bluuebunny/crossref_metadata_2025_split huggingface dataset:
LOCOM: A logistic regression model for testing differential
abundance in compositional microbiome data with false discovery rate control
Authors: Hu Yingtian , Satten Glen , Hu Yijuan 
Published: October 2021

Abstract
Motivation: Compositional analysis is based on the premise that a relatively small proportion of taxa are differentially abundant", while the ratios of the relative abundances of the remaining taxa remain unchanged. Most existing methods of compositional analysis such as ANCOM or ANCOM-BC use log-transformed data, but log-transformation of data with pervasive zero counts is problematic, and these methods cannot always control the false discovery
rate (FDR). Further, high-throughput microbiome data such as 16S amplicon or metagenomic sequencing are subject to experimental biases that are introduced in every step of the experimental workflow. McLaren, Willis and Callahan [1] have recently proposed a model for how these biases affect relative abundance data.

Methods: Motivated by [1], we show that the (log) odds ratios in a logistic regression comparing counts in two taxa are invariant to experimental biases. With this motivation, we propose LOCOM, a robust logistic regression approach to compositional analysis, that does not require pseudocounts. We use a Firth bias-corrected estimating function to account for sparse data. Inference is based on permutation to account for overdispersion and small sample sizes. Traits can be either binary or continuous, and adjustment for continuous and/or discrete confounding covariates is supported.

Results: Our simulations indicate that LOCOM always preserved FDR and had much improved sensitivity over existing methods. In contrast, ANCOM often had inflated FDR; ANCOM-BC largely controlled FDR but still had modest inflation occasionally; ALDEx2
generally had low sensitivity. LOCOM and ANCOM were robust to experimental biases in every situation, while ANCOM-BC and ALDEx2 had elevated FDR when biases at causal and non-causal taxa were differentially distributed. The flexibility of our method for a variety of microbiome studies is illustrated by the analysis of data from two microbiome studies.

Availability and implementation: Our R package LOCOM is available on GitHub at https://github.com/yijuanhu/LOCOM in formats appropriate for Macintosh or Windows.
Identification of Key Pathways and Targets of Kai Xin San in The Treatment of Alzheimer's Disease Based On a Network Pharmacology Approach and Experimental Validation
Authors: Yang Rong , Wang Kan , Li Tuo , Liao Mianmian , Kong Mingwang 
Published: October 2021

Abstract
Background: Alzheimer's disease (AD) is the commonest neurodegenerative disease characterized with a progressive loss of cognitive functions and memory decline. Kai Xin San (KXS), a traditional Chinese herbal classic prescription, has been used to ameliorate cognitive dysfunction for thousands of years. However, its specific pharmacological molecular mechanisms have not been fully clarified.Methods: The ingredients of KXS and their corresponding targets were firstly screened from ETCM database. AD-related target proteins were obtained from Malacards database and DisGeNet database. Venn diagram was used to intersect the common targets between KXS and AD. Then, key ingredients and key targets were identified from compound-target-disease network and protein-protein interaction (PPI) network analysis respectively. Moreover, the binding affinity between the key ingredients and targets were verified by molecular docking. KEGG enrichment analysis further predicted the potential key signaling pathway involved in the treatment of KXS on AD, and the predicted signaling pathway was validated via experimental approach.Results: A total of 38 ingredients and 469 corresponding targets were screened, and 264 target proteins associated with AD were obtained. Compound-target-disease network and PPI identified the key active ingredients and targets, which correlate with the treatment of KXS on AD. Molecular docking revealed a good binding affinity between key ingredients and targets. KEGG pathway analysis suggested the potential effect of KXS in treatment of AD via Aβ-GSK3β-Tau pathway. Aβ1-42-injected induced a decline in spatial learning and memory and upregulated the expression of GSK3β and CDK5 along with the downregulated PP1 and PP2 expression. However, KXS significantly improve the cognitive deficits induced by Aβ1-42, decrease the GSK3β and CDK5 levels and increase the expression of PP1 and PP2.Conclusions: Our research elucidated that KXS exerted neuroprotective effects through regulating the Aβ-GSK3β-Tau signaling pathway, which provided a novel insight into the therapeutic mechanism of KXS in treatment of AD.
Loss of Stat3 in Osteoblasts Impaired the Bone Remodeling in Inflammatory Microenvironment
Authors: Feng Jingyi , Huang Zijing , Chan Laiting , Lu Jiarui , Feng Xin , Lei Lizhen , Huang Zhuwei , Lin Lichieh , Yao Yichen , Zhang Xiaolei 
Published: October 2021

Abstract
Introduction: Oral diseases including periodontitis, periapical periodontitis, and peri-implantitis are characterized by inflammation and loss of alveolar bone. Signal transducer and activator of transcription 3 (Stat3) involved in bone formation and maintenance. This study aimed to investigate the effect of Stat3 on the osteoblast-mediated bone remodeling in the inflammatory lesion.Methods: The conditional knockout of Stat3 in osteoblasts (Stat3 CKO) was generated via the Cre-loxP recombination system using Osterix-Cre (Osx-Cre) transgenic mice. The lipopolysaccharide (LPS)-induced calvarial bone inflammatory lesions were harvested at day 3, 7 and 14 for micro-CT scanning, histological staining, quantitative real-time PCR (qRT-PCR) and western blot to assess the bone remodeling. Osteoblasts were harvested from Stat3 CKO and wildtype mice and were cultured in vitro. In response to LPS-stimulation, the cells were subjected to alizarin red staining, qRT-PCR and western blot to examine the formation of calcium deposit, the expression of osteogenic markers (i.e. Runx2, OPN, COL1A1) and osteoclast-related markers (i.e. RANKL, OPG). The EdU and transwell assays were performed to assess the proliferation and migration of the cells.Results: Compared with the wildtype control, a decrease of bone mass and an increase of osteolysis were found in the inflammatory lesions on Stat3 CKO mice. More osteoclastic-like cells, as well as an increased expression of RANKL, were observed in the lesions on Stat3 CKO mice. Both mRNA and protein expressions of Stat3 and osteogenic markers in the lesions was significantly decreased on Stat3 CKO mice. After co-cultured with osteogenic medium, the Stat3-deficient osteoblasts were found with a significant decrease of calcium deposits and the expression of osteogenic markers, and with a significant increased expression of RANKL, when compared with the control osteoblasts. The impaired ossification of Stat3-deficient osteoblasts was even more pronounced with the presence of LPS in vitro. According to the EdU and transwell assays, the most decrease of cell proliferation and migration was found in Stat3-deficient osteoblasts in response to LPS. Conclusions: Loss of Stat3 in osteoblasts impaired bone regeneration in inflammatory microenvironment, which might be resulted from the effect of Stat3 on the ossification, activation of osteoclast activationic signals, proliferation and migration of osteoblasts.
Selected Aspects of a Cold Forging Process for Hollow Balls
Authors: Samolyk Grzegorz , Winiarski Grzegorz 
Published: October 2021

Abstract
This paper presents the results of a study investigating a cold forging process for producing hollow balls with different wall thicknesses. The study was performed by FEM numerical modelling, which made it possible to obtain a wide spectrum of results. For the analysis of FEM results obtained for problematic cases (shape defects in forged balls), novel hypotheses for results interpretation are proposed. The FEM numerical model and hypotheses are then verified via experimental testing, and selected theoretical results are compared with experimental findings. Finally, obtained results are discussed (e.g. the effect of billet dimensions on forging conditions, wall thickness and hole size), a method for FEM results interpretation is presented, and design-related solutions ensuring the production of defect-free hollow balls are proposed.
Upregulation of MMPs in Metastatic Cascade of Breast Cancer To Brain
Authors: Farahani Mohammad Kamalabadi , Atashi Amir , Bitaraf Fateme Sadat , Karimi Roqaye , Eslami Mohammad Masoud 
Published: October 2021

Abstract
Background

Brain metastasis is a lethal complication in triple negative breast cancer (TNBC) patients. Many factors including tumor cell molecular characteristics and biological environment are the main determinant in the brain metastasis process. Matrix metalloproteinases (MMPs) play a key role in extracellular matrix degradation, implicated in numerous aspects of metastasis processes of breast cancer.
Methods

After development of syngenic animal model of TNBC, primary breast cancer cells named 4T1T were isolated from tumor mass. Highly metastatic tumor cells named 4T1B were isolated and expanded from brain metastasis lesions of cancerous mice. Quantitative real-time polymerase chain reaction and gelatinase zymography were performed to analyze the expression of MMPs in transcriptomic and proteomic level in 4T1T and 4T1B.
Results

Our data revealed that, expression of MMPs was significantly upregulated in brain metastatic tumor cells. In transcriptomic level, MMP-2 and MMP-9 genes expression were up-regulated 4 and 3.4 folds in 4T1B, respectively. Zymographic analysis could be detect MMPs activity only in 4T1B.
Conclusion

These findings provided important insights regarding the gross alteration of MMPs expression in brain metastatic cascade of TNBC for the first time. Analysis of molecular properties of brain metastatic tumor cells can be used for understanding of molecular and genetic aspects of brain metastasis and also designing a targeted therapeutic strategies in combat with brain metastasis of TNBC.
Treatment of Severe Kyphotic Deformity Secondary to Ankylosing Spondylitis by Staged Osteotomy in Lateral Decubitus Position: A Retrospective Study
Authors: Zhong Rui , Hu Zhengjun , Zhao Deng , Wang Fei , Huang Huaqiang , Jiang Dengxu , Zhang Zhong , Yijian Liang 
Published: October 2021

Abstract
Background: Patients are often complicated with severe kyphotic deformity (Cobb>100 °) in the advanced stage of ankylosing spondylitis (AS). Corrective osteotomy based on prone position seems to be the only effective treatment. Sometimes, it is difficult to place AS patients with severe kyphosis in a prone position even with a specially prepared folding bed.Methods: 23 patients who underwent staged osteotomy in lateral position from October 2015 to June 2017 were analyzed. All but one patient underwent a single-level Ponte osteotomy in the first stage surgery; pedicle subtraction osteotomy was then carried out in the second stage surgery. The average follow-up was 30.8±4.6 months. The global kyphosis (GK), thoracic kyphosis (TK), lumbar lordosis (LL), the sagittal vertical axis (SVA), the osteotomized vertebra intervertebral angle (OVI), Chin-brow vertical angle (CBVA), the Oswestry Disability Index (ODI) score and the Scoliosis Research Society-22 Patient Questionnaire (SRS-22), were compared pre-and post-operation.Results：All kyphosis parameters were significantly improved (all P< 0.05). The GK was corrected from 115.0± 13.4 ° to 46.5 ± 9.0 ° postoperatively, with a mean correction of 68.5 °. The SVA was improved from 21.2 ± 5.1 cm to 5.1 ± 1.8 cm postoperatively. The CBVA was corrected from 64.1±23.2 ° to 5.7±10.6 ° postoperatively; The OVI was corrected from 9.0±2.7 ° to -20.1±5.6 ° postoperatively. There were significant improvements in the ODI and SRS-22 (all P< 0.05). 4 mild complications were observed perioperatively.Conclusion：Satisfactory correction is safely achieved by staged osteotomy in lateral decubitus position in AS patients with severe kyphosis, which can not only correct the sagittal imbalance of the spine with acceptable complications but also facilitate the placement of intraoperative position.
A Missing Piece of the Puzzle in Pulmonary Fibrosis: Anoikis Resistance Promotes Fibroblast Activation
Authors: Yin Juan , Wang Jing , Zhang Xinxin , Liao Yan , Luo Wei , Wang Sha , Ding Jiawei , Huang Jie , Chen Mengling , Wang Wei , Fang Shencun , Chao Jie 
Published: October 2021

Abstract
Background Pulmonary fibrosis initiates a pneumonic cascade that leads to the dysfunction of fibroblasts characterized by excess proliferation. Anoikis is a physiological process that ensures tissue development and homeostasis. Whether disruption of anoikis is involved in pulmonary fibrosis remains unclear. Results Here, we investigated the mechanism by which silica induces fibroblast activation via anoikis resistance in the subsequent fibrosis. Anoikis of lung fibroblasts, alveolar epithelial cells and endothelial cells during the process of fibrosis was detected by CCK-8, western blot, cell count and flow cytometry (FCM) assays. While the three cell types showed similar increases in cell proliferation, the expression of NTRK2, a marker of anoikis resistance, was upregulated specifically in fibroblasts, indicating the unique proliferative mechanism of fibroblasts in pulmonary fibrosis, which may be related to anoikis resistance. Furthermore, the CRISPR/Cas9 system was used to investigate the molecular mechanism of anoikis resistance; the SiO2-induced inflammatory response activated the MAPK/PI3K signaling pathway in lung fibroblasts and then induced the protein expression of ZC3H4, which specifically mediated anoikis resistance, followed by pulmonary fibrosis. Conclusion The current study revealed a specific pattern of fibroblast proliferation, and targeting anoikis resistance may inhibit the pathological process of pulmonary fibrosis. This result provides a new approach for treating pulmonary fibrosis and new insights for the potential application of ZC3H4 in the development of novel therapeutic strategies for mitigating pulmonary fibrosis.
Identification of Novel Prognostic Factors Focusing on Clinical Outcomes in Patients With Non-small Cell Lung Cancers After Stereotactic Body Radiotherapy
Authors: Sato Hikari , Ito Fumiki , Hasegawa Kazuki , Saga Ryo , Hosokawa Yoichiro , Tanaka Mitsuki , Aoki Masahiko 
Published: October 2021

Abstract
BackgroundStereotactic body radiotherapy (SBRT) has extensively attracted attention as an effective treatment for patients with early-stage non-small cell lung cancers (NSCLCs). However, the factors affecting prognosis after SBRT have not been fully elucidated. The purpose of this study was to investigate the prognostic factors associated with overall survival (OS) and local control (LC) after SBRT.MethodsFrom March, 2003 to March, 2020, 497 patients with primary or oligo-metastatic lung cancer who underwent SBRT treatment were retrospectively reviewed. Univariate analysis was performed against various factors related to patient and tumor characteristics using Kaplan–Meier method. Furthermore, the factors with a statistically significant differences identified via univariate analysis were put in a stratified Cox proportional hazard regression analysis.ResultsThe median follow-up period for all patients was 26.17 months (range, 0.36–194.37), and the 5-year OS and LC rates were 66.3% and 86.0%, respectively. Multivariate analysis showed that surfactant protein-D (SP-D), tumor CT values (TCTV) and iodine density values (IDV) were independent prognostic factors for OS, and histology, TCTV, and IDV were for LC. Although histology was not selected as a prognostic factor related to OS, it was indicated that squamous cell carcinoma patients were associated with the SP-D high group compared to the SP-D normal group. In addition, TCTV was correlated to water density values (WDV) which tended to decrease with increasing IDV.ConclusionThis study suggested that SP-D and TCTV are new candidate prognostic factors after SBRT. There is possibility that combining SP-D and histology, and TCTV and IDV might be improved the accuracy of prognostic prediction.
Neural circuitry for maternal oxytocin release induced by infant cries
Authors: Froemke Robert , Valtcheva Silvana , Issa Habon , Martin Kathleen , Jung Kanghoon , Kwon Hyung-Bae 
Published: October 2021

Abstract
Oxytocin is a neuropeptide important for maternal physiology and childcare, including parturition and milk ejection during nursing1-8. Suckling triggers oxytocin release, but other sensory cues- specifically infant cries- can elevate oxytocin levels in new human mothers9-11 indicating that cries can activate hypothalamic oxytocin neurons. Here we describe a neural circuit routing auditory information about infant vocalizations to mouse oxytocin neurons. We performed in vivo electrophysiological recordings and photometry from identified oxytocin neurons in awake maternal mice presented with pup calls. We found that oxytocin neurons responded to pup vocalizations, but not pure tones, via input from the posterior intralaminar thalamus, and repetitive thalamic stimulation induced lasting disinhibition of oxytocin neurons. This circuit gates central oxytocin release and maternal behavior in response to calls, providing a mechanism for the integration of sensory cues from the offspring in maternal endocrine networks to ensure modulation of brain state for successful parenting.
Postoperative Changes After Phacoemulsification with Posterior Intraocular Lens Implantation Combined with Goniosynechialysis in Patients with Different Axial Lengths
Authors: Xia Jiali , Hu Fei , Fan Liqi , Yu Ling , Ye Jian 
Published: October 2021

Abstract
Background: With the aging of the global population, the incidence of primary angle-closure glaucoma (PACG) or primary angle closure (PAC) with concomitant cataracts has been increasing. We aimed to compare the corneal higher-order aberrations, refractive error and ocular biological parameters changes after phacoemulsification with posterior intraocular lens implantation combined with goniosynechialysis (Phaco-IOL-GSL) was performed in PACG or PAC patients with concomitant cataracts and different axial lengths. Methods: 83 eyes of 69 patients in cataracts with PACG or PAC were divided into two groups according to the axial length (AL): the short (AL ≤ 22.5 mm) and normal axial group (22.5 < AL ≤ 24.5 mm). The intraocular pressure (IOP) and best-corrected visual acuity (BCVA) were measured before surgery and 1-day, 1-week, 1-month, 3-month, 6-month, 12-month after surgery. The corneal higher-order aberrations, antiglaucoma medications, visual fields, refractive diopter and other ocular biological parameters were measured before surgery and at the last follow-up. The difference between the two groups was assessed after surgery. Results: Compared with the baseline, the BCVA significantly improved, while IOP was decreased in both groups (P < 0.01). Both anterior and total cornea HOAs and Z (3,-3) were increased in both groups (P < 0.05 and P < 0.05, respectively) and the larger increments in Z (3,-3) were found in normal axial group. The anterior chamber depth (ACD) and the AL were increased in both groups after Phaco-IOL-GSL ( P< 0.01 and P < 0.01, respectively); however, no difference was found between two groups (P = 0.191, P = 0.066). The refractive outcomes were significantly different in both groups (P = 0.029), and a slight shift towards hyperopia was observed in normal axial group (P = 0.002). Correlation analysis found that refractive error was positively correlated with increments in ACD (r = 0.373, P = 0.001) and decrements in AL (r = 0.331, P = 0.002). Conclusions: Phaco-IOL-GSL is an effective surgery for cataract patients with PACG or PAC. After surgery, anterior and total cornea Z (3, -3) varied with different AL at one-year follow-up. The refractive errors such as hyperopic shifts increased when the ACD was increased, and AL was decreased after surgery, especially in patients with normal axial lengths.
The Impact of Age in Acute Type A Aortic Dissection: a Retrospective Study
Authors: Wang Junxia , Xue Yunxing , Zhu Xiyu , Chong Hoshun , Chen Zhong , Zhou Qing , Qu Jason Zhensheng , Wang Dongjin 
Published: October 2021

Abstract
Background: Acute type A aortic dissection (aTAAD) is a lethal disease and age is an important risk factor for outcomes. This retrospective study was to analyze the impact of age stratification in aTAAD, and to provide clues for surgeons when they make choices of therapy strategies. Methods: From January 2011 to December 2019, 1092 aTAAD patients from Nanjing Drum Tower Hospital received surgical therapy. Patients were divided into 7 groups according to every ten-year interval (20s-80s). The differences between the groups were analyzed in terms of the baseline preoperative conditions, surgical methods and postoperative outcomes of patients of different age groups. During a median follow-up term of 17 months, the survival rates were compared among 7 groups through Kaplan-Meier analysis.Results: The median age was 52.0 years old in whole cohort. The multiple comorbidities were more common in old age groups (60s, 70s, 80s), while the 20s group patients had the highest proportion of Marfan syndrome (28.1%). Preoperative hypotension was highest in 80s (16.7%, P=0.038). Young age groups (20s-60s) had a higher rate of root replacement and total arch replacement, which led to a longer duration of operation and hypothermic circulation arrest. The overall mortality was 14.1%, the tendency of mortality was increased with age except 20s group (33.3% in 80s, P=0.016). The postoperative morbidity of gastrointestinal bleeding and bowel ischemia were 16.7% and 11.1% in 80s group. Conclusions: Age is a major impact factor for aTAAD surgery. Old patients presented more comorbidities before surgery, the mortality and complications rate were significantly higher even with less invasive and conservative surgical therapy. But the favorable long term survival indicated that the simple or less extensive arch repair is the preferred surgery for patients over 70 years old.