bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic Characterization of Carbapenem-Non-susceptible Pseudomonas aeruginosa Clinical Isolates From Saudi Arabia Revealed a Global Dissemination of GES-5-Producing ST235 and VIM-2-Producing ST233 Sub-Lineages
Authors: Doumith Michel , Alhassinah Sarah , Alswaji Abdulrahman , Alzayer Maha , Alrashidi Essa , Okdah Liliane , Aljohani Sameera ,   NGHA AMR Surveillance Group, Balkhy Hanan H. , Alghoribi Majed F.
Published: January 2022

Carbapenem-resistant P. aeruginosa has become a major clinical problem due to limited treatment options. However, studies assessing the trends in the molecular epidemiology and mechanisms of antibiotic resistance in this pathogen are lacking in Saudi Arabia. Here, we reported the genome characterization in a global context of carbapenem non-susceptible clinical isolates from a nationally representative survey. The antibiotic resistance profiles of the isolates (n = 635) collected over 14 months between March 2018 and April 2019 from different geographical regions of Saudi Arabia showed resistance rates to relevant β-lactams, aminoglycosides and quinolones ranging between 6.93 and 27.56%. Overall, 22.52% (143/635) of the isolates exhibited resistance to both imipenem and meropenem that were mainly explained by porin loss and efflux overexpression. However, 18.18% of resistant isolates harbored genes encoding GES (69.23%), VIM (23.07%), NDM (3.85%) or OXA-48-like (3.85%) carbapenemases. Most common GES-positive isolates produced GESs −5, −15 or −1 and all belonged to ST235 whereas the VIM-positive isolates produced mainly VIM-2 and belonged to ST233 or ST257. GES and VIM producers were detected at different sampling periods and in different surveyed regions. Interestingly, a genome-wide comparison revealed that the GES-positive ST235 and VIM-2-positive ST233 genomes sequenced in this study and those available through public databases from various locations worldwide, constituted each a phylogenetically closely related sub-lineage. Profiles of virulence determinants, antimicrobial resistance genes and associated mobile elements confirmed relatedness within each of these two different sub-lineages. Sequence analysis located the blaGES gene in nearly all studied genomes (95.4%) in the same integrative conjugative element that also harbored the acc(6′)-Ib, aph(3′)-XV, aadA6, sul1, tet(G), and catB resistance genes while blaVIM–2 in most (98.89%) ST233-positive genomes was co-located with aac(6′)-I1, dfrB-5, and aac(3′)-Id in the same class I integron. The study findings revealed the global spread of GES-5 ST235 and VIM-2 ST233 sub-lineages and highlighted the importance of routine detection of rare β-lactamases.
Long-Term Effects of Aircraft Noise Exposure on Vascular Oxidative Stress, Endothelial Function and Blood Pressure: No Evidence for Adaptation or Tolerance Development
Authors: Frenis Katie , Kalinovic Sanela , Ernst Benjamin P. , Kvandova Miroslava , Al Zuabi Ahmad , Kuntic Marin , Oelze Matthias , Stamm Paul , Bayo Jimenez Maria Teresa , Kij Agnieszka , Keppeler Karin , Klein Veronique , Strohm Lea , Ubbens Henning , Daub Steffen , Hahad Omar , Kröller-Schön Swenja , Schmeisser Michael J. , Chlopicki Stefan , Eckrich Jonas , Strieth Sebastian , Daiber Andreas , Steven Sebastian , Münzel Thomas
Published: January 2022

Transportation noise is recognized as an important cardiovascular risk factor. Key mechanisms are noise-triggered vascular inflammation and oxidative stress with subsequent endothelial dysfunction. Here, we test for adaptation or tolerance mechanisms in mice in response to chronic noise exposure. C57BL/6J mice were exposed to aircraft noise for 0, 4, 7, 14 and 28d at a mean sound pressure level of 72 dB(A) and peak levels of 85 dB(A). Chronic aircraft noise exposure up to 28d caused persistent endothelial dysfunction and elevation of blood pressure. Likewise, reactive oxygen species (ROS) formation as determined by dihydroethidium (DHE) staining and HPLC-based measurement of superoxide formation in the aorta/heart/brain was time-dependently increased by noise. Oxidative burst in the whole blood showed a maximum at 4d or 7d of noise exposure. Increased superoxide formation in the brain was mirrored by a downregulation of neuronal nitric oxide synthase (Nos3) and transcription factor Foxo3 genes, whereas Vcam1 mRNA, a marker for inflammation was upregulated in all noise exposure groups. Induction of a pronounced hearing loss in the mice was excluded by auditory brainstem response audiometry. Endothelial dysfunction and inflammation were present during the entire 28d of aircraft noise exposure. ROS formation gradually increases with ongoing exposure without significant adaptation or tolerance in mice in response to chronic noise stress at moderate levels. These data further illustrate health side effects of long-term noise exposure and further strengthen a consequent implementation of the WHO noise guidelines in order to prevent the development of noise-related future cardiovascular disease.
Aged Cattle Brain Displays Alzheimer's Disease-Like Pathology and Promotes Brain Amyloidosis in a Transgenic Animal Model
Authors: Moreno-Gonzalez Ines , Edwards George , Morales Rodrigo , Duran-Aniotz Claudia , Escobedo Gabriel , Marquez Mercedes , Pumarola Marti , Soto Claudio
Published: January 2022

Alzheimer's disease (AD) is one of the leading causes of dementia in late life. Although the cause of AD neurodegenerative changes is not fully understood, extensive evidence suggests that the misfolding, aggregation and cerebral accumulation of amyloid beta (Aβ) and tau proteins are hallmark events. Recent reports have shown that protein misfolding and aggregation can be induced by administration of small quantities of preformed aggregates, following a similar principle by which prion diseases can be transmitted by infection. In the past few years, many of the typical properties that characterize prions as infectious agents were also shown in Aβ aggregates. Interestingly, prion diseases affect not only humans, but also various species of mammals, and it has been demonstrated that infectious prions present in animal tissues, particularly cattle affected by bovine spongiform encephalopathy (BSE), can infect humans. It has been reported that protein deposits resembling Aβ amyloid plaques are present in the brain of several aged non-human mammals, including monkeys, bears, dogs, and cheetahs. In this study, we investigated the presence of Aβ aggregates in the brain of aged cattle, their similarities with the protein deposits observed in AD patients, and their capability to promote AD pathological features when intracerebrally inoculated into transgenic animal models of AD. Our data show that aged cattle can develop AD-like neuropathological abnormalities, including amyloid plaques, as studied histologically. Importantly, cow-derived aggregates accelerate Aβ amyloid deposition in the brain of AD transgenic animals. Surprisingly, the rate of induction produced by administration of the cattle material was substantially higher than induction produced by injection of similar amounts of human AD material. Our findings demonstrate that cows develop seeding-competent Aβ aggregates, similarly as observed in AD patients.
Brain-Predicted Age Difference Moderates the Association Between Muscle Strength and Mobility
Authors: Vaughan Brooke A. , Simon Janet E. , Grooms Dustin R. , Clark Leatha A. , Wages Nathan P. , Clark Brian C.
Published: January 2022

Background

Approximately 35% of individuals over age 70 report difficulty with mobility. Muscle weakness has been demonstrated to be one contributor to mobility limitations in older adults. The purpose of this study was to examine the moderating effect of brain-predicted age difference (an index of biological brain age/health derived from structural neuroimaging) on the relationship between leg strength and mobility.

Methods

In community dwelling older adults (N= 57, 74.7 ± 6.93 years; 68% women), we assessed the relationship between isokinetic leg extensor strength and a composite measure of mobility [mobility battery assessment (MBA)] using partial Pearson correlations and multifactorial regression modeling. Brain predicted age (BPA) was calculated from T1 MR-images using a validated machine learning Gaussian Process regression model to explore the moderating effect of BPA difference (BPAD; BPA minus chronological age).

Results

Leg strength was significantly correlated with BPAD (r= −0.317,p< 0.05) and MBA score (r= 0.541,p< 0.001). Chronological age, sex, leg strength, and BPAD explained 63% of the variance in MBA performance (p< 0.001). BPAD was a significant moderator of the relationship between strength and MBA, accounting for 7.0% of MBA score variance [△R2= 0.044,F(1,51) = 6.83,p= 0.01]. Conditional moderation effects of BPAD indicate strength was a stronger predictor of mobility in those with a great BPAD.

Conclusion

The relationship between strength and mobility appears to be influenced by brain aging, with strength serving as a possible compensation for decline in neural integrity.
The Vestibular Column in the Mouse: A Rhombomeric Perspective
Authors: Diaz Carmen , Glover Joel C.
Published: January 2022

The vestibular column is located in the hindbrain between the sensory auditory (dorsal) and trigeminal (ventral) columns, spanning rhombomeres r1 (or r2) to r9. It contains the vestibular nuclear complex that receives sensory innervation from the labyrinthine end organs in the inner ear. Gene expression studies and experimental manipulations of developmental genes, particularly Hox genes and other developmental patterning genes, are providing insight into the morphological and functional organization of the vestibular nuclear complex, particularly from a segmental standpoint. Here, we will review studies of the classical vestibular nuclei and of vestibular projection neurons that innervate distinct targets in relation to individual rhombomeres and the expression of specific genes. Studies in different species have demonstrated that the vestibular complex is organized into a hodological mosaic that relates axon trajectory and target to specific hindbrain rhombomeres and intrarhombomeric domains, with a molecular underpinning in the form of transcription factor signatures, which has been highly conserved during the evolution of the vertebrate lineage.
Differential Involvement of Lateral Semicircular Canal and Otolith Organs in Common Vestibular Disorders
Authors: Kim Yehree , Kang Byung Chul , Yoo Myung Hoon , Park Hong Ju
Published: January 2022

Semicircular canal and otolith functions came to be evaluated recently, but comprehensive and comparative analysis of canal and otolith dysfunction in common vestibular disorders is lacking. We aimed to analyze the abnormal rates of canal and otolith function in common vestibular disorders. We enrolled 302 patients who were managed for 2 months in a dizziness clinic. Results of caloric, video head impulse test (vHIT), and cervical and ocular vestibular evoked myogenic potential (cVEMP and oVEMP) tests were analyzed and compared among various diagnoses. Vestibular disorders diagnosed included recurrent vestibulopathy (RV, 27%), vestibular migraine (VM, 21%), benign paroxysmal positional vertigo (BPPV, 17%), Meniere's disease (MD, 11%), vestibular neuritis (VN, 10%), orthostatic dizziness (7%), and central lesions (3%). Lateral canal dysfunction was found most in VN (100%) and less commonly in definite MD (75%), RV (46%) and definite VM (29%). Abnormal caloric results were more common than abnormal vHIT in all disorders. Otolith dysfunction was found more frequently than lateral canal dysfunction in most vestibular disorders except VN. An abnormal cVEMP was more frequent in definite MD than the other disorders. Isolated otolith dysfunction without lateral canal dysfunction was the most found in BPPV, followed by definite VM, RV, and definite MD in decreasing order. Various patterns of involvement in canal and otoliths were revealed in vestibular disorders, suggesting different pathogenesis.
Mid-Luteal Olfactory Abilities Reveal Healthy Women’s Emotional and Cognitive Functions
Authors: Yao Fangshu , Chen Kepu , Zhuang Yiyun , Shen Xueer , Wang Xiaochun
Published: January 2022

Ovarian hormones modulate women’s physical and psychological states periodically. Although the olfactory function is increasingly recognized as a reflection of physical and mental health conditions in the clinic, the role of olfaction in emotional and cognitive functions for healthy individuals has yet to be elucidated, especially when taking the menstrual cycle into account. We carried out a comprehensive investigation to explore whether the menstrual cycle could modulate women’s olfactory function and whether healthy women’s emotional symptoms and behavioral impulsivity could be characterized by their olfactory abilities at a specific menstrual cycle stage. Twenty-nine healthy young women were evaluated repeatedly using a standard olfactory test battery during the late follicular and mid-luteal phases. Their emotional symptoms and behavioral impulsivity were separately quantified via psychometric scales and a stop-signal task. We observed enhanced olfactory discrimination performance during the mid-luteal phase than the late follicular phase. We also found that women’s better olfactory discrimination and worse olfactory threshold in the mid-luteal phase predicted fewer individual emotional symptoms and lower behavioral impulsivity, respectively. These relationships were nonetheless absent in the late follicular phase. Our data extend previous clinical observations of the coexistence of olfactory deficits and neuropsychiatric disorders, providing new insights into the significance of olfaction and ovarian hormones for emotional and cognitive functions.
Association of Vitamin K Insufficiency With Cognitive Dysfunction in Community-Dwelling Older Adults
Authors: Azuma Kotaro , Osuka Yosuke , Kojima Narumi , Sasai Hiroyuki , Kim Hunkyung , Inoue Satoshi
Published: January 2022

Vitamin K is a fat-soluble vitamin shown to be associated with several age-related diseases. Although a small number of epidemiological studies described the relationship between vitamin K status and cognitive impairment, vitamin K status was estimated by relatively special methods in previous reports. Here, we demonstrated the association of the concentration of undercarboxylated osteocalcin (ucOC) in serum, which is a biomarker for vitamin K insufficiency, with cognitive function in a cross-sectional study. A total of 800 community-dwelling older adults (mean age = 75.9) were invited to geriatric health examination, including a Mini-Mental State Examination (MMSE) and a blood test. By using binary logistic regression analysis, the risk of cognitive impairment equivalent or below the mild cognitive impairment level for each tertile of ucOC was examined, with the lowest tertile as the reference. We found a significant association of impaired cognitive function and concentration of ucOC in the highest tertile of ucOC, with the odds ratio of 1.65 (95% CI, 1.06 to 2.59, P = 0.028). When the analysis was repeated with each domain of MMSE, the highest tertile of ucOC was associated with impaired orientation, calculation, and language. As far as we know, this is the first report on the significant association of single ucOC measurement and cognitive impairment. Our analysis also suggests that vitamin K insufficiency could be associated with selected categories of cognitive function. Since the single measurement of ucOC in serum is a simple and widely available method for vitamin K evaluation, it could be useful as a biomarker of neurodegenerative diseases affecting the cognitive functions.
Imaging Findings From Different Pathological Types of Oral and Maxillofacial Intramuscular Hemangiomas for Selecting Optimum Management
Authors: Zhu Dan , Dai Xiaoqing , Wang Jingbo , Zhang Chunye , Tao Xiaofeng , Wu Lizhong , Zhu Ling
Published: January 2022

Objectives

To assess computed tomography (CT) and magnetic resonance imaging (MRI) findings of intramuscular hemangiomas (IMHs) in oral and maxillofacial region and correlate them with the histopathological classifications for selecting optimum management.

Methods

The clinical data and pretreatment findings of 32 patients with pathologically proven IMHs on CT (n = 10), MRI (n = 27), or both (n = 5) were analyzed retrospectively. Correspondence of clinical and imaging characters with 3 different pathological classifications (cavernous, capillary, and mixed) of IMHs was studied. A number of pitfalls and overlap of imaging features can result in misdiagnosis of different IMHs lesions.

Results

Four patients had multi-muscular lesions, and 28 had single-muscular lesions. The predilection site were the tongue (11 cases, 34.4%) and the masseter muscle (10 cases, 31.2%). Cavernous type (17 cases, 53.1%) was the most common IMHs type. All patients showed slightly hypointense or isointense on T1-weighted imaging, 3 patients showed hyperintense on T2-weighted imaging and the others showed slightly hyperintense. The most common enhancement pattern was progressive (29 cases, 90.6%). The capillary type (9 cases, 28.1%) and mixed type (6 cases, 28.1%) of IMHs on imaging indicated characteristics of lesions with rich blood supply status, the cavernous type (17cases, 53.1%) of IMHs belonged to relatively poor blood supply lesions. A total of 5 patients (15.6%) were initially misdiagnosed, there were recurrences in 4 IMHs patients. Extra functional MRI (fMRI) was performed on these 5 misdiagnosed patients, the average ADC of the 5 patients was 1.50 × 10−3 mm2/s. The presence of vermicular vessels was different among these three types of IMHs.

Conclusions

The reason for the misdiagnosis in localized IMHs may be the obvious border of mass-like lesions and the lack of enlarged vessels. Combined evaluation of presence of vermicular vessels and fMRI might be more accurately for determining the IMHs and create a preoperative plan.
A Combined Model to Improve the Prediction of Local Control for Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy Based on Radiomic Signature Plus Clinical and Dosimetric Parameters
Authors: Luo Li-Mei , Huang Bao-Tian , Chen Chuang-Zhen , Wang Ying , Su Chuang-Huang , Peng Guo-Bo , Zeng Cheng-Bing , Wu Yan-Xuan , Wang Ruo-Heng , Huang Kang , Qiu Zi-Han
Published: January 2022

Purpose

Stereotactic body radiotherapy (SBRT) is an important treatment modality for lung cancer patients, however, tumor local recurrence rate remains some challenge and there is no reliable prediction tool. This study aims to develop a prediction model of local control for lung cancer patients undergoing SBRT based on radiomics signature combining with clinical and dosimetric parameters.

Methods

The radiomics model, clinical model and combined model were developed by radiomics features, incorporating clinical and dosimetric parameters and radiomics signatures plus clinical and dosimetric parameters, respectively. Three models were established by logistic regression (LR), decision tree (DT) or support vector machine (SVM). The performance of models was assessed by receiver operating characteristic curve (ROC) and DeLong test. Furthermore, a nomogram was built and was assessed by calibration curve, Hosmer-Lemeshow and decision curve.

Results

The LR method was selected for model establishment. The radiomics model, clinical model and combined model showed favorite performance and calibration (Area under the ROC curve (AUC) 0.811, 0.845 and 0.911 in the training group, 0.702, 0.786 and 0.818 in the validation group, respectively). The performance of combined model was significantly superior than the other two models. In addition, Calibration curve and Hosmer-Lemeshow (training group: P = 0.898, validation group: P = 0.891) showed good calibration of combined nomogram and decision curve proved its clinical utility.

Conclusions

The combined model based on radiomics features plus clinical and dosimetric parameters can improve the prediction of 1-year local control for lung cancer patients undergoing SBRT.
Augmented Features Synergize Radiomics in Post-Operative Survival Prediction and Adjuvant Therapy Recommendation for Non-Small Cell Lung Cancer
Authors: Chan Lawrence Wing-Chi , Ding Tong , Shao Huiling , Huang Mohan , Hui William Fuk-Yuen , Cho William Chi-Shing , Wong Sze-Chuen Cesar , Tong Ka Wai , Chiu Keith Wan-Hang , Huang Luyu , Zhou Haiyu
Published: January 2022

Background

Owing to the cytotoxic effect, it is challenging for clinicians to decide whether post-operative adjuvant therapy is appropriate for a non-small cell lung cancer (NSCLC) patient. Radiomics has proven its promising ability in predicting survival but research on its actionable model, particularly for supporting the decision of adjuvant therapy, is limited.

Methods

Pre-operative contrast-enhanced CT images of 123 NSCLC cases were collected, including 76, 13, 16, and 18 cases from R01 and AMC cohorts of The Cancer Imaging Archive (TCIA), Jiangxi Cancer Hospital and Guangdong Provincial People’s Hospital respectively. From each tumor region, 851 radiomic features were extracted and two augmented features were derived therewith to estimate the likelihood of adjuvant therapy. Both Cox regression and machine learning models with the selected main and interaction effects of 853 features were trained using 76 cases from R01 cohort, and their test performances on survival prediction were compared using 47 cases from the AMC cohort and two hospitals. For those cases where adjuvant therapy was unnecessary, recommendations on adjuvant therapy were made again by the outperforming model and compared with those by IBM Watson for Oncology (WFO).

Results

The Cox model outperformed the machine learning model in predicting survival on the test set (C-Index: 0.765 vs. 0.675). The Cox model consists of 5 predictors, interestingly 4 of which are interactions with augmented features facilitating the modulation of adjuvant therapy option. While WFO recommended no adjuvant therapy for only 13.6% of cases that received unnecessary adjuvant therapy, the same recommendations by the identified Cox model were extended to 54.5% of cases (McNemar’s test p = 0.0003).

Conclusions

A Cox model with radiomic and augmented features could predict survival accurately and support the decision of adjuvant therapy for bettering the benefit of NSCLC patients.
Association Between Cholecystectomy and Gastric Cancer Risk: A Systematic Review and Meta-Analysis
Authors: Yang Ying , Liu Ming-Hua , Li Yan
Published: January 2022

Objectives

Although several epidemiological studies have attempted to evaluate the relationship between cholecystectomy and gastric cancer risk, the findings have been controversial. This study aimed to carry out a systematic review and meta-analysis following the reporting guidelines to comprehensively analyze and quantify the evidence of the aforementioned association.

Methods

Studies were identified by searching the Medline (PubMed), Embase, and Web of Science from inception to November 30, 2020, with only studies published in English being considered. Summary relative risks (RRs) and 95% confidence intervals (CIs) were calculated by random-effects models.

Results

Eight studies (five cohort studies and three case–control studies) with a total of 26,063 gastric cancer patients and 848,081 participants were included. The summarized RR of the relationship between cholecystectomy and gastric cancer risk was 1.11 (95%CI: 1.03–1.20), with low heterogeneity (P = 0.117, I2 = 37.8%). These positive findings were consistent in most subgroup analyses like region in Asia, number of cases ≥200, cohort study design, sex in male, low risk of bias, exposure collection by database, and adjustments made for age, gender, calendar year. Of note, we also observed positive association between cholecystectomy and non-cardia of gastric cancer risk (RR = 1.17, 95%CI: 1.04–1.33). No publication bias was present.

Conclusions

The aforementioned evidence suggested that a history of cholecystectomy was associated with a slightly elevated risk of gastric cancer. Results of most subgroup analyses also supported the main findings. More prospective studies are warranted to further validate these findings.
Nucleolar and Coiled-Body Phosphoprotein 1 Is Associated With Stemness and Represents a Potential Therapeutic Target in Triple-Negative Breast Cancer
Authors: Chen Sisi , Li Ying , Wu Muyao , Xue Lian , Zhu Jianyu , Wu Mi , Zhang Qiuting , He Guangchun , Li Guifei , Fu Shujun , Zheng Chanjuan , Deng Xiyun
Published: January 2022

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer and lacks approved specific targeted therapies. One of the major reasons why TNBC is difficult to treat is the high proportion of cancer stem cells within the tumor tissue. Nucleolus is the location of ribosome biogenesis which is frequently overactivated in cancer cells and overactivation of ribosome biogenesis frequently drives the malignant transformation of cancer. Nucleolar and coiled-body phosphoprotein 1 (NOLC1) is a nucleolar protein responsible for nucleolus organization and rRNA synthesis and plays an important role in ribosome biogenesis. However, the correlation of NOLC1 expression with patient prognosis and its value as a therapeutic target have not been evaluated in TNBC. In the current study, based on bioinformatics analysis of the online databases, we found that the expression of NOLC1 was higher in breast cancer tissues than normal tissues, and NOLC1 was expressed at a higher level in TNBC than other subtypes of breast cancer. GSEA analysis revealed that stemness-related pathways were significantly enriched in breast cancer with high NOLC1 gene expression. Further analyses using gene expression profiling interactive analysis 2 (GEPIA2), tumor immune estimation resource (TIMER) and search tool for retrieval of interacting genes/proteins (STRING) demonstrated that NOLC1 was significantly associated with stemness in both all breast cancer and basal-like breast cancer/TNBC patients at both gene and protein levels. Knockdown of NOLC1 by siRNA decreased the protein level of the key stemness regulators MYC and ALDH and inhibited the sphere-forming capacity in TNBC cell line MDA-MB-231. Univariate and multivariate Cox regression analyses demonstrated that NOLC1 was an independent risk factor for overall survival in breast cancer. PrognoScan and Kaplan-Meier plotter analyses revealed that high expression of NOLC1 was associated with poor prognosis in both all breast cancer and TNBC patients. Further immunohistochemical analysis of breast cancer patient samples revealed that TNBC cells had a lower level of NOLC1 in the nucleus compared with non-TNBC cells. These findings suggest that NOLC1 is closely associated with the stemness properties of TNBC and represents a potential therapeutic target for TNBC.
Epigenetic Regulation of Ferroptosis-Associated Genes and Its Implication in Cancer Therapy
Authors: Pei Yanzi , Qian Yujie , Wang Hao , Tan Li
Published: January 2022

Ferroptosis is an evolutionarily conserved form of regulated cell death triggered by iron-dependent phospholipid peroxidation. Ferroptosis contributes to the maintenance of tissue homeostasis under physiological conditions while its aberration is tightly connected with lots of pathophysiological processes such as acute tissue injury, chronic degenerative disease, and tumorigenesis. Epigenetic regulation controls chromatin structure and gene expression by writing/reading/erasing the covalent modifications on DNA, histone, and RNA, without altering the DNA sequence. Accumulating evidences suggest that epigenetic regulation is involved in the determination of cellular vulnerability to ferroptosis. Here, we summarize the recent advances on the epigenetic mechanisms that control the expression of ferroptosis-associated genes and thereby the ferroptosis process. Moreover, the potential value of epigenetic drugs in targeting or synergizing ferroptosis during cancer therapy is also discussed.
Imaging Biomarkers of Glioblastoma Treatment Response: A Systematic Review and Meta-Analysis of Recent Machine Learning Studies
Authors: Booth Thomas C. , Grzeda Mariusz , Chelliah Alysha , Roman Andrei , Al Busaidi Ayisha , Dragos Carmen , Shuaib Haris , Luis Aysha , Mirchandani Ayesha , Alparslan Burcu , Mansoor Nina , Lavrador Jose , Vergani Francesco , Ashkan Keyoumars , Modat Marc , Ourselin Sebastien
Published: January 2022

Objective

Monitoring biomarkers using machine learning (ML) may determine glioblastoma treatment response. We systematically reviewed quality and performance accuracy of recently published studies.

Methods

Following Preferred Reporting Items for Systematic Reviews and Meta-Analysis: Diagnostic Test Accuracy, we extracted articles from MEDLINE, EMBASE and Cochrane Register between 09/2018–01/2021. Included study participants were adults with glioblastoma having undergone standard treatment (maximal resection, radiotherapy with concomitant and adjuvant temozolomide), and follow-up imaging to determine treatment response status (specifically, distinguishing progression/recurrence from progression/recurrence mimics, the target condition). Using Quality Assessment of Diagnostic Accuracy Studies Two/Checklist for Artificial Intelligence in Medical Imaging, we assessed bias risk and applicability concerns. We determined test set performance accuracy (sensitivity, specificity, precision, F1-score, balanced accuracy). We used a bivariate random-effect model to determine pooled sensitivity, specificity, area-under the receiver operator characteristic curve (ROC-AUC). Pooled measures of balanced accuracy, positive/negative likelihood ratios (PLR/NLR) and diagnostic odds ratio (DOR) were calculated. PROSPERO registered (CRD42021261965).

Results

Eighteen studies were included (1335/384 patients for training/testing respectively). Small patient numbers, high bias risk, applicability concerns (particularly confounding in reference standard and patient selection) and low level of evidence, allow limited conclusions from studies. Ten studies (10/18, 56%) included in meta-analysis gave 0.769 (0.649-0.858) sensitivity [pooled (95% CI)]; 0.648 (0.749-0.532) specificity; 0.706 (0.623-0.779) balanced accuracy; 2.220 (1.560-3.140) PLR; 0.366 (0.213-0.572) NLR; 6.670 (2.800-13.500) DOR; 0.765 ROC-AUC.

Conclusion

ML models using MRI features to distinguish between progression and mimics appear to demonstrate good diagnostic performance. However, study quality and design require improvement.
Pigment Epithelium Derived Factor Is Involved in the Late Phase of Osteosarcoma Metastasis by Increasing Extravasation and Cell-Cell Adhesion
Authors: Kuriyama Sei , Tanaka Gentaro , Takagane Kurara , Itoh Go , Tanaka Masamitsu
Published: January 2022

Organ tropism of metastatic cells is not well understood. To determine the key factors involved in the selection of a specific organ upon metastasis, we established metastatic cell lines and analyzed their homing to specific tissues. Toward this, 143B osteosarcoma cells were injected intracardially until the kidney-metastasizing sub-cell line Bkid was established, which significantly differed from the parental 143B cells. The candidate genes responsible for kidney metastasis were validated, and SerpinF1/Pigment epithelium derived factor (PEDF) was identified as the primary target. Bkid cells with PEDF knockdown injected intracardially did not metastasize to the kidneys. In contrast, PEDF overexpressing 143B cells injected into femur metastasized to the lungs and kidneys. PEDF triggered mesenchymal-to-epithelial transition (MET) in vitro as well as in vivo. Based on these results, we hypothesized that the MET might be a potential barrier to extravasation. PEDF overexpression in various osteosarcoma cell lines increased their extravasation to the kidneys and lungs. Moreover, when cultured close to the renal endothelial cell line TKD2, Bkid cells disturbed the TKD2 layer and hindered wound healing via the PEDF-laminin receptor (lamR) axis. Furthermore, novel interactions were observed among PEDF, lamR, lysyl oxidase-like 1 (Loxl1), and SNAI3 (Snail-like transcription factor) during endothelial-to-mesenchymal transition (EndoMT). Collectively, our results show that PEDF induces cancer cell extravasation by increasing the permeability of kidney and lung vasculature acting via lamR and its downstream genes. We also speculate that PEDF promotes extravasation via inhibiting EndoMT, and this warrants investigation in future studies.
Research Advances in Cardio-Cerebrovascular Diseases of Ligusticum chuanxiong Hort.
Authors: Li Dan , Long Yu , Yu Shuang , Shi Ai , Wan Jinyan , Wen Jing , Li Xiaoqiu , Liu Songyu , Zhang Yulu , Li Nan , Zheng Chuan , Yang Ming , Shen Lin
Published: January 2022

Cardio-cerebrovascular diseases (CVDs) are a serious threat to human health and account for 31% of global mortality. Ligusticum chuanxiong Hort. (CX) is derived from umbellifer plants. Its rhizome, leaves, and fibrous roots are similar in composition but have different contents. It has been used in Japanese, Korean, and other traditional medicine for over 2000 years. Currently, it is mostly cultivated and has high safety and low side effects. Due to the lack of a systematic summary of the efficacy of CX in the treatment of CVDs, this article describes the material basis, molecular mechanism, and clinical efficacy of CX, as well as its combined application in the treatment of CVDs, and has been summarized from the perspective of safety. In particular, the pharmacological effect of CX in the treatment of CVDs is highlighted from the point of view of its mechanism, and the complex mechanism network has been determined to improve the understanding of CX’s multi-link and multi-target therapeutic effects, including anti-inflammatory, antioxidant, and endothelial cells. This article offers a new and modern perspective on the impact of CX on CVDs.
New Insights Into the Epigenetic Regulation of Inflammatory Bowel Disease
Authors: Xu Jing , Xu Hao-ming , Yang Mei-feng , Liang Yu-jie , Peng Quan-zhou , Zhang Yuan , Tian Cheng-mei , Wang Li-sheng , Yao Jun , Nie Yu-qiang , Li De-feng
Published: January 2022

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the colonic mucosa. Environmental factors, genetics, intestinal microbiota, and the immune system are all involved in the pathophysiology of IBD. Lately, accumulating evidence has shown that abnormal epigenetic changes in DNA methylation, histone markers, and non-coding RNA expression greatly contribute to the development of the entire disease. Epigenetics regulates many functions, such as maintaining the homeostasis of the intestinal epithelium and regulating the immune system of the immune cells. In the present study, we systematically summarized the latest advances in epigenetic modification of IBD and how epigenetics reveals new mechanisms of IBD. Our present review provided new insights into the pathophysiology of IBD. Moreover, exploring the patterns of DNA methylation and histone modification through epigenetics can not only be used as biomarkers of IBD but also as a new target for therapeutic intervention in IBD patients.
Mismatch Between Specific and Genetic Diversity in an Evergreen Broadleaf Forest in Southeast China: A Study Case of 10.24 ha Forest Dynamics Plot of Huangshan
Authors: Xie Lei , Chen ShuiFei , Feng YueYao , Li Yao , Wang Lu , He LiHeng , Huang LiQun , Wu Jun , Guo Ke , Ding Hui , Fang YanMing
Published: January 2022

For a long time, forestry management has often focused on the protection of species diversity, and mistakenly believed that protecting species diversity protects genetic diversity. Therefore, research that integrates community ecology and population genetics has become important because it can help elucidate whether the targets for protecting specific and genetic diversity are congruent. In this study, we have emphasized the impact of the community on the population because no previous studies have considered the community composition of a place a priori. Based on the Huangshan 10.24 ha dynamics forest plot, we a priori considered the community composition in the plot to test species-genetic diversity among the tree layers. Firstly, a redundancy analysis (RDA) found that Castanopsis eyrei and Pinus massoniana were the dominant species. Secondly, specific and genetic diversity are not congruent in Huang Shan. Finally, the structural equation model (SEM) showed that the different degrees of response by community composition and population structure to environmental heterogeneity are the main reasons for the mismatch between species diversity and genetic diversity. The results suggest that we must focus on genetic diversity, as well as on protecting species diversity.
Avoidant Attachment, Withdrawal-Aggression Conflict Pattern, and Relationship Satisfaction: A Mediational Dyadic Model
Authors: Bretaña Ione , Alonso-Arbiol Itziar , Recio Patricia , Molero Fernando
Published: January 2022

This study was conducted with the purpose of analyzing the combined and mediating effect of actor’s withdrawal–partner’s demand conflict resolution strategies between avoidance attachment dimension and relationship satisfaction. We conducted a dyadic study with 175 heterosexual couples (aged between 18 and 72 years) who filled in the questionnaires. Six hypotheses were tested using the actor–partner interdependence model with mediation analysis (APIMeM). Results showed that the avoidance dimension of attachment was more strongly associated with actor’s withdrawal strategy than with demand/aggression strategy. Furthermore, avoidance attachment was negatively associated with both actor’s and partner’s relationship satisfaction, the actor effect being higher. Withdrawal strategy was a mediator between actor’s avoidance and actor’s relationship satisfaction, but it was not a mediator for partner’s relationship satisfaction. The interactive pattern of actor’s withdrawal–partner’s demand/aggression was associated with low levels of both actor’s and partner’s relationship satisfaction. These results point out to the need of discerning the interactive pattern of conflict-solving strategies as well as their intertwined effect on relationship satisfaction.
Examining Gifted Students' Evaluations of Their Education Programs in Terms of Their Project Production and Management
Authors: Özbek Gülnur , Dağyar Miray
Published: January 2022

The aim of this study is to examine gifted students' evaluations of their education programs in terms of their project production and management by considering the basic principles of gifted education and training programs. In evaluating the effectiveness of programs for gifted students, it is regarded as important to consider the evaluations of the individuals for whom the programs are implemented. Project production and management was taken as the basis for the principles and guidelines of the programs implemented for gifted students. A mixed research design was used in the study. In the quantitative part of the research, the views of 300 randomly selected gifted students, who were attending the project production and management (PPM) and special talent development (STD) programs at Science and Art Centers (SACs) throughout Turkey, regarding their evaluation of the education programs, were analyzed. In the qualitative part of the research, the project production and management of the gifted individuals in the upper and lower groups according to their program evaluations were evaluated descriptively by examining the project proposals they developed. In the analysis of the quantitative data, it was determined that the participants had positive views about the effectiveness of the program, but that there was a significant difference between the upper and lower groups in terms of program evaluation scores. Considering this situation, the data of 10 participants in total (five participants included in each of the upper and lower groups) were subjected to qualitative analysis in the second stage. As a result of the study, it was determined that all of the gifted students in the upper and lower groups were able to produce projects, but that in the categories specified in their projects, there were differences in favor of the upper group in terms of depth, originality, taking their talents into account, acting consciously, acting in accordance with the plan, participating in more prestigious competitions, and quality.
Link Between Perception of Treatment Need and Craving Reports in Addiction
Authors: Lambert Laura , Serre Fuschia , Thirioux Berangere , Jaafari Nematollah , Roux Perrine , Jauffret-Roustide Marie , Lalanne Laurence , Daulouède Jean-Pierre , Auriacombe Marc
Published: January 2022

Background

Perception of treatment need (PTN), a component of clinical insight, is associated to negative addiction treatment outcomes when low. Our hypothesis was that lower PTN was associated with less craving when reported retrospectively, the most common measure of craving in clinical settings.

Objective

To explore the association between PTN and craving among a dataset of subjects with severe substance use disorders.

Methods

Participants were recruited from outpatient addiction clinic admissions or harm reduction program services. Good and low PTN were based on consistency between severe addiction (at least six DSM-5 criteria) and self-report need for addiction treatment from the Addiction Severity Index. Craving was retrospectively characterized over the past 30 days. Multiple regression analyses were conducted.

Results

Participants with low PTN (n = 97) retrospectively reported less frequent and intense episodes of craving, compared with participants with good PTN (n = 566) after controlling for sociodemographic factors, addiction type, and severity (p < 0.0001).

Conclusion

Low perception of treatment need among subjects with severe addictions is associated to less retrospective report of craving, which may contribute to reduced efficiency of treatment. Further studies are needed to explore the mechanisms of the association.
Symptom Clusters and Quality of Life in Cervical Cancer Patients Receiving Concurrent Chemoradiotherapy: The Mediating Role of Illness Perceptions
Authors: Zhang Lan , Wang Jia , Chen Tangzhen , Tian Min , Zhou Qimin , Ren Jianhua
Published: January 2022

Objectives

Although studies shows that symptom clusters and illness perceptions are negatively associated with quality of life (QoL), it is unclear how these variables of cervical cancer patients who receive concurrent chemoradiotherapy (CCRT) relate to each other. This study aimed to identify the symptom clusters in cervical cancer patients who receive CCRT and evaluate the mediating effect of illness perceptions on the relationship between symptom clusters and QoL.

Methods

A cross-sectional survey was conducted on 286 cervical cancer patients receiving CCRT from October 2019 to October 2020. M.D. Anderson Symptom Inventory, Brief Illness Perception Questionnaire, and Functional Assessment Cancer Therapy-Cervix were applied to investigate the symptom clusters, illness perceptions and QoL of the participants, respectively. Exploratory factor analysis was conducted to identify symptom clusters. The relationships among symptom clusters, illness perceptions, and QoL were analyzed with the structural equation modeling.

Results

A total of four symptom clusters were identified, including psychological status symptom cluster, therapy side-effect symptom cluster, sickness symptom cluster, and gastrointestinal symptom cluster (χ2 = 1,552.282, Df = 78, P < 0.001). Symptom clusters, illness perceptions, and QoL were significantly correlated. Symptom clusters had significant direct (β = −0.38, P < 0.001) and indirect effects (β = −0.21, P < 0.001) on QoL.

Conclusion

Illness perceptions played a significant mediating role between symptom clusters and QoL in cervical cancer patients receiving CCRT. Strategies like prompting effective symptom management for the purposes of alleviating illness perceptions may contribute to improving their QoL.
Interprofessional Team-Based Learning: A Qualitative Study on the Experiences of Nursing and Physiotherapy Students
Authors: Ho Jacqueline Mei-Chi , Wong Arnold Yu-Lok , Schoeb Veronika , Chan Alex Siu-Wing , Tang Patrick Ming-Kuen , Wong Frances Kam-Yuet
Published: January 2022

Traditional discipline-specific training has limitations in facilitating inter-professional communication and collaboration. To address this issue, two local universities in Hong Kong launched an interprofessional team-based learning program to allow the undergraduate healthcare students to form teams and experience collaborative problem-solving. This study aimed to evaluate the experiences of nursing and physiotherapy undergraduates following interprofessional learning activities. Twenty-seven 3rd-year nursing and physiotherapy undergraduates were recruited through purposive sampling. Semi-structured interviews were conducted, and written feedback was solicited until data saturation was achieved. An inductive thematic analysis was used for the data, and each theme was mutually exclusive. The findings revealed the positive experiences of the students with this interprofessional learning activity. Three main themes emerged: (1) the process of interprofessional learning; (2) profession-related outcomes of interprofessional learning; and (3) patient-related outcomes of interprofessional learning. The study indicated that interprofessional team-based learning activities enhanced learning experiences of the students through interactive learning with other healthcare students. Experiences of relationships that are trustful and complementary allow students to develop confidence in knowledge transfer and in interprofessional collaboration, as well as in providing a holistic patient-centered care. These findings substantiate the importance and value of interprofessional learning in healthcare education.
Realizing Promising Educational Practices in Academic Public Health: A Model for the Scholarship of Teaching and Learning
Authors: Neubauer Leah C. , Merzel Cheryl , Weist Elizabeth M. , Corvin Jaime Antoinette , Forsman Allan , Fraser Jacquie , Henderson Heather L. , Hinyard Leslie J. , Opacich Karin Joann , Runnerstrom Miryha G.
Published: January 2022

This paper presents a conceptual framework and critical considerations for the scholarship of teaching and learning (SoTL) in academic public health. Academic education for public health has undergone significant transformation over the last two decades as the demand for responsive and innovative public health pedagogy and training for preparing graduates to deploy an increasing array of skills has grown. The authors suggest that the role of schools, administrators, faculty, and educational staff in developing promising practices for teaching and learning in public health involves an articulated conceptual framework to guide the development and dissemination of scholarly, pedagogical innovations. Building on seminal philosophical foundations of SoTL, the authors conceptualize SoTL from the foundational belief that knowing and learning are communal tasks and that faculty are both scholars and learners in the practice of education. The paper advocates for SoTL as a form of engaged practice and scholarly inquiry that exists in contextually rich, diverse educational environments that abounds with uncertainty. SoTL is guided by an educational philosophy, values, and learning theories that envision educators critically examining themselves, their teaching practice, scholarly literature, and students' learning to improve their teaching, enhance learning, and promote further inquiry. The authors suggest that SoTL involves the search for multiple forms of evidence and fosters dialogues on multiple interpretations and perspectives of the most promising practices of teaching and learning. The authors advocate for the term promising practices as an outcome of SoTL that supports and nurtures ongoing scientific discovery and knowledge generation, instead of supporting the search for best-ness in teaching and learning endeavors. SoTL should occur across formal, informal, and nonformal education