dipeptidyl-peptidase-like protein 6 (DPPX), a potassium channel subunit, is rare. The illness is typically characterized by a triad of weight loss, CNS hyperexcitability and cognitive symptoms, but recent reports suggest that the clinical picture may be more heterogeneous. Here, we describe the case of a 63-year-old female who was admitted to the hospital with severe extremity pain, which had been preceded by diarrhea and weight loss. She later developed cognitive changes, and her general condition rapidly deteriorated. Extensive workup did not reveal gastrointestinal illness or underlying malignancies. MRI of the brain was normal. Analyses of blood and cerebrospinal fluid showed normal cell counts but high titres of DPPX antibodies in blood and cerebrospinal fluid. The patient was treated with intravenous methylprednisolone followed by rituximab. At 1-year follow-up, she was without pain and had completely recovered. In this case, DPPX-associated autoimmune encephalitis was dominated by severe extremity pain, illustrating that sensory symptoms may be one of the main complaints in these patients. It is important for clinicians to be aware of the heterogeneous clinical picture in this serious condition, since correct diagnosis and treatment with immunosuppressants are associated with favorable prognosis.
Multimodal brain age prediction fusing morphometric and imaging data and association with cardiovascular risk factors
Authors: Mouches Pauline , Wilms Matthias , Aulakh Agampreet , Langner Sönke , Forkert Nils D.
Published: December 2022

Introduction

The difference between the chronological and biological brain age, called the brain age gap (BAG), has been identified as a promising biomarker to detect deviation from normal brain aging and to indicate the presence of neurodegenerative diseases. Moreover, the BAG has been shown to encode biological information about general health, which can be measured through cardiovascular risk factors. Current approaches for biological brain age estimation, and therefore BAG estimation, either depend on hand-crafted, morphological measurements extracted from brain magnetic resonance imaging (MRI) or on direct analysis of brain MRI images. The former can be processed with traditional machine learning models while the latter is commonly processed with convolutional neural networks (CNNs). Using a multimodal setting, this study aims to compare both approaches in terms of biological brain age prediction accuracy and biological information captured in the BAG.

Methods

T1-weighted MRI, containing brain tissue information, and magnetic resonance angiography (MRA), providing information about brain arteries, from 1,658 predominantly healthy adults were used. The volumes, surface areas, and cortical thickness of brain structures were extracted from the T1-weighted MRI data, while artery density and thickness within the major blood flow territories and thickness of the major arteries were extracted from MRA data. Independent multilayer perceptron and CNN models were trained to estimate the brain age from the hand-crafted features and image data, respectively. Next, both approaches were fused to assess the benefits of combining image data and hand-crafted features for brain age prediction.

Results

The combined model achieved a mean absolute error of 4 years between the chronological and predicted biological brain age. Among the independent models, the lowest mean absolute error was observed for the CNN using T1-weighted MRI data (4.2 years). When evaluating the BAGs obtained using the different approaches and imaging modalities, diverging associations between cardiovascular risk factors were found. For example, BAGs obtained from the CNN models showed an association with systolic blood pressure, while BAGs obtained from hand-crafted measurements showed greater associations with obesity markers.

Discussion

In conclusion, the use of more diverse sources of data can improve brain age estimation modeling and capture more diverse biological deviations from normal aging.
Preparation, biological characterization and preliminary human imaging studies of 68Ga-DOTA-IBA
Authors: Wang Yingwei , Wang Qixin , Chen Zan , Yang Jian , Liu Hanxiang , Peng Dengsai , Lei Lei , Liu Lin , Wang Li , Xing Naiguo , Qiu Lin , Feng Yue , Chen Yue
Published: December 2022

Purpose

In this study, DOTA-IBA was radiolabeled with 68Ga and we determined the optimum labelling conditions and assessed the biological properties of 68Ga-DOTA-IBA. We investigated the biodistribution of 68Ga-DOTA-IBA in normal animals and undertook PET/CT imaging in humans. Finally, we explored the feasibility 68Ga-DOTA-IBA as a bone imaging agent and demonstrated its potential for the therapeutic release of 177Lu/225Ac-DOTA-IBA.

Methods

The controlled variables method was used to assess the impact of variables on the radiochemical purity of 68Ga-DOTA-IBA. The biological properties of 68Ga-DOTA-IBA were investigated.68Ga-DOTA-IBA micro-PET/CT imaging was performed on animals. Volunteers were recruited for 68Ga-DOTA-IBA imaging and data were compared to 99mTc-MDP imaging studies to calculate the target to non-target ratio (T/NT) of the lesions.

Results

The prepared 68Ga-DOTA-IBA had a radiochemical purity of >97% and demonstrated good biological properties with a good safety profile in normal mice. PET/CT imaging of the animals showed rapid blood clearance with high contrast between the bone and stroma. Human imaging showed that 68Ga-DOTA-IBA could detect more lesions compared to 99mTc-MDP and had a higher targeted to untargeted ratio.

Conclusions

68Ga-DOTA-IBA is an osteophilic radiopharmaceutical that can be synthesized using a simple labelling method. 68Ga-DOTA-IBA has high radiochemical purity and is stable in vitro stability. It is rapidly cleared from the blood, has low toxicity and has strong targeting to the bone with long retention times. We also found that it is rapidly cleared in non-target tissues and has high contrast on whole-body bone imaging. 68Ga-DOTA-IBA PET/CT has potential as a novel bone imaging bone modality in patients with metastatic disease.