bluuebunny/crossref_metadata_2025 huggingface dataset:
Development and Validation of a Prognostic Model to Predict High-Risk Patients for Coronary Heart Disease in Snorers With Uncontrolled Hypertension
Authors: Wang Meng-hui , Heizhati Mulalibieke , Li Nan-fang , Yao Xiao-guang , Luo Qin , Lin Meng-yue , Hong Jing , Ma Yue , Wang Run , Sun Le , Ren Ying-li , Yue Na
Published: April 2022

Purpose

Snoring or obstructive sleep apnea, with or without uncontrolled hypertension, is common and significantly increases the risk of coronary heart disease (CHD). The aim of this study was to develop and validate a prognostic model to predict and identify high-risk patients for CHD among snorers with uncontrolled hypertension.

Methods

Records from 1,822 snorers with uncontrolled hypertension were randomly divided into a training set (n = 1,275, 70%) and validation set (n = 547, 30%). Predictors for CHD were extracted to construct a nomogram model based on multivariate Cox regression analysis. We performed a single-split verification and 1,000 bootstraps resampling internal validation to assess the discrimination and consistency of the prediction model using area under the receiver operating characteristic curve (AUC) and calibration plots. Based on the linear predictors, a risk classifier for CHD could be set.

Results

Age, waist circumference (WC), and high- and low-density lipoprotein cholesterol (HDL-C and LDL-C) were extracted as the predictors to generate this nomogram model. The C-index was 0.720 (95% confidence interval 0.663–0.777) in the derivation cohort and 0.703 (0.630–0.776) in the validation cohort. The AUC was 0.757 (0.626–0.887), 0.739 (0.647–0.831), and 0.732 (0.665–0.799) in the training set and 0.689 (0.542–0.837), 0.701 (0.606–0.796), and 0.712 (0.615–0.808) in the validation set at 3, 5, and 8 years, respectively. The calibration plots showed acceptable consistency between the probability of CHD-free survival and the observed CHD-free survival in the training and validation sets. A total of more than 134 points in the nomogram can be used in the identification of high-risk patients for CHD among snorers with uncontrolled hypertension.

Conclusion

We developed a CHD risk prediction model in snorers with uncontrolled hypertension, which includes age, WC, HDL-C, and LDL-C, and can help clinicians with early and quick identification of patients with a high risk for CHD.
Genetics of Anthracycline-Associated Cardiotoxicity
Authors: Al-Otaibi Talal Khalid , Weitzman Benjamin , Tahir Usman A. , Asnani Aarti
Published: April 2022

Anthracyclines are a major component of chemotherapies used in many pediatric and adult malignancies. Anthracycline-associated cardiotoxicity (ACT) is a dose-dependent adverse effect that has substantial impact on morbidity and mortality. Therefore, the identification of genetic variants associated with increased risk of ACT has the potential for significant clinical impact to improve patient care. The goal of this review is to summarize the current evidence supporting genetic variants associated with ACT, identify gaps and limitations in current knowledge, and propose future directions for incorporating genetics into clinical practice for patients treated with anthracyclines. We will discuss mechanisms of ACT that could be illuminated by genetics and discuss clinical applications for the cardiologist/cardio-oncologist.
Acceptability of Time-Limited Eating in Pediatric Weight Management
Authors: Tucker Jared M. , Siegel Robert , Murray Pamela J. , Han Joan C. , Boyer Katherine , Reed Nichole , Allenby Taylor , Novick Marsha
Published: April 2022

Background

Adherence to dietary interventions is a significant barrier in the treatment of childhood obesity. Time-limited eating (TLE) is a simple dietary approach that limits food intake to a given number of consecutive hours per day, but parental and youth acceptability of TLE in youth with obesity is unknown. This study explored the feasibility of utilizing TLE among parents and youth attending pediatric weight management (PWM).

Methods

Members of COMPASS (Childhood Obesity Multi-Program Analysis and Study System) developed a survey to assess the acceptability of TLE in families attending PWM, which included patient characteristics, current diet and sleep schedules, and interests in trying TLE. The survey was administered electronically via REDCap or manually to parents of patients between the ages of 8-17 years old and to patients 11-17 years old attending one of five PWM practices in the COMPASS network.

Results

Patients (n=213) were 13.0 ± 2.5 years old, 58% female, 52% White, 22% Black, 17% Hispanic/Latino, and 47% reported a diagnosed psychological disorder. On average, parents reported their child’s daily eating spanned 12.5 ± 1.9 hours (7:35am - 8:05pm) and included 5.6 ± 1.6 eating bouts (meals + snacks). Most parents reported being likely to try TLE ≤12 hours/d (TLE12: 66%), which was similar to the likelihood of following a nutrient-balanced diet (59%). Likelihood was lower for TLE ≤10 hours/d (TLE10: 39%) or ≤8 hours/d (TLE8: 26%) (p<0.001 for both). Interest in TLE was not consistently related to patient age, sex, or ethnicity, but was lower in patients with a psychiatric diagnosis vs. no diagnosis (TLE8: 19% vs. 32%; p=0.034). Patients of parents who reported being likely to try TLE, compared to those unlikely to try TLE, had shorter eating windows (p<0.001) and ate fewer snacks (p=0.006).

Conclusions

Two-thirds of parents with children attending PWM programs report interest in TLE ≤12 hours/d regardless of demographic characteristics, but interest wanes when limiting eating to ≤10 or ≤8 hours per day. Time-limited eating appears to be a feasible option in PWM settings provided treatment options are individualized based on the interests and barriers of patients and their families.
Comparative Analysis of Heat Release, Bound Water Content and Compressive Strength of Alkali-Activated Slag-Fly Ash
Authors: Joseph Shiju , Cizer Özlem
Published: April 2022

Optimizing the mix composition of alkali-activated materials is sometimes overwhelming due to the higher number of potential parameters that could be varied compared to designing a mix based on Portland cement. The present work focuses on understanding the correlations between compressive strength, bound water content, and heat release from the calorimeter. Different slag and fly ash proportions are studied at two different solution-to-binder (S/B) ratios. Alkali solutions are made with 5 M NaOH and water glass to have a final silica modulus of 1.28. Results indicate that, at similar S/B ratios, mixes with high amounts of slag develop high compressive strength corresponding to high bound water contents until 28 days and high heat release until 7 days. A good correlation exists between compressive strength with cumulative heat release and bound water content when the water-to-solid ratio of the initial mixture is also considered. These findings promise a less tedious method that could be employed to optimize the process for the mix design of alkali-activated materials.
Designing Magnetic Semiconductors From a Ferromagnetic Metallic Glass
Authors: Wang Xinchao , Li Xuan , Chen Na , Zhang Tao
Published: April 2022

Utilizing both charge and spin degrees of freedom of electrons simultaneously in magnetic semiconductors promises new device concepts by creating an opportunity to realize data processing, transportation and storage in one single spintronic device. Unlike most of the traditional diluted magnetic semiconductors, which obtain intrinsic ferromagnetism by adding magnetic elements to non-magnetic semiconductors, we attempt to develop new magnetic semiconductors via a metal-semiconductor transition by introducing oxygen into a ferromagnetic Co-Fe-B metallic glass. The atomic structure and electronic structure of the Co-Fe-B-O sample are explored by using first-principles calculations. The total pair correlation functions of both the Co-Fe-B and Co-Fe-B-O samples evidence their glass structures. The bond pair and coordination number analysis together demonstrate that the oxygen addition enables the bond types to change from the dominant metallic bonding in the Co-Fe-B metallic glass to the mixture of metallic, ionic and covalent bonding in the Co-Fe-B-O oxide glass. This results in the localization of electron charge density and the opening of the band gap in the Co-Fe-B-O oxide glass. The density of states suggests the Co-Fe-B-O oxide glass is semiconducting with a band gap of about 1.7 eV, but there are intermediate energy levels in the band gap. Meanwhile, the Co-Fe-B-O oxide glass remains to be ferromagnetic. These results indicate that the Co-Fe-B-O oxide glass is a magnetic semiconductor transferred from a ferromagnetic Co-Fe-B metallic glass, which is further verified by the experimental realization of a Co-Fe-B-O magnetic semiconductor. Furthermore, our calculation results reveal that a hybridization of the 4s/4p, 3d electrons of ferromagnetic Co and Fe atoms and O 2p electrons exists. Such s, p-d exchange interaction is essential to bridge the mutual interaction between the electrical conduction arising from s-like electrons and ferromagnetism supported by 3d electrons in magnetic semiconductors, thereby enabling the control of ferromagnetism by electrical means. Our calculation results represent an important step to gain a deeper understanding of the oxygen addition induced metal-semiconductor transition in an amorphous alloy Co-Fe-B system. We anticipate that our calculation results provide theoretical fundamentals for experimentally transferring many other ferromagnetic amorphous alloys into ferromagnetic semiconductors with attractive magnetoelectric coupling properties.
Early Estimated Glomerular Filtration Rate Trajectories After Kidney Transplant Biopsy as a Surrogate Endpoint for Graft Survival in Late Antibody-Mediated Rejection
Authors: Borski Anita , Kainz Alexander , Kozakowski Nicolas , Regele Heinz , Kläger Johannes , Strassl Robert , Fischer Gottfried , Faé Ingrid , Wenda Sabine , Kikić Željko , Bond Gregor , Reindl-Schwaighofer Roman , Mayer Katharina A. , Eder Michael , Wahrmann Markus , Haindl Susanne , Doberer Konstantin , Böhmig Georg A. , Eskandary Farsad
Published: April 2022

Background

Late antibody-mediated rejection (ABMR) after kidney transplantation is a major cause of long-term allograft loss with currently no proven treatment strategy. Design for trials testing treatment for late ABMR poses a major challenge as hard clinical endpoints require large sample sizes. We performed a retrospective cohort study applying commonly used selection criteria to evaluate the slope of the estimated glomerular filtration rate (eGFR) within an early and short timeframe after biopsy as a surrogate of future allograft loss for clinical trials addressing late ABMR.

Methods

Study subjects were identified upon screening of the Vienna transplant biopsy database. Main inclusion criteria were (i) a solitary kidney transplant between 2000 and 2013, (ii) diagnosis of ABMR according to the Banff 2015 scheme at >12 months post-transplantation, (iii) age 15–75 years at ABMR diagnosis, (iv) an eGFR > 25 mL/min/1.73 m2 at ABMR diagnosis, and (v) a follow-up for at least 36 months after ABMR diagnosis. The primary outcome variable was death-censored graft survival. A mixed effects model with linear splines was used for eGFR slope modeling and association of graft failure and eGFR slope was assessed applying a multivariate competing risk analysis with landmarks set at 12 and 24 months after index biopsy.

Results

A total of 70 allografts from 68 patients were included. An eGFR loss of 1 ml/min/1.73 m2 per year significantly increased the risk for allograft failure, when eGFR slopes were modeled over 12 months [HR 1.1 (95% CI: 1.01–1.3), p = 0.020] or over 24 months [HR 1.3 (95% CI: 1.1–1.4), p = 0.001] after diagnosis of ABMR with landmarks set at both time points. Covariables influencing graft loss in all models were histologic evidence of glomerulonephritis concurring with ABMR as well as the administration of anti-thymocyte globulin (ATG) at the time of transplantation.

Conclusion

Our study supports the use of the eGFR slope modeled for at least 12 months after biopsy-proven diagnosis of late ABMR, as a surrogate parameter for future allograft loss. The simultaneous occurrence of glomerulonephritis together with ABMR at index biopsy and the use of ATG at the time of transplantation–likely representing a confounder in pre-sensitized recipients–were strongly associated with worse transplant outcomes.
Phosphorus Limitation Enhances Diazotroph Zinc Quotas
Authors: Wang Xuechao , Browning Thomas J. , Achterberg Eric P. , Gledhill Martha
Published: April 2022

Trichodesmium spp. is a colonial diazotrophic cyanobacterium found in the oligotrophic (sub)tropical oceans, where dissolved inorganic phosphorus (DIP) can be depleted. To cope with low P concentrations, P can be scavenged from the dissolved organic P (DOP) pool. This requires the deployment of multiple enzymes activated by trace metals, potentially enhancing metal requirements under stronger P limitations. To test this, we grew Trichodesmium under trace-metal-controlled conditions, where P was supplied as either DIP or DOP (methylphosphonic acid). Mean steady-state biomass under the DOP treatment was only 40% of that grown under equivalent DIP supply, carbon normalized alkaline phosphorus activity was elevated 4-fold, and the zinc (Zn)–carbon ratio was elevated 3.5-fold. Our finding matches the known, dominant Zn requirement across a diversity of enzymes involved in P stress responses and supports an important interaction in the oceanic cycles of these two nutrients.
Reduced Chemical Fertilizer Combined With Bio-Organic Fertilizer Affects the Soil Microbial Community and Yield and Quality of Lettuce
Authors: Jin Ning , Jin Li , Wang Shuya , Li Jinwu , Liu Fanhong , Liu Zeci , Luo Shilie , Wu Yue , Lyu Jian , Yu Jihua
Published: April 2022

Reducing chemical fertilizers in combination with bio-organic fertilizers can limit the use of chemical fertilizers while maintaining soil fertility. However, the effects of combined fertilization on soil chemical properties, microbial community structure, and crop yield and quality are unknown. Using high-throughput sequencing, we conducted field experiments using lettuce plants subjected to five fertilization treatments: chemical fertilizer with conventional fertilization rate (CK), chemical fertilizer reduction by 30% + 6,000 kg ha–1 bio-organic fertilizer (T1), chemical fertilizer reduction by 30% + 9,000 kg ha–1 bio-organic fertilizer (T2), chemical fertilizer reduction by 40% + 6,000 kg ha–1 bio-organic fertilizer (T3), and chemical fertilizer reduction by 40% + 9,000 kg ha–1 bio-organic fertilizer (T4). Compared with CK, the T1–T4 had significantly higher soil pH and soil organic matter (SOM) and showed increased richness and diversity of the bacterial community, and decreased richness and diversity of the fungal community. Principal coordinate analysis evidenced that the bacterial and fungal communities of CK and T1–T4 were distinctly separated. The Kruskal-Wallis H-test demonstrated that the fungal community was more sensitive than the bacterial community to chemical fertilizer reduction combined with bio-organic fertilizer. Among the soil chemical parameters measured, only TN (total nitrogen) was significantly correlated with bacterial and fungal community composition. The T1 and T2 increased lettuce yield. Moreover, T1–T4 characterized reduced nitrate content and increased levels of soluble sugars and vitamin C in lettuce. Overall, the combined application of reduced chemical fertilizer and bio-organic fertilizer effectively improved soil fertility, microbial community structure, and lettuce yield and quality. These findings have valuable implications for vegetable safety and long-term environmental sustainability.
Ten Points to Improve Reproducibility and Translation of Animal Research
Authors: Spanagel Rainer
Published: April 2022

Findings from animal experiments are often difficult to transfer to humans. In this perspective article I discuss two questions. First, why are the results of animal experiments often so difficult to transfer to humans? And second, what can be done to improve translation from animal experiments to humans? Translation failures are often the result of poor methodology. It is not merely the fact that low statistical power of basic and preclinical studies undermine a “real effect,” but the accuracy with which data from animal studies are collected and described, and the resulting robustness of the data is generally very low and often does not allow translation to a much more heterogeneous human condition. Equally important is the fact that the vast majority of publications in the biomedical field in the last few decades have reported positive findings and have thus generated a knowledge bias. Further contributions to reproducibility and translation failures are discussed in this paper, and 10 points of recommendation to improve reproducibility and translation are outlined. These recommendations are: (i) prior to planning an actual study, a systematic review or potential preclinical meta-analysis should be considered. (ii) An a priori power calculation should be carried out. (iii) The experimental study protocol should be pre-registered. (iv) The execution of the study should be in accordance with the most recent ARRIVE guidelines. (v) When planning the study, the generalizability of the data to be collected should also be considered (e.g., sex or age differences). (vi) “Method-hopping” should be avoided, meaning that it is not necessary to use the most advanced technology but rather to have the applied methodology under control. (vii) National or international networks should be considered to carry out multicenter preclinical studies or to obtain convergent evidence. (viii) Animal models that capture DSM-5 or ICD-11 criteria should be considered in the context of research on psychiatric disorders. (ix) Raw data of publication should be made publicly available and should be in accordance with the FAIR Guiding Principles for scientific data management. (x) Finally, negative findings should be published to counteract publication bias. The application of these 10 points of recommendation, especially for preclinical confirmatory studies but also to some degree for exploratory studies, will ultimately improve the reproducibility and translation of animal research.
Microglia-Mediated Inflammation and Neural Stem Cell Differentiation in Alzheimer’s Disease: Possible Therapeutic Role of KV1.3 Channel Blockade
Authors: Revuelta Miren , Urrutia Janire , Villarroel Alvaro , Casis Oscar
Published: April 2022

Increase of deposits of amyloid β peptides in the extracellular matrix is landmark during Alzheimer’s Disease (AD) due to the imbalance in the production vs. clearance. This accumulation of amyloid β deposits triggers microglial activation. Microglia plays a dual role in AD, a protective role by clearing the deposits of amyloid β peptides increasing the phagocytic response (CD163, IGF-1orBDNF) and a cytotoxic role, releasing free radicals (ROS or NO) and proinflammatory cytokines (TNF-α,IL-1β) in response to reactive gliosis activated by the amyloid β aggregates. Microglia activation correlated with an increase KV1.3 channels expression, protein levels and current density. Several studies highlight the importance of KV1.3 in the activation of inflammatory response and inhibition of neural progenitor cell proliferation and neuronal differentiation. However, little is known about the pathways of this activation in neural stem cells differentiation and proliferation and the role in amyloid β accumulation. In recent studies usingin vitrocells derived from mice models, it has been demonstrated that KV1.3 blockers inhibit microglia-mediated neurotoxicity in culture reducing the expression and production of the pro-inflammatory cytokinesIL-1β andTNF-α through the NF-kB and p38MAPK pathway. Overall, we conclude that KV1.3 blockers change the course of AD development, reducing microglial cytotoxic activation and increasing neural stem cell differentiation. However, further investigations are needed to establish the specific pathway and to validate the use of this blocker as therapeutic treatment in Alzheimer patients.
When the Renal (Function) Begins to Fall: A Mini-Review of Acute Kidney Injury Related to Acute Respiratory Distress Syndrome in Critically Ill Patients
Authors: Marchiset Antoine , Jamme Matthieu
Published: April 2022

Acute kidney injury (AKI) is one of the most frequent causes of organ failure encountered in patients in the intensive care unit (ICU). Because of its predisposition to occur in the most critically ill patients, it is not surprising to observe a high frequency of AKI in patients with acute respiratory distress syndrome (ARDS). However, few studies have been carried out to assess the epidemiology of AKI in subgroups of ARDS patients using recommended KDIGO criteria. Moreover, the mechanisms involved in the physio-pathogenesis of AKI are still poorly understood, in particular the impact of mechanical ventilation on the kidneys. We carried out a review of the literature, focusing on the epidemiology and physiopathology of AKI in patients with ARDS admitted to the ICU. We addressed the importance of clinical management, focusing on mechanical ventilation for improving outcomes, on AKI. Finally, we also propose candidate treatment strategies and management perspectives. Our literature search showed that AKI is particularly common in ICU patients with ARDS. In association with the classic risk factors for AKI, such as comorbidities and iatrogeny, changes in mechanical ventilation parameters, which have been exclusively evaluated for their outcomes on respiratory function and death, must be considered carefully in terms of their impact on the short-term renal prognosis.
Research Hotspots and Trends Analysis of TFEB: A Bibliometric and Scientometric Analysis
Authors: Zhou Runjin , Lin Xiaoling , Liu Dongmin , Li Zhao , Zeng Jingchun , Lin Xingdong , Liang Xiaodi
Published: April 2022

Objective

To explore the development context, research hotspots and frontiers of Transcription factor EB (TFEB) from 1991 to 2021 by bibliometric analysis.

Methods

Publications about TFEB research from 1991 to 2021 were retrieved from the Web of Science Core Collection (WoSCC). Excel 2007 was used to collect basic information, including publications, research areas. VOSviewer 1.6.17 was used to analyze co-authorship of countries, institutes and authors. Co-citation of cited authors, cited references were analyzed by CiteSpace V.5.8.R3. In addition, CiteSpace was used to analyze keywords cluster and forecast research frontiers.

Results

A total of 1,059 literatures were retrieved, including 1,340 research institutes and 393 academic journals. The main area of research related to TFEB is biology (340), the most published country and institutes were the United States (487) and Baylor College of Medicine (70). Settembre C owned the highest co-citations (663). Trending keywords may indicate frontier topics, including “Alzheimer’s disease,” “Parkinson’s disease,” “(p21; q12),” “melanoma,” “pancreatic cancer,” “breast cancer,” “calcineurin,” “TFE3,” “trehalose,” and “curcumin.”

Conclusion

This research provides valuable information for the study of TFEB. Disease research focuses more on neurodegenerative diseases (NDs) and tumors. Trehalose and curcumin are novel agents acting on TFEB. Rap-TRPML1-Calcineurin-TFEB and TFE3 are increasing signal pathway researches, similarly, the molecular biological mechanism of TFEB needs further exploration.
Multimodality Characterization of Cancer-Associated Fibroblasts in Tumor Microenvironment and Its Correlation With Ultrasound Shear Wave-Measured Tissue Stiffness in Localized Prostate Cancer
Authors: Ageeli Wael , Zhang Xinyu , Ogbonnaya Chidozie N. , Bray Susan E. , Kernohan Neil M. , Wilson Jennifer , Li Chunhui , Nabi Ghulam
Published: April 2022

Introduction

Growing evidence suggests that the tumor microenvironment (TME) represented by cellular and acellular components plays a key role in the multistep process of metastases and response to therapies. However, imaging and molecular characterization of the TME in prostate cancer (PCa) and its role in predicting aggressive tumor behavior and disease progression is largely unexplored. The study explores the PCa TME through the characterization of cancer-associated fibroblasts (CAFs) using both immunohistochemistry (IHC) and genomics approaches. This is then correlated with transrectal ultrasound shear wave elastography (USWE)-measured tissue stiffness.

Patients and Methods

Thirty patients with clinically localized PCa undergoing radical prostatectomy for different risk categories of tumor (low, intermediate, and high) defined by Gleason score (GS) were prospectively recruited into this study. Prostatic tissue stiffness was measured using USWE prior to surgery. The CAFs within the TME were identified by IHC using a panel of six antibodies (FAP, SMAα, FSP1, CD36, PDGFRα, and PDGFRβ) as well as gene expression profiling using TempO-sequence analysis. Whether the pattern and degree of immunohistochemical positivity (measured by Quick score method) and expression of genes characterizing CAFs were correlated with USWE- and GS-measured tissue stiffnesses were tested using Spearman’s rank correlation and Pearson correlation.

Results

There was a statistically significant correlation between GS of cancers, the pattern of staining for CAFs by immunohistochemical staining, and tissue stiffness measured in kPa using USWE (p < 0.001). Significant differences were also observed in immunohistochemical staining patterns between normal prostate and prostatic cancerous tissue. PDGFRβ and SMAα immunostaining scores increased linearly with increasing the USWE stiffness and the GS of PCa. There was a significant positive correlation between increasing tissue stiffness in tumor stroma and SMAα and PDGFRβ gene expression in the fibromuscular stroma (p < 0.001).

Conclusion

USWE-measured tissue stiffness correlates with increased SMAα and PDGFRβ expressing CAFs and PCa GSs. This mechanistic correlation could be used for predicting the upgrading of GS from biopsies to radical surgery and response to novel treatments.
Fasting Insulin and Risk of Overall and 14 Site-Specific Cancers: Evidence From Genetic Data
Authors: Zhang Han , Li Doudou , Liu Xiaozhuan , Wan Zhongxiao , Yu Zengli , Wang Yuming , Li Xue
Published: April 2022

Objective

Whether fasting insulin (FI) plays a role in cancer risk remains unclear. This study aimed to investigate the association between FI and cancer risk and to explore its potential mediator role in the association between type 2 diabetes mellitus (T2DM) and cancer.

Methods

Two-sample Mendelian randomization (TSMR) analysis was performed to evaluate the effect of FI on overall and 14 site-specific cancers using genome-wide association study (GWAS) summary-level data from Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) and consortia of 14 site-specific cancers. The primary MR approach was conducted by using the random-effect inverse-variance weighted (IVW) method, and sensitivity analyses were implemented by adopting weighted-median, weighted-mode, MR-Egger, and MR-PRESSO tests. Polygenic risk score analysis was executed by using individual-level data from UK Biobank to validate the findings from TSMR analyses. Multivariable Mendelian randomization (MVMR) was carried out to estimate the mediation effect of FI on the association between T2DM and cancer.

Results

TSMR study suggested that genetically determined high FI levels were associated with increased risk of colorectal cancer (odds ratio (OR) = 1.87, 95% CI: 1.23–2.84, p = 0.003) and endometrial cancer (OR = 1.89, 95% CI: 1.08–3.01, p = 0.008), but not associated with overall cancer risk or the other 12 studied cancer sites. Polygenic risk score analysis successfully replicated the association between genetic liability to high FI levels and the increased risk of colorectal and endometrial cancers. MVMR and MR mediation analyses detected an intermediary effect of FI and quantified that FI mediated 21.3% of the association between T2DM and endometrial cancer.

Conclusions

This study demonstrated that FI levels are associated with the risk of colorectal and endometrial cancers, and FI was found to play an intermediary role in the association between T2DM and endometrial cancer. The associations between FI and other cancers need to be further studied.
Acceptability of Drugs in the Treatment of Unresectable/Metastatic BRAF V600-Mutant Melanoma: A Systematic Review and Network Meta-Analysis
Authors: Hong Ling , Huang Ping , Zheng Xiaochun , Ye Xiaolan , Zhao Hongying , Wang Jianwei , Shao Yanfei
Published: April 2022

Background

Although many novel regimens have entered the treatment paradigm for unresectable/metastatic BRAF V600-mutant melanoma, there is still a lack of head-to-head comparison in terms of security. We conducted a network meta-analysis to compare the risk of adverse events (AEs) across different treatments and to provide an acceptability ranking for patients.

Methods

A systematic literature review was conducted in Embase, PubMed, WHO International Clinical Trials Registry Platform, and Clinical Trials.gov with a time frame from database inception to December 24, 2021. We retrieved evidence on the cumulative incidence of any-grade AEs means grades 1-5 AEs (regardless of severity) and severe AEs based on the pooled risk ratios (RRs) and 95% credible intervals (95% CrI).

Results

Twelve publications and thirteen treatments enrolling 5,803 patients were included. For any-grade AEs, the acceptability of combined dabrafenib and trametinib is superior to the combination of vemurafenib and cobimetinib (RR: 0.94; Crl: 0.89, 0.98). Furthermore, nivolumab combined with ipilimumab increases any-grade AEs than single-agent ipilimumab (RR: 0.90; Crl: 0.83, 0.96) or nivolumab (RR: 0.90; Crl: 0.84, 0.97). For severe AEs, dabrafenib has the best acceptability than single-agent vemurafenib (RR: 0.66; Crl: 0.50, 0.87) or encorafenib (RR: 0.64; Crl: 0.43, 0.94). In addition, ipilimumab (SUCRA: 0.87) ranks first in the acceptability for any-grade AEs, and nivolumab (SUCRA: 0.95) ranks first in the acceptability for severe AEs. The ranking of the combination of vemurafenib and cobimetinib (SUCRA: 0.66) is superior to encorafenib in combination with binimetinib (SUCRA: 0.39) and combination of vemurafenib and cobimetinib (SUCRA: 0.18).

Conclusions

We identified the lowest AE risk treatment options for BRAF V600-mutant melanoma patients. In general, immunotherapy (ipilimumab or nivolumab) has better acceptability than most targeted therapies, and triplet therapies are related with the worst acceptability. Moreover, single-agent dabrafenib can be used as the first choice in monotherapy, and the combination of dabrafenib and trametinib is the preferred combination therapy. Overall, the combination of immunotherapy drugs increases any-grade and severe AEs than a single agent, whereas the condition of targeted therapy drugs cannot be simply generalized. Therefore, this information can facilitate evidence-based decision-making and support optimizing treatment and outcomes in clinical practice.
Synthesis and Evaluation of Technetium-99m-Labeled pH (Low) Insertion Peptide Variant 7 for Early Diagnosis of MDA-MB-231 Triple-Negative Breast Cancer by Targeting the Tumor Microenvironment
Authors: Chen Yuehua , Su Yuan , Pang Xufeng , Song Xiaoxia , Zhao Wanjun , Yu Mingming
Published: April 2022

Objective

To prepare technetium-99m (99mTc)-labeled pH (low) insertion peptide variant 7 [pHLIP (Var7)] and carry out small-animal single-photon-emission computed tomography (SPECT)/computed tomography (CT) imaging of tumor-bearing nude mice in vivo to study its value in the early diagnosis of triple-negative breast cancer (TNBC).

Methods

The pHLIP (Var7) sequence was synthesized via solid-phase peptide synthesis. Four amino acids, Gly-(D)-Ala-Gly-Gly, were attached to the N-terminus of pHLIP (Var7) to form a strong chelating group containing an N4 structure. The peptide was labeled with 99mTc using a direct labeling method. We determined the in vitro binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells. Serial biodistribution studies and small-animal SPECT/CT imaging in MDA-MB-231 TNBC-bearing mice were performed using 99mTc-pHLIP (Var7).

Results

The radiochemical yield and purity of 99mTc-pHLIP (Var7) were 99.49 ± 0.17% and 99.63 ± 0.44%, respectively. The radiochemical purity was still more than 96% after 24 h in serum. The binding fraction of 99mTc-pHLIP (Var7) to MDA-MB-231 cells continuously increased in an acidic environment and was significantly higher than the cell-binding fraction (P < 0.01) at pH = 7.4 and the cell-binding fraction (P < 0.01) of 99mTc-kVar7 at different pH values (pH = 6.0, 6.5, 7.0 and 7.4) at each time point (P < 0.01). The distribution of 99mTc-pHLIP (Var7) in tumors at each time point was significantly greater than that of 99mTc-kVar7 (P < 0.01). SPECT/CT imaging was largely consistent with the biodistribution results; the tumor was clearly imaged at each time point after injection of 99mTc-pHLIP (Var7) but could not be imaged after injection of 99mTc-kVar7.

Conclusion

99mTc-pHLIP (Var7) showed a high radiochemical yield and stability and was highly concentrated in tumor tissues. Although there was strong radioactive background in the abdomen of tumor-bearing nude mice, it did not hinder early diagnosis of TNBC.
A Chromosome-Level Genome of the Camphor Tree and the Underlying Genetic and Climatic Factors for Its Top-Geoherbalism
Authors: Jiang Rihong , Chen Xinlian , Liao Xuezhu , Peng Dan , Han Xiaoxu , Zhu Changsan , Wang Ping , Hufnagel David E. , Wang Li , Li Kaixiang , Li Cheng
Published: April 2022

Camphor tree [Cinnamomum camphora (L.) J. Presl], a species in the magnoliid family Lauraceae, is known for its rich volatile oils and is used as a medical cardiotonic and as a scent in many perfumed hygiene products. Here, we present a high-quality chromosome-scale genome of C. camphora with a scaffold N50 of 64.34 Mb and an assembled genome size of 755.41 Mb. Phylogenetic inference revealed that the magnoliids are a sister group to the clade of eudicots and monocots. Comparative genomic analyses identified two rounds of ancient whole-genome duplication (WGD). Tandem duplicated genes exhibited a higher evolutionary rate, a more recent evolutionary history and a more clustered distribution on chromosomes, contributing to the production of secondary metabolites, especially monoterpenes and sesquiterpenes, which are the principal essential oil components. Three-dimensional analyses of the volatile metabolites, gene expression and climate data of samples with the same genotype grown in different locations showed that low temperature and low precipitation during the cold season modulate the expression of genes in the terpenoid biosynthesis pathways, especially TPS genes, which facilitates the accumulation of volatile compounds. Our study lays a theoretical foundation for policy-making regarding the agroforestry applications of camphor tree.
Deep Learning-Based Artistic Inheritance and Cultural Emotion Color Dissemination of Qin Opera
Authors: Yu Han
Published: April 2022

How to enable the computer to accurately analyze the emotional information and story background of characters in Qin opera is a problem that needs to be studied. To promote the artistic inheritance and cultural emotion color dissemination of Qin opera, an emotion analysis model of Qin opera based on attention residual network (ResNet) is presented. The neural network is improved and optimized from the perspective of the model, learning rate, network layers, and the network itself, and then multi-head attention is added to the ResNet to increase the recognition ability of the model. The convolutional neural network (CNN) is optimized from the internal depth, and the fitting ability and stability of the model are enhanced through the ResNet model. Combined with the attention mechanism, the expression of each weight information is strengthened. The multi-head attention mechanism is introduced in the model and a multi-head attention ResNet, namely, MHAtt_ResNet, is proposed. The network structure can effectively identify the features of the spectrogram, improve the weight information of spectrogram features, and deepen the relationship between distant information in long-time series. Through experiments, the proposed model has high emotional classification accuracy for Qin opera, and with the increase of the number of data sets, the model will train a better classification effect.
Detection of Microstructural Medial Prefrontal Cortex Changes Using Magnetic Resonance Imaging Texture Analysis in a Post-Traumatic Stress Disorder Rat Model
Authors: Zheng Shilei , Wang Han , Han Fang , Chu Jianyi , Zhang Fan , Zhang Xianglin , Shi Yuxiu , Zhang Lili
Published: April 2022

Background

Radiomics is characterized by high-throughput extraction of texture features from medical images and the mining of information that can potentially be used to define neuroimaging markers in many neurological or psychiatric diseases. However, there have been few studies concerning MRI radiomics in post-traumatic stress disorder (PTSD). The study's aims were to appraise changes in microstructure of the medial prefrontal cortex (mPFC) in a PTSD animal model, specifically single-prolonged stress (SPS) rats, by using MRI texture analysis. The feasibility of using a radiomics approach to classify PTSD rats was examined.

Methods

Morris water maze and elevated plus maze were used to assess behavioral changes in the rats. Two hundred and sixty two texture features were extracted from each region of interest in T2-weighted images. Stepwise discriminant analysis (SDA) and LASSO regression were used to perform feature selection and radiomics signature building to identify mPFC radiomics signatures consisting of optimal features, respectively. Receiver operating characteristic curve plots were used to evaluate the classification performance. Immunofluorescence techniques were used to examine the expression of glial fibrillary acidic protein (GFAP) and neuronal nuclei (NeuN) in the mPFC. Nuclear pycnosis was detected using 4′,6-diamidino-2-phenylindole (DAPI) staining.

Results

Behavioral results indicated decreased learning and spatial memory performance and increased anxiety-like behavior after SPS stimulation. SDA analysis showed that the general non-cross-validated and cross-validated discrimination accuracies were 86.5% and 80.4%. After LASSO dimensionality reduction, 10 classification models were established. For classifying PTSD rats between the control and each SPS group, these models achieved AUCs of 0.944, 0.950, 0.959, and 0.936. Among four SPS groups, the AUCs were 0.927, 0.943, 0.967, 0.916, 0.932, and 0.893, respectively. The number of GFAP-positive cells and intensity of GFAP-IR within the mPFC increased 1 day after SPS treatment, and then decreased. The intensity of NeuN-IR and number of NeuN-positive cells significantly decreased from 1 to 14 days after SPS stimulation. The brightness levels of DAPI-stained nuclei increased in SPS groups.

Conclusion

Non-invasive MRI radiomics features present an efficient and sensitive way to detect microstructural changes in the mPFC after SPS stimulation, and they could potentially serve as a novel neuroimaging marker in PTSD diagnosis.
Power and Powerlessness in a Group Based Digital Story Telling Project-An Exploration of Community Perceptions of Health Concerns in Urban Malawi
Authors: Nyirenda Deborah , Payesa Chipiliro , Ntaba Jolly , Mhango Rachel , Kingori Patricia , Parker Michael , Desmond Nicola
Published: April 2022

Digital Story Telling (DST) is an art-based research method used to explore embodied experience of health and initiate dialogue with under-represented groups on issues affecting them. It involves engaging participants to create and share their stories using photos, drawings, and audio recordings in short videos. Benefits of DST include enhancing co-creation of knowledge, empowering participants to confront dominant narratives and revise inaccurate representations. We report our experiences and reflections of using DST to explore community perceptions of health concerns in urban Malawi. Community leaders were briefed about the project before and after study related activities. Three participatory workshops were organized to train community members in DST, support them to develop videos and discuss their experiences of DST. Twenty-six participants from two high density urban communities consented to be part of the workshops. They were all new to DST. All the 26 participants were invited together to the three workshops and their DSTs were developed in smaller groups (n = 7), based on their geographical location. Although we engaged residents from selected communities to share priority health concerns, all the seven groups presented challenges pertaining to Water, Sanitation and Hygiene (WASH), and their powerlessness to address the complex challenges. The collective focus on WASH showed that DST effectively empowered communities to present priority health concerns. The inability of community members to address the challenges without external assistance or failure to use findings from DST to generate social change however raise questions on the ideals of empowerment and social justice. In addition, lack of financial resources or technical know-how to produce digital stories and unequal power relationships between service providers and community, may affect the use of DST for community activism among socio-economically disadvantaged groups. We conclude that DST empowered participants to articulate genuine health challenges that they felt powerless to address. We question the realization of “empowerment” and social justice of vulnerable participants in cases where structural challenges present obstacles to effectively address social inequalities.
A Glowing Protein Helps Scientists Visualize Brain Cell Activity
Authors: Bouccara Sophie , Yizhar Ofer
Published: April 2022

Neurons are brain cells that can represent and store information, and they help our bodies to respond to events happening around us. How is information represented, processed and stored by neurons? Which neurons are activated while we perform a specific behavior? These are fundamental scientific questions. One important experimental approach to answering these questions is to record the activity of neurons inside the brain. In 2001, scientists developed an approach that uses light and a fascinating protein that becomes brightly fluorescent when neurons are active. This engineered protein, called GCaMP, responds to the amount of calcium inside the neurons considering that once a neuron is active, calcium inside it increases. GCaMP is now commonly used in laboratories all over the world to study neurons activity. In this article, we explain how this tool works and what makes it so useful for studying the brain.
Is Fat Tissue “Plastic”?
Authors: Soares Ana C. F. , Figueiredo Rita E. , Martins Fátima O. , Conde Silvia V.
Published: April 2022

Fat tissue, called adipose tissue, is our energy storage and it plays a vital role in the growing process. Did you know that we have three different types of adipose tissue that can convert into each other during our lives? The white adipose tissue stores fat from the foods we eat. The brown adipose tissue is responsible for heat production. And lastly, the beige adipose tissue is a form that is halfway between these two. The white and brown adipose tissues are very important to the body’s functioning. But, if we eat a lot of sugar and fat, the metabolism and functions of these tissues change, which can result in diseases like obesity and diabetes. Nowadays, scientists are studying the possibility of turning white adipose tissue into brown adipose tissue, in an attempt to prevent and reverse some of these diseases.
Using Self-Compassion to Manage Difficult Sport Experiences
Authors: Ferguson Leah J. , McHugh Tara-Leigh F.
Published: April 2022

Do you ever have that awful feeling in your gut after you mess up during an important competition? When training is really tough, do you ever say to yourself, “I am not good enough”? Do not worry, you are not alone in these tough times. All athletes—including us, the authors of this paper—have difficult sport experiences. Fortunately, there are skills we can learn to manage these difficult experiences! We can learn to recognize that sport is sometimes difficult and that all athletes mess up from time to time. We can also learn to be kind to, and supportive of, ourselves just like we would be to a close friend or teammate. Having self-compassion in sport can reduce the negative thoughts and feelings we might have about ourselves, and can decrease fears we might have about failing. Self-compassion can contribute to reaching our potential in sport; but how can we be self-compassionate?
Three Ways That Peers Matter in Youth Sport
Authors: Smith Alan L. , Mellano Kathleen T.
Published: April 2022

There are many features of youth sport that can make it exciting and motivating or, alternatively, make it dull, stressful, or otherwise uninviting. Among those features are the participants themselves. When young athletes sign up for a sport, opt to stay with a particular team, invest time and energy into practicing, or consider their competitive successes and failures, their peers (those of similar age, standing, and power) often play a part. Teammates are probably the most important peers in shaping youth sport choices and experiences, but other peers at school and elsewhere can also influence young athletes. In this article, we describe three ways that peers matter in youth sport. We argue that the quality of young athletes’ sport experiences is tied to specific friendships, broader acceptance by peers, and how athletes compare themselves to their peers. These aspects of peer relationships play important roles in shaping athlete motivation and performance.
Does It Matter What Kind of Dairy Products We Eat?
Authors: Rundblad Amanda , Holven Kirsten B. , Øyri Linn K. L. , Hansson Patrik , Ivan Ingvild H. , Gjevestad Gyrd O. , Thoresen Magne , Ulven Stine M.
Published: April 2022

Dairy is important in many people’s diets. Although all dairy products are made from cow’s milk, various dairy products are made by different processes. This means that they can end up having different nutrients and properties. Researchers and nutritionists usually group all dairy as one food group, but this might miss information about the health effects of eating different dairy products. Immune cells are important to protect us when we get sick. Sometimes, immune cells can be turned on for the wrong reasons and cause too much inflammation, which can lead to diseases. We studied immune cells from people who ate meals with either butter, cheese, whipped cream, or sour cream. After eating cheese and sour cream, immune cells showed fewer signs of inflammatory processes than after eating butter and whipped cream. This may mean that cheese and sour cream could be healthier than butter and whipped cream.
How Will Climate Change Affect Where You Live?
Authors: Viceto Carolina , Wongpan Pat , Fraser Alexander D.
Published: April 2022

In recent times, scientists have seen large changes in our planet’s climate. Although climate change is a global issue, the effects of climate change are not the same around the world. Each continent, country, and area will experience different effects. These effects include different speeds of warming or, in some places, cooling, and changes to rain- and snowfall. Since the climate is global, what happens in other places can also impact the place where you live. In this article, you will learn how various places on Earth have been affected by climate change up to now. We will also show you what kind of climate changes can be expected in the future.