bluuebunny/crossref_metadata_2025 huggingface dataset:
TREM2-independent neuroprotection is mediated by monocyte-derived macrophages in a mouse model of Alzheimer’s disease
Authors: Dvir-Szternfeld Raz , Castellani Giulia , Arad Michal , Cahalon Liora , Colaiuta Sarah-Phoebeluc , Keren-Shaul Hadas , Croese Tommaso , Ulland Tyler , Colonna Marco , Weiner Assaf , Amit Ido , Schwartz Michal
Published: December 2020

The contributions of disease-associated microglia (DAM) and infiltrating monocyte-derived macrophages (MDM) to Alzheimer’s disease (AD) are still controversial. Here, using Trem2−/−5xFAD DAM-deficient mice, we addressed this issue by targeting the programmed cell death ligand-1 (PD-L1) immune checkpoint, shown to modify AD via MDM recruitment. Treating Trem2−/−5xFAD mice resulted in cognitive improvement, rescue of synapses, and reduction of soluble-amyloid beta (Aβ)1−42, with no effect on insoluble Aβ1−42. In Trem2+/+5xFAD mice, the treatment enhanced cognitive performance, led to elevation in DAM levels, and reduced insoluble Aβ1−42. Single-cell RNA-sequencing revealed that MDM, derived from both Trem2−/− and Trem2+/+ 5xFAD mouse brains, express a unique set of scavenger receptors and anti-inflammatory genes. Eliminating monocytes abrogated the beneficial effect of anti-PD-L1. The results highlight the need for MDM for neuroprotection even when microglia are fully activated, and demonstrate that their activity occurs through a TREM2-independent mechanism, with the potential to overcome TREM2 polymorphism in patients.
Spontaneous traveling waves naturally emerge from horizontal fiber time delays and travel through locally asynchronous-irregular states
Authors: Davis Zachary , Benigno Gabriel , Fletterman Charlee , Desbordes Theo , Sejnowski Terrence , Reynolds John , Muller Lyle
Published: December 2020

Sensory neuroscience has focused a great deal of its attention on characterizing the mean firing rate that is evoked by a stimulus, and while it has long been recognized that the firing rates of individual neurons fluctuate around the mean, these fluctuations are often treated as a form of internally generated noise1. There is, however, evidence that these “ongoing” fluctuations of activity in sensory cortex during normal, waking function shape neuronal excitability and responses to external input2,3. We have recently found that spontaneous fluctuations are organized into waves traveling at speeds consistent with the speed of action potentials traversing unmyelinated horizontal cortical fibers (0.1-0.6 m/s)4 across the cortical surface5. These waves systematically modulate excitability across the retinotopic map, strongly affecting perceptual sensitivity as measured in a visual detection task. The underlying mechanism for these waves, however, is unknown. Further, it is unclear whether waves are consistent with the low rate, highly irregular, and weakly correlated “asynchronous-irregular” dynamics observed in computational models6 and cortical recordings in vivo7. Here, we study a large-scale computational model of a cortical sheet, with connections ranging up to biological scales. Using an efficient custom simulation framework, we study networks with topographically-organized connectivity and distance-dependent axonal conduction delays from several thousand up to one million neurons. We find that spontaneous traveling waves are a general property of these networks and are consistent with the asynchronous-irregular regime. These waves are well matched to spontaneous waves recorded in the neocortex of awake monkeys. Further, individual neurons sparsely participate in waves, yielding a sparse-wave regime that offers a unique operating mode, where traveling waves coexist with locally asynchronous-irregular dynamics, without inducing deleterious neuronal correlations8.
“The Impact of Coronavirus Outbreak on Breastfeeding Guidelines Among Brazilian Hospitals and Maternity Services: A Cross-Sectional Study”
Authors: Gonçalves-Ferri Walusa Assad , Pereira-Cellini Fábia Martins , Coca Kelly Pereira , Aragon Davi Casale , Nader Paulo de Jesus Hartmann , Lyra João Cesar , Vale Maryneia Silva do , Marba Sérgio Tadeu Martins , Araujo Katiaci Janice Chaves , Dias Laura de Fátima Afonso , Ferreira Daniela Marques de Lima Mota , Nieto Gislayne Souza , Anchieta Lêni Marcia , Silveira Rita de Cássia , de Moura Marta David Rocha , Calil Valdenise Martins L. Tuma , Moraes Viviane Christina Cortez , de Almeida João Henrique Carvalho Leme , Magalhães Maurício , Sonini Thaise Cristina Branchee , Javorsky Juliane Barleta , Ribeiro Érica Lobato Acaui , Ferreira Rodrigo , de Almeida Louise Dantas Cavalcante , Garbers Rosângela , Faria Gabriella Maset da Silva , Roosch Anelise , de Mesquita Ana Ruth Antunes , Pinto Rebecca Meirelles de Oliveira
Published: December 2020

BackgroundRecommended by the World Health Organization, exclusive breastfeeding is a safe source of nutrition available for children in humanitarian emergencies, as in the current pandemic caused by the severe acute respiratory syndrome coronavirus 2. Despite the Brazilian Guideline protecting breastfeeding practice, there are many concerns about how to protect babies from their infected mothers. This study aimed to analyze how the Brazilian hospitals and maternity services promote and support mothers suspected or diagnosed with coronavirus disease (COVID-19). MethodsThis is a descriptive cross-sectional and multicenter study collecting data from 24 Brazilian hospitals and maternity services from March to July 2020. Representatives of the institutions completed a questionnaire based on acts to promote and support breastfeeding, Baby-Friendly Hospital Initiative, and Brazil’s law recommendations.ResultsThe results showed that in delivery rooms, 98.5% of the services prohibited immediate and uninterrupted skin-to-skin contact and companions for the mother and did not support mothers to initiate breastfeeding in the first hour. In rooming-in, 98.5% of the services allowed breastfeeding and recommend care for babies following the respiratory hygiene practices to prevent transmission of COVID-19 and whether companions are forbidden (83.3%). Hospital discharge was mostly early (79.1%); the guidelines were not individualized. Additionally, a lack of support was noticed from the health community network in the home environment (83.3%). Hospital and home breast pumping were allowed (87.5%), but breast milk donation was not accepted (95.8%). ConclusionsIn Brazil, the hospitals are not able to approach recommendations to protect, promote, and support breastfeeding properly during the COVID-19 outbreak. The scientific community needs to discuss how to improve maternal and baby care services to protect breastfeeding in the current pandemic.
Polar Vortexes and Charged Domain Walls in a Room Temperature Magnetoelectric Thin Film
Authors: Moore Kalani , O'Connell Eoghan , Keeney Lynette , Downing Clive , Schmidt Michael , Nicolosi Valeria , Bangert Ursel , Conroy Michele
Published: December 2020

Multiferroic domain walls are an emerging solution for future low-power nanoelectronics due to their combined tuneable functionality and mobility. Here we show that the magnetoelectric multiferroic Aurivillius phase Bi6TixFeyMnzO18 (B6TFMO) crystal is an ideal platform for domain wall-based nanoelectronic devices. The unit cell of B6TFMO is distinctive as it consists of a multiferroic layer between dielectric layers. We utilise atomic resolution scanning transmission electron microscopy and spectroscopy to map the sub-unit-cell polarisation in B6TFMO thin films. 180˚ charged head-to-head and tail-to-tail domain walls are found to pass through > 8 ferroelectric-dielectric layers of the film. They are structurally similar to BiFeO3 DWs but contain a large surface charge density (σ_s) = 1.09 |e|per perovskite cell, where |e| is elementary charge. Although polarisation is primarily in-plane, c-axis polarisation is identified at head-to-tail domain walls with an associated electromechanical coupling of strain and polarisation. Finally, we reveal that with controlled strain engineering during thin film growth, room-temperature vortexes are formed in the ferroelectric layer. These results confirm that sub-unit-cell topological features can play an important role in controlling the conduction properties and magnetisation state of Aurivillius phase films and other multiferroic heterostructures.
Immunoglobulin kappa light chain produced by cardiomyocytes and participates in maintaining intercalated disc integrity
Authors: Qiu Xiaoyan , Zhu Zhu , Shi Zhan , Zhang Meng , Zhou Wenjing , Lan Feng , Liao Qinyuan
Published: December 2020

It is widely accepted that immunoglobulins (Igs) are produced only by B cells and function as antibodies. However, growing evidence has proven that almost all non-B cells also produce Igs with nonconventional roles, such as promotion of cell survival, proliferation and migration. In this study, we identified Ig light chain (κ chain) expression in mouse and human cardiomyocytes, especially on intercalated discs (ICDs). Unexpectedly, conditional knockout (cKO) of Igκ in adult cardiomyocytes in mice resulted in significant hypotension, a rapid decrease in cardiac contractility and conduction defects. Histologically, Igκ knockout in mouse cardiomyocytes led to structural disruption of intercalated discs (ICDs) and loss of localization of adhesion-related N-cadherin and CX43 on ICDs. Mechanistic investigation indicated that Igκ can bind with plectin/desmoplakin, a complex that connects desmin and desmosomes and enhances the protein stability of plectin. In conclusion, Our findings identify Igκ expressed by cardiomyocytes as a new ICD-related molecule that participates in cardiomyocyte contraction and conduction by stabilizing plectin.
Could age increase the strength of inverse association between ultraviolet B exposure and colorectal cancer?
Authors: Purushothaman Vidya Lakshmi , Cuomo Raphael E , Garland Cedric , Mackey Timothy
Published: December 2020

Background: Vitamin D has been identified as a potential protective factor the development of colorectal cancer (CRC). We expect to see a stronger association of ultraviolet B (UVB) exposure and CRC crude rates with increasing age since chronic vitamin D deficiency leads to sustained molecular changes that increase cancer risk. The DINOMIT (disjunction, initiation, natural selection, overgrowth, metastasis, involution, and transition) model postulates various stages of cancer development due to vitamin D deficiency and the associated latency period. The purpose of this study is to examine this age-dependent inverse relationship globally.Methods: In this ecological study, a series of linear and polynomial regression tests were performed between country specific UVB estimates adjusted for cloud cover and crude incidence rates of CRC for different age groups. Multiple linear regression was used to investigate the association between crude incidence rates of colorectal cancer and UVB estimate adjusting for urbanization, skin pigmentation, smoking, animal consumption, per capita GDP, and life expectancy. Statistical analysis was followed by geospatial visualization by producing choropleth maps.Results: The inverse relationship between UVB exposure and CRC crude rates was stronger in older age groups at the country level. Quadratic curve fitting was preferred, and these models were statistically significant for all age groups. The inverse association between crude incidence rates of CRC and UVB exposure was statistically significant for age groups above 45 years, after controlling for covariates.Conclusion: The age-dependent inverse association between UVB exposure and incidence of colorectal cancer exhibits a greater effect size among older age groups in global analyses. Studying the effect of chronic vitamin D deficiency on colorectal cancer etiology will help in understanding the necessity for population wide screening programs for vitamin D deficiency, especially in regions with inadequate UVB exposure. Further studies are required to assess the need for adequate public health programs such as selective supplementation and food fortification.
Step Back and Reassess - What Physicians See as Challenges in Treating Patients with Acute Bleeding: International, Mixed Qualitative and Quantitative Study.
Authors: Roche Tadzio , Wetli Doreen , Braun Julia , Kataife Ezequiel , Mileo Federico , Spahn Donat , Tscholl David , Said Sadiq
Published: December 2020

Background: Acute bleeding is an omnipresent challenge for all physicians. Uncontrolled hemorrhage is the most common preventable cause of death after trauma worldwide. In different surgical disciplines, hemorrhage represents an independent risk factor for increased postoperative morbimortality, directly affecting patients’ outcomes. This study asked anesthesiologists about their personal perceived challenges when treating bleeding patients. Methods: This investigator-initiated, prospective, international, dual-center, mixed qualitative and quantitative study interrogated anesthesiologists about what they found easy and what difficult in treating acutely bleeding patients. Following the template approach for qualitative research, we identified major and minor topics through free inductive coding and word count. In a second step, we derived ten statements from the participants’ answers. Using a field survey, we then asked the participants to rate their level of agreement with the derived statements. We analyzed the answers using one sample Wilcoxon test and the Mann-Whitney test. Results: We included a total of 84 physicians in the qualitative interrogations and a different group of 42 anesthesiologists in the quantitative part. We identified 11 major topics and 19 associated subtopics. The main topics and the degree of agreement (here as agree or strongly agree) were as follows: “Complexity of the topic” (52.4% agreed to find the topic complex), “Cognitive aids” (92.9% agreed to find them helpful), “Time management” (64.3% agreed to feeling time pressure), “Human factors” (95.2% agreed that human factors are essential), “Resources” (95.2% agreed that resources are essential), “Experience” and “Low frequency of cases” (57.1% agreed to lack practice), “Diagnostic methods” (31.0% agreed that the interpretation of test results is difficult), “Anticoagulation” (85.7% agreed to it being difficult), “Treatment” (81.0% agreed to knowing the first therapeutic steps), and “Nothing”.Conclusions: Anesthesiologists in two large tertiary care facilities in different parts of the world found coagulation management, especially in anticoagulated patients, complex. We identified the delayed diagnostic test results and their interpretation as challenges. Resources, treatment protocols and human factors such as team communication were perceived to facilitate management. Future studies should explore the challenges in smaller hospitals and other parts of the world and test new technologies addressing the identified difficulties.
Shorter TR Combination with Finer Atlas Positively Modulate Topological Organization of Brain Networks: A Resting State fMRI Study
Authors: Zhang Yan , HU QILI , Liang Jiali , Hu Zhenghui , Qian Tianyi , Li Kuncheng , Zhao Xiaohu , Liang Peipeng
Published: December 2020

BackgroundThe simultaneous multislice echo planar imaging technique can shorten the repetition time (TR) of blood oxygen level-dependent acquisition and thus acquires more information. However, little is known about the influence of higher temporal resolution on functional networks. Whether the topological organization of small-world networks is modulated in the multispectra at high temporal resolution is still unclear. Results: The network reconstruction based on the shorter TR and the finer atlas, showed significant (p<0.05, Bonferroni correction) increases in normalized clustering coefficient, small-worldness, clustering coefficient, local efficiency and global efficiency, and reductions in normalized characteristic path length and characteristic path length. ConclusionsThe shorter TR coupled with the finer atlas can positively modulate topological characteristics of brain networks. Although five multispectra present properties of small-world networks, the properties of the network in 0.082-0.1 Hz are weaker than those in 0.01-0.082 Hz. These findings provide new insights into the topological patterns of brain networks and have implications for the study of brain connectomes and their applications in brain disease.
Protecting P-glycoprotein at the Blood-Brain Barrier from Degradation in an Alzheimer’s Disease Mouse Model
Authors: Ding Yujie , Zhong Yu , Baldeshwiler Andrea , Abner Erin L. , Bauer Björn , Hartz Anika
Published: December 2020

Background. Failure to clear Aβ from the brain is partly responsible for Aβ brain accumulation in Alzheimer’s disease (AD). A critical protein for clearing Aβ across the blood-brain barrier is the efflux transporter P-glycoprotein (P-gp). In AD, P-gp levels are reduced, which contributes to impaired Aβ brain clearance. However, the mechanism responsible for decreased P-gp levels is poorly understood and there are no strategies available to protect P-gp. We previously demonstrated in isolated brain capillaries ex vivo that human Aβ40 (hAβ40) triggers P-gp degradation by activating the ubiquitin-proteasome pathway. In this pathway, hAβ40 initiates P-gp ubiquitination, leading to internalization and proteasomal degradation of P-gp, which then results in decreased P-gp protein expression and transport activity levels. Here, we extend this line of research and present results from an in vivo study using a transgenic mouse model of AD (human amyloid precursor protein (hAPP)-overexpressing mice; Tg2576). Methods. In our study, hAPP mice were treated with vehicle, nocodazole (NCZ, microtubule inhibitor to block P-gp internalization), or a combination of NCZ and the P-gp inhibitor cyclosporin A (CSA). We determined P-gp protein expression and transport activity levels in isolated mouse brain capillaries and Aβ levels in plasma and brain tissue. Results. Treating hAPP mice with 5 mg/kg NCZ for 14 days protected P-gp from degradation. Consistent with this, P-gp-mediated hAβ42 transport in brain capillaries was increased in NCZ-treated hAPP mice compared to untreated hAPP mice. Importantly, NCZ treatment significantly lowered hAβ40 and hAβ42 brain levels in hAPP mice, whereas hAβ40 and hAβ42 levels in plasma remained unchanged. Conclusions. These findings provide in vivo proof that blocking P-gp internalization protects P-gp from degradation and maintains P-gp protein expression and transport activity levels, which in turn lowers hAβ brain levels. Thus, protecting P-gp at the blood-brain barrier may provide a novel therapeutic target for AD and other Aβ-based pathologies.
Influence of Government-driven Quality Assessment Program on Patients with Chronic Obstructive Pulmonary Disease
Authors: Park Hye Jung , Kim Sung-Ryeol , Kim Sinae , Lee Hye Sun , Kim Bo Yeon , Kim Hye Kyoung , Ahn Sang In , Shin Ji Hyeon , Lee Jae-Hyun , Park Jung-Won
Published: December 2020

Background: The Korean Health Insurance Review and Assessment Service (HIRA) has launched the Chronic Obstructive Pulmonary Disease (COPD) Quality Assessment Program (CQAP) since 2014. We aimed to reveal the influence of this national program on clinical outcomes and the burden of COPD in Korea. Methods: The CQAP is conducted annually. We used healthcare claims data linked with the results of the program provided by HIRA between May 2014 and April 2017. Patients were considered to have COPD if they visited a hospital for COPD management during the assessment term. Those who visited a medical institution for COPD and were prescribed COPD medications at least twice were assessed by the CQAP (assessed subjects, AS; not-assessed subjects, NAS). CQAP evaluated the pulmonary function test conduction rate, regular visitation rate, and prescription rates of COPD medications.Results: Among the 560,000 patients with COPD, about 140,000 were assessed by the CQAP annually. In both groups, the pulmonary function test conduction rate and inhaled bronchodilator prescription rate improved since 2014. Compared to the NAS group, the risk of admission and all-cause mortality rate in the AS group were significantly reduced by 21.2% and 40.7%, respectively. In patients who were assessed for 3 consecutive years, all of the above variables were high at baseline and did not improve much from the CQAP. In matching analysis, we observed this improvement to be limited in the COPD quality assessment year. Conclusions: The CQAP by the health insurance bureau has improved the management protocol and prognosis of COPD.
Pre-Existing Interstitial Lung Disease is Associated With Onset of Nivolumab-Induced Pneumonitis in Patients With Solid Tumors: A Retrospective Analysis
Authors: Yamaguchi Teppei , Shimizu Junichi , Hasegawa Takaaki , Horio Yoshitsugu , Inaba Yoshitaka , Hanai Nobuhiro , Muro Kei , Hida Toyoaki
Published: December 2020

BackgroundNivolumab-induced pneumonitis is occasionally serious and life-threatening immune-related adverse event. However, the association between the pre-existing interstitial lung disease (ILD) and incidence of nivolumab-induced pneumonitis among different types of tumors remains unclear. The aim of this study was to examine the association between pre-existing interstitial lung disease (ILD) on chest computed tomography (CT) and nivolumab-induced pneumonitis among different types of solid tumors.Patients and MethodsWe retrospectively collected the clinical data and baseline chest CT of 311 nivolumab treated patients with non-small cell lung cancer (NSCLC), head and neck cancer (HNC), or gastric cancer (GC). We investigated the relationship between pre-existing ILD on baseline chest CT and nivolumab-induced pneumonitis onset.ResultsFinally, 188 patients were included in the analysis: 96 patients with NSCLC, 43 patients with HNC, and 49 patients with GC. NSCLC had a significantly higher rate of pre-existing ILD compared with HNC/GC (P=0.047). Nivolumab-induced pneumonitis occurred in 11.7%, including 14.6% of NSCLC, and 8.7% of HNC/GC. Multivariate logistic regression analyses revealed that pre-existing ILD (P=0.0008) and male sex (P=0.049) significantly increased the risk of nivolumab-induced pneumonitis.ConclusionOur results indicated that pre-existing ILD is a risk factor for nivolumab-induced pneumonitis in solid tumors.
Predictors of Exercise-Induced Bronchoconstriction in Subjects with Mild Asthma
Authors: Salameh Maroon , Pini Laura , Quadri Federico , Spreafico Fabio , Bottone Damiano , Tantucci Claudio
Published: December 2020

Background: Physical effort is one of the natural stimuli capable of triggering airway obstruction in asthmatics, the so called exercise-induced bronchoconstriction in asthma (EIBa). This study was performed in subjects with mild persistent asthma suspected for EIBa, aiming to find predictors among functional parameters at rest and during exercise for developing EIBa. Methods: In 20 subjects with mild asthma in stable conditions who reported respiratory symptoms on exertion in the past, measurements of baseline functional respiratory parameters and airways responsiveness by a methacholine challenge were obtained on the first day of the study after an adequate pharmacological washout. The day after, a maximal symptom-limited incremental cardiopulmonary exercise test (CPExT) was performed, with subsequent, repeated maneuvers of maximal full forced expiration to monitor the FEV1 change at 1,3,5,7,10 and 15 minutes after the end of exercise for diagnosing EIBa.Results: 19 subjects aged 27±5 years completed the two-days protocol. No functional parameters both at rest and during effort were useful to predict EIBa after stopping exercise that actually occurred in 12 individuals. In contrast to asthmatics without EIBa, in those with EIBa, however, mean Inspiratory Capacity (IC) did not increase with increasing ventilatory requirements during CPExT because 6 of them (50%) displayed dynamic pulmonary hyperinflation (DH) throughout the exercise, as documented by the progressive increase of end-expiratory lung volume. This subgroup of asthmatics with EIBa who in turn showed earlier and greater post-exercise FEV1 fall had significantly lower forced mean expiratory flow between 25% and 75% of forced vital capacity (FEF25-75%) at rest (p<0.05) and higher airways responsiveness, expressed as PD20FEV1 (p<0.05).Conclusions No functional respiratory parameters either at rest or during the effort seem to predict EIBa in mild asthmatics after maximal exercise test. In those with EIBa, however, a subgroup developed DH during exercise, and this was associated with baseline reduced forced expiratory flow-rates at lower lung volumes and higher airway hyperresponsiveness, suggesting a prominent small airways impairment.
Associations Between CD160 Polymorphisms and Autoimmune Thyroid Disease: A Case-Control Study
Authors: He Weiwei , Zhao Jing , Liu Xuerong , Li Sheli , Mu Kaida , Zhang Jing , Zhang Jin-an
Published: December 2020

Background/AimsRecent researches suggest that the CD160/HVEM/LIGHT/BTLA signaling pathway may contribute to the pathogeneses of autoimmune diseases, but the relationship between CD160 polymorphisms and autoimmune thyroid disease (AITD) has not been reported yet. This study aimed to evaluate the associations between CD160 polymorphisms and AITD.MethodsA total of 1017 patients with AITD (634 Graves' disease and 383 Hashimoto's thyroiditis) and 856 unrelated healthy controls were recruited into our study. Odds ratios (ORs) with 95% confidence interval (95%CI) were calculated through logistic regression analyses. The CD160 SNPs were detected using Hi-SNP high-throughput genotyping. ResultsThere was a statistically significant difference between Graves' disease patients and the control group with respect to both the genotype distribution (P=0.014) and allele frequency of rs744877 (P=0.034). A significant association of CD160 rs744877 with AITD was observed before adjusted age and gender under a dominant model (OR= 0.79, 95%CI 0.66-0.95; P= 0.013) and an additive model (OR= 0.77, 95%CI 0.64-0.94, P=0.008), and was also observed after adjusted age and gender under a dominant model (OR= 0.78, 95%CI 0.65-0.95; P= 0.011) and an additive model (OR= 0.76, 95%CI 0.63-0.93, P=0.007). A significant association of rs744877 with Graves' disease was observed under an allele model (OR= 0.84, 95%CI 0.71-0.98, P=0.027), a dominant model (OR= 0.74, 95%CI 0.60-0.91; P= 0.005), and an additive model (OR= 0.72, 95%CI 0.58-0.90, P=0.004). Multivariate logistic regression analyses suggested that the association remained significant after adjustment for age and gender. However, rs744877 was not related to Hashimoto's thyroiditis. Furthermore, CD160 rs3766526 was not significantly related to either Graves' disease or Hashimoto's thyroiditis.ConclusionThis is the first identification of the association of CD160 rs744877 with Graves' disease. Our findings add new data to the genetic contribution to Graves' disease susceptibility and support the crucial role of the CD160/HVEM/LIGHT/BTLA pathway in the pathogenesis of Graves' disease.
Systemic Immune‐Inflammation Index Has Prognostic Significance In Pancreatic Carcinoma Patients: A Meta-Analysis
Authors: Li Xiaocheng , Lin Huapeng , Ouyang Renbin , Yang Yaowei , Peng Jing
Published: December 2020

Background: Systemic immune-inflammation index (SII) is reportedly a prognostic indicator for several malignancies, including pancreatic carcinoma, although there exists no consensus regarding its significance. In the current study, we used a systematically meta-analysis to evaluate the association between SII and prognosis in pancreatic carcinoma patients.Methods: We screened PubMed, Embase and Cochrane Library databases, through May 2020, and retrieved studies describing the prognostic role of SII in pancreatic carcinoma. We calculated pooled hazard ratio (HR) and 95% confidence interval (CI) using a random or fixed effects models to reveal the correlation between SII and prognosis.Results: A total of 4 studies, comprising 1,749 patients, met our inclusion criteria and were therefore eligible for inclusion. Our meta-analysis showed that elevated SII indicated significantly worse overall survival in patients with pancreatic carcinoma (HR: 1.43, 95% CI: 1.24-1.65, P < 0.001), with subgroup analyses, stratified by the TNM stage and treatment, further validating these results. In addition, patients with high SII had poorer cancer-specific survival (HR: 2.32, 95% CI: 1.55-3.48, P < 0.001). However, we found no significant associations between SII with disease-free and relapse-free survival.Conclusions: These findings indicate that SII is a potential non-invasive and promising tool for predicting clinical outcomes of pancreatic carcinoma patients. However, further studies using adequate designs and larger sample sizes are required to validate our findings.
Similar effects as shade tolerance induced by dust accumulation and size penetration of particulates on cotton leaves
Authors: Li Li , Mu Guijin
Published: December 2020

Background: Dust accumulation covers the leaf’s surface and influences foliar physiological activity. Two independent experiments were carried out to instigate the foliar responses to dust accumulation and the penetration limitation of small dust particles (<1 μm) on the foliar surface, respectively. In experiment I, three dust accumulation intensities were achieved by a dust spraying treatment. Photosynthesis CO2 exchange and fast chlorophyll fluorescence transient were measured, as well as chlorophyll contents and leaf thickness. In experiment II, the penetration limits of small particulates on the leaf surface were examined by feeding nano-fluorescent microspheres. Results: Dust accumulation alleviated the photoinhibition of Photosystem II and decreased photosynthesis, as represented by net photosynthetic rates (PN) and stomatal conductance to water vapor (gs). Photosynthetic response curves between net photosynthetic rate (PN) and photosynthetically active radiation (PAR) showed that heavy dust accumulation (34.98 ± 2.6 mg cm-2) increased the light compensation point (LCP) and light saturation point (LSP) and decreased photosynthesis rates under saturating light (PNmax). Leaves became thin due to the lack of a palisade layer while chlorophyll content increased under dust accumulation. Confocal laser scanning microscopy (CLSM) images showed that the larger particles (1 μm) distributed in the regions below the stomata and the smaller ones (0.1 μm) were detected in the wider areas below stomata. Conclusions: These results suggested that dust accumulation induced similar effects as shade tolerance in cotton leaves but did not trigger more photochemical acclimation to low light. Dust particles (<1 μm) penetrated leaf surface through stomata.
Brusatol-enriched Brucea Javanica Oil Ameliorated Dextran Sulfate Sodium-induced Colitis in Mice: Involvement of NF-κB and RhoA/ROCK Signaling Pathways
Authors: zheng xing han , mai li ting , wang tong tong , xu ying , su zi ren , chen jian nan , zeng hui fang , xie you liang
Published: December 2020

Background: Our previous study indicates that Brucea javanica oil (BJO) is beneficial for treatment of ulcerative colitis (UC), and that quassinoids in particular brusatol are bioactive components. However, it is still uncertain whether or not other components in BJO, such as oleic acid and fatty acids, have anti-UC effect.Purpose: The present study aimed to compare the anti-UC effects between brusatol-enriched BJO (BE-BJO) and brusatol-free BJO (BF-BJO), and to explore the effects and mechanisms of BE-BJO on colon inflammation and intestinal epithelial barrier function.Methods: Balb/C mice received 3% (wt/vol) DSS for one weeks to establish the UC model. Different doses of BE-BJO, BF-BJO or BJO were treated. Body weight and colon length were measured. Disease activity index (DAI) and histological analysis were evaluated. The levels of pro-inflammatory cytokines in the colon tissues were measured by enzyme linked immunosorbent assay (ELISA). The expressions of tight junction proteins were tested to investigate the intestinal epithelial barrier function. The effects of BE-BJO on NF-κB and RhoA/ROCK pathways were studied.Results: BE-BJO alleviated DSS-induced loss of body weight, increase of DAI and shortening of colon, whereas BF-BJO did not have these protective effects. BE-BJO treatment improved the morphology of colon tissue, inhibited the production and release of pro-inflammatory cytokines including TNF-α、 IFN-γ、 IL-6 and IL-1β in the colon tissue, as well as reversed the decreased expressions of ZO-1, Occludin, Claudin-1and E-cadherin induced by DSS, but augmented Claudin-2 expression. Mechanistically, BE-BJO repressed phosphorylation of NF-κB subunit p65, suppressed RhoA activation, downregulated ROCK, and prevented phosphorylation of myosin light chain (MLC) in DSS-treated mice.Conclusions: This work demonstrated that BE-BJO could ameliorate DSS-induced UC by preventing colon inflammation and enhancing intestinal epithelial barrier function, probably via suppression of NF-κB and RhoA/ROCK signaling pathways. These findings confirm that quassinoids are active compounds from BJO and suggest the therapeutic potential of quassinoids and BE-BJO in the treatment of UC.
Correlation of Glycemic Regulation and Endotrophin in Patients with Type 2 Diabetes; Pilot Study
Authors: YOLDEMIR Sengul AYDIN , Arman Yucel , Akarsu Murat , Altun Ozgur , Ozcan Mustafa , Tukek Tufan
Published: December 2020

Background: Endotrophin is one of the extracellular matrix proteins secreted by adipose tissue. In this study, we aimed to investigate the effects of changes in blood glucose levels on serum endotropin levels secreted by adipose tissue and thus on diabetes.Methods: In this prospective pilot study included 78 patients with type 2 diabete(T2D) with hemoglobin A1c level >9%. Data of anthropometric measurements, fractional excretion of UA (FEUA), serum lipid parameters and endotrophin were collected in patients; all examinations were repeated after 3 months. Analysis was performed using Paired-Samles T test and Spearman tests. Results: Of patients, 23 were female (54.8%) and 19 were male (45.2%). Mean age was 55.2 years, with mean diabetes age of 8.14 ± 5.35 years. After 3 months follow-up, HbA1c, fasting glucose, CRP, UACR and endotrophin levels were observed to clearly reduce. The variation in serum endotrophin levels examined at the start of the study and in the 3rd month was identified to have a positive correlation with the variation in HbA1c and UACR levels (r=0.342, p=0.02; r=0.484, p=0.001). Multiple linear regression analysis showed percentage variation values (d) -endotrophin levels were only independently correlated with (d)-UACR (model r2=0.257, P value=0.00).Conclusions: The decrease in HbA1c causes a significant decrease in endotropin levels. Unexpectedly, this reduction in endotrophin levels is closely related to the decrease in UACR, regardless of blood glucose regulation. We think that studies targeting endotrophin will contribute to the diagnosis, treatment and follow-up of diabetic nephropathy in the future.
No Evidence for a Pathogen Associated With Pulmonary MALT Lymphoma: A Metagenomics Investigation
Authors: borie raphael , CAro Valerie , nunes hilario , Kambouchner Marianne , Cazes Aurelie , Antoine MArtine , Crestani Bruno , leroy karen , Copie-Bergman Christiane , Kwasiborski Aurelia , Hennequin Christophe , vandenbogaert mathias , hourdel veronique , Cadranel Jacques
Published: December 2020

Mucosa-associated lymphoid tissue (MALT) lymphoma is generally associated with chronic antigen stimulation: auto-antigens or of microbial origin. Only one study suggested association between Achromobacter xylosoxidans and pulmonary MALT lymphoma. We aimed to investigate the presence of virus or any infectious agents in pulmonary MALT lymphoma by using metagenomic next-generation sequencing (mNGS).All lung samples were centrally reviewed. The t(11;18) (q21;q21) was evaluated by FISH analysis. The snap frozen large lung biopsies were analyzed by mNGS. After lung biopsies homogenization total nucleic acids (RNA and DNA) were extracted, amplified and classified according to their taxonomic assignment, after exclusion of host DNA.We included 13 samples from pulmonary MALT lymphoma (mean age: 60.3 years, 7 women, 3 with auto-immune background) and 10 controls. The diagnosis of MALT lymphoma was confirmed for the 13 samples, 3 showed API2-MALT1 translocation (23%). No evidence of the presence of a specific pathogen was clearly identified in the group of patients with pulmonary MALT lymphoma. We identified A. xylosoxidans sequence in 4/13 patients and in 4/10 controls.This study did not find evidence for a DNA or RNA virus, a fungi, a parasite or a bacteria associated with pulmonary MALT lymphoma either in the stroma or in tumor cells.
A Novel De Novo Ddx3x Missense Variant in a Female With Brachycephaly and Intellectual Disability: A Case Report
Authors: Moresco Giada , Costanza Jole , Santaniello Carlo , Rondinone Ornella , Grilli Federico , Prada Elisabetta , Orcesi Simona , Coro Ilaria , Marchisio Paola , Miozzo Monica , Fontana Laura , Milani Donatella
Published: December 2020

Background: De novo pathogenic variants in the DDX3X gene are reported to account for 1–3% of unexplained intellectual disability (ID) in females, leading to the rare disease known as DDX3X syndrome (MRXSSB, OMIM #300958). Besides ID, these patients manifest a variable clinical presentation, which includes neurological and behavioral defects, and abnormal brain MRIs. Case presentation: We report a 10-year-old girl affected by delayed psychomotor development, delayed myelination, and polymicrogyria (PMG). We identified a novel de novo missense mutation in the DDX3X gene (c.C625G) by exome sequencing. The DDX3X gene encodes a DEAD-box ATP-dependent RNA-helicase broadly implicated in gene expression through regulation of mRNA metabolism. The identified mutation is located just upstream the helicase domain and is suggested to impair the protein activity, thus resulting in the altered translation of DDX3X-dependent mRNAs. The proband, presenting with the typical PMG phenotype related to the syndrome, does not show other clinical signs frequently reported in presence of missense DDX3X mutations that are associated with a most severe clinical presentation. In addition, she has brachycephaly, never described in female DDX3X patients, and macroglossia, that has never been associated with the syndrome.Conclusions: This case expands the knowledge of DDX3X pathogenic variants and the associated DDX3X syndrome phenotypic spectrum.
The Epidemiology of Hospital Death Following Pediatric Severe Community Acquired Pneumonia
Authors: Ao Xiao-Xiao , Tan Li-Ping , Wan Qiu-Feng , Li Yong-Qin
Published: December 2020

BackgroundCommunity acquired pneumonia is the primary cause of pediatric hospitalizations and deaths in children under 5 years of age. But the epidemiology of death in pediatric severe community acquired pneumonia was not well characterized. MethodsThis retrospective observational study was performed at the academic Emergency department and intensive care unit and we investigated the timing, cause, mode and attribution of death in children with severe community acquired pneumonia. ResultsOf 962 subjects with severe community acquired pneumonia, there were 57 non-survivors (5.9% mortality). Median time to death was 7 [IQR 3,16] days from severe community acquired pneumonia recognition. Patients dying ≤ 7 days were younger, had greater illness severity and higher rate of congenital heart disease, who were more likely to die of a cardiovascular cause. Multiple organ dysfunction syndrome predominated in deaths > 7 days. Unsuccessful cardiopulmonary resuscitation was the most common mode of death at all timepoints. Our findings suggested that in pediatric severe community acquired pneumonia, early deaths were due primarily to cardiovascular dysfunction, while later deaths were more commonly due to multiple organ dysfunction syndrome. ConclusionsDeaths from non-pulmonary factors accounted for a substantial portion of non-survivors. Respiratory dysfunction accounted for only a minority of deaths. Our study highlighted limitations associated with rescuing patients with severe pneumonia from death if extrapulmonary organ dysfunctions could not be simultaneously managed.
Effectiveness of Tirobot-assisted Vertebroplasty in Treating Thoracolumbar Osteoporotic Compression Fracture
Authors: Wang Boyao , Cao Jiang , Chang Jie , Yin Guoyong , Cai Weihua , Li Qingqing , Huang Zhenfei , Yu Lipeng , Cao Xiaojian
Published: December 2020

Background: Percutaneous kyphoplasty is the main method for the treatment of thoracolumbar osteoporotic compression fractures. However, much radiation exposure during the operation could harm the health of the surgeon and the patient. In addition, the accuracy of its surgery still needs to be improved. This study aimed to assess the radiation exposure and clinical efficacy of Tirobot-assisted vertebroplasty in treating thoracolumbar osteoporotic compression fracture.Methods: A total of 60 patients with thoracolumbar osteoporotic compression fracture who underwent unilateral vertebroplasty at our hospital between June 2019 and June 2020 were included in this retrospective cohort study. All of them were between 60 and 90 years old and free of systemic diseases. All the patients were assigned to Tirobot group (treated with Tirobot-assisted approach) and control group (treated with traditional approach). Fluoroscopic frequency, operative duration, length of stay (LOS), post-operative complications (cement leakage, infection, and thrombosis), pre-operative and pre-discharge indexes (VAS scores, JOA scores, and Cobb’s angles) were compared.Results: The fluoroscopic frequency(P<0.001), post-operative complications(P=0.035) in Tirobot group was significantly lower than those in control group. The operative duration and LOS in Tirobot group were shorter than those in control group, but the differences were not statistically significant (P=0.183). Pre-discharge VAS score and Cobb’s angle decreased, and JOA increased after surgeries in both groups. These three indexes showed significant differences after surgery in each group (P<0.001), but not between groups (PVAS=0.175, PCobb’s=0.585, PJOA =0.448).Conclusion: As a safe and effective strategy, Tirobot-assisted vertebroplasty can reduce radiation exposure and be clinically replicated.
What validation tests can be done by the clinical medical physicist while waiting for the standardization of quantitative SPECT/CT imaging?
Authors: Piwowarska-Bilska Hanna , Supińska Aleksandra , Birkenfeld Bożena
Published: December 2020

Objective The aim of the study was to assess the accuracy of quantitative SPECT/CT imaging in a clinical setting and to compare test results from two nuclear medicine departments.Methods Phantom studies were carried out with two gamma cameras manufactured by GE Healthcare: Discovery NM/CT 670 and NM/CT 850, used in two nuclear medicine departments.Results The convergence of activity concentration recovery was validated for the two gamma cameras operating in two medical centres using a homogeneous 3D phantom. The comparison of results revealed a 5% difference in the calibration factor Bg. cal; 6% difference in COV, and a 0.6% difference in total activity deviation ∆Atot.Recovery coefficients (RCmax) for activity concentration in spheres of the anthropomorphic phantom was measured for different image reconstruction techniques. RCmax was in the range of 0.2-0.4 for the smallest sphere (ϕ10 mm), and 1.3-1.4 for the largest sphere (ϕ37 mm). Conversion factors for SUVmax and SUVmean for the gamma camera systems used were 0.99 and 1.13, respectively.Conclusions 1) Measurements taken in our study confirmed the clinical suitability of 5 parameters of image quality (Bg. cal- background calibration factor, ∆Atot- total activity deviation, COV- noise level estimation, QH- hot contrast, AM-accuracy of measurements or RC- recovery coefficient) for the validation of SPECT/CT system performance in terms of correct quantitative acquisitions of images. 2) This work shows that absolute SPECT/CT quantification is achievable in clinical nuclear medicine centers. Results variation of quantitative analyzes between centers is mainly related to the use of different reconstruction methods. 3) It is necessary to standardize the technique of measuring the SUV conversion factor obtained with different SPECT/CT scanners.
Identification and characterization of amphibian SLC26A5 using RNA-Seq
Authors: Wang Zhongying , Wang Qixuan , Wu Hao , Huang Zhiwu
Published: December 2020

Background
Prestin (SLC26A5) is responsible for acute sensitivity and frequency selectivity in the vertebrate auditory system. Due to lacking of the 3D structure, most of the mechanism of prestin is from experiments using site-directed mutagenesis or domain-swapping techniques after the amino acid residues were identified by comparing the sequence of prestin to those of its paralogs and orthologs. Frog prestin is the only representative in amphibian lineage. The knowledge of frog SLC26A5 is quite limited with only one species has been identified.
Results
Here we report a new coding sequence of SLC26A5 for a frog species, the American bullfrog (Rana catesbeiana). In our study, the SLC26A5 gene of bullfrog has been mapped, sequenced and cloned successively using RNA-SEq. The comparative study revealed an alignment with nearly 40% identity among bullfrogs and mammalian species. The predicted 3D protein structure showed that the frog prestin possessed a transmembrane domain (TM) and a STAS domain similar to the mammalian prestin. The function of prestin crucially relies on its integration into the cell membrane. Such localization was observed when a prestin-EGFP fusion protein was expressed in HEK293T cells. We measured the nonlinear capacitance (NLC) of prestin both in the hair cells of frog’s inner ear and HEK293T cells transfected with this new coding gene. We observed that HEK293T cells expressing frog prestin showed electrophysiological features similar to that of hair cells from the amphibian’s inner ear.
Conclusions
We mapped and sequenced the SLC26A5 of the American bullfrog from its inner ear cDNA using RNA-SEq. The frog SLC26A5 cDNA was 2,292 bp long, encoding a polypeptide of 763 amino acid residues, with 40% identity to mammals. After isolating the prestin gene of the frog, we generated a stable cell line transfected with this new coding gene and found it possessing similar electrophysiological features as the hair cells from the frog’s auditory organ. Our experiment demonstrated that the new coding gene could encode a functionally active protein conferring NLC to both frog HCs and the mammalian cell line.