bluuebunny/crossref_metadata_2025 huggingface dataset:
Obstructive Sleep Apnea Impacts Cardiac Function in Dilated Cardiomyopathy Patients Through Circulating Exosomes
Authors: Gong Hui , Lyu Xing , Dong Lini , Tan Shengyu , Li Shizhen , Peng Jieting , Liu Yang , Zhang Xiangyu
Published: March 2022

Background

Obstructive sleep apnea (OSA) is common and independently associated with heart failure. This study aimed to investigate the impact of OSA on heart function in patients with dilated cardiomyopathy (DCM) as well as the possible mechanism related to exosomes regulated autophagy.

Methods and Results

A total of 126 patients with DCM who underwent sleep evaluations were analyzed retrospectively. Cardiomyocytes were treated with exosomes isolated from untreated OSA patients and healthy controls. Fibrotic and hypertrophic markers were evaluated, and Akt/mTOR pathway-mediated autophagy was investigated. DCM patients with severe OSA had larger right ventricular end-diastolic diameter (RVEDd) and right atrial diameter (RAD) and increased N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels than DCM patients without OSA. Moreover, NT-proBNP and diabetes mellitus were independently correlated with the apnea-hypopnea index in multiple linear regression analysis. Treatment with OSA-derived exosomes significantly increased Col1A1, ANP, and BNP protein expression and decreased the expression of the autophagy markers LC3B II/I and beclin1. Rapamycin treatment significantly increased the decreased autophagy markers and attenuated the increased expression of Col1A1, ANP and BNP induced by OSA-derived exosomes.

Conclusion

The severity of OSA is significantly associated with cardiac injury and remodeling. The underlying mechanism may be related to changed autophagy levels, which are regulated by circulating exosomes via the Akt/mTOR signaling pathway. This study may provide a new clue for the treatment of heart failure with OSA.
Renal Venous Stasis Index Reflects Renal Congestion and Predicts Adverse Outcomes in Patients With Heart Failure
Authors: Ohara Himika , Yoshihisa Akiomi , Horikoshi Yuko , Ishibashi Shinji , Matsuda Mitsuko , Yamadera Yukio , Sugawara Yukiko , Ichijo Yasuhiro , Hotsuki Yu , Watanabe Koichiro , Sato Yu , Misaka Tomofumi , Kaneshiro Takashi , Oikawa Masayoshi , Kobayashi Atsushi , Takeishi Yasuchika
Published: March 2022

Background

It has been recently reported that the renal venous stasis index (RVSI) assessed by renal Doppler ultrasonography provides information to stratify pulmonary hypertension that can lead to right-sided heart failure (HF). However, the clinical significance of RVSI in HF patients has not been sufficiently examined. We aimed to examine the associations of RVSI with parameters of cardiac function and right heart catheterization (RHC), as well as with prognosis, in patients with HF.

Methods

We performed renal Doppler ultrasonography, echocardiography and RHC in hospitalized patients with HF (n = 388). RVSI was calculated as follows: RVSI = (cardiac cycle time-venous flow time)/cardiac cycle time. The patients were classified to three groups based on RVSI: control group (RVSI = 0, n = 260, 67%), low RVSI group (0 < RVSI ≤ 0.21, n = 63, 16%) and high RVSI group (RVSI > 0.21, n = 65, 17%). We examined associations of RVSI with parameters of cardiac function and RHC, and followed up for cardiac events defined as cardiac death or worsening HF.

Results

There were significant correlations of RVSI with mean right atrial pressure (mRAP; R = 0.253, P < 0.001), right atrial area (R = 0.327, P < 0.001) and inferior vena cava diameter (R = 0.327, P < 0.001), but not with cardiac index (R = −0.019, P = 0.769). During the follow-up period (median 412 days), cardiac events occurred in 60 patients. In the Kaplan–Meier analysis, the cumulative cardiac event rate increased with increasing RVSI (log-rank, P = 0.001). In the multivariate Cox proportional hazard analysis, the cardiac event rate was independently associated with RVSI (high RVSI group vs. control group: hazard ratio, 1.908; 95% confidence interval, 1.046–3.479, P = 0.035).

Conclusion

RVSI assessed by renal Doppler ultrasonography reflects right-sided overload and is associated with adverse prognosis in HF patients.
Surgery for Primary Cardiac Tumors in Children: Successful Management of Large Fibromas
Authors: Qian Tao , Wu Zhongshi , Yang Yifeng , Xie Li , Yin Ni , Lu Ting , Huang Can , Yang Hui
Published: March 2022

Background

Pediatric primary cardiac tumors (PCTs) are rare. Its clinical features and prognoses are not well defined. The management of asymptomatic patients with cardiac fibromas remains controversial.

Objective

We aimed to examine our experience in surgical resection of pediatric PCT, with specific focuses on the management of large fibromas.

Methods

This study included all the children who underwent surgical resection of PCT in our institution between December 2008 and June 2021. The last follow-up was performed between June 1st and August 26th, 2021. Kaplan–Meier method was used to estimate the postoperative survival, freedom from reoperation, event-free survival, and also related risk factors. The tumor volume and volume index (volume divided by body surface area) were measured for cardiac fibromas.

Results

Of the 39 patients with median operative age of 9.5 [interquartile range (IQR): 1.2–16.5] years, 35 (89.7%) had benign tumors (fibromas for 15, myxomas for 13, and others for 7). The length and volume of fibromas were independent of age and symptoms (Ps > 0.05). The fibroma volume index was negatively correlated with age (P = 0.039), with a mean value of 105 ± 70 ml/m2. Of the 15 patients with fibromas, 5 were asymptomatic, 4 received partial resection, 4 required transmural resection, and 4 presented postoperative left ventricular (LV) dysfunction (ejection fraction <50%). During the median follow-up period of 3.1 years and maximum of 12.5 years, adverse events included 2 early and 1 late death, 4 reoperations, 4 tumor recurrences, and 1 LV dysfunction lasting over one year. The 8-year survival, freedom from reoperation, and event-free survival rates were 90.4, 81.8, and 64.2%, respectively. Malignant tumor (P < 0.001) was associated with more adverse events. Transmural resection (P = 0.022) and larger tumor volume index than LV end-diastolic volume (P = 0.046) were risk factors for LV dysfunction following fibromas resection.

Conclusion

Pediatric surgery for PCT can be performed with low mortalities and few adverse events. The size of cardiac fibroma in children relatively decreases with the increase of age. Larger tumor volume index than LV end-diastolic volume index and transmural tumor resection predicts postoperative LV dysfunction.
Association Between Serum Aldehydes and Hypertension in Adults: A Cross-Sectional Analysis of the National Health and Nutrition Examination Survey
Authors: Zhu Yongjian , Liu Mingjing , Fu Wanrong , Bo Yacong
Published: March 2022

Background

Exposure to ambient pollutants and chemicals were found to be associated with increased risk of hypertension. However, the relationship between the increased aldehyde exposure and hypertension are still unclear. This study aimed to investigate the potential associations of serum aldehydes levels with prevalent hypertension.

Methods

A total of 1,733 U.S. adults with data on hypertension outcome and serum aldehydes measurement from the National Health and Nutrition Examination Survey 2013–2014 were included. The serum levels of aldehydes were measured via an automated analytical method using solid phase microextraction gas chromatography and high-resolution mass spectrometry. Multivariate logistic regression models were adopted to assess the associations between six selected aldehydes exposure (benzaldehyde, butyraldehyde, heptanaldehyde, hexanaldehyde, isopentanaldehyde, and propanaldehyde) and prevalence of hypertension.

Results

The mean age was 48.0 ± 16.7 years and an approximately equivalent of sex distribution was observed (female 49.9%). There seems to be a numerically higher level of hexanaldehyde in participants with hypertension when compared to participants without hypertension (2.6 ± 3.9 ng/mL vs. 2.3 ± 1.1 ng/mL). After adjusting for potential confounders, the odds ratio (OR) for hypertension was 2.15 [95% confidence interval (CI): 1.33–3.51] in participants from the highest quartile of serum hexanaldehyde concentration in comparison to those from the lowest quartile. Subgroup analyses and sensitivity analyses showed generally similar results.

Conclusion

In summary, current evidence suggested that increased serum hexanaldehyde level was positively associated with prevalent hypertension in U.S. adults.
Compatibility of Diatom Valve Records With Sedimentary Ancient DNA Amplicon Data: A Case Study in a Brackish, Alkaline Tibetan Lake
Authors: Anslan Sten , Kang Wengang , Dulias Katharina , Wünnemann Bernd , Echeverría-Galindo Paula , Börner Nicole , Schwarz Anja , Liu Yongqin , Liu Keshao , Künzel Sven , Kisand Veljo , Rioual Patrick , Peng Ping , Wang Junbo , Zhu Liping , Vences Miguel , Schwalb Antje
Published: March 2022

Lake sediments represent valuable and widely used archives for tracking environmental and biotic changes over time. Past aquatic communities are traditionally studied via morphological identification of the remains of organisms. However, molecular identification tools, such as DNA metabarcoding, have revolutionized the field of biomonitoring by enabling high-throughput and fast identification of organisms from environmental samples (e.g., sediments and soil). Sedimentary ancient DNA (sedaDNA) metabarcoding, an approach to track the biodiversity of target organisms from sediment cores, spanning thousands of years, has been successfully applied in many studies. However, researchers seldom explore how well the signals from sedaDNA data correlate with the fossil records of target organisms. This information is essential to infer past environmental conditions and community changes of bioindicators when the increasingly popular molecular identification method, metabarcoding, is desired instead of a morphological identification approach. In this study, we explore the correlations of diatom valve records across the last ∼940 years with the diatom sedaDNA metabarcoding data from the same sediment core from lake Nam Co (Tibetan Plateau). Overall, the results from valve vs. sedaDNA data revealed concordant diatom richness as well as community patterns. However, several mismatches in the diatom taxonomic composition existed between the data sets. In general, sedaDNA data harbored much higher diatom diversity, but due to the lack of reference sequences in public databases, many molecular units (amplicon sequence variants) remained unclassified to lower taxonomic levels. As our study lake, Nam Co, is characterized by brackish water and alkaline pH, some likely cases for the observed taxonomic composition mismatches may be due to a valve dissolution issue. Nevertheless, significant drivers for the diatom richness and community structure largely corresponded between data sets. Both valve and sedaDNA data demonstrated similar breakpoints for historical diatom community shifts. A particularly strong shift in the diatom community structure occurred after ∼1950 CE, which may be associated with abrupt environmental changes on the Tibetan Plateau. Altogether, our study indicates that environmentally driven signals reflected by the diatom communities are successfully recovered via microfossil as well as molecular identification methods.
Responses of Tropical Background State and ENSO Behaviors to Mid-Holocene Forcing Simulated by PMIP3 and PMIP4 Models
Authors: Song Meng-Er , Chen Lin
Published: March 2022

The mid-Holocene (MH), a period about 6,000 years ago, provides an opportunity to understand climate change in response to orbital forcing change. Numerical model simulation is an effective tool through which we can study the climate change in the MH, although the climate in the MH can be partly inferred from proxy data. As the Paleoclimate Model Inter-comparison Project phase 4 (PMIP4) recently released the latest simulations for different past climate scenarios, we investigated tropical climate changes, including both the basic state and interannual variability, and tried to find out whether the PMIP phase 3 (PMIP3) and PMIP4 results can be reconciled. Almost all the modelling results show that the inter-hemisphere contrast was enhanced over the tropical Pacific, with warmer and wetter condition on the northern side of the equator and an intensified cross-equatorial flow in the MH than at present, and the annual cycle of the sea-surface temperature (SST) during the MH was reduced. Such background mean state changes arose from the seasonal changes of the solar incident radiation in the MH. In addition to the consistent changes in background mean state changes, some El Niño-Southern Oscillation (ENSO) features, such as the seasonal phase locking feature and periodicity, show consistent changes across the PMIP3 and PMIP4 models, that is, both suites of models exhibit no marked difference in the MH with respect to present-day simulations. In contrast, the modeling results show only agreement on the sign of the ENSO amplitude change (i.e., decrease in the ENSO amplitude in the MH), while the range of reduction varied with model and region. Additionally, the occurrence probability of central Pacific El Niño events increases in the MH, whereas the significance is quite marginal. The modeled changes in the mean state and ENSO serve as a test bed for studying tropical climate system’s response to natural warming, which may provide some insights into understanding climate changes in response to the current anthropogenic warming.
The Association Between Thyroid Diseases and Alzheimer’s Disease in a National Health Screening Cohort in Korea
Authors: Kim Ji Hee , Lee Heui Seung , Kim Yoo Hwan , Kwon Mi Jung , Kim Joo-Hee , Min Chan Yang , Yoo Dae Myoung , Choi Hyo Geun
Published: March 2022

Objectives

Thyroid dysfunction is linked to an increased risk of cognitive impairment. However, studies on the relationships between thyroid diseases and Alzheimer’s disease (AD) have reported conflicting results. We investigated the associations between several thyroid diseases and AD in a nested case-control study.

Methods

A total of 1,977 participants with AD were identified by claims data from 2002-2015 among a random sample of half a million people in the Korean National Health Insurance database. We recruited 16,473 age- and sex-matched (1:4 ratio) control participants and applied conditional logistic regression to estimate the relationships between thyroid diseases and AD, with adjustments for potential confounders, such as basic demographics, lifestyle factors, and various medical conditions or comorbidities.

Results

The prevalence rates of hypothyroidism (odds ratio [OR]=1.14, 95% confidence interval [CI]=1.00-1.30), thyroiditis (OR=1.22, 95% CI=1.05-1.40), and hyperthyroidism (OR=1.13, 95% CI=1.01-1.28) were significantly higher in participants with AD than in control participants after adjustment for confounders.

Conclusion

In this large national sample, we found significant relationships between several thyroid diseases and AD. Despite of the need for further investigation, these findings could better support to appreciate the pathophysiology of AD.
Omicron Variant of SARS-CoV-2 Virus: In Silico Evaluation of the Possible Impact on People Affected by Diabetes Mellitus
Authors: Bassani Davide , Ragazzi Eugenio , Lapolla Annunziata , Sartore Giovanni , Moro Stefano
Published: March 2022

The Omicron variant of SARS-CoV-2 (Spike mutant B.1.1.529) carrying more than 30-point mutations in its structure, of which 15 are localized in the receptor-binding domain (RBD), allows to hypothesize a relevant change in interactivity with ACE2. In previous reports we hypothesized that the worse outcome of the COVID-19 disease in diabetes mellitus condition could be related to the non-enzymatic glycation of ACE2 receptor and an in silico evaluation led to the demonstration that the number of interactions is decreased in comparison to the unmodified model, possibly shifting the virus attack through different, multiple alternative entry routes. Given the evidenced features of this variant, we aimed to investigate with a computational approach the characteristics of Omicron SARS-CoV-2 with respect to its binding to human ACE-2 receptor, in a particular population, namely people affected by diabetes mellitus, at risk for unfavorable outcomes of the COVID-19. The computational analysis, considering the case in which all the lysine residues in the system are subjected to non-enzymatic glycation, confirmed that lysine glycation causes a general loss of interactivity between wild-type (WT)-Spike-RBD and ACE2. In the Omicron variant, Lys417 mutates into an asparagine, preventing the possible non-enzymatic glycation of this residue. Therefore, if non-enzymatic glycation seemed to cause a shift in the way in which the virus enters the cell from the ACE2-mediated mechanism to other pathways, in the case of the Omicron variant the ACE2-mediated approach of the virus seems to remain an important event to take into account. Indeed, interaction profile analysis, together with molecular mechanics–generalized Born surface area (MM-GBSA) calculations, suggests that the Omicron-Spike-RBD maintains a higher affinity for ACE2 subsequently to non-enzymatic glycation with respect to WT-Spike-RBD. The finding of the present computational study may suggest a different clinical relevance of the Omicron variant for the diabetes mellitus field, also in the possible direction of a lower severity of the disease.
Understanding the Compositional Effects of SAFs on Combustion Intermediates
Authors: Mehl M. , Pelucchi M. , Osswald P.
Published: March 2022

This work analyses, experimentally and numerically, the combustion behavior of three aviation fuels: a standard Jet A-1, a high aromatic content fuel, and an isoparaffinic Alcohol to Jet (ATJ) fuel. The goal is to demonstrate the ability of a chemical kinetic model to capture the chemistry underlying the combustion behavior of a wide range of jet fuels, starting from compositional information. Real fuels containing up to hundreds of components are modeled as surrogates containing less than 10 components, which represent the chemical functionalities of the real fuel. By using an in-house numerical optimizer, the fuel components and their relative quantities are selected, and a semi-detailed kinetic model (containing about 450 species) is used to simulate the formation of the main oxidation products and reaction intermediates. Calculations are compared with species profiles measured in a laminar flow reactor to validate the model and provide insights into the reactivity of the fuels. Finally, starting from the results, general observations on the strengths and limits of the approach are provided, highlighting areas where further investigations are required.
Correlation Between Changes in Environmental Temperature and Performance of High-Discharge Lithium-Polymer Batteries
Authors: Choi Jaehun , Park Heesung
Published: March 2022

Electric vehicles (EVs) have been developed to solve environmental problems and the depletion of energy resources, and batteries have been used as their main energy source. The battery used in this study was a lithium polymer battery with the same chemical structure as lithium-ion. The use of a solid electrolyte has advantages, such as lack of leakage of electrolyte, high density per size, and convenient shape design. In this study, we analyzed the heat generation and performance characteristics of EV batteries through experiments on changes in environmental temperature. There is a difference in the heat generation depending on the discharge rate, and the performance characteristics of the battery improves as the environmental temperature rises. In the experiment, the battery discharge performance and heat generation were meaningful at 40°C environmental temperature, the worst battery discharge performance and heat generation at −30°C environmental temperature were 25.1 W (1 C), 81.0 W (2 C), and 151.5 W (3 C). In this study, the heat generation and performance characteristics of the battery were analyzed according to the change in the environmental temperature and discharge rate of the battery. We proposed a relationship between heat generation and environmental temperature in terms of discharge rate. The relationship is significant in designing thermal management system for battery powered devices.
Unsteady Motion of Shock Wave for a Supersonic Compression Ramp Flow Based on Large Eddy Simulation
Authors: Huang Xing , Wang Li-Xu , Zhong Dong-Dong , Ge Ning
Published: March 2022

A large eddy simulation (LES) is conducted to investigate shock wave/turbulent boundary layer interaction in a 24° compression ramp at a high inlet Mach number of Ma=2.9. The recycling/rescaling Method is used as the inflow turbulence generation technique. The shock wave structure and boundary layer flow in the interaction region are studied by flow visualization methods, such as vortex recognition and numerical schlieren. The distributions of turbulent kinetic energy and Reynolds normal stresses at different streamwise locations are analyzed. The results show that a strong anisotropy turbulent flow appears in the reattached boundary layer after the interaction of the shock wave. The large-scale unsteady motion of the separation shock wave is analyzed by using the intermittent factor and power spectrum. It is found that the shock moves around the averaged separation position, and the length scale is equal to 72% of the inlet boundary layer thickness. The power spectrum analysis reveals the existence of low-frequency instability in the separation region.
Impact of Land-Use Changes on Soil Properties and Carbon Pools in India: A Meta-analysis
Authors: Padbhushan Rajeev , Kumar Upendra , Sharma Sheetal , Rana D. S. , Kumar Rajkishore , Kohli Anshuman , Kumari Priyanka , Parmar Brajendra , Kaviraj Megha , Sinha Abhas Kumar , Annapurna K. , Gupta Vadakattu V. S. R.
Published: March 2022

Land-use changes (LUC), primarily due to deforestation and soil disturbance, are one of the major causes of soil quality degradation and greenhouse gas emissions. Effects of LUC on soil physicochemical properties and changes in soil quality and land use management strategies that can effectively restore soil carbon and microbial biomass levels have been reported from all over the world, but the impact analysis of such practices in the Indian context is limited. In this study, over 1,786 paired datasets (for meta-analysis) on land uses (LUs) were collected from Indian literature (1990–2019) to determine the magnitude of the influence of LUC on soil carbon, microbial biomass, and other physical and chemical properties at three soil depths. Meta-analysis results showed that grasslands (36.1%) lost the most soil organic carbon (SOC) compared to native forest lands, followed by plantation lands (35.5%), cultivated lands (31.1%), barren lands (27.3%), and horticulture lands (11.5%). Our findings also revealed that, when compared to forest land, the microbial quotient was lower in other LUs. Due to the depletion of SOC stock, carbon dioxide equivalent (CO2 eq) emissions were significantly higher in all LUs than in forest land. Results also showed that due to the conversion of forest land to cultivated land, total carbon, labile carbon, non-labile carbon, microbial biomass carbon, and SOC stocks were lost by 21%, 25%, 32%, 26%, and 41.2%, respectively. Changes in soil carbon pools and properties were more pronounced in surface (0–15 cm) soils than in subsurface soils (15–30 cm and 30–45 cm). Restoration of the SOC stocks from different LUs ranged from a minimum of 2% (grasslands) to a maximum of 48% (plantation lands). Overall, this study showed that soil carbon pools decreased as LUC transitioned from native forestland to other LUs, and it is suggested that adopting crop-production systems that can reduce CO2 emissions from the intensive LUs such as the ones evaluated here could contribute to improvements in soil quality and mitigation of climate change impacts, particularly under Indian agro-climatic conditions.
Roles of Arbuscular Mycorrhizal Fungi on Soil Fertility: Contribution in the Improvement of Physical, Chemical, and Biological Properties of the Soil
Authors: Fall Abdoulaye Fofana , Nakabonge Grace , Ssekandi Joseph , Founoune-Mboup Hassna , Apori Samuel Obeng , Ndiaye Abibatou , Badji Arfang , Ngom Khady
Published: March 2022

Many of the world's soils are experiencing degradation at an alarming rate. Climate change and some agricultural management practices, such as tillage and excessive use of chemicals, have all contributed to the degradation of soil fertility. Arbuscular Mycorrhizal Fungi (AMFs) contribute to the improvement of soil fertility. Here, a short review focusing on the role of AMF in improving soil fertility is presented. The aim of this review was to explore the role of AMF in improving the chemical, physical, and biological properties of the soil. We highlight some beneficial effects of AMF on soil carbon sequestration, nutrient contents, microbial activities, and soil structure. AMF has a positive impact on the soil by producing organic acids and glomalin, which protect from soil erosion, chelate heavy metals, improve carbon sequestration, and stabilize soil macro-aggregation. AMF also recruits bacteria that produce alkaline phosphatase, a mineralization soil enzyme associated with organic phosphorus availability. Moreover, AMFs influence the composition, diversity, and activity of microbial communities in the soil through mechanisms of antagonism or cooperation. All of these AMF activities contribute to improve soil fertility. Knowledge gaps are identified and discussed in the context of future research in this review. This will help us better understand AMF, stimulate further research, and help in sustaining the soil fertility.
Low-Energy Electron Irradiation of Tick-Borne Encephalitis Virus Provides a Protective Inactivated Vaccine
Authors: Finkensieper Julia , Issmail Leila , Fertey Jasmin , Rockstroh Alexandra , Schopf Simone , Standfest Bastian , Thoma Martin , Grunwald Thomas , Ulbert Sebastian
Published: March 2022

Tick-borne encephalitis virus (TBEV) is a zoonotic flavivirus which is endemic in many European and Asian countries. Humans can get infected with TBEV usually via ticks, and possible symptoms of the infection range from fever to severe neurological complications such as encephalitis. Vaccines to protect against TBEV-induced disease are widely used and most of them consist of whole viruses, which are inactivated by formaldehyde. Although this production process is well established, it has several drawbacks, including the usage of hazardous chemicals, the long inactivation times required and the potential modification of antigens by formaldehyde. As an alternative to chemical treatment, low-energy electron irradiation (LEEI) is known to efficiently inactivate pathogens by predominantly damaging nucleic acids. In contrast to other methods of ionizing radiation, LEEI does not require substantial shielding constructions and can be used in standard laboratories. Here, we have analyzed the potential of LEEI to generate a TBEV vaccine and immunized mice with three doses of irradiated or chemically inactivated TBEV. LEEI-inactivated TBEV induced binding antibodies of higher titer compared to the formaldehyde-inactivated virus. This was also observed for the avidity of the antibodies measured after the second dose. After viral challenge, the mice immunized with LEEI- or formaldehyde-inactivated TBEV were completely protected from disease and had no detectable virus in the central nervous system. Taken together, the results indicate that LEEI could be an alternative to chemical inactivation for the production of a TBEV vaccine.
High Levels of Cerebrospinal Fluid Kappa Free Light Chains Relate to IgM Intrathecal Synthesis and Might Have Prognostic Implications in Relapsing Multiple Sclerosis
Authors: Castillo-Villalba Jéssica , Gil-Perotín Sara , Gasque-Rubio Raquel , Cubas-Nuñez Laura , Carratalà-Boscà Sara , Alcalá Carmen , Quintanilla-Bordás Carlos , Pérez-Miralles Francisco , Ferrer Cristina , Cañada Martínez Antonio , Tortosa Jordi , Solís-Tarazona Luís , Campos Luisa , Leivas Alberto , Laíz Marro Begoña , Casanova Bonaventura
Published: March 2022

Cerebrospinal kappa free light chain (KFLC)-index is a marker of intrathecal immunoglobulin synthesis that aids in the diagnosis of multiple sclerosis (MS). However, little evidence exists on its prognostic role. Our aim is to analyze the relationship between KFLC-index and other MS biomarkers and to explore its prognostic role. This is a monocentric observational study in a cohort of 52 people with relapsing MS (pwRMS) performed on prospectively acquired clinical data and with retrospective evaluation of biomarkers. We measured KFLC-index, immunoglobulin intrathecal synthesis, cerebrospinal fluid (CSF) chitinase 3-like 1 (CHI3L1), and neurofilament light protein (NFL) and reviewed MRI to detect leptomeningeal contrast enhancement (LMCE). We compared time to Expanded Disability Status Scale (EDSS) 3 and to initiation of high-efficacy disease-modifying therapies (heDMTs) by multivariate Cox regression analysis. Median KFLC-index correlated with IgG/IgM indexes (p < 0.0001/p < 0.05) and IgG-oligoclonal bands (OCGBs) (p < 0.001). Patients with IgM-oligoclonal bands (OCMBs) had a higher KFLC-index (p = 0.049). KFLC-index was higher in patients with LMCE (p = 0.008) and correlated with CHI3L1 (p = 0.007), but disease activity had no effect on its value. Bivariate and multivariate analyses confirmed KFLC-index > 58 as an independent risk factor for reaching an EDSS of 3 (hazard ratio (HR) = 12.4; 95% CI = 1.1–147; p = 0.047) and for the need of treatment with heDMTs (HR = 3.0; 95% CI = 1.2–7.1; p = 0.0013). To conclude, our data suggest a potential prognostic role of the KFLC-index during the MS course.
Preoperative Breast Immune Prognostic Index as Prognostic Factor Predicts the Clinical Outcomes of Breast Cancer Patients Receiving Neoadjuvant Chemotherapy
Authors: Chen Li , Kong Xiangyi , Huang Shaolong , Su Zhaohui , Zhu Mengliu , Fang Yi , Zhang Lin , Li Xingrui , Wang Jing
Published: March 2022

Objective

This study aims at investigating the potential prognostic significance of the breast immune prognostic index (BIPI) in breast cancer patients who received neoadjuvant chemotherapy (NACT).

Methods

The optimal cutoff value was calculated through the receiver operating characteristic curve (ROC). The correlations between BIPI and clinicopathologic characteristics were determined by the chi-square test or Fisher’s exact test. The Kaplan–Meier method was used to estimate the survival probability, and the log-rank test was used to analyze the differences in the survival probability among patients. The univariate and multivariate Cox proportional hazard regression model was used to screen the independent prognostic factors. A prognostic nomogram for disease-free survival (DFS) and overall survival (OS) was built on the basis of the multivariate analyses. Furthermore, the calibration curve and decision curve analysis (DCA) were used to assess the predictive performance of the nomogram.

Results

All enrolled patients were split into three subgroups based on the BIPI score. The mean DFS and OS of the BIPI score 0 group and BIPI score 1 group were significantly longer than those of the BIPI score 2 group (42.02 vs. 38.61 vs. 26.01 months, 77.61 vs. 71.83 vs. 53.15 months; p < 0.05). Univariate and multivariate analyses indicated that BIPI was an independent prognostic factor for patients’ DFS and OS (DFS, hazard ratio (HR): 6.720, 95% confidence interval (CI): 1.629–27.717; OS, HR: 8.006, 95% CI: 1.638–39.119). A nomogram with a C-index of 0.873 (95% CI: 0.779–0.966) and 0.801 (95% CI: 0.702–0.901) had a favorable performance for predicting DFS and OS survival rates for clinical use by combining immune scores with other clinical features. The calibration curves at 1-, 3-, and 5-year survival suggested a good consistency between the predicted and actual DFS and OS probability. The DCA demonstrated that the constructed nomogram had better clinical predictive usefulness than only BIPI in predictive clinical applications of 5-year DFS and OS prognostic assessments.

Conclusions

The patients with low BIPI score have better prognoses and longer DFS and OS. Furthermore, the BIPI-based nomogram may serve as a convenient prognostic tool for breast cancer and help in clinical decision-making.
TIGIT Blockade Exerts Synergistic Effects on Microwave Ablation Against Cancer
Authors: Chen Yaping , Huang Hao , Li Yuan , Xiao Wenlu , Liu Yingting , Chen Rongzhang , Zhu Yulan , Zheng Xiao , Wu Changping , Chen Lujun
Published: March 2022

Background

Combination immunotherapy based on immune checkpoint inhibitors (ICIs) has shown great success in the treatment of many types of cancers and has become the mainstream in the comprehensive treatment of cancers. Ablation in combination with immunotherapy has achieved tremendous efficacy in some preclinical and clinical studies. To date, our team proved that ablation in combination with ICIs was a promising antitumor therapeutic strategy for the liver metastasis of colorectal cancer (CRC). Moreover, we found that the expression of T cell immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domain (TIGIT) expression was up-regulated after microwave ablation (MWA), indicating that TIGIT was involved in immunosuppression, and the combination of MWA and TIGIT blockade represented a potential clinical treatment strategy.

Methods

In the present study, we examined the expression of TIGIT using a preclinical mouse model treated with MWA. Moreover, we evaluated the antitumor functions of MWA alone or in combination with TIGIT blockade by monitoring tumor growth and survival of the mice. Besides, we also detected the numbers of tumor-infiltrating lymphocytes (TILs), and effector molecules of CD8+ T cells using flow cytometry. Finally, we analyzed the single-cell RNA sequencing (scRNA-seq) data from the MWA and MWA plus anti-TIGIT groups.

Results

The expression of TIGIT in various immune cells was up-regulated after MWA, and the addition of TIGIT blockade to MWA prolonged survival and delayed tumor growth in the MC38 tumor model. Taken together, our findings showed that TIGIT blockade in combination with MWA significantly promoted the expansion and functions of CD8+ TILs and reshaped myeloid cells in the tumor microenvironment (TME) using flow cytometry and scRNA-seq analysis.

Conclusions

TIGIT blockade in combination with MWA was a novel treatment strategy for the liver metastasis of CRC, and this combination therapy could reprogram the TME toward an antitumor environment.
Reduced Plasma Extracellular Vesicle CD5L Content in Patients With Acute-On-Chronic Liver Failure: Interplay With Specialized Pro-Resolving Lipid Mediators
Authors: Sánchez-Rodríguez María Belen , Téllez Érica , Casulleras Mireia , Borràs Francesc E. , Arroyo Vicente , Clària Joan , Sarrias Maria-Rosa
Published: March 2022

Acute-on chronic liver failure (ACLF) is a syndrome that develops in patients with acutely decompensated cirrhosis (AD). It is characterized by a systemic hyperinflammatory state, leading to multiple organ failure. Our objective was to analyze macrophage anti-inflammatory protein CD5L in plasma extracellular vesicles (EVs) and assess its as yet unknown relationship with lipid mediators in ACLF. With this aim, EVs were purified by size exclusion chromatography from the plasma of healthy subjects (HS) (n=6) and patients with compensated cirrhosis (CC) (n=6), AD (n=11) and ACLF (n=11), which were defined as positive for CD9, CD5L and CD63 and their size, number, morphology and lipid mediator content were characterized by NTA, EM, and LC-MS/MS, respectively. Additionally, plasma CD5L was quantified by ELISA in 10 HS, 20 CC and 149 AD patients (69 ACLF). Moreover, macrophage CD5L expression and the biosynthesis of specialized lipid mediators (SPMs) were characterized in vitro in primary cells. Our results indicate that circulating EVs were significantly suppressed in cirrhosis, regardless of severity, and showed considerable alterations in CD5L and lipid mediator content as the disease progressed. In AD, levels of EV CD5L correlated best with those of the SPM RvE1. Analysis of total plasma supported these data and showed that, in ACLF, low CD5L levels were associated with circulatory (p<0.001), brain (p<0.008) and respiratory (p<0.05) failure (Mann-Whitney test). Functional studies in macrophages indicated a positive feedback loop between CD5L and RvE1 biosynthesis. In summary, we have determined a significant alteration of circulating EV contents in ACLF, with a loss of anti-inflammatory and pro-resolving molecules involved in the control of acute inflammation in this condition.
Risk Factors for Mortality in Anti-NMDAR, Anti-LGI1, and Anti-GABABR Encephalitis
Authors: Zhong Rui , Chen Qingling , Zhang Xinyue , Zhang Hanyu , Lin Weihong
Published: March 2022

Objective

We aimed to investigate the mortality rate and identify the predictors of death in patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis.

Methods

Patients with anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis were recruited from the Neurology Department of the First Hospital of Jilin University from March 2015 to November 2021. The primary outcome variable was a binary variable of death vs. survival. The potential risk factors for mortality were evaluated. The mortality rates were determined, and the independent predictors of death were identified using multivariable logistic regression analysis.

Results

A total of 100 hospitalized patients with anti-NMDAR, anti-LGI1, or anti-GABABR encephalitis were included in the final analysis. Fifteen patients (15%) died during a median follow-up period of 18 months. The mortality rates were 10% for anti-NMDAR encephalitis, 2.8% for anti-LGI1 encephalitis, and 41.7% for anti-GABABR encephalitis. The multivariable analysis results showed that older age at onset [adjusted odds ratio (OR) = 1.017, 95% confidence interval (CI) = 1.009–1.136; p = 0.023] was independently associated with an increased risk of death. Antibody type was also associated with mortality. Patients with anti-GABABR encephalitis had 13.458-fold greater odds of dying than patients with anti-LGI1 encephalitis (adjusted OR = 13.458, 95% CI = 1.270–142.631; p = 0.031).

Conclusion

The general mortality rate of anti-NMDAR, anti-LGI1, and anti-GABABR encephalitis was 15%. Age at onset and type of autoimmune encephalitis antibody were independent predictors of death in these patients.
Taxonomy and Phylogeny of Two Tintinnid Ciliates of Leprotintinnus (Protista, Ciliophora, Choreotrichida) Combining the Loricae, Cytological, Ontogenetic Features, and Barcoding Genes
Authors: Hu Tao , Wang Zhaoyi , Liu Weiwei , Lin Xiaofeng
Published: March 2022

Tintinnid ciliates are a highly diverse and essential group in the marine planktonic microbial loop. However, most of the known tintinnids were recorded only by the lorica characters and very few of them had been studied on their cytological features. In this study, the morphological characters of the lorica, ciliary pattern, nuclear apparatus, ontogenesis, and the molecular phylogeny of two poorly known tintinnid ciliates,Leprotintinnus nordqvisti(Brandt, 1906)Kofoid and Campbell (1929)andL. simplexSchmidt (1902), isolated from coastal waters of southern China, were investigated based on living observation, silver staining, three nuclear ribosomal DNA markers (18S, ITS1-5.8S-ITS2, and 28S genes) and one mitochondrial DNA marker (CO1gene). For the first time, the somatic ciliary pattern of the genusLeprotintinnuswas disclosed,viz., comprising a ventral, a dorsal, and a posterior kinety as well as a right, a left, and a lateral ciliary field. The diagnoses of bothLeprotintinnusspecies were improved and the neotype was assigned. The ontogenesis ofL. nordqvistiwas in enantiotropic division mode with the new dorsal and posterior kineties generatedde novo. The molecular phylogeny confirmed thatLeprotintinnusspecies are closely related to some species ofTintinnopsis,Stylicauda,Rhizodomus, andClimacocylis. The anterior extending of the ventral kinety together with some of the lateral kinety is likely to be a distinguishing feature to determine their systematic relationships. This study also revealed that (i) the lorica ofL. nordqvistiis polymorphic or plastic; (ii)Leprotintinnus tubulosusRoxas (1941)might be a synonym ofL.nordqvisti; (iii)Leprotintinnus neriticussensuYoo et al. (1988)might be a misidentification ofL. simplex.
Revising the Impact and Prospects of Activity and Ventilation Rate Bio-Loggers for Tracking Welfare and Fish-Environment Interactions in Salmonids and Mediterranean Farmed Fish
Authors: Calduch-Giner Josep , Holhorea Paul George , Ferrer Miguel Ángel , Naya-Català Fernando , Rosell-Moll Enrique , Vega García Carlos , Prunet Patrick , Espmark Åsa M. , Leguen Isabelle , Kolarevic Jelena , Vega Aurelio , Kerneis Thierry , Goardon Lionel , Afonso Juan Manuel , Pérez-Sánchez Jaume
Published: March 2022

Behavioral parameters are reliable and useful operational welfare indicators that yield information on fish health and welfare status in aquaculture. However, aquatic environment is still constraining for some solutions based on underwater cameras or echo sounder transmitters. Thus, the use of bio-loggers internally or externally attached to sentinel fish emerges as a solution for fish welfare monitoring in tanks- and sea cages-rearing systems. This review is focused on the recently developed AEFishBIT, a small and light data storage tag designed to be externally attached to fish operculum for individual and simultaneous monitoring of swimming activity and ventilation rates under steady and unsteady swimming conditions for short-term periods. AEFishBIT is a tri-axial accelerometer with a frequency sampling of 50–100 Hz that is able to provide proxy measurements of physical and metabolic activities validated by video recording, exercise tests in swim tunnel respirometers, and differential operculum and body tail movements across fish species with differences in swimming capabilities. Tagging procedures based on tag piercing and surgery procedures are adapted to species anatomical head and operculum features, which allowed trained operators to quickly complete the tagging procedure with a fast post-tagging recovery of just 2.5–7 h in both salmonid (rainbow trout, Atlantic salmon) and non-salmonid (gilthead sea bream, European sea bass) farmed fish. Dual recorded data are processed by on-board algorithms, providing valuable information on adaptive behavior through the productive cycle with the changing environment and genetics. Such biosensing approach also provides valuable information on social behavior in terms of adaptive capacities or changes in daily or seasonal activity, linking respiratory rates with changes in metabolic rates and energy partitioning between growth and physical activity. At short-term, upcoming improvements in device design and accompanying software are envisaged, including energy-harvesting techniques aimed to prolong the battery life and the addition of a gyroscope for the estimation of the spatial distribution of fish movements. Altogether, the measured features of AEFishBIT will assist researchers, fish farmers and breeders to establish stricter welfare criteria, suitable feeding strategies, and to produce more robust and efficient fish in a changing environment, helping to improve fish management and aquaculture profitability.
Acupuncture for Atraumatic Shoulder Conditions: Protocol for a Systematic Review and Meta-Analysis
Authors: Wang Yi , Xu Yan , Peng Yu , Liao Shichuan , Dai Guogang , Li Tao
Published: March 2022

Introduction

Shoulder pain is one of the most common musculoskeletal disorders among adults and is caused by a variety of shoulder conditions. The popularity of different acupuncture methods in the nonsurgical treatment of shoulder pain has recently increased. However, evidence regarding the efficacy of acupuncture for shoulder pain is inconsistent, and there is a lack of supporting evidence regarding the overall efficacy of different acupuncture methods for shoulder pain.

Methods and Analysis

A systematic review will be conducted to assess the effectiveness of a wide range of acupuncture techniques for atraumatic shoulder conditions. The PubMed, EMBASE, Cochrane Central Register of Controlled Trials, Web of Science, Ovid MEDLINE, Chinese Biomedical Literature, Chinese National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases will be searched to identify eligible studies. Studies will be selected according to preset inclusion and exclusion criteria and relevant data will be extracted from the final included studies. The heterogeneity, risk of bias, publication bias and evidence quality of the studies will be assessed, and a subgroup analysis and sensitivity analysis will be performed.

Systematic Review Registration

PROSPERO registration number CRD42021249625.
Therapeutic Targeting of GSK3β-Regulated Nrf2 and NFκB Signaling Pathways by Salvianolic Acid A Ameliorates Peritoneal Fibrosis
Authors: Zhou Fan , Yao Lan , Lu Xiaoqing , Li Yubao , Han Xingmin , Wang Pei
Published: March 2022

Peritoneal fibrosis is a devastating complication in patients undergoing peritoneal dialysis, with no definite therapy yet available. Salvia miltiorrhiza and its major active component Salvianolic acid A (Sal A) have demonstrated a beneficial effect in myriad diseases. However, their effect on peritoneal fibrosis is unknown. In murine models of peritoneal dialysis, daily Sal A treatment substantially improved the peritoneal dialysis fluid (PDF) elicited peritoneal fibrosis, marked by thickening of the submesothelial compact zone, accumulation of extracellular matrix and increased expression of vimentin and PAI-1, concomitant with attenuation of GSK3β hyperactivity. This coincided with diminished nitrotyrosine in peritoneal tissues and increased Nrf2 nuclear translocation, entailing a lessened oxidative injury and reinforced Nrf2 antioxidant response. Meanwhile, inflammatory infiltration and maladaptive angiogenesis in peritoneal tissues provoked by PDF injury were also mitigated by Sal A, associated with a suppressed NFκB activation. Mechanistically, ectopic expression of the constitutively active GSK3β blunted the NFκB-suppressing and Nrf2-activating efficacy of Sal A in peritoneal mesothelial cells exposed to hypertonic dextrose, suggesting that GSK3β inhibition mediates the protective effect of Sal A. Collectively, our findings may open the avenue for developing a novel therapy based on Sal A for preventing peritoneal fibrosis in peritoneal dialysis.