bluuebunny/crossref_metadata_2025_split huggingface dataset:
Artificial intelligence for quantifying immune infiltrates interacting with stroma in colorectal cancer
Authors: Yang Jing , Ye Huifen , Fan Xinjuan , Li Yajun , Wu Xiaomei , Zhao Minning , Hu Qingru , Ye Yunrui , Wu Lin , Li Zhenhui , Zhang Xueli , Liang Changhong , Wang Yingyi , Xu Yao , Li Qian , Yao Su , You Dingyun , Zhao Ke , Liu Zaiyi 
Published: October 2022

Abstract

Background
We proposed an artificial intelligence-based immune index, Deep-immune score, quantifying the infiltration of immune cells interacting with the tumor stroma in hematoxylin and eosin-stained whole-slide images of colorectal cancer.

Methods
A total of 1010 colorectal cancer patients from three centers were enrolled in this retrospective study, divided into a primary (N = 544) and a validation cohort (N = 466). We proposed the Deep-immune score, which reflected both tumor stroma proportion and the infiltration of immune cells in the stroma region. We further analyzed the correlation between the score and CD3+ T cells density in the stroma region using immunohistochemistry-stained whole-slide images. Survival analysis was performed using the Cox proportional hazard model, and the endpoint of the event was the overall survival.

Result
Patients were classified into 4-level score groups (score 1–4). A high Deep-immune score was associated with a high level of CD3+ T cells infiltration in the stroma region. In the primary cohort, survival analysis showed a significant difference in 5-year survival rates between score 4 and score 1 groups: 87.4% vs. 58.2% (Hazard ratio for score 4 vs. score 1 0.27, 95% confidence interval 0.15–0.48, P < 0.001). Similar trends were observed in the validation cohort (89.8% vs. 67.0%; 0.31, 0.15–0.62, < 0.001). Stratified analysis showed that the Deep-immune score could distinguish high-risk and low-risk patients in stage II colorectal cancer (P = 0.018).

Conclusion
The proposed Deep-immune score quantified by artificial intelligence can reflect the immune status of patients with colorectal cancer and is associate with favorable survival. This digital pathology-based finding might advocate change in risk stratification and consequent precision medicine.
CTRP1 prevents high fat diet-induced obesity and improves glucose homeostasis in obese and STZ-induced diabetic mice
Authors: Ren Mingzhi , Pan Jianfei , Yu Xueying , Chang Kaile , Yuan Xiaopeng , Zhang Chunbo 
Published: October 2022

Abstract
Background
C1q/tumor necrosis factor-related protein 1 (CTRP1) is an adipokine secreted by adipose tissue, related to chondrocyte proliferation, inflammation, and glucose homeostasis. However, the therapeutic effects on metabolic disorders and the underlying mechanism were unclear. Here, we investigated the functions and mechanisms of CTRP1 in treating obesity and diabetes.

Methods
The plasmid containing human CTRP1 was delivered to mice by hydrodynamic injection, which sustained expression of CTRP1 in the liver and high protein level in the blood. High-fat diet (HFD) fed mice and STZ-induced diabetes model were used to study the effects of CTRP1 on obesity, glucose homeostasis, insulin resistance, and hepatic lipid accumulation. The lipid accumulation in liver and adipose tissue, glucose tolerance, insulin sensitivity, food intake, and energy expenditure were detected by H&E staining, Oil-Red O staining, glucose tolerance test, insulin tolerance test, and metabolic cage, respectively. The metabolic-related genes and signal pathways were determined using qPCR and western blotting.

Results
With high blood circulation, CTRP1 prevented obesity, hyperglycemia, insulin resistance, and fatty liver in HFD-fed mice. CTRP1 also improved glucose metabolism and insulin resistance in obese and STZ-induced diabetic mice. The metabolic cage study revealed that CTRP1 reduced food intake and enhanced energy expenditure. The mechanistic study demonstrated that CTRP1 upregulated the protein level of leptin in blood, thermogenic gene expression in brown adipose tissue, and the gene expression responsible for lipolysis and glycolysis in white adipose tissue (WAT). CTRP1 also downregulated the expression of inflammatory genes in WAT. Overexpression of CTRP1 activated AMPK and PI3K/Akt signaling pathways and inhibited ERK signaling pathway.

Conclusion
These results demonstrate that CTRP1 could improve glucose homeostasis and prevent HFD-induced obesity and fatty liver through upregulating the energy expenditure and reducing food intake, suggesting CTRP1 may serve as a promising target for treating metabolic diseases.
Inhibition of Schwann cell pannexin 1 attenuates neuropathic pain through the suppression of inflammatory responses
Authors: Wang Qian , Li Han-yang , Ling Zhuo-min , Chen Gang , Wei Zhong-Ya 
Published: October 2022

Abstract
Background
Neuropathic pain is still a challenge for clinical treatment as a result of the comprehensive pathogenesis. Although emerging evidence demonstrates the pivotal role of glial cells in regulating neuropathic pain, the role of Schwann cells and their underlying mechanisms still need to be uncovered. Pannexin 1 (Panx 1), an important membrane channel for the release of ATP and inflammatory cytokines, as well as its activation in central glial cells, contributes to pain development. Here, we hypothesized that Schwann cell Panx 1 participates in the regulation of neuroinflammation and contributes to neuropathic pain.

Methods
A mouse model of chronic constriction injury (CCI) in CD1 adult mice or P0-Cre transgenic mice, and in vitro cultured Schwann cells were used. Intrasciatic injection with Panx 1 blockers or the desired virus was used to knock down the expression of Panx 1. Mechanical and thermal sensitivity was assessed using Von Frey and a hot plate assay. The expression of Panx 1 was measured using qPCR, western blotting, and immunofluorescence. The production of cytokines was monitored through qPCR and enzyme-linked immunosorbent assay (ELISA). Panx1 channel activity was detected by ethidium bromide (EB) uptake.

Results
CCI induced persistent neuroinflammatory responses and upregulation of Panx 1 in Schwann cells. Intrasciatic injection of Panx 1 blockers, carbenoxolone (CBX), probenecid, and Panx 1 mimetic peptide (10Panx) effectively reduced mechanical and heat hyperalgesia. Probenecid treatment of CCI-induced mice significantly reduced Panx 1 expression in Schwann cells, but not in dorsal root ganglion (DRG). In addition, Panx 1 knockdown in Schwann cells with Panx 1 shRNA-AAV in P0-Cre mice significantly reduced CCI-induced neuropathic pain. To determine whether Schwann cell Panx 1 participates in the regulation of neuroinflammation and contributes to neuropathic pain, we evaluated its effect in LPS-treated Schwann cells. We found that inhibition of Panx 1 via CBX and Panx 1-siRNA effectively attenuated the production of selective cytokines, as well as its mechanism of action being dependent on both Panx 1 channel activity and its expression.

Conclusion
In this study, we found that CCI-related neuroinflammation correlates with Panx 1 activation in Schwann cells, indicating that inhibition of Panx 1 channels in Schwann cells reduces neuropathic pain through the suppression of neuroinflammatory responses.
Different gender-derived gut microbiota influence stroke outcomes by mitigating inflammation
Authors: Wang Jinchen , Zhong Yi , Zhu Hua , Mahgoub Omer Kamal , Jian Zhihong , Gu Lijuan , Xiong Xiaoxing 
Published: October 2022

Abstract
Background and purpose
Stroke is associated with high disability and mortality rates and increases the incidence of organ-related complications. Research has revealed that the outcomes and prognosis of stroke are regulated by the state of the intestinal microbiota. However, the possibility that the manipulation of the intestinal microbiota can alter sex-related stroke outcomes remain unknown.

Methods
To verify the different effects of microbiota from different sexes on stroke outcomes, we performed mouse fecal microbiota transplantation (FMT) and established a model of ischemic stroke. Male and female mice received either male or female microbiota through FMT. Ischemic stroke was triggered by MCAO (middle cerebral artery occlusion), and sham surgery served as a control. Over the next few weeks, the mice underwent neurological evaluation and metabolite and inflammatory level detection, and we collected fecal samples for 16S ribosomal RNA analysis.

Results
We found that when the female mice were not treated with FMT, the microbiota (especially the Firmicutes-to-Bacteroidetes ratio) and the levels of three main metabolites tended to resemble those of male mice after experimental stroke, indicating that stroke can induce an ecological imbalance in the biological community. Through intragastric administration, the gut microbiota of male and female mice was altered to resemble that of the other sex. In general, in female mice after MCAO, the survival rate was increased, the infarct area was reduced, behavioral test performance was improved, the release of beneficial metabolites was promoted and the level of inflammation was mitigated. In contrast, mice that received male microbiota were much more hampered in terms of protection against brain damage and the recovery of neurological function.

Conclusion
A female-like biological community reduces the level of systemic proinflammatory cytokines after ischemic stroke. Poor stroke outcomes can be positively modulated following supplementation with female gut microbiota.
Person-centered maternity care during childbirth and associated factors at selected public hospitals in Addis Ababa, Ethiopia, 2021: a cross-sectional study
Authors: Tarekegne Azezew Ambachew , Giru Berhanu Wordofa , Mekonnen Bazie 
Published: October 2022

AbstractBackgroundPerson-centered maternity care is respectful and responsive care to individual women’s preferences, needs, and values and ensuring that their values guide all clinical decisions during childbirth. It is recognized as a key dimension of the quality of maternity care that increases client satisfaction and institutional delivery. However, little research has been conducted about person-centered maternity care in Ethiopia.ObjectiveThe aim of this study was to assess the status of person-centered maternity care and associated factors among mothers who gave birth at selected public hospitals in Addis Ababa city, Addis Ababa, Ethiopia, 2021.MethodA facility-based cross-sectional study was conducted at selected public hospitals in Addis Ababa city. A structured questionnaire was used to collect data from post-natal mothers selected by systematic random sampling. Data were collected using face-to-face interview technique. The data was coded and entered using Epi-data version 4.6 and analyzed using SPSS version 25. Bivariate and multivariable linear regression analysis was used to identify factors associated with person-centered maternity care. The strength of association between independent and dependent variables was reported by using unstandardized β at 95% CI and p-value < 0.05 were considered statistically significant.ResultsIn this study 384 mothers were participated with a response rate of 99.2%. The overall prevalence of person-centered maternity care was 65.8% and the percentage mean Person Centered Maternity Care (PCMC) score of the respondents was 65.8% with percentage standard deviation of 17.06. Respondents who had no ANC follow-up (β = -5.39, 95% CI: -10.52, -0.26), < 4 Antenatal Care (ANC) follow up (β = -3.99, 95% CI: -6.63, -1.36), night time delivery (β = -3.95, 95% CI: -5.91, -1.98) and complications during delivery (β = -3.18, 95% CI: -6.01, -0.35) were factors significantly associated with person-centered maternity care.Conclusion and RecommendationsThe finding of this study showed that the proportion of person-centered maternity care among mothers who gave birth in public hospitals of Addis Ababa was high as compared to previous studies. The factors affecting person-centered maternity care are manageable to interventions. Therefore, Policymakers should develop and implement guidelines about person-centered maternity care. Training should be given to health care providers on the importance of person-centered maternity care and patient and provider rights. Hospital managers should increase the number of staffs who got PCMC training, especially during nighttime to improve the provision of person-centered maternity care. Health care providers should implement person-centered maternity care for all mothers who gave birth in the health care facility.
A custom library construction method for super-resolution ribosome profiling in Arabidopsis
Authors: Wu Hsin-Yen Larry , Hsu Polly Yingshan 
Published: October 2022

Abstract
Background
Ribosome profiling, also known as Ribo-seq, is a powerful technique to study genome-wide mRNA translation. It reveals the precise positions and quantification of ribosomes on mRNAs through deep sequencing of ribosome footprints. We previously optimized the resolution of this technique in plants. However, several key reagents in our original method have been discontinued, and thus, there is an urgent need to establish an alternative protocol.

Results
Here we describe a step-by-step protocol that combines our optimized ribosome footprinting in plants with available custom library construction methods established in yeast and bacteria. We tested this protocol in 7-day-old Arabidopsis seedlings and evaluated the quality of the sequencing data regarding ribosome footprint length, mapped genomic features, and the periodic properties corresponding to actively translating ribosomes through open resource bioinformatic tools. We successfully generated high-quality Ribo-seq data comparable with our original method.

Conclusions
We established a custom library construction method for super-resolution Ribo-seq in Arabidopsis. The experimental protocol and bioinformatic pipeline should be readily applicable to other plant tissues and species.
Promoting rational antibiotic therapy among high antibiotic prescribers in German primary care—study protocol of the ElektRA 4-arm cluster-randomized controlled trial
Authors: Löffler Christin , Buuck Theresa , Iwen Julia , Schulz Maike , Zapf Antonia , Kropp Peter , Wollny Anja , Krause Linda , Müller Britta , Ozga Ann-Katrin , Goldschmidt Elisabeth , Altiner Attila 
Published: October 2022

Abstract
Background
The rational use of antibiotics is of great importance in health care. In primary care, acute respiratory infections are the most common cause of inappropriate antibiotic prescribing. Since existing studies aiming to optimize antibiotic use are usually based on the voluntary participation of physicians, general practitioners (GPs) with inappropriate prescribing behavior are underrepresented. For the first time in Germany, the ElektRA study will assess and compare the effects of three interventions on antibiotic prescribing rates for respiratory and urinary tract infections among high prescribers in primary care.

Method
ElektRA is a 4-arm cluster-randomized controlled trial among German GPs in nine regional Associations of Statutory Health Insurance Physicians. On their behalf, the Central Research Institute of Ambulatory Health Care in Germany (Zi) analyses all outpatient claims and prescription data. Based on this database, high antibiotic prescribing GPs are identified and randomized into four groups: a control group (N=2000) and three intervention arms. We test social norm feedback on antibiotic prescribing (N=2000), social norm feedback plus online training on rational prescribing practice and communication strategies (N=2000), and social norm feedback plus online peer-moderated training on rational antibiotic prescribing, communication strategies, and sustainable behavior change (N=1250). The primary outcome is the overall rate of antibiotic prescriptions. Outcomes are measured before intervention (T0, October 2020–September 2022) and over a period of 15 months (T1, October 2022 to December 2023) after randomization.

Discussion
The aim of the study is to implement individualized, low-threshold interventions to reduce antibiotic prescribing among high prescribers in primary care. If successful, a change in behavior among otherwise difficult-to-reach high prescribers will directly improve patient care. The increase in quality of care will ideally be achieved both in terms of the quantity of antibiotics used as well as the kind of substances prescribed. Also, if effective strategies for high prescribers are identified through this study, they can be applied not only to the antibiotics addressed in this study, but also to other areas of prescription management.

Trial registration
Current Controlled Trials ISRCTN95468513.
Donor neo-atrial cuff construction after accidental lower lobe vein transection
Authors: Werner Raphael S. , Caviezel Claudio , Opitz Isabelle , Inci Ilhan 
Published: October 2022

Abstract
Background
An inadequate donor left atrial cuff is a rare technical issue after graft procurement for lung transplantation. With regard to the shortage of suitable donor organs for lung transplantation, these organs should be surgically reconstructed to avoid the loss of an organ and a futile intervention in the critically ill recipient.

Case presentation
We report a case of a 62-year old patient who underwent bilateral sequential lung transplantation for chronic obstructive pulmonary disease. During isolated lung procurement, the right inferior pulmonary vein was circumferentially transsected and separated from the right superior pulmonary and middle lobe veins. Subsequently, a reconstruction of the left atrial cuff with an acellular biological patch was performed to complete the atrium anastomosis. The patient experienced an uneventful postoperative recovery and a follow-up ventilation/perfusion scan showed normal perfusion of the right lower lobe.

Conclusions
This case demonstrates that reconstruction of an inadequate left atrial cuff with a biological patch is feasible and allows for an adequate venous drainage and therefore normal transplant organ function.
Distinct immune signature predicts progression of vestibular schwannoma and unveils a possible viral etiology
Authors: Amit Moran , Xie Tongxin , Gleber-Netto Frederico O. , Hunt Patrick J. , Mehta Gautam U. , Bell Diana , Silverman Deborah A. , Yaman Ismail , Ye Yi , Burks Jared K. , Fuller Gregory N. , Gidley Paul W. , Nader Marc-Elie , Raza Shaan M. , DeMonte Franco 
Published: October 2022

AbstractBackgroundThe management of sub-totally resected sporadic vestibular schwannoma (VS) may include observation, re-resection or irradiation. Identifying the optimal choice can be difficult due to the disease’s variable progression rate.We aimed to define an immune signature and associated transcriptomic fingerprint characteristic of rapidly-progressing VS to elucidate the underpinnings of rapidly progressing VS and identify a prognostic model for determining rate of progression.MethodsWe used multiplex immunofluorescence to characterize the immune microenvironment in 17 patients with sporadic VS treated with subtotal surgical resection alone. Transcriptomic analysis revealed differentially-expressed genes and dysregulated pathways when comparing rapidly-progressing VS to slowly or non-progressing VS.ResultsRapidly progressing VS was distinctly enriched in CD4+, CD8+, CD20+, and CD68+immune cells. RNA data indicated the upregulation of anti-viral innate immune response and T-cell senescence. K − Top Scoring Pair analysis identified 6 pairs of immunosenescence-related genes (CD38-KDR, CD22-STAT5A, APCS-CXCR6, MADCAM1-MPL, IL6-NFATC3,andCXCL2-TLR6) that had high sensitivity (100%) and specificity (78%) for identifying rapid VS progression.ConclusionRapid progression of residual vestibular schwannoma following subtotal surgical resection has an underlying immune etiology that may be virally originating; and despite an abundant adaptive immune response, T-cell immunosenescence may be associated with rapid progression of VS. These findings provide a rationale for clinical trials evaluating immunotherapy in patients with rapidly progressing VS.
Gender-specific relationship between thigh muscle and fat mass and brain amyloid-β positivity
Authors: Kang Sung Hoon , Lee Kyung Hyun , Chang Yoosoo , Choe Yeong Sim , Kim Jun Pyo , Jang Hyemin , Shin Hee Young , Kim Hee Jin , Koh Seong-Beom , Na Duk L. , Seo Sang Won , Kang Mira 
Published: October 2022

AbstractBackgroundThe relationship of specific body composition in the thighs and brain amyloid-beta (Aβ) deposition remained unclear, although there were growing evidence that higher muscle and fat mass in thighs had a protective effect against cardiometabolic syndromes. To determine whether muscle mass and fat mass in the thighs affected amyloid-beta (Aβ) positivity differently in relation to gender, we investigated the association of muscle mass and fat mass with Aβ positivity using positron emission tomography (PET) in individuals without dementia.MethodsWe recruited 240 participants (134 [55.8%] males, 106 [44.2%] females) without dementia ≥45 years of age who underwent Aβ PET, bioelectrical impedance analysis (BIA) and dual-energy X-ray absorptiometry (DEXA) scans of the hip in the health promotion center at Samsung Medical Center in Seoul, Korea. Lower extremity skeletal muscle mass index (LASMI) was measured using BIA, and gluteofemoral fat percentage (GFFP) was estimated using DEXA scans of the hip. We investigated the associations of LASMI and GFFP with Aβ positivity using logistic regression analyses after controlling for age,APOE4genotype, and cognitive stage.ResultsHigher muscle mass in the thighs, measured as LASMI (odds ratio [OR]=0.27, 95% confidence interval [CI] 0.08 to 0.84,p=0.031) was associated with a lesser risk of Aβ positivity in only females. Higher fat mass in the thighs, measured as GFFP (OR=0.84, 95% CI 0.73 to 0.95,p=0.008) was associated with a lesser risk of Aβ positivity in only males. However, the association between LAMSI (p for interaction= 0.810), GFFP (p for interaction= 0.075) and Aβ positivity did not significantly differ by gender. Furthermore, LAMSI only negatively correlated with centiloid (CL) values in females (r=−0.205,p=0.037), and GFFP only negatively correlated with CL values only in males (r=−0.253,p=0.004).ConclusionsOur findings highlight the importance of recognizing that gender differences exist with respect to the specific body composition to potentially protect against Aβ deposition. Therefore, our results may help in designing gender-specific strategies for controlling body composition to prevent Aβ deposition.
A joint DOA and polarization estimation method based on the conformal polarization sensitive array from the sparse reconstruction perspective
Authors: Lan Xiaoyu , Jiang Lai , Xu Peng 
Published: October 2022

AbstractThe conformal polarization sensitive array (CPSA) is formed by placing some vector sensors on the conformal array and it has a wide range of practical application in direction of arrival (DOA) and polarization parameters estimation. However, due to the diversity of each sensor’s direction, the performance of the conventional parameters estimation methods based on the CPSA would decrease greatly, especially under the low signal to noise ratio (SNR) and limited snapshots. In order to solve this problem, a unified framework and sparse reconstruction perspective for joint DOA and polarization estimation based on CPSA is proposed in this paper. Specifically, the array received signal model of the CPSA is formulated first and the two-dimensional spatial sparsity of the incident signals is then exploited. Subsequently, after employing the singular value decomposition method to reduce the dimension of array output matrix, the variational sparse Bayesian learning and orthogonal matching pursuit methods are utilized to solve the source DOA estimation, respectively. Finally, the polarization parameters are obtained by the minimum eigenvector method. Simulation results demonstrate that the novel approaches can provide improved estimation accuracy and resolution with low SNR and limited snapshots.