bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosting anti-PD-1 therapy with metformin-loaded macrophage-derived microparticles
Authors: Wei Zhaohan , Zhang Xiaoqiong , Yong Tuying , Bie Nana , Zhan Guiting , Li Xin , Liang Qingle , Li Jianye , Yu Jingjing , Huang Gang , Yan Yuchen , Zhang Zelong , Zhang Bixiang , Gan Lu , Huang Bo , Yang Xiangliang
Published: January 2021

The main challenges for programmed cell death 1(PD-1)/PD-1 ligand (PD-L1) checkpoint blockade lie in a lack of sufficient T cell infiltration, tumor immunosuppressive microenvironment, and the inadequate tumor accumulation and penetration of anti-PD-1/PD-L1 antibody. Resetting tumor-associated macrophages (TAMs) is a promising strategy to enhance T-cell antitumor immunity and ameliorate tumor immunosuppression. Here, mannose-modified macrophage-derived microparticles (Man-MPs) loading metformin (Met@Man-MPs) are developed to efficiently target to M2-like TAMs to repolarize into M1-like phenotype. Met@Man-MPs-reset TAMs remodel the tumor immune microenvironment by increasing the recruitment of CD8+ T cells into tumor tissues and decreasing immunosuppressive infiltration of myeloid-derived suppressor cells and regulatory T cells. More importantly, the collagen-degrading capacity of Man-MPs contributes to the infiltration of CD8+ T cells into tumor interiors and enhances tumor accumulation and penetration of anti-PD-1 antibody. These unique features of Met@Man-MPs contribute to boost anti-PD-1 antibody therapy, improving anticancer efficacy and long-term memory immunity after combination treatment. Our results support Met@Man-MPs as a potential drug to improve tumor resistance to anti-PD-1 therapy.
A network-based framework for shape analysis enables accurate characterization of leaf epidermal cells
Authors: Nowak Jacqueline , Eng Ryan Christopher , Matz Timon , Waack Matti , Persson Staffan , Sampathkumar Arun , Nikoloski Zoran
Published: January 2021

Cell shape is crucial for the function and development of organisms. Yet, versatile frameworks for cell shape quantification, comparison, and classification remain underdeveloped. Here, we introduce a visibility graph representation of shapes that facilitates network-driven characterization and analyses across shapes encountered in different domains. Using the example of complex shape of leaf pavement cells, we show that our framework accurately quantifies cell protrusions and invaginations and provides additional functionality in comparison to the contending approaches. We further show that structural properties of the visibility graphs can be used to quantify pavement cell shape complexity and allow for classification of plants into their respective phylogenetic clades. Therefore, the visibility graphs provide a robust and unique framework to accurately quantify and classify the shape of different objects.
Low-carbon pathways for the booming express delivery sector in China
Authors: Kang Peng , Song Guanghan , Xu Ming , Miller Travis R. , Wang Haikun , Zhang Hui , Liu Gang , Zhou Ya , Ren Junshu , Zhong Ruoyu , Duan Huabo
Published: January 2021

Express delivery services are booming in both developed and emerging economies due to their low cost, convenience, and the fast growth in online shopping. The increasing environmental impacts of express delivery services and mitigation potentials, however, remain largely unexplored. Here we addressed such a gap for China, a country which is expanding online retail sales and express delivery rapidly. We found a total of 8.8 Mt of scrap packaging materials were generated by the express delivery sector in China in 2018. Its transportation-related GHG emissions surged from 0.3 Mt in 2007 to 13.7 Mt of CO2-equivalent (CO2e) in 2018, with an average of 0.27 kgCO2e per piece. Over 80% from online shopping deliveries. We predict these emissions will reach 75 MtCO2e by 2035. Nevertheless, it is possible to mitigate such GHG emissions by 102~134 MtCO2e between 2020 and 2035 if a suite of policies is adopted, including a slowdown of delivery speed, fuel system upgrades, packaging materials reduction, logistics optimization, and carbon pricing.
Preserving a robust CsPbI3 perovskite phase via pressure-directed octahedral tilt
Authors: Ke Feng , Wang Chenxu , Jia Chunjing , Wolf Nathan R. , Yan Jiejuan , Niu Shanyuan , Devereaux Thomas P. , Karunadasa Hemamala I. , Mao Wendy L. , Lin Yu
Published: January 2021

Functional CsPbI3 perovskite phases are not stable at ambient conditions and spontaneously convert to a non-perovskite δ phase, limiting their applications as solar cell materials. We demonstrate the preservation of a black CsPbI3 perovskite structure to room temperature by subjecting the δ phase to pressures of 0.1 – 0.6 GPa followed by heating and rapid cooling. Synchrotron X-ray diffraction and Raman spectroscopy indicate that this perovskite phase is consistent with orthorhombic γ-CsPbI3. Once formed, γ-CsPbI3 could be then retained after releasing pressure to ambient conditions and shows substantial stability at 35% relative humidity. First-principles density functional theory calculations indicate that compression directs the out-of-phase and in-phase tilt between the [PbI6]4− octahedra which in turn tune the energy difference between δ- and γ-CsPbI3, leading to the preservation of γ-CsPbI3. Here, we present a high-pressure strategy for manipulating the (meta)stability of halide perovskites for the synthesis of desirable phases with enhanced materials functionality.
Cataract type and pupillary response to blue and white light stimuli
Authors: Kuze Manami , Negishi Kazuno , Koyasu Toshiyuki , Kondo Mineo , Tsubota Kazuo , Ayaki Masahiko
Published: January 2021

We evaluated the pupil reaction to blue and white light stimulation in 70 eyes with cataract and in 38 eyes with a selective blue-light filtering intra-ocular lens. The diameter of the pupil before stimulation was set as baseline (BPD) and, after a stimulus duration of 1 s, the post-illumination pupillary response (PIPR) was measured using an electronic pupillometer. The BPD showed no significant difference among three grades of nuclear sclerosis (NS). In contrast, the PIPRs differed significantly among the NS grades eyes including with and without subcapsular cataract (SC) and IOL eyes for white light (p < 0.05, Kruskal–Wallis test), but not for blue light. Subcapsular opacity did not affect the BPD or PIPR in all cataract grades for either light stimulus. The tendency of larger PIPR in the pseudophakic eyes than the cataract eyes for both lights, however significant difference was found only for white light (p < 0.05 for white light, p > 0.05 for blue light). Our study demonstrates retention of the PIPR for blue light, but not for white light in cataract eyes. We also confirmed that the pupillary response in pseudohakic eyes with a selective blue light-filtering intra ocular lens was greater than that in cataractous eyes for white light.
Role of dislocation elastic field on impurity segregation in Fe-based alloys
Authors: Medouni I. , Portavoce A. , Maugis P. , Eyméoud P. , Yescas M. , Hoummada K.
Published: January 2021

Dislocation engineering in crystalline materials is essential when designing materials for a large range of applications. Segregation of additional elements at dislocations is frequently used to modify the influence of dislocations on material properties. Thus, the influence of the dislocation elastic field on impurity segregation is of major interest, as its understanding should lead to engineering solutions that improve the material properties. We report the experimental study of the elastic field influence on atomic segregation in the core and in the area surrounding edge dislocations in Fe-based alloys. Each element is found either to segregate in the edge dislocation core or to form atmospheres. The elastic field has a strong effect on the segregation atmosphere, but no effect on the dislocation core segregation. The theory is in good agreement with experiments, and should support dislocation engineering.
Potential biomarkers of childhood brain tumor identified by proteomics of cerebrospinal fluid from extraventricular drainage (EVD)
Authors: Bruschi Maurizio , Petretto Andrea , Cama Armando , Pavanello Marco , Bartolucci Martina , Morana Giovanni , Ramenghi Luca Antonio , Garré Maria Luisa , Ghiggeri Gian Marco , Panfoli Isabella , Candiano Giovanni
Published: January 2021

Brain tumors are the most common solid tumors in childhood. There is the need for biomarkers of residual disease, therapy response and recurrence. Cerebrospinal fluid (CSF) is a source of brain tumor biomarkers. We analyzed the proteome of waste CSF from extraventricular drainage (EVD) from 29 children bearing different brain tumors and 17 controls needing EVD insertion for unrelated causes. 1598 and 1526 proteins were identified by liquid chromatography-coupled tandem mass spectrometry proteomics in CSF control and brain tumor patients, respectively, 263 and 191 proteins being exclusive of either condition. Bioinformatic analysis revealed promising protein biomarkers for the discrimination between control and tumor (TATA-binding protein-associated factor 15 and S100 protein B). Moreover, Thymosin beta-4 (TMSB4X) and CD109, and 14.3.3 and HSP90 alpha could discriminate among other brain tumors and low-grade gliomas plus glyoneuronal tumors/pilocytic astrocytoma, or embryonal tumors/medulloblastoma. Biomarkers were validated by ELISA assay. Our method was able to distinguish among brain tumor vs non-tumor/hemorrhagic conditions (controls) and to differentiate two large classes of brain tumors. Further prospective studies may assess whether the biomarkers proposed by our discovery approach can be identified in other bodily fluids, therefore less invasively, and are useful to guide therapy and predict recurrences.
Differential relationships of PTSD symptom clusters with cortical thickness and grey matter volumes among women with PTSD
Authors: Crombie Kevin M. , Ross Marisa C. , Letkiewicz Allison M. , Sartin-Tarm Anneliis , Cisler Josh M.
Published: January 2021

Structural neuroimaging studies of posttraumatic stress disorder (PTSD) have typically reported reduced cortical thickness (CT) and gray matter volume (GMV) in subcortical structures and networks involved in memory retrieval, emotional processing and regulation, and fear acquisition and extinction. Although PTSD is more common in women, and interpersonal violence (IPV) exposure is a more potent risk factor for developing PTSD relative to other forms of trauma, most of the existing literature examined combat-exposed men with PTSD. Vertex-wise CT and subcortical GMV analyses were conducted to examine potential differences in a large, well-characterized sample of women with PTSD stemming from IPV-exposure (n = 99) compared to healthy trauma-free women without a diagnosis of PTSD (n = 22). Subgroup analyses were also conducted to determine whether symptom severity within specific PTSD symptom clusters (e.g., re-experiencing, active avoidance, hyperarousal) predict CT and GMV after controlling for comorbid depression and anxiety. Results indicated that a diagnosis of PTSD in women with IPV-exposure did not significantly predict differences in CT across the cortex or GMV in the amygdala or hippocampus compared to healthy controls. However, within the PTSD group, greater re-experiencing symptom severity was associated with decreased CT in the left inferior and middle temporal gyrus, and decreased CT in the right parahippocampal and medial temporal gyrus. In contrast, greater active avoidance symptom severity was associated with greater CT in the left lateral fissure, postcentral gyrus, and middle/lateral occipital cortex, and greater CT in the right paracentral, posterior cingulate, and superior occipital gyrus. In terms of GMV, greater hyperarousal symptom severity was associated with reduced left amygdala GMV, while greater active avoidance symptom severity was associated with greater right amygdala GMV. These findings suggest that structural brain alterations among women with IPV-related PTSD may be driven by symptom severity within specific symptom clusters and that PTSD symptom clusters may have a differential (increased or decreased) association with brain structures.
Blood-based protein profiling identifies serum protein c-KIT as a novel biomarker for hypertrophic cardiomyopathy
Authors: Sonnenschein Kristina , Fiedler Jan , de Gonzalo-Calvo David , Xiao Ke , Pfanne Angelika , Just Annette , Zwadlo Carolin , Soltani Samira , Bavendiek Udo , Kraft Theresia , Dos Remedios Cristobal , Cebotari Serghei , Bauersachs Johann , Thum Thomas
Published: January 2021

Hypertrophic cardiomyopathy (HCM) is one of the most common hereditary heart diseases and can be classified into an obstructive (HOCM) and non-obstructive (HNCM) form. Major characteristics for HCM are the hypertrophy of cardiomyocytes and development of cardiac fibrosis. Patients with HCM have a higher risk for sudden cardiac death compared to a healthy population. In the present study, we investigated the abundancy of selected proteins as potential biomarkers in patients with HCM. We included 60 patients with HCM and 28 healthy controls and quantitatively measured the rate of a set of 92 proteins already known to be associated with cardiometabolic processes via protein screening using the proximity extension assay technology in a subgroup of these patients (20 HCM and 10 healthy controls). After validation of four hits in the whole cohort of patients consisting of 88 individuals (60 HCM patients, 28 healthy controls) we found only one candidate, c-KIT, which was regulated significantly different between HCM patients and healthy controls and thus was chosen for further analyses. c-KIT is a tyrosine-protein kinase acting as receptor for the stem cell factor and activating several pathways essential for cell proliferation and survival, hematopoiesis, gametogenesis and melanogenesis. Serum protein levels of c-KIT were significantly lower in patients with HCM than in healthy controls, even after adjusting for confounding factors age and sex. In addition, c-KIT levels in human cardiac tissue of patients with HOCM were significant higher compared to controls indicating high levels of c-KIT in fibrotic myocardium. Furthermore, c-KIT concentration in serum significantly correlated with left ventricular end-diastolic diameter in HOCM, but not HCM patients. The present data suggest c-KIT as a novel biomarker differentiating between patients with HCM and healthy population and might provide further functional insights into fibrosis-related processes of HOCM.
Classification and prediction of protein–protein interaction interface using machine learning algorithm
Authors: Das Subhrangshu , Chakrabarti Saikat
Published: January 2021

Structural insight of the protein–protein interaction (PPI) interface can provide knowledge about the kinetics, thermodynamics and molecular functions of the complex while elucidating its role in diseases and further enabling it as a potential therapeutic target. However, owing to experimental lag in solving protein–protein complex structures, three-dimensional (3D) knowledge of the PPI interfaces can be gained via computational approaches like molecular docking and post-docking analyses. Despite development of numerous docking tools and techniques, success in identification of native like interfaces based on docking score functions is limited. Hence, we employed an in-depth investigation of the structural features of the interface that might successfully delineate native complexes from non-native ones. We identify interface properties, which show statistically significant difference between native and non-native interfaces belonging to homo and hetero, protein–protein complexes. Utilizing these properties, a support vector machine (SVM) based classification scheme has been implemented to differentiate native and non-native like complexes generated using docking decoys. Benchmarking and comparative analyses suggest very good performance of our SVM classifiers. Further, protein interactions, which are proven via experimental findings but not resolved structurally, were subjected to this approach where 3D-models of the complexes were generated and most likely interfaces were predicted. A web server calledProteinComplexPrediction byInterfaceProperties (PCPIP) is developed to predict whether interface of a given protein–protein dimer complex resembles known protein interfaces. The server is freely available athttp://www.hpppi.iicb.res.in/pcpip/.
Impact of immune checkpoint gene CD155 Ala67Thr and CD226 Gly307Ser polymorphisms on small cell lung cancer clinical outcome
Authors: Lee Jang Hyuck , Yoo Seung Soo , Hong Mi Jeong , Choi Jin Eun , Kim Soyoun , Kang Hyo-Gyoung , Do Sook Kyung , Kim Ji Hyun , Baek Sun Ah , Lee Won Kee , Do Yoo Jae , Choi Sun Ha , Lee Yong Hoon , Seo Hyewon , Lee Jaehee , Lee Shin Yup , Cha Seung Ick , Kim Chang Ho , Park Jae Yong
Published: January 2021

This study was conducted to investigate the impact of genetic variants of immune checkpoint genes on the treatment outcome in small cell lung cancer (SCLC). In the present study, 261 platinum doublet-treated SCLC patients were enrolled. A total of 96 polymorphisms in 33 immune checkpoint-related genes were selected, and their association with chemotherapy response and survival outcomes were analyzed. Among the polymorphisms studied, CD155 rs1058402G > A (Ala67Thr, A67T) and CD226 rs763361C > T (Gly307Ser, G307S) were significantly associated with SCLC treatment outcome. The rs1058402G > A had a worse chemotherapy response and overall survival (under a dominant model, adjusted odds ratio [aOR] = 0.52, 95% confidence interval [CI] = 0.27–0.99, P = 0.05; adjusted hazard ratio [aHR] = 1.55, 95% CI = 1.12–2.14, P = 0.01, respectively). The rs763361C > T had better chemotherapy response and overall survival (under a dominant model, aOR = 2.03, 95% CI = 1.10–3.75, P = 0.02; aHR = 0.69, 95% CI = 0.51–0.94, P = 0.02, respectively). When the rs1058402GA/AA and rs763361CC genotypes were combined, the chemotherapy response and overall survival were significantly decreased as the number of bad genotypes increased (aOR = 0.52, 95% CI = 0.33–0.81, Ptrend = 0.004; aHR = 1.48, 95% CI = 1.19–1.84, Ptrend = 4 × 10−4, respectively). The 3-D structural model showed that CD155 A67T created a new hydrogen bond and structural change on CD155. These changes resulted in extending the distance and losing the hydrogen bonds between CD155 and CD226, thus weakening CD155/CD226 binding activity. In conclusion, CD155 rs1058402G > A and CD226 rs763361C > T may be useful for predicting the clinical outcomes of SCLC patients after chemotherapy.
A comparative study of evaluating missing value imputation methods in label-free proteomics
Authors: Jin Liang , Bi Yingtao , Hu Chenqi , Qu Jun , Shen Shichen , Wang Xue , Tian Yu
Published: January 2021

The presence of missing values (MVs) in label-free quantitative proteomics greatly reduces the completeness of data. Imputation has been widely utilized to handle MVs, and selection of the proper method is critical for the accuracy and reliability of imputation. Here we present a comparative study that evaluates the performance of seven popular imputation methods with a large-scale benchmark dataset and an immune cell dataset. Simulated MVs were incorporated into the complete part of each dataset with different combinations of MV rates and missing not at random (MNAR) rates. Normalized root mean square error (NRMSE) was applied to evaluate the accuracy of protein abundances and intergroup protein ratios after imputation. Detection of true positives (TPs) and false altered-protein discovery rate (FADR) between groups were also compared using the benchmark dataset. Furthermore, the accuracy of handling real MVs was assessed by comparing enriched pathways and signature genes of cell activation after imputing the immune cell dataset. We observed that the accuracy of imputation is primarily affected by the MNAR rate rather than the MV rate, and downstream analysis can be largely impacted by the selection of imputation methods. A random forest-based imputation method consistently outperformed other popular methods by achieving the lowest NRMSE, high amount of TPs with the average FADR < 5%, and the best detection of relevant pathways and signature genes, highlighting it as the most suitable method for label-free proteomics.
Field performance on grain yield and quality and genetic diversity of overwintering cultivated rice (Oryza sativa L.) in southwest China
Authors: Liang Yongshu , Nan Wenbin , Qin Xiaojian , Zhang Hanma
Published: January 2021

Understanding the field performance on grain yield and quality and the genetic diversity of overwintering (OW) cultivated rice (Oryza sativa L.) across main crop (MC) and ratooning crop (RC) is the premise to make strategies for the future OW rice variety improvement in rice production. The present field experiments were conducted in RC of 2016, in MC of both 2017 and 2018, and RC in 2019 to identify genotypes OW rice that perform stable in terms of grain yield and quality across different climate conditions. The grain yield plant-1 (GYP) and its components in six genotypes of OW rice exhibited significant difference across the 4 years (P ≤ 0.05), the maximum GYP in OW6 rice was harvested (60.28 g) in MC of 2017, but the minimum GYP in OW1 rice was harvested (33.01 g) in MC of 2018. Within six genotypes of OW rice, four grain shape traits displayed a relative small significant difference, four grain quality traits exhibited a relative small significant difference except for chalkiness rate (CR), there 226 pairs of significant PCC values between GYP and its components were calculated in all tested rice and varied from six in OW6 to eleven in OW1, there 130 pairs of significant PCC values among the four grain shape traits were calculated and ranged from twenty-one in OW1, 3, 5 to twenty-three in OW2, there 118 pairs of significant PCC values among the four grain quality traits were calculated and ranged from seventeen in OW2 to twenty-three in OW1. The numbers, directions, and size of PCC values for the grain yield and quality characters in all tested rice displayed a series of irregular variations. Six genotypes of OW rice were apparently distinguished by employing 196 pairs of simple-sequence repeats (SSRs) markers and exhibited abundant genetic diversity at the DNA level. Data from this study provide an extensive archive for the future exploration and innovation of overwintering cultivated rice variety.
The poor prognosis and influencing factors of high D-dimer levels for COVID-19 patients
Authors: He Xiaokang , Yao Fei , Chen Jie , Wang Yan , Fang Xiangming , Lin Xuan , Long Hui , Wang Qiang , Wu Qingming
Published: January 2021

To explore the value, and influencing factors, of D-dimer on the prognosis of patients with COVID-19. A total of 1,114 patients with confirmed COVID-19 who were admitted to three designated COVID-19 hospitals in Wuhan, China from January 18, 2020, to March 24, 2020, were included in this study. We examined the relationship between peripheral blood levels of D-dimer, and clinical classification and prognosis, as well as its related influencing factors. D-dimer levels were found to be related to the clinical classification and the prognosis of clinical outcome. D-dimer levels were more likely to be abnormal in severely and critically ill patients compared with mild and ordinary cases, while D-dimer levels of patients who had died were significantly higher than those of surviving patients according to the results of the first and last lab tests. The results from ROC analyses for mortality risk showed that the AUCs of D-dimer were 0.909, YI was 0.765 at the last lab test, and a D-dimer value of 2.025 mg/L was regarded to be the optimal probability cutoff for a prognosis of death. In addition, we found that patients with advanced age, male gender, dyspnea symptoms, and some underlying diseases have a higher D-dimer value (p < 0.05). In short, D-dimer is related to the clinical classification and can be used to evaluate the prognosis of COVID-19 patients. The D-dimer value of 2.025 mg/L was the optimal probability cutoff for judging an outcome of death. Advanced age, male gender, dyspnea symptoms, and some underlying diseases are influencing factors for D-dimer levels, which impacts the prognosis of patients.
Weighted gene co-expression network analysis identifies molecular pathways and hub genes involved in broiler White Striping and Wooden Breast myopathies
Authors: Bordini Martina , Zappaterra Martina , Soglia Francesca , Petracci Massimiliano , Davoli Roberta
Published: January 2021

In recent years, the poultry industry has experienced an increased incidence of myopathies affecting breasts of fast-growing broilers, such as White Striping (WS) and Wooden Breast (WB) defects. To explore the molecular mechanisms and genes involved in WS and WB onset, we decided to perform a Weighted Gene Co-expression Network Analysis (WGCNA) using the gene expression profile and meat quality parameters of Pectoralis major muscles analysed in our previous study. Among the 212 modules identified by WGCNA, the red, darkred, midnightblue and paleturquoise4 modules were chosen for subsequent analysis. Functional analysis evidenced pathways involved in extracellular matrix (ECM) organization, collagen metabolism, cellular signaling and unfolded protein response. The hub gene analysis showed several genes coding for ECM components as the most interconnected nodes in the gene network (e.g. COL4A1, COL4A2, LAMA2, LAMA4, FBLN5 and FBN1). In this regard, this study suggests that alterations in ECM composition could somehow activate the cascade of biological reactions that result in the growth-related myopathies onset, and the involvement of Collagen IV alterations in activating the endoplasmic reticulum (ER) stress response may be hypothesized. Therefore, our findings provide further and innovative knowledge concerning the molecular mechanisms related to the breast abnormalities occurrence in modern broilers.
Serum immunoglobulin free light chains and their association with clinical phenotypes, serology and activity in patients with IgG4-related disease
Authors: Martín-Nares Eduardo , Saavedra-González Vanessa , Fagundo-Sierra Reynerio , Santinelli-Núñez Blanca Estela , Romero-Maceda Teresa , Calderón-Vasquez Karla , Hernandez-Molina Gabriela
Published: January 2021

The clinical utility of serum immunoglobulin free light chains (sFLC) in IgG4-related disease (IgG4-RD) is unknown. Herein we evaluated their association with clinical phenotypes, serology and activity in patients with IgG4-RD. Cross-sectional study that included 45 patients with IgG4-RD, and as controls 25 with Sjögren’s syndrome (SS) and 15 with sarcoidosis. IgG4-RD patients were classified in clinical phenotypes: pancreato-hepato-biliary, retroperitoneum/aorta, head/neck-limited and Mikulicz/systemic; as well as proliferative vs. fibrotic phenotypes. We assessed the IgG4-RD Responder Index (IgG4-RD RI) at recruitment and measured IgG1, IgG4, κ and λ sFLC serum levels by turbidometry. sFLC levels were similar among IgG4-RD, SS and sarcoidosis groups. Regarding the IgG4-RD patients, the mean age was 49 years, 24 (53.3%) were men and 55.5% had activity. Eight (17.7%) belonged to pancreato-hepato-biliary, 6 (13.3%) to retroperitoneum/aorta, 14 (31.1%) to head/neck-limited, 16 (35.5%) to Mikulicz/systemic phenotypes, whereas 36 (80%) to proliferative and 9 (20%) to fibrotic phenotypes. High κ sFLC, λ sFLC and κ/λ ratio were present in 29 (64.4%), 13 (28.9%) and 13 (28.9%) of IgG4-RD patients, respectively. There were no differences in sFLC among IgG4-RD phenotypes. κ sFLC and κ/λ ratio correlated positively with the number of involved organs and IgG4-RD RI. Patients with renal involvement had higher κ sFLC and λ sFLC. The AUC for κ sFLC and λ sFLC, for renal involvement was 0.78 and 0.72, respectively. Active IgG4-RD had higher levels of κ sFLC and more frequently a high κ/λ ratio. The AUC for κ sFLC and κ/λ ratio for predicting active IgG4-RD was 0.67 and 0.70, respectively. sFLC correlated positively with IgG1 and IgG4 levels. sFLC may be useful as a biomarker of disease activity as well as multiorgan and renal involvement. In particular, a high κ/λ ratio may identify patients with active disease.
Preoperative CT-based detection of extrapancreatic perineural invasion in pancreatic cancer
Authors: Khristenko Ekaterina , Shrainer Igor , Setdikova Galia , Palkina Oxana , Sinitsyn Valentin , Lyadov Vladimir
Published: January 2021

Accuracy for computed tomography (CT) diagnosis of extrapancreatic perineural invasion (EPNI) in pancreatic ductal adenocarcinoma (PDAC), which is a significant cause of recurrence, has not been established. The aim of the study was to evaluate the diagnostic accuracy of CT in detecting EPNI preoperatively in resectable PDAC of the pancreatic head. Retrospective study design was approved by institutional review board. Preoperative CT-series of 46 patients with resectable PDAC were evaluated by two independent observers. Plexus Pancreaticus Capitalis-II (PPC-II) was assessed as this area is more susceptible for EPNI. All patients underwent surgery with dedicated histopathology, which served as the reference standard. Histologically EPNI was confirmed in 63.1%. Sensitivity of MDCT was 93.1% (95% confidence interval (CI) 77.23% to 99.15%), specificity 64.7% (95% CI 38.33% to 85.79%) with area under the curve (AUC) 0.789 for the first observer. Positive predictive value (PPV) was 81.82% (95% CI 70.12% to 89.62%), negative predictive value (NPV—84.62% (95% CI 57.98% to 95.64%) with diagnostic accuracy of 82.61% (95% CI 68.58% to 92.18%). Interobserver agreement showed k-value of 0.893 ($${p} < 0.001$$

p
<
0.001

), which represents very good agreement between observers. Median actual survival in patients without EPNI was 30 months (95% CI 18.284–41.716), in patients with EPNI—13 months (95% CI 12.115–13.885). CT provides sufficient diagnostic information to detect PPC-II invasion in patients with resectable PDAC of the pancreatic head. Preoperative detection of EPNI might be an additional argument to perform neoadjuvant chemotherapy in patients with resectable PDAC. It should be included in preoperative evaluation form of CT-findings.
Identifying threshold sizes for enlarged abdominal lymph nodes in different age ranges from about 200,000 individual’s data
Authors: He Lili , Sun Yinghua , Huang Guoying
Published: January 2021

The threshold size for enlarged abdominal lymph nodes (E-ALNs), a common pediatric disorder, has yet to be standardized. According to the maximum short-axis diameter, this study divided ALNs into Grade A (≥ 10 mm), Grade B (8–10 mm), Grade C (5–8 mm), and Grade D (< 5 mm, normal). To identify the threshold size for E-ALNs, the prevalence of each grade was compared between asymptomatic individuals and symptomatic (e.g., abdominal pain) individuals without other diseases (e.g., appendicitis) that could explain the symptoms for different ages using data from > 200,000 individuals. The results showed the following: (1) For ages 1–3 years, the recommended threshold size is 8 mm, as the differences in the prevalence between the two groups were nonsignificant for Grade C but significant (p < 0.05) for both Grades A and B. (2) For ages 3–14 years, the recommended threshold size is 5 mm, as the differences between the two groups were significant (p < 0.05) for Grades A, B, and C. (3) The prevalence of Grades A, B, and C was very low for ages 0–1 years and high for ages 1–6 years. (4) The prevalence for males was generally higher than that for females for Grades A and B.
White matter integrity in young medication-naïve bipolar II depressed adults
Authors: Mak Arthur Dun Ping , Leung Owen Ngo Wang , Chou Idy Wing Yi , Wong Sheila Lok Yiu , Chu Winnie Chiu-wing , Yeung David , So Suzanne Ho-wai , Ma Suk Ling , Lam Linda Chiu Wah , Leung Chi Ming , Lee Sing
Published: January 2021

It is unknown if young medication-naïve bipolar II (BPII) depressed patients have increased white matter (WM) disruptions. 27 each of young (average 23 years) and treatment-naïve BPII depressed, unipolar depressed (UD) patients and age–sex–education matched healthy controls (HC) underwent 3 T MRIs with diffusion tensor imaging. Diagnostic ratings included Structured Clinical Interview for DSM Disorders (SCID), Montgomery-Åsberg Depression Rating Scale (MADRS), Young Mania Rating Scale (YMRS) and Hamilton Anxiety Rating Scale (HAM-A). Patients were clinically depressed (MADRS-BPII: 26.15 [SD9.25], UD: 25.56 [5.24], p = 0.86). Compared to UD, BPII had increased family bipolarity (BPII 13.6% vs UD 2.5%, p = 0.01, φc = 0.28), hypomanic symptoms (YMRS-BPII: 4.22 [4.24], UD: 1.33 [2], p = 0.02, d = 0.87), lifetime number of depressive episodes (BPII: 2.37 [1.23], UD: 1.44 [0.75], p = 0.02, d = 0.91), lifetime and current-year number of episodes (lifetime BPII: 50.85 [95.47], UD: 1.7 [1.03]; current-year BPII: 9.93 [16.29], UD: 1.11 [0.32], ps = 0.04, ds = 0.73–0.77) and longer illness duration (BPII: 4.96 years [3.96], UD: 2.99 [3.33], p = 0.15, d = 0.54). BPII showed no increased WM disruptions vs UD or HC in any of the 15 a priori WM tracts. UD had lower right superior longitudinal fasciculus (SLF) (temporal) axial diffusivity (AD) (1.14 vs 1.17 (BPII), 1.16 (HC); F = 6.93, 95% CI of$${F}_{B}$$

F
B

: 0.00073, 5.22, ηp2 = 0.15). Principal component analysis followed by exploratory linear discriminant analysis showed that increased R-SLF (temporal) AD, YMRS and family bipolarity distinguished BPII from UD (81.5% sensitivity, 85.2% specificity) independent of episode number and frequency. Young, medication-naïve adults with BPII depression did not show the WM disruptions distinguishing more chronically ill BP patients from UD. These WM disruptions may therefore be partly attributable to illness chronicity. Longitudinal studies should examine the trajectory of WM changes in BPII and UD and predictive validity of these baseline clinical and imaging parameters.
A novel and sensitive real-time PCR system for universal detection of poxviruses
Authors: Luciani Léa , Inchauste Lucia , Ferraris Olivier , Charrel Rémi , Nougairède Antoine , Piorkowski Géraldine , Peyrefitte Christophe , Bertagnoli Stéphane , de Lamballerie Xavier , Priet Stéphane
Published: January 2021

Success in smallpox eradication was enabled by the absence of non-human reservoir for smallpox virus. However, other poxviruses with a wider host spectrum can infect humans and represent a potential health threat to humans, highlighted by a progressively increasing number of infections by (re)emerging poxviruses, requiring new improved diagnostic and epidemiological tools. We describe here a real-time PCR assay targeting a highly conserved region of the poxvirus genome, thus allowing a pan-Poxvirus detection (Chordopoxvirinae and Entomopoxvirinae). This system is specific (99.8% for vertebrate samples and 99.7% for arthropods samples), sensitive (100% for vertebrate samples and 86.3% for arthropods samples) and presents low limit of detection (< 1000 DNA copies/reaction). In addition, this system could be also valuable for virus discovery and epidemiological projects.
Integrin α2β1 plays an important role in the interaction between human articular cartilage-derived chondrocytes and atelocollagen gel
Authors: Kanamoto Takashi , Hikida Minami , Sato Seira , Oyama Shohei , Tachi Yoshihito , Kuroda Sanae , Mazuka Takeo , Ebina Kosuke , Nakai Tsuyoshi , Nakata Ken
Published: January 2021

Although atelocollagen gel is used as a scaffold for culturing human articular cartilage-derived chondrocytes, little is known about cell–gel interactions. In this study, we investigated the mechanism via which atelocollagen gel affects human articular cartilage-derived chondrocytes. Two types of three-dimensional cultures of human articular cartilage-derived chondrocytes (i.e., with and without atelocollagen gel) were compared. While the amount of atelocollagen gel in culture gradually decreased with time, it promoted the expression of matrix metalloproteinases (MMPs) during the early stages of culture. Genome-wide differential gene expression analysis revealed that cell membrane- and extracellular matrix-related genes were highly ranked among up- and down-regulated groups in cells cultured in the presence of atelocollagen gel. Among the integrin family of genes, the expression of integrin subunit alpha 2 and integrin subunit alpha 10 was significantly increased in the presence of atelocollagen gel. Blocking α2β1 integrin with the specific inhibitor BTT 3033 had a significant effect on cell proliferation, MMP expression, and cell shape, as well as on the response to mechanical stimulation. Taken together, our findings indicate that the α2β1 integrin pathway plays an important role in the interaction of atelocollagen gel with human articular cartilage-derived chondrocytes and may be a potential therapeutic target for articular cartilage disorders.
Decreased serum betatrophin may correlate with the improvement of obstructive sleep apnea after Roux-en-Y Gastric Bypass surgery
Authors: Song Zhiyuan , Guo Kaifeng , Huang Weijun , Xu Huajun , Liu Yupu , Guan Jian , Yin Shankai , Yu Haoyong , Yi Hongliang , Zou Jianyin
Published: January 2021

Obesity is strongly correlated with obstructive sleep apnea (OSA), and bariatric surgery can effectively treat obesity and alleviate OSA. However, the contributing factors are still unclear. We aimed to explore the relationship between betatrophin and OSA in patients undergoing Roux-en-Y gastric bypass (RYGB) surgery. Our study consisted of thirty-seven individuals with OSA and type 2 diabetes (16 males, 21 females) undergoing RYGB surgery. The polysomnography test, anthropometric results, serum betatrophin, and abdominal magnetic resonance images were evaluated both before and 1 year after RYGB surgery. Factors that may correlate with the alleviation of OSA were investigated. In our study, RYGB surgery significantly decreased apnea hypopnea index (AHI) and serum betatrophin concentration (p < 0.001). The abdominal visceral fat area, subcutaneous fat area and HOMA-IR were also significantly decreased (p < 0.001). The preoperative AHI, postoperative AHI and the change in AHI were significantly correlated with the preoperative betatrophin, postoperative betatrophin and the change in betatrophin, respectively (p < 0.05). These correlations were still significant after adjustment for other risk factors. The change in betatrophin was also independently associated with the change in minimum oxygen saturation (p < 0.001). Our data might indicate that serum betatrophin was significantly independently correlated with the improvement of OSA after bariatric surgery.
A cross-sectional study of ocular surface discomfort and corneal nerve dysfunction after paclitaxel treatment for cancer
Authors: Chiang Jeremy Chung Bo , Goldstein David , Trinh Terry , Au Kimberley , Park Susanna B. , Krishnan Arun V. , Markoulli Maria
Published: January 2021

Ocular surface dysfunction is common in patients receiving anti-cancer drug treatment. The effects of paclitaxel, a neurotoxic chemotherapeutic drug, on ocular surface discomfort associated with dry eye disease was investigated. Patients with cancer who had completed paclitaxel treatment between 3 and 24 months prior to assessment (n = 29) and age- and sex-matched healthy control subjects (n = 29) were recruited and assessed with the Ocular Surface Disease Index (OSDI) to measure ocular surface discomfort. In-vivo corneal confocal microscopy was used to evaluate corneal nerve parameters in the right eye. Peripheral neurotoxicity was assessed using patient-reported outcomes and clinical grading scales. The paclitaxel group had significantly worse OSDI total scores compared with controls (Median, Md = 19.3 and Md = 0, p = 0.007, respectively). Corneal nerve fiber and inferior whorl lengths were reduced in the paclitaxel group compared with controls (14.2 ± 4.0 and 14.4 ± 4.0 mm/mm2 vs. 16.4 ± 4.0 and 16.9 ± 4.9 mm/mm2, respectively, p = 0.04). When analyzed by presence of peripheral neuropathy, paclitaxel-treated patients with neuropathy showed worse OSDI total scores compared to those without peripheral neuropathy post-treatment (p = 0.001) and healthy controls (p < 0.001). More severe ocular discomfort and worse visual function was associated with greater peripheral neurotoxicity symptoms (r = 0.60, p = 0.001) and neuropathy severity (r = 0.49, p = 0.008), respectively. Patients who have been treated with paclitaxel have a higher risk of ocular surface discomfort associated with dry eye disease, particularly those with peripheral neuropathy. Future longitudinal studies should investigate the clinical impact of corneal nerve reduction in dry eye disease.
Magnetic flux noise in superconducting qubits and the gap states continuum
Authors: Szczęśniak Dominik , Kais Sabre
Published: January 2021

In the present study we investigate the selected local aspects of the metal-induced gap states (MIGSs) at the disordered metal–insulator interface, that were previously proposed to produce magnetic moments responsible for the magnetic flux noise in some of the superconducting qubit modalities. Our analysis attempts to supplement the available studies and provide new theoretical contribution toward their validation. In particular, we explicitly discuss the behavior of the MIGSs in the momentum space as a function of the onsite energy deviation, that mimics random potential disorder at the interface in the local approximation. It is found, that when the difference between the characteristic electronic potentials in the insulator increases, the corresponding MIGSs become more localized. This effect is associated with the increasing degree of the potential disorder that was earlier observed to produce highly localized MIGSs in the superconducting qubits. At the same time, the presented findings show that the disorder-induced localization of the MIGSs can be related directly to the decay characteristics of these states as well as to the bulk electronic properties of the insulator. As a result, our study reinforces plausibility of the previous corresponding investigations on the origin of the flux noise, but also allows to draw future directions toward their better verification.
Identification of potential key genes and pathways associated with the Pashmina fiber initiation using RNA-Seq and integrated bioinformatics analysis
Authors: Bhat Basharat , Yaseen Mifftha , Singh Ashutosh , Ahmad Syed Mudasir , Ganai Nazir A.
Published: January 2021

Pashmina goat (Capra hircus) is an economically important livestock species, which habitats the cold arid desert of the Ladakh region (India), and produces a princely animal fiber called Pashmina. The Pashmina goat has a double coat fleece as an adaptation to the very harsh cold winters the outer long coarse hair (guard hair) produced from primary hair follicles and the inner fine Pashmina fiber produced from secondary hair follicles. Pashmina fiber undergoes a circannual and synchronized growth cycle. In the present study, we analyzed transcriptome profiles from 10 different Pashmina goats during anagen and telogen to delineate genes and signaling pathways regulating active (anagen) and regressive (telogen) phases of the follicle growth. During anagen, 150 genes were expressed at significantly higher levels with log (FC) > 2 and padj < 0.05. The RNA seq results were subjected to qRT-PCR validation. Among the nine genes selected, the expression of HAS1, TRIB2, P2RX1. PRG4, CNR2, and MMP25 were significantly higher (p < 0.05) in the anagen phase, whereas MC4R, GIPC2, and CDO1 were significantly expressed (p < 0.05) in the telogen phase which supports and validates the gene expression pattern from the RNA-sequencing. Differentially expressed genes revealed that Pashmina fiber initiation is largely controlled by signaling pathways like Wnt, NF-Kappa, JAK-STAT, Hippo, MAPK, Calcium, and PI3K-Akt. Expression of genes from the Integrin family, Cell adhesion molecules, and ECM-receptors were observed to be at much higher levels during anagen. We identified key genes (IL36RN, IGF2, ITGAV, ITGA5, ITCCR7, CXCL5, C3, CCL19, and CXCR3) and a collagen cluster which might be tightly correlated with anagen-induction. The regulatory network suggests the potential role of RUNX3, NR2F1/2, and GATA family transcription factors in anagen-initiation and maintaining fiber quality in Pashmina goats.
Drosophila Hox genes induce melanized pseudo-tumors when misexpressed in hemocytes
Authors: Ponrathnam Titus , Saini Ravina , Banu Sofia , Mishra Rakesh K.
Published: January 2021

Hox genes are early determinants of cell identity along the anterior–posterior body axis across bilaterians. Several late non-homeotic functions of Hox genes have emerged in a variety of processes involved in organogenesis in several organisms, including mammals. Several studies have reported the misexpression of Hox genes in a variety of malignancies including acute myeloid leukemia. The Hox genes Dfd, Ubx, abd-A and Abd-B were overexpressed via the UAS-Gal4 system using Cg-Gal4, Lsp2-Gal4, He-Gal4 and HmlD3-Gal4 as specific drivers. Genetic interaction was tested by bringing overexpression lines in heterozygous mutant backgrounds of Polycomb and trithorax group factors. Larvae were visually scored for melanized bodies. Circulating hemocytes were quantified and tested for differentiation. Pupal lethality was assessed. Expression of Dfd, Ubx and abd-A, but not Abd-B in the hematopoietic compartment of Drosophila led to the appearance of circulating melanized bodies, an increase in cell number, cell-autonomous proliferation, and differentiation of hemocytes. Pupal lethality and melanized pseudo-tumors were suppressed in Psc1 and esc2 backgrounds while polycomb group member mutations Pc1 and Su(z)123 and trithorax group member mutation TrlR85 enhanced the phenotype. Dfd, Ubx and abd-A are leukemogenic. Mutations in Polycomb and trithorax group members modulate the leukemogenic phenotype. Our RNAseq of Cg-Gal4 > UAS-abd-A hemocytes may contain genes important to Hox gene induced leukemias.
NCAA Division I American football players with sickle cell trait have altered hematological responses and hydration status
Authors: Wang Haoyan , Martone Matt , Owens Michael E. , Lemoine Nathan P. , Marucci Jack , Calvert Derek , Mullenix Shelly , Church Timothy S. , Rood Jennifer , Harrell Brian , Irving Brian A. , Spielmann Guillaume , Johannsen Neil M.
Published: January 2021

Sickle cell trait (SCT) is a risk factor of collapse and sudden death in athletes. We conducted a longitudinal study to determine the hematological responses and hydration status in NCAA Division I American football players with SCT. The study took place over 2 years with 6 SCT and 6 position-matched controls (CON) in year 1; and 4 SCT and 4 CON in year 2. In year 2, three of the four SCT players were recruited and re-enrolled with new position-matched controls (total sample data = 10 SCT and 10 CON). Blood samples were taken at three visits: pre-camp, post-camp, and post-season to examine hemoglobin variants, complete blood counts, and chemistry panel 26. Hydration status was assessed by measuring body weight change, urine specific gravity, and urine and sweat electrolyte concentrations during the pre-season training camp. All SCT players were confirmed to have SCT (HbS = 37.9 ± 2.4%) and had greater red cell distribution width (RDW) compared to CON across all visits. Serum uric acid was higher in SCT (7.3 ± 1.0 mg/dL) compared to CON (6.1 ± 0.6 mg/dL; p = 0.001). Furthermore, serum creatine kinase levels were greater in SCT (1617.0 ± 1034.8 IU/L) at pre-camp compared to CON (1037.4 ± 602.8 IU/L; p = 0.03). SCT players exhibited lower pre- and post-practice urine electrolytes and urine specific gravity (SCT pre: 1.019 ± 0.005 vs. CON pre: 1.026 ± 0.008 p < 0.001; SCT post: 1.020 ± 0.005 vs. CON post: 1.030 ± 0.008 p < 0.01), whereas sweat sodium concentrations were higher in SCT players (55.4 ± 13.6 mmol/L) compared to CON (45.5 ± 10.6 mmol/L; p < 0.001). Given the evidence, greater uric acid and CPK levels in SCT players compared to CON may be an early indicator of altered kidney function and muscle damage, which could be added into NCAA guidelines for surveillance among SCT players. Consistent education and reinforcement of the importance of adequate fluid balance during exercise are critical for both SCT and CON players.