bluuebunny/crossref_metadata_2025 huggingface dataset:
Machine Learning-based Binarization Technique of Hand-drawn Floor Plans
Authors: Suh Hanew , Kim Hyunjung , Yu Kiyun
Published: September 2022

Purpose: In this study, we propose a two-step binarization method for hand-drawn architectural floor plans to transform them into usable formats for indoor spatial modeling.Methods: First, a Gaussian mixture modeling was adopted to remove texture-like noise from the background. Second, 24 features were extracted to train the random forest model and the remaining line or spot-like noise was removed from the image. Moreover, the proposed method was applied to a completely different architectural drawing set to evaluate its generalization performance.Results: The experimental results indicated that the proposed method outperformed the other binarization techniques. Moreover, binarization result was outperforming with 0.987 F1-score. Conclusion: The experimental results showed that the overall performance of the proposed method was significantly superior to that of the other binarization methods. Moreover, they indicated that the proposed method is applicable to different types of architectural drawing, thereby proving its generalization.
Clinicopathologic features and prognosis of gastrointestinal stromal tumors: A retrospective study
Authors: shen lulu , Zhang Xin , Jia Yi , Geng Xiaoxin , Li Decheng , Peng Xiao , Li Jiawen , Zan Likun
Published: September 2022

ObjectiveGastrointestinal stromal tumors (GISTs) are rare but are the most common mesenchymal tumors of the digestive tract. GISTs represent a spectrum of tumors characterized by variable behaviors and activating mutations in KIT proto-oncogene, receptor tyrosine kinase (KIT) or platelet derived growth factor receptor α (PDGFRA) genes. This study aimed to analyze the histological and molecular characteristics of GISTs and the clinicopathologic features associated with its prognosis.MethodsWe retrospectively analyzed clinical, pathological and prognostic data for 941 patients who underwent GIST surgery at our hospital from 2010 to 2020. Influencing factors associated with GIST gene mutations and clinicopathological features related to patient prognosis were evaluated. The Kaplan-Meier method was used for survival analysis.ResultsGISTs were found to be more common in women than in men, to occur at an older age, and were located mainly in the stomach. GISTs were generally small in size, had a low mitotic index and were more often rated as very low risk/low risk. Immunohistochemistry showed that 96.7% and 98.4% of tumors were positive for CD117 and DOG-1. KIT and PDGFRA mutations were identified in 113 (76.4%) and 4 (4.0%) cases, respectively. Survival analysis showed GIST patient prognosis to be related to sex, age, tumor site, tumor size, mitotic count and the combined with other tumors. Patients with exon 11 mutation in KIT had a better prognosis than those with exon 9 mutation in KIT. Relapse or metastasis occurred in 39 patients during the follow-up period. Most relapsed or metastatic GISTs had concordant pathological and mutational characteristics with the primary tumor; they carried an identical KIT/PDGFRA mutation, and the mitotic index was usually high. But 4 metastatic GISTs carried a different KIT mutation compared to the promary tumor. Furthermore, coexistence of double mutations in KIT was observed in five tumors, with worse prognostic features.ConclusionsClinicopathological features( sex, age, site, tumor size, mitotic count, and the coexisting with other types of tumors) of GISTs, and mutation sites of KIT and PDGFRA were associated with the risk of GIST progression, which may contribute to optimization of individualized adjuvant therapy.
EGFR and MMP-9 are associated with neointimal hyperplasia in systemic-to-pulmonary shunts in children with complex cyanotic heart disease
Authors: Kottmann Philip , Eildermann Katja , Murthi Sarala Raj , Cleuziou Julie , Lemmer Julia , Vitanova Keti , von Stumm Maria , Lehmann Luisa , Hörer Jürgen , Ewert Peter , Sigler Matthias , Lange Rüdiger , Lahm Harald , Dreßen Martina , Lichtner Peter , Wolf Cordula
Published: September 2022

INTRODUCTION:
Systemic-to-pulmonary (SP) shunt malfunction contributes to morbidity in infants with single ventricle physiology after palliative procedure. Neointimal hyperplasia might play a role in the pathogenesis, increasing risk for shunt obstruction. Epidermal growth factor receptor (EGFR) and matrix-metalloproteinase 9 (MMP-9) are described as contributors for neointimal formation in other diseases.
Aim of this study was to quantify EGFR and MMP-9 in SP shunts by immunohistochemistry and to identify risk alleles in genes encoding related proteins.
METHODS:
Immunohistochemistry was performed with anti-EGFR and anti-MMP-9 on 31 SP shunts removed at follow-up palliative or corrective procedure at the time of surgery. Whole-genome single nucleotide polymorphisms genotyping was performed on DNA extracted from patients´ blood samples and allele frequencies were compared between the group of patients with shunts displaying severe stenosis (≥40% shunt stenosis) and the remaining group.
RESULTS:
In immunohistochemistry we mainly detected EGFR and MMP-9in the luminal area of the shunt. Cross sectional area of EGFR and MMP-9 measured in median 0.19 mm2(IQR, 0.1-0.3 mm2) and 0.04 mm2 (IQR, 0.03-0.09 mm2) respectively, and correlated positively with the area of neointimal measured on histology (r=0.729, p<0.001 and r=0.0479, p=0.018). Certain alleles in epidermal growth factor (EGF) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were associated with increased stenosis and neointimal hyperplasia within shunts.
CONCLUSION:
EGFR and MMP-9 contribute to neointimal proliferation in SP shunts of children with complex cyanotic heart disease. SP shunts from patients carrying certain risk alleles in the genes encoding for EGF and TIMP-1 displayed increased neointima.
Analyzing Network (Non-)Neutrality for Monopolistic, Competing, or Vertically Integrated Content Providers with a Unified Model
Authors: Kumar Vedant Joseph , Maillé Patrick , Tuffin Bruno
Published: September 2022

This paper deals with the hot and sensitive network neutrality debate. It designs a model simultaneously encompassing several scenarios regarding the content-providing market structure: a monopolistic content provider, competitive ones, and a vertically-integrated one facing a non vertically-integrated competitor. We each time compare the outputs when non-neutral, weak neutral or strong neutral policies are applied, in order to get insights regarding the possible consequences of each type of neutrality regulation.
NLRC5 promotes tumorigenesis by regulating the PI3K/AKT/autophagy pathway in cervical cancer
Authors: Ling Lin , Zhan Lei , Fu Juanjuan , He Runhua , Wang Wenyan , Wei Bing , Ma Xiaofeng , Cao Yunxia
Published: September 2022

Background
NLR Family CARD Domain Containing 5, (NLRC5) plays an important role in tumorigenesis. However, its effect in cervical cancer (CC) remains unclear. This study was aimed to investigate the function of NLRC5 on CC.
Methods
The expression of NLRC5 as well as LC3 and Beclin1 were detected by immunohistochemical SP method. The relationships between the NLRC5 expression and the clinicopathological parameters of the patents were analyzed with rank sum test. Kaplan-Meier survival curve was used to analyze the correlation between NLRC5, LC3, Beclin1 expression and the clinical prognosis. In addition, univariate analysis and multivariate survival analysis were used to examine the effect of NLRC5 on prognosis. The function of NLRC5 in CC was validated by CCK8 assay and Transwell assay using Hela cell with knowdown or over-expressed NLRC5. The regulation mechanism of NLRC5 was investigated by western blot.
Results
We found that NLRC5 was down-regulated in CC tissues compared with normal cervical tissues. Patients with higher NLRC5 expression, age, HPV infection, lymph node metastasis, recurrence and histological grade had better prognosis independently. Univariate and multivariate analyses showed NLRC5 was a prognostic factor for CC. Pearson correlation analysis showed NLRC5 may exert its function in CC by autophagy related proteins especially for LC3. In vitro cell experiment proved that NLRC5 regulated the level LC3 and promoted the proliferation, migration and invasion of cervical cancer cell by activating AKT signaling pathway. In the presence of AKT signaling pathway inhibitor LY294002, the positive role of NLRC5 in proliferation, migration, and invasion of cervical cancer cell was restricted.
Conclusions
These findings presented NLRC5 may as a promising predictor in patients with cervical cancer. Additionally, NLRC5 regulate LC3 expression to promote HeLa cell proliferation, migration and Invasion by activating the AKT Signaling Pathway.
Characterizing functional modules in the human thalamus: Coactivation-based parcellation and systems-level functional decoding
Authors: Boeken Ole Jonas , Cieslik Edna C. , Langner Robert , Markett Sebastian
Published: September 2022

The human thalamus relays sensory signals to the cortex and facilitates brain-wide communication. The thalamus is also more directly involved in sensorimotor and various cognitive functions but a full characterization of its functional repertoire, particularly in regard to its internal anatomical structure, is still outstanding. As a putative hub in the human connectome, the thalamus might reveal its functional profile only in conjunction with interconnected brain areas. We therefore developed a novel systems-level Bayesian reverse inference decoding that complements the traditional neuroinformatics approach towards a network account of thalamic function. The systems-level decoding considers the functional repertoire (i.e., the terms associated with a brain region) of all regions showing co-activations with a predefined seed region in a brain-wide fashion. Here, we used task-constrained meta-analytic connectivity-based parcellation (MACM-CBP) to identify thalamic subregions as seed regions and applied the systems-level decoding to these subregions in conjunction with functionally connected cortical regions. Our results confirm thalamic structure–function relationships known from animal and clinical studies and revealed further associations with language, memory, and locomotion that have not been detailed in the cognitive neuroscience literature before. The systems-level decoding further uncovered large thalamic-centered systems engaged in autobiographical memory and nociception. We propose this novel decoding approach as a useful tool to detect previously unknown structure–function relationships at the brain network level, and to build viable starting points for future studies.
SIRT2 regulates HMGB1 nucleoplasmic shuttle and degradation via deacetylation in microglia by LPS
Authors: Xing Wan-Qun , Han Qi , Shi Hui-Ying , Wu Wen-Cong , Si Fan , Lu Jing-Jing , Zhou Tie-Zhong , Li Shi-Ze , Guo Jing-Ru , Xu Bin
Published: September 2022

Background
It is widely accepted that high mobility group box 1 (HMGB1) is a key inflammatory mediator in the pathogenesis of sepsis. HMGB1 promotes inflammation during sterile and infectious damage and plays a crucial role in disease development. Mobilization from the nucleus to the cytoplasm is the first important step in the release of HMGB1 from activated immune cells. Sirtuin 2 (SIRT2) is a member of the sirtuin family, nicotinamide adenine dinucleotide+-dependent deacylases, which participates in modulation of cell cycle control and neurodegeneration
Methods
A sepsis mouse modle was established using C57BL/6 and SIRT2-/- mice by LPS induction. Assessment of microglia polarization and pro-inflammatory markers, such as tumor necrosis factor IL-1β, IL-6, and HMGB1. Immunofluorescent staining and western blot analysis were used to detect HMGB1 nuclear translocation. The impact of SIRT2 deacetylase activity on HMGB1 acetylation and the interaction between HMGB1 and SIRT2.
Results
The results of our study showed that HMGB1 was reduced after SIRT2 knockdown. SIRT2 overexpression increased HMGB1. SIRT2 affected the translocation of HMGB1 from the nucleus to the cytoplasm. In addition, SIRT2 interacts with HMGB1 and deacetylates the K43 lysine sites. In vivo, a decrease in HMGB1 due to the absence of SIRT2. SIRT2 depletion increased HMGB1 ubiquitination and had an impact on the nucleoplasmic shuttle.
Conclusion
These discoveries are the first to shed light on the SIRT2 nucleoplasmic shuttle, which influences HMGB1 and its degradation, hence revealing novel therapeutic targets and avenues for sepsis treatment.
The kinetics of circulating cell-free DNA to predict the clinical efficacy of first-line chemotherapy in patients with metastatic colorectal cancer
Authors: Sun Zijian , Zhong Jie , Lu Jianwei , Si Lixiang , Pan Xiaohua , He Kang , Wang Qiangcheng , Zhang Yao , Bao Jun
Published: September 2022

Purpose: The purpose of this study was to evaluate the value of circulating cell-free DNA (cfDNA) as a biomarker for predicting the efficacy of first-line chemotherapy in patients with metastatic colorectal cancer (mCRC).Methods: A total of 118 mCRC patients who received the first-line chemotherapy in Jiangsu Cancer Hospital from July 2018 to April 2020 were enrolled. CfDNA was quantitatively detected in plasma collected from colorectal cancer patients before and during the first-line chemotherapy. Correlations between cfDNA baseline levels and clinicopathological characteristics, cfDNA kinetics and progression-free survival (PFS) were then analyzed by SPSS25 (IBMCorph, Armonk, NY).Results: We found that elevated cfDNA baseline levels were associated with adenocarcinoma, liver metastases, rectal cancer, carcinoembryonic antigen (CEA) and lactate dehydrogenase (LDH) above upper limit of normal (ULN). Of note, patients with cfDNA levels＜24.13ng/ml and cfDNA kinetics (the ratio of post-chemotherapeutic cfDNA to cfDNA baseline levels) ≤ 1.215 after 4 cycles of chemotherapy had higher PFS. By multivariate COX model, we found that cfDNA levels and cfDNA kinetics after 4 cycles of first-line chemotherapy were independent predictive factors of first-line chemotherapy in mCRC patients.Conclusion: The cfDNA levels and the cfDNA kinetics in plasma after 4 cycles of first-line chemotherapy can be used as efficacy predictors for mCRC patients receiving first-line chemotherapy.
Targeting gut microbiota in bone health of livestock and poultry: roles of short-chain fatty acids
Authors: Huang Shu-cheng , He Yan-feng , Lin Lu-xi , Xu Ting-ting , Shaukat Aftab
Published: September 2022

The regulation and maintenance of bone metabolic homeostasis plays a pivotal role in animal skeletal health. Several skeletal diseases have been confirmed to be closely related to ecological dysbiosis and structural changes in the gut microbiota. Gut microbiota and its metabolites, mainly short-chain fatty acids (SCFAs), affect almost all organs, including the skeleton. SCFAs positively affect bone healing by acting directly on cells involved in fracture healing or by shaping appropriate anti-inflammatory and immunomodulatory responses. Moreover, recent studies have shown that SCFAs play a biological role in regulating bone metabolism in four areas: immune function, calcium absorption, osteogenesis and osteolysis, thus havingpotential benefits in maintaining bone health in livestock and poultry. This review focuses on the role of SCFAs in the regulation of bone metabolism by gut microbiota and provides a theoretical basis for studies related to bone health in livestock and poultry.
Quantification of morphological variability expressed by a “log sem” statistic: Examples from extant and extinct hominoid species (craniodental anatomy)
Authors: Thackeray Francis
Published: September 2022

In this review of a morphometric technique, conspecific pairwise comparisons are made between craniodental measurements of adult hominoid specimens (representing extant and extinct species), in least squares linear regression analyses which are associated with equations of the form y = mx + c, where m is the slope and c is the intercept. The log of the standard error of the m-coefficient (“log sem”) is a reflection of the degree of scatter around a regression line, related to variability in shape. The m-coefficient is a reflection of size. Regressions are undertaken when measurements of any specimen P are on the x-axis, and those of another (conspecific) specimen Q on the y-axis; and vice-versa. Respectively, mean log sem values of -1.61 ± 0.13 and − 1.62 ± 0.12 have been observed in the context of crania and dentition of extant (Holocene) Homo, Pan (chimpanzee) and Gorilla conspecifics. Values of circa − 1.61 also appear to be the case in conspecific comparisons of extinct Plio-Pleistocene hominins, notably Early Homo (Early Pleistocene), Paranthropus (also Early Pleistocene) and Pliocene Australopithecus. A mean log sem value of -1.61 ± 0.1 is confirmed as a reflection of a typical degree of morphological variability within hominoid species if not also in other taxa.
Design and performance analysis of eight channel demultiplexer using 2D photonic crystal with trapezium cavity
Authors: Kavitha V. , Balaji V. R. , Dhanabalan Shanmuga Sundar , Sridarsh T , Robinson S. , Sugesh Jeswanth
Published: September 2022

In this work, an eight-channel Dense Wavelength Division Multiplexing (DWDM) demultiplexer is designed with a 2D Photonic Crystal (PC) Triangular lattice. The proposed demultiplexer consists of a centre bus waveguide, an isosceles trapezium resonant cavity, and an eight circular ring cavity (CR1, CR2, CR3, CR4, CR5, CR6, CR7, and CR8). The point defect resonant cavity consists of seven rods to drop different wavelengths from eight cavities, each of eight drop waveguides. The design is very simple for realistic systems. The Finite Difference Time Domain (FDTD) and Plane Wave Expansion Method (PWE) methods are used to determine the proposed design's band structure and transmission spectrum. The resonant wavelengths are 1.5441μm, 1.5443μm 1.54449μm 1.5447μm 1.5449μm 1.5551μm 1.5553μm, and 1.5555μm respectively. The proposed device provides a high-quality factor, transmission efficiency, and low Crosstalk. The device's footprint is 451.2 μm2 easily incorporated into a Photonic Integrated Circuits (PIC).
DOAC in the treatment of cancer-associated venous thromboembolism: a retrospective cohort study beyond the guidelines
Authors: Cominacini Mattia , Suardi Silvia , Ferrari Giulia , Ciresa Roberto , Tosi Federica , De Marchi Sergio , Valenti Maria Teresa , Carbonare Luca Dalle
Published: September 2022

BACKGROUND: the emerging use of direct oral anticoagulants (DOAC) in the management of cancer-associated venous thromboembolism (CAT) is significantly improving therapeutic adherence and quality of life. Despite this, many conditions can restrict the therapeutic index of these drugs. For all these reasons the latest guidelines recommend the use of heparins in the treatment of CAT as the preferred treatment in some clinical settings.
OBJECTIVES: we evaluated the efficacy and the safety of DOAC, in terms of recurrent venous thromboembolism (VTE) and major bleeding (MB), as a composite primary outcome. Mortality and clinically relevant non-major bleeding (CRNMB) were evaluated as secondary outcomes.
METHODS: we performed a retrospective study on 209 patients to compare the effects of DOAC versus heparins for the treatment of CAT. 127 patients with a high bleeding risk neoplasia were enrolled.
RESULTS: A primary-outcome event occurred in 11.3% of patients treated with heparins and in 10.5% treated with DOAC (Relative Risk 0.92; 95% CI 0.42-2.01, p= 0.84). Recurrent VTE occurred in 6.1% in the heparins group and in 8.4% in the DOAC group (RR 1.37; 95% CI 0.51-3.64, p= 0.52). MB occurred in 5.2% in the heparins group and in 2.1% in the DOAC group (RR 0.40; 95% CI 0.08-1.93, p = 0.25).
CONCLUSIONS: DOAC seem to be as effective and safe as heparins in the treatment of CAT. Most bleeding events occurred in patients with high-risk bleeding neoplasms regardless of the type of anticoagulant. Considering the characteristics and satisfaction of patients using DOAC in this setting, this approach should be considered as a first choice.
Observed Variability and Trends in Global Precipitation During 1979-2020
Authors: Gu Guojun , Adler Robert F.
Published: September 2022

How global precipitation might have changed on the interdecadal-to-trend time scales during the satellite (post-1979) era is examined by means of the satellite-based GPCP V2.3 monthly precipitation analysis. Comparisons with the results from CMIP6 and AMIP6 are further made in terms of global mean precipitation change and regional features of precipitation change, aiming to provide not only an improved understanding of the effects of major physical mechanisms on precipitation change, but also an assessment of the skills of current climate models and likely some clues for diagnosing possible limitations in observed precipitation. Long-term change/trend in global mean precipitation is generally weak in GPCP. Although the GPCP trend is statistically significant at the 90% confidence level over global land + ocean during 1979–2020, it is not significant over either global land or ocean separately. For the shorter, overlap period with the CMIP6 historical experiments (1979–2014), GPCP positive trends can’t reach the 90% confidence level, while significant and more intense precipitation trends appear in CMIP6 ensemble-means. However, a roughly similar global sensitivity to surface temperature change can be derived in GPCP, CMIP6, and AMIP6, providing confidence in both observed and simulated global mean precipitation change. Large regional trends with positive and negative values can readily be seen across the world in GPCP. AMIP6 can generally reproduce these large-scale spatial features. Comparisons with CMIP6 confirm the combined effects from anthropogenic greenhouse-gases (GHG) forcing and internal modes of climate variability such as the Pacific Decadal Oscillation (PDO) and Atlantic Multidecadal Oscillation (AMO). Limiting the PDO/AMO effect makes the trend patterns in GPCP residuals more similar to those in CMIP6, implying that the GHG effect would become more readily detectable in observed precipitation in the near future with regards to both global mean and regional precipitation changes. Furthermore, similar changes in precipitation seasonal range, especially over global lands, occur in GPCP, CMIP6, and AMIP6, suggesting that the GHG effect might already be discernible in certain aspects of precipitation change.
Bronchopulmonary dysplasia in extremely premature infants: A scoping review for identifying risk factors
Authors: Ito Masato , Kato Shin , Saito Makoto , Miyahara Naoyuki , Arai Hirokazu , Namba Fumihiko , Ota Erika , Nakanishi Hidehiko
Published: September 2022

Background: With recent advances in respiratory support and improved survival rate of periviable infants, the etiology of bronchopulmonary dysplasia (BPD) might be changing over time. The aim of this scoping review was to screen available evidence regarding perinatal and neonatal risk factors associated with the development and severity of BPD for future revision of BPD classification.
Methods: The eligibility criteria of the studies were year of publication between 2016 and 2021; setting of a developed country; English or Japanese as study language; and randomized controlled, cohort, or case-control design. The titles and abstracts of the studies were screened by independent reviewers.
Results: Of 8,189 eligible studies, three were included for severe BPD and 26 were included for moderate BPD. The risk factors of severe BPD were male sex, iatrogenic preterm birth, maternal hypertensive disorders of pregnancy (HDP), low gestational age, small-for-gestational-age (SGA) birth weight, mechanical ventilation on day 1, and need for patent ductus arteriosus (PDA) management. The risk factors of moderate or severe BPD included male sex, premature rupture of membranes, chorioamnionitis, maternal HDP, SGA birth weight, bubbly/cystic appearance on X-ray, and PDA management.
Conclusion: We identified several risk factors for BPD that might predict respiratory outcomes earlier. We plan to confirm whether those factors could actually be predictors of BPD using the large cohort.
Machine Learning Soft Voting Algorithm for Prediction and Detection of Nonalcoholic Fatty Liver Disease
Authors: Cao Guoxin , Zhang Haomin
Published: September 2022

Nonalcoholic fatty liver disease (NAFLD) is one of the most commonly diagnosed chronic liver diseases in the world and has become an essential public health problem. Introduction of machine learning algorithms to evaluate the best predictive clinical model for NAFLD. In this paper, this study proposes a machine learning Voting algorithm with Genetic Algorithm, Neural Network, Random Forest, and Logistic Regression for NAFLD detection and diagnosis. First, 2,522 of the 10,508 samples met the diagnostic criteria for NAFLD. Visualizing the distribution of missing values, and KNN algorithm is used to fill the missing values. Doing Kolmogorov-Smirnov Z test and the heatmap of 19 variables. The PPFS feature selection method is used to perform the feature selection and the final 11 features are retained. Alanine aminotransferase (ALT), body mass index (BMI), triglycerides (TG), γ-glutamyl transpeptidase (γGT), and Low-density lipoprotein cholesterol (LDL) were the top 5 features contributing to NAFLD. 10 basic machine learning algorithms were used, and the four machine learning algorithms with the highest accuracy were Genetic Algorithm, Neural Network, Random Forest, and Logistic Regression. These four algorithms are fused into the proposed Voting algorithm through the Soft Voting method of Ensemble learning. 10-fold cross-validation was used in the classification. To verify the proposed Voting algorithm, it is compared with other 10 basic machine learning algorithms It achieved accuracy, recall, precision, \({F}_{1}\) score, AUC of up to 0.846212, 0.573248, 0.725806, 0.640569, 0.894010, respectively. According to the results, the proposed Voting algorithm demonstrated the best performance.
Differential antigen expression between human apocrine sweat glands and eccrine sweat glands
Authors: Cao Manxiu , Zhang Lei , Cheng Jiaqi , Wang Cangyu , Zhao Junhong , Liu Xiang , Yan Yongjing , Tang Yue , Chen Zixiu , Zhang Cuiping , Li Haihong
Published: September 2022

Bromhidrosis has a great negative impact on personal occupation and social psychology. It is not yet clear whether bromhidrosis is caused by apocrine sweat glands or the co-action of apocrine sweat glands and eccrine sweat glands. To distinguish between apocrine sweat glands and eccrine sweat glands, specific antigen markers for apocrine sweat glands and eccrine sweat glands must be found first. In the study, we detected the expression of K7, K18, K19, Na+-K+-2Cl− cotransporter 1 (NKCC1), carbonic anhydrase II (CAII), Forkhead transcription factor a1 (Foxa1), homeobox transcription factor engrailed homeobox1 (En1), gross cystic disease fluid protein-15 (GCDFP-15), mucin-1 (MUC-1), cluster of differentiation 15 (CD15) and apolipoprotein (APOD) in eccrine sweat glands and apocrine sweat glands by immunofluorescence staining. The results showed that K7, K18, K19, Foxa1, GCDFP-15 and MUC-1 were expressed in both apocrine and eccrine sweat glands, CD15 and APOD were only expressed in apocrine sweat glands, and CAII, NKCC1 and En1 were only expressed in eccrine sweat glands. We conclude that CD15 and APOD can serve as specific markers for apocrine sweat glands, while CAII, NKCC1 and En1 can serve as specific markers for eccrine sweat glands to differentiate the two sweat glands.
Offloading compiler to reduce pipeline dependencies through hardware interlocking by rebuilding MIPS
Authors: Khandelwal Rajat
Published: September 2022

MIPS is a family of reduced instruction set computer (RISC) ISAs, developed by Prof. John Hennessey at the Stanford University in the early 80s. The goal was to develop a simple processor with hardware equipped to perform traditional five stage pipelining making a large room for general purpose registers. MIPS has a processor along with a coprocessor designed for floating point arithmetic and logic.
However, MIPS uses software methods to avoid dependencies in its pipeline, hence the complete overload to generate NOPs in case of dependencies is done by the compiler.
RISC aims for a simple processor with pipelining, if possible, making compiler development complex and tricky. The logic to avoid dependencies in the pipeline adds an additional layer of complexity to the compiler which can be inherently avoided by switching to hardware to detect dependencies and act upon it accordingly. The paper aims to refine MIPS with hardware equipped to handle dependencies along with a comprehensive disquisition on its build.
CCDC103: A Novel Biomarker with Potential Prognostic in Glioma
Authors: Xu Haitao , Chen Xi , Niu Xiaoqun , Pu Jun
Published: September 2022

The coiled-coil domain-containing protein 103 (CCDC103), a predicted coiled-coil domain containing (CCDC) protein, whose role in tumors has never been reported. However, the diagnostic value and biological function of CCDC103 have not been elucidated in glioma. In this study, immunohistochemistry, qRT-PCR, GrowthCurve and migration experiments were used to explore the roles of CCDC103 on glioma biological function. Differential expression of CCDC103 at the mRNA level was evaluated using the Cancer Genome Atlas (TCGA), GEO and Chinese Glioma Genome Atlas (CGGA) databases. Correlations between CCDC103 expression and clinical outcomes of glioma were explored by TCGA and CGGA databases. GO, KEGG and GSEA were used to explore the molecular function of CCDC103. Different algorithms of immune infiltration were used to analyze the association between CCDC103 and immune infiltration. We found that CCDC103 was highly expressed in glioma tissues and cells, and knockdown of CCDC103 expression can significantly inhibit the growth and migration of glioma cells. In addition, CCDC103 was associated with immune infiltration in glioma and positively correlated with multiple immune checkpoint molecules. In summary, our study indicated that CCDC103 was highly expressed in glioma tissues and cell lines, and that patients with high expression of CCDC103 have a worse prognosis. In addition, knockdown of CCDC103 significantly inhibited the growth and migration of glioma cell lines. These results suggest that CCDC103 plays a crucial funtion in the development of glioma and may act as a new prognostic marker in glioma.
Manual acupuncture alleviates bladder dysfunction by up-regulating expression of NGF and its receptors in bladder tissue of diabetic neurogenic bladder rats
Authors: He Yujun , Lin Rui , Qin Ningjing , Fan Yushan , Zhang Hui , Miao Furui , Huang Jingwen
Published: September 2022

Objective
To investigate the effect of manual acupuncture on diabetic neurogenic bladder (DNB) rats through the protein and mRNA expression of nerve growth factor (NGF), tropomyosin receptor kinase A (TrkA), p75neurotrophinreceptor (p75NTR) in bladder tissue, as well as the levels of substance P (SP) and calcitonin gene-related peptides (CGRP).
Methods
A DNB rat model was induced using intraperitoneal injection of streptozotocin (STZ). The rats were randomly divided into a blank control group, a model group, and a manual acupuncture group (n = 10). For the manual acupuncture group, the manual acupuncture was applied after modeling. These groups were compared regarding body weight, fasting blood-glucose (FBG), and bladder wet weight. The histomorphology of muscle fibers were observed after hematoxylin and eosin (H&E) staining of bladder tissue sections. Protein and mRNA expression of NGF, TrkA and p75NTR in the bladder tissue were determined by Western blot and real-time PCR analysis, respectively. Levels of SP and CGRP in the bladder tissue were determined by ELISA.
Results
Compared to the blank control group, the model group and manual acupuncture group both showed higher FBG and lower body weight after STZ injection (P < 0.05). Compared to the blank control group, the model group and manual acupuncture group both showed higher bladder wet weight (P < 0.05). Histopathological evaluation indicated that manual acupuncture improved muscle fiber alignment disorders and detrusor cells compensatory hypertrophy in bladder tissue. The protein and mRNA expression of NGF, TrkA, p75NTR and the levels of SP and CGRP in bladder tissue of the manual acupuncture group were significantly higher than those of the model group (P < 0.01).
Conclusions
The therapeutic effect of manual acupuncture on bladder dysfunction in DNB may be mediated by up-regulating of the protein and mRNA expression of NGF, TrkA, p75NTR and the levels of SP and CGRP in bladder tissue.
EIF4A3-induced Circ_0001187 facilitates AML suppression through promoting ubiquitin-proteasomal degradation of METTL3 and decreasing m6A modification level mediated by miR-499a-5p/RNF113A pathway
Authors: Yang Xinyu , Han Fengjiao , Hu Xiang , Wu Hanyang , Can Can , Wei Yihong , Liu Jinting , Wang Ruiqing , Jia Wenbo , ji Chunyan , Ma Daoxin
Published: September 2022

Aberrant expression of circRNAs has been proven to play a crucial role in the progression of acute myeloid leukemia (AML), but its regulatory mechanism remains unclear. Herein, we identify a novel m6A modification-related circRNA, Circ_0001187, which is downregulated in AML patients, and its low level contributes to a poor prognosis. We find that the expression of Circ_0001187 is regulated by the modification of DNA methylation and histone acetylation, and its biogenesis is meditated by splicing factor EIF4A3. Knockdown of Circ_0001187 significantly promotes the proliferation and inhibits the apoptosis of AML cells in vitro and in vivo, while overexpression of Circ_0001187 exerts the opposite effects. Moreover, we prove that Circ_0001187 enhances METTL3 protein degradation, which further decreases mRNA m6A modification in AML cells. Mechanistically, Circ_0001187 sponges miR-499a-5p to enhance the expression RNF113A. And RNF113A functions as an E3 ubiquitin ligase to mediate METTL3 ubiquitin/proteasome-dependent degradation by K48-linked polyubiquitin chains. Collectively, our findings highlight the potential clinical implications of Circ_0001187 as a key tumor suppressor of AML via the miR-499a-5p/RNF113A/METTL3 pathway.
Potential Mechanism of Qinggong Shoutao Pill Alleviates Age-associated Memory Decline in D-Galactose-Injured Mice Based on Network Pharmacology, Molecular Docking, and Experimental Verification Integration Strategy
Authors: Pan Guiyun , Chai Lijuan , Chen Rui , Yuan Qing , Song Zhihui , Feng Wanying , Wei Jinna , Yang Zhihua , Zhang Yuhang , Xie Guinan , Yan An , Lv Qingbo , Wang Caijun , Zhao Yingqiang , Wang Yi
Published: September 2022

Background Qinggong Shoutao Pill (QGSTW) is extensively used as a traditional medicine to prevent and treat age-associated memory decline. However, its potential therapeutic mechanisms and targets are unclear. Methods Network pharmacology and molecular Docking approach was utilized to identified the main active components of QGSTW, the potential pathway and target of QGSTW effect on memory decline. Age-associated memory impairment of mouse model induced by D-galactose was established to verified the pathway and target of QGSTW effectiveness on memory decline, as shown by behavioral tests, immunofluorescence staining and western blot. Results By retrieving, 206 chemical components were identified in QGSTW. Based on these chemical components, network pharmacology demonstrated that the targets of active components were significantly enriched in the pathways in neuroactive ligand-receptor interaction, cAMP signaling pathway and calcium signaling pathway, which were closely related with signal transduction and chemical synaptic transmission. The interrelationships between common targets were analyzed by PPI network and ten biomarkers were discovered. Ten QGSTW active components were revealed furtherly. The affinity between the top five targets and their corresponding active ingredients was predicted by molecular docking. Finally, experiments showed that QGSTW could upregulate the expression of cAMP signaling pathway related targets PKA, CREB, and synaptic plasticity related proteins GluN1, GluA1, CaMKⅡ-α, c-Fos and SYN, contributing to the recovery of memory decline in D-galactose-injured mice. Conclusions This paper revealed the key nodes of QGSTW effect on anti-memory decline are cAMP signaling pathway and synaptic plasticity.
A Framework for Optimizing Ensemble Learning for Offensive Tweet Identification
Authors: Mullah Nanlir Sallau , Zainon Wan Mohd Nazmee Wan , Wahab Mohd Nadhir Ab
Published: September 2022

Online derogatory comments are ubiquitous on social media and areraising serious concerns across the globe. Social media data is riddenwith high dimensional search space due to noise, redundant features,and non-standardized writing style. These problems lead to high computationalcosts, longer training time, and low predictive accuracy inmachine learning models. The researchers proposed a framework for optimizingstacked generalized ensemble learning to address these problemsand enhance model performance. The main components of the frameworkinclude feature optimizer (FO), ensemble classifiers, and stratifiedK-foldCV (skfCV) through stacked generalization ensemble architecture.The ensemble classifiers, FO, and skfCV components make our methodstable and computationally efficient with the best performance. Theproposed method was validated using three benchmark datasets. The proposed method outperformed the state-of-the-art results in all theevaluation metrics used in those three articles adopted for comparison.
Patient and Family Experiences of Lysosomal Storage Diseases: A Qualitative Interview Study
Authors: Awada Nahya , Holcik Martin
Published: September 2022

Background
Patients and families affected by rare genetic lysosomal storage diseases (LSDs) suffer from a variety of challenges related to disease management, including issues navigating healthcare and social support services, access to orphan drugs, and intensive treatment regimens. All of these challenges significantly impact people’s quality of life, yet they remain obscure and have not been the subject of comprehensive analysis. Thus, we conducted qualitative interviews with Canadian patients living with LSDs and their families to enrich and advance current understanding of their experiences with rare-disease management and health systems navigation in order to support patient-focused rare disease policies and programs and improve health outcomes of the 2.8 million Canadians affected by rare diseases.
Methods
This study employed a qualitative research design with inductive thematic content analysis. The data for this study was collected using semi-structured interviews. Thirty Canadian participants were interviewed in person or remotely via video chat service to allow for an interactive discussion and the acquisition of rich, comprehensive data relating to the insights and perceptions of people living with LSDs.
Results
Between April and November 2018, 30 participants (16 patients and 14 parents of children with LSDs) with experiences of nine different types of LSDs and living in seven Canadian provinces were interviewed.
Five themes were identified and categorized using comprehensive thematic analysis for each interview. These themes were the complexity of the diagnosis process; navigation of healthcare systems; the psychological, social, and financial implications of LSDs; access to social support services; and access to orphan drugs.
Conclusion
With regards to participants’ experiences with patient care, the study results highlight the importance of establishing a rare-disease strategy and bridging the gaps that currently exist between health and social care for patients with rare conditions. These findings reveal that the process of accessing orphan drugs is extremely complex and convoluted, and patients’ access to appropriate healthcare and social services are subject to significant delays. In addition, the study’s findings illuminate a lack of coordination between all aspects of rare-disease care, including medical and social support services. Policymakers should utilize these results when developing future policies and programs to employ a holistic approach to rare-disease patient care.
Modulation of gut microbiota and anti-inflammatory effect of a probiotic cocktail in an inflammatory bowel disease-induced mouse model by fecal transplantation
Authors: Salimi Afsaneh , Sepehr Amin , Hejazifar Niloofar , Talebi Maliheh , Rohani Mahdi , Pourshafie Mohammad Reza
Published: September 2022

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract due to altered interaction between the immune system and the gut microbiota. The aim of this study was to investigate the role of a probiotic cocktail in modulating immune dysregulation induced in mice. Mice were divided into five groups (n = 5/group) and inflammation was induced by fecal microbiota transplantation (FMT) from the stool of human with IBD and dextran sulfate sodium (DSS). The cocktail of Lactobacillus spp. and Bifidobacterium spp. (10⁸CFU/kg/day) was administered daily for a total of 28 days. The alteration of the gut microbiota and the expression of some genes involved in the regulation of the inflammatory response were studied in the probiotic-treated and untreated groups by quantitative real-time PCR. The gut microbiota of the FMT and DSS groups showed similar patterns on day 28 after each treatment. In the probiotic-treated groups, the population of the gut microbiota normalized and, in contrast to the DSS and FMT groups, the abundance of phyla Firmicutes and Actinobacteria increased. The expression of genes related to immune response and tight junctions was positively affected by the probiotic. Changes in the gut microbiota could influence the inflammatory status in the gut, and probiotics as a preventive or complementary treatment could improve the well-being of patients with inflammatory bowel disease symptoms.
Prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia: a systematic review and meta-analysis
Authors: Masahata Kazunori , Yamoto Masaya , Umeda Satoshi , Nagata Kouji , Terui Keita , Fujii Makoto , Shiraishi Masayuki , Hayakawa Masahiro , Amari Shoichiro , Masumoto Kouji , Okazaki Tadaharu , Inamura Noboru , Toyoshima Katsuaki , Koike Yuki , Furukawa Taizo , Yazaki Yuta , Yokoi Akiko , Endo Masayuki , Tazuke Yuko , Okuyama Hiroomi , Usui Noriaki
Published: September 2022

Purpose
This study aimed to evaluate prenatal predictors of mortality in fetuses with congenital diaphragmatic hernia (CDH).
Methods
A systematic literature search was performed to identify relevant observational studies that evaluated the ability of lung-to-head ratio (LHR), observed-to-expected LHR (o/e-LHR), observed-to-expected total fetal lung volume (o/e-TFLV), lung-to-thorax transverse area ratio (L/T ratio), intrathoracic herniation of the liver and the stomach, and side of diaphragmatic hernia, using a threshold for the prediction of mortality in fetuses with CDH. Study quality was assessed using the QUADAS-2 tool. Hierarchical summary receiver operating characteristic curves were constructed.
Results
A total of 50 articles were included in this meta-analysis. The QUADAS-2 tool identified a high risk of bias in more than one domain scored in all parameters. Among those parameters, the diagnostic odds ratio of mortality with o/e-LHR < 25%, o/e-TFLV < 25%, and L/T ratio < 0.08 were 11.98 (95% confidence interval (CI), 4.65–30.89), 11.14 (95%CI, 5.19–23.89), and 10.28 (95%CI, 3.38–31.31), respectively. The predictive values for mortality were similar between the presence of liver herniation and retrocardiac fetal stomach position.
Conclusions
This systematic review suggests that o/e-LHR, o/e-TFLV, and L/T ratio are equally good predictors of neonatal mortality in fetuses with isolated CDH.
Impact of pretransplant donor-specific anti-HLA antibodies in HLA-mismatched peripheral blood stem cell transplantation
Authors: Hagino Takeshi , Ikegame Kazuhiro , Tanaka Hidenori , Kanda Yoshinobu , Kaida Katsuji , Fukuda Takahiro , Kondo Yukio , Sato Maho , Doki Noriko , Nakamae Hirohisa , Matsuoka Ken-ichi , Mori Yasuo , Sano Hideki , Eto Tetsuya , Kawakita Toshiro , Hashii Yoshiko , Ichinohe Tatsuo , Atsuta Yoshiko , Kanda Junya
Published: September 2022

The cut-off levels of donor-specific anti-HLA antibodies (DSAs) that are considered to predict a high risk of graft failure remain unclear. Using peripheral blood stem cell transplantation (PBSCT) data from the Japanese Society for Transplantation and Cellular Therapy/Japanese Data Center for Hematopoietic Cell Transplantation (JSTCT/JDCHCT), we examined the role of DSAs, and performed a retrospective analysis of patients whose recipients underwent related PBSCT between 2010 and 2014 with pre-transplant anti-HLA antibodies. Patients were divided into 3 groups using a mean fluorescence intensity (MFI) of 5,000 as a cut-off value: DSA positive (n = 8), anti-HLA antibody-positive (n = 137) and anti-HLA antibody-negative (n = 3657). There was a significant difference in the number of CD34-positive cells (median: 4.31, 3.97, and 5.33×106/kg, respectively; p < 0.05). Regarding the eight DSA-positive patients, only two underwent therapeutic intervention, and neutrophils were engrafted in all but one patient (median, 10 days). Although there was a statistically significant difference in neutrophil and platelet engraftment among the 3 groups (both p < 0.05), neutrophil engraftment was faster in the DSA group, with no significant difference in the overall survival (p = 0.46). Our results, based on JSTCT/JDCHCT data, suggest that DSAs may not affect the risk in related PBSCT.
Age-related radiographic parameters difference between the degenerative lumbar spinal stenosis patients and healthy people and correlation analysis
Authors: Li Donglai , Wang Lianlei , Wang Zheng , Li Chao , Yuan Suomao , Tian Yonghao , Liu Xinyu
Published: September 2022

Objectives: To identify age-related radiographic risk factors for DLSS and analyze correlations among them.
Methods: 180 cases were enrolled in this study, and lumbar magnetic resonance was performed. Among them, 93 cases suffered DLSS and lumbar dynamic X-ray were examined. And following parameters were measured: intervertebral disc height(IDH), the ratio of IDH(IDHL4-5/L3-4), initial IDH of L4-5(iIDHL4-5) in the DLSS group, disc degeneration (DD), cartilaginous endplate failure(CEF), Modic changes, the thickness of ligamentum flavum(LF), range of intervertebral motion(ROM), facet joint opening(FJO), facet joint angle(FJA)， the standard cross-sectional area(SCSA) of the multifidus, erector spinae and psoas major muscles. The data of two groups were compared, and the possible risk factors of DLSS were analyzed.
Results: Compared with the control group, the DLSS group had higher IDH except for L4-5, and larger iIDHL4-5(P<0.05). Significant differences were shown in CEF and the thickness of LF at L1-S1, and DD at L4-5(P<0.05). The DLSS group had smaller SCSA of multifidus, erector spinae, and psoas major muscles but greater FJA、FJO(P<0.05). And the risk of DLSS increased when iIDHL4-5≥10.73mm, FJA≥52.03° or FJO≥3.75mm. IDH positively correlated with SCSA of multifidus and psoas major muscles and ROM at L1-S1 (P<0.05). DD showed negative linear relations with SCSA of multifidus and psoas muscle and positive linear relation with CEF at L1-2, L2-3, and L5-S1(P<0.05).
Conclusion: Larger initial disc height and excessive CEF may induce DLSS by increasing intervertebral mobility to promote DD, and atrophied paravertebral muscles by weakening the stability of lumbar spine.
Coalitional Manipulation of Voting Rules: Simulations on Empirical Data
Authors: Durand François
Published: September 2022

Using computer simulations based on empirical data, we show that seven voting rules that we call the IRV family (Instant-Runoff Voting, exhaustive ballot, Condorcet-IRV, Benham, Smith-IRV, Tideman and Woodall) are less sensitive to coalitional manipulation than a large selection of prominent voting rules. While the relative performances of these seven rules still deserve further investigation, we show that the differences are at most marginal.