bluuebunny/crossref_metadata_2025 huggingface dataset:
Integrated Bioinformatics-Based Identification of Potential Diagnostic Biomarkers Associated with Diabetic Foot Ulcer Development
Authors: Qian Long , Xia Zhipeng , Zhang Ming , Han Qiong , Hu Die , Qi Sha , Xing Danmou , Chen Yan , Zhao Xin
Published: September 2021

The present study was designed to detect possible biomarkers associated with diabetic foot ulcer (DFU) incidence in an effort to develop novel treatments for this condition. The GSE7014 and GSE29221 gene expression datasets were downloaded from the Gene Expression Omnibus (GEO) database, after which differentially expressed genes (DEGs) were identified between DFU and healthy samples. These DEGs were then arranged into a protein-protein interaction (PPI) network, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) term enrichment analyses were performed to explore the functional roles of these genes. In total, 1192 DEGs were identified in the GSE7014 dataset (900 upregulated, 292 downregulated), while 1177 were identified in the GSE29221 dataset (257 upregulated, 919 downregulated). GO analyses revealed these DEGs to be significantly enriched in biological processes including sarcomere organization, muscle filament sliding, and the regulation of cardiac conduction, molecular functions including structural constituent of muscle, protein binding, and calcium ion binding, and cellular components including Z disc, myosin filament, and M band. These DEGs were also enriched in the adrenergic signaling in cardiomyoctes, dilated cardiomyopathy, and tight junction KEGG pathways. Together, the findings of these bioinformatics analyses thus identified key hub genes associated with DFU development.
[Retracted] Dysregulated Circulating Apoptosis‐ and Autophagy‐Related lncRNAs as Diagnostic Markers in Coronary Artery Disease
Authors: Zhang Lijiao , Lou Dayuan , He Dan , Wang Ying , Wu Yuhang , Cao Xinyang , Qu Peng
Published: September 2021

Objective. Increasing evidence emphasizes the implications of dysregulated apoptosis and autophagy cellular processes in coronary artery disease (CAD). Herein, we aimed to explore apoptosis‐ and autophagy‐related long noncoding RNAs (lncRNAs) in peripheral blood of CAD patients. Methods. The mRNA and lncRNA expression profiles were retrieved from the Gene Expression Omnibus (GEO) database. With ∣fold change | >1.5 and adjusted p value < 0.05, differentially expressed apoptosis‐ and autophagy‐related mRNAs were screened between CAD and healthy blood samples. Also, differentially expressed lncRNAs were identified for CAD. Using the psych package, apoptosis‐ and autophagy‐related lncRNAs were defined with Spearson’s correlation analysis. Receiver operating characteristic (ROC) curves were conducted for the assessment of the diagnosed efficacy of these apoptosis‐ and autophagy‐related lncRNAs. Results. Our results showed that 24 apoptosis‐ and autophagy‐related mRNAs were abnormally expressed in CAD than normal controls. 12 circulating upregulated and 1 downregulated apoptosis‐ and autophagy‐related lncRNAs were identified for CAD. The ROCs confirmed that AC004485.3 (AUC = 0.899), AC004920.3 (AUC = 0.93), AJ006998.2 (AUC = 0.776), H19 (AUC = 0.943), RP5‐902P8.10 (AUC = 0.956), RP5‐1114G22.2 (AUC = 0.883), RP11‐247A12.1 (AUC = 0.885), RP11‐288L9.4 (AUC = 0.928), RP11‐344B5.2 (AUC = 0.858), RP11‐452C8.1 (AUC = 0.929), RP11‐565A3.1 (AUC = 0.893), and XXbac‐B33L19.4 (AUC = 0.932) exhibited good performance in differentiating CAD from healthy controls. Conclusion. Collectively, our findings proposed that circulating apoptosis‐ and autophagy‐related lncRNAs could become underlying diagnostic markers for CAD in clinical practice.
ABCC7/CFTR Expression Is Associated with the Clinical Course of Ulcerative Colitis Patients
Authors: Villeda-Ramírez Marco A. , Meza-Guillen Daniela , Barreto-Zúñiga Rafael , Yamamoto-Furusho Jesús K.
Published: September 2021

Inflammatory bowel disease includes ulcerative colitis (UC) and Crohn’s disease (CD) of unknown etiology. The expression of ATP-binding cassette (ABC) family proteins has been associated with drug resistance and development of UC. The cystic fibrosis transmembrane conductance regulator (CFTR) or also known as ABCC7 is involved in the inflammatory chronic response. The aim of this study was to evaluate the role of ABCC7/CFTR in UC patients and normal controls without inflammation. This is an exploratory, observational, and cross-sectional study that included a total of 62 patients with UC and normal controls. Gene expression of CFTR was measured by RT-PCR, and protein expression of CFTR was determined by western blot analysis. We found a significant downregulation of the CFTR gene expression in patients with active UC compared to normal controls without inflammation (

P
<
0.004

); even the gene expression of CFTR was decreased in remission UC patients compared to normal controls without inflammation (

P
=
0.04

). The CFTR gene expression was associated with the clinical course of UC and the protein expression of CFTR was decreased in active UC patients compared to normal controls without inflammation suggesting that this molecule might play a role in the inflammation in UC patients.
Programmed NP Cell Death Induced by Mitochondrial ROS in a One‐Strike Loading Disc Degeneration Organ Culture Model
Authors: Li Bao-Liang , Liu Xizhe , Gao Manman , Zhang Fu , Chen Xu , He Zhongyuan , Wang Jianmin , Tian Wei , Chen Dafu , Zhou Zhiyu , Liu Shaoyu
Published: September 2021

Increasing evidence has indicated that mitochondrial reactive oxygen species (ROS) play critical roles in mechanical stress‐induced lumbar degenerative disc disease (DDD). However, the detailed underlying pathological mechanism needs further investigation. In this study, we utilized a one‐strike loading disc degeneration organ culture model to explore the responses of intervertebral discs (IVDs) to mechanical stress. IVDs were subjected to a strain of 40% of the disc height for one second and then cultured under physiological loading. Mitoquinone mesylate (MitoQ) or other inhibitors were injected into the IVDs. IVDs subjected to only physiological loading culture were used as controls. Mitochondrial membrane potential was significantly depressed immediately after mechanical stress (P < 0.01). The percentage of ROS‐positive cells significantly increased in the first 12 hours after mechanical stress and then declined to a low level by 48 hours. Pretreatment with MitoQ or rotenone significantly decreased the proportion of ROS‐positive cells (P < 0.01). Nucleus pulposus (NP) cell viability was sharply reduced at 12 hours after mechanical stress and reached a stable status by 48 hours. While the levels of necroptosis‐ and apoptosis‐related markers were significantly increased at 12 hours after mechanical stress, no significant changes were observed at day 7. Pretreatment with MitoQ increased NP cell viability and alleviated the marker changes by 12 hours after mechanical stress. Elevated mitochondrial ROS levels were also related to extracellular matrix (ECM) degeneration signs, including catabolic marker upregulation, anabolic marker downregulation, increased glycosaminoglycan (GAG) loss, IVD dynamic compressive stiffness reduction, and morphological degradation changes at the early time points after mechanical stress. Pretreatment with MitoQ alleviated some of these degenerative changes by 12 hours after mechanical stress. These changes were eliminated by day 7. Taken together, our findings demonstrate that mitochondrial ROS act as important regulators of programmed NP cell death and ECM degeneration in IVDs at early time points after mechanical stress.
Study on Lateral Deformation and Failure Characteristics of Coal Based on Different Confining Pressures
Authors: Ren Jian-jun , Wei Shan-Yang , Shu Shi-Hai , Luo Wei-Dong
Published: September 2021

To study the lateral deformation characteristics of coal under different confining pressures, coal compression experiments with confining pressures of 0 MPa, 3 MPa, 5 MPa, and 7 MPa were conducted under the same loading rate by using the TAW‐2000 electrohydraulic servo rock mechanics experimental machine. The results of the study showed the following: at the initial stage of loading, the lateral strain of coal was about 12.22%–46.9% of the axial strain at the elastic deformation stage and 41.18%–64.96% of the axial strain at the inelastic deformation to peak stress stage. Compared with the experiment under 0 MPa confining pressure, the growth rate of the lateral strain of the coal under 3 MPa, 5 MPa, and 7 MPa confining pressures was much smaller than that of the corresponding axial strain. When the coal was damaged under different confining pressures, the lateral strain was maintained at about 0.6 × 10−2. Based on the field verification, we proposed that the lateral strain during the coal failure and the nonlinear region of the lateral axis ratio changing with time can be used as potential parameters for predicting the coal failure.
Multitarget Detection and Tracking Method in Remote Sensing Satellite Video
Authors: Lei Lei , Guo Dongen
Published: September 2021

A remote sensing video satellite multiple object detection and tracking method based on road masking, Gaussian mixture model (GMM), and data association is proposed. This method first extracts the road network from the remote sensing video based on deep learning. In the detection stage, the background subtraction algorithm is used based on the GMM to obtain the detection results of the moving targets on the road. In the tracking stage, the data association of the same target detection result in adjacent frames is realized based on the neighborhood search algorithm, so as to obtain the continuous tracking trajectory of each target. The experiments about multiobject detection and tracking are conducted on data measure by real remote sensing satellites, and the results verified the feasibility of the proposed method.
Grid-Based Anomaly Detection of Freight Vehicle Trajectory considering Local Temporal Window
Authors: Zhang Zixian , Qi Geqi , Ceder Avishai (Avi) , Guan Wei , Guo Rongge , Wei Zhenlin
Published: September 2021

The security travel of freight vehicles is of high societal concern and is the key issue for urban managers to effectively supervise and assess the possible social security risks. With continuous improvements in motion-based technology, the trajectories of freight vehicles are readily available, whose unusual changes may indicate hidden urban risks. Moreover, the increasing high spatial and temporal resolution of trajectories provides the opportunity for the real-time recognition of the abnormal or risky vehicle motion. However, the existing researches mainly focus on the spatial anomaly detection, and there are few researches on the real-time temporal anomaly detection. In this paper, a grid-based algorithm, which combines the spatial and temporal anomaly detection, is proposed for tracing the risk of urban freight vehicles trajectory by considering local temporal window. The travel time probability distribution of vehicle historical trajectory is analyzed to meet the time complexity requirements of real-time anomaly calculation. The developed methodology is applied to a case study in Beijing to demonstrate its accuracy and effectiveness.
Numerical Study of the Effect of Perforation Friction and Engineering Parameters on Multicluster Fracturing in Horizontal Wells
Authors: Jiao Zixi , Zhang Anlin , Du Longhuan , Yang Yang , Fan Hua
Published: September 2021

Simultaneous multiple-fracture treatments in horizontal wellbores have become one of the key methods for economically and efficiently developing oil and gas resources in unconventional reservoirs. However, field data show that some perforation clusters have difficulty propagating fractures due to the internal mechanism of competing initiation and propagation among the fractures. In this paper, the physical mechanisms that influence simultaneous multiple-fracture initiation and propagation are investigated, and the effects of engineering parameters and in situ conditions on the nonuniform development of multiple fractures are discussed. A 3D fracture propagation model was established with ABAQUS to show the influence of the stress shadow effects and dynamic partitioning of the flow rate by simulating the propagation of multiple competing fractures generated in the perforation clusters. Based on the results of these simulations, simultaneous flow in multiple fractures can propagate evenly. Through adjusting the number of perforations in each cluster or the perforation diameter, the effect of the stress shadow can be significantly reduced by increasing the perforation friction, and the factors that affect the development of multiple fractures are changed, from the stress shadow effect to the dynamic partitioning of the flow rate. When the stress shadow effect is dominant, increasing the fracturing fluid viscosity promotes the uniform development of multiple fractures and increases the fracture width. When the dynamic partitioning of the flow rate is dominant, increasing the injection rate greatly affects the uniform development of multiple fractures.
The Role of mRNA Translational Control in Tumor Immune Escape and Immunotherapy Resistance
Authors: Cerezo Michaël , Robert Caroline , Liu Lunxu , Shen Shensi
Published: September 2021

Tremendous advances have been made in cancer immunotherapy over the last decade. Among the different steps of gene expression, translation of mRNA is emerging as an essential player in both cancer and immunity. Changes in mRNA translation are both rapid and adaptive, and translational reprogramming is known to be necessary for sustaining cancer cell proliferation. However, the role of mRNA translation in shaping an immune microenvironment permissive to tumors has not been extensively studied. Recent studies on immunotherapy approaches have indicated critical roles of mRNA translation in regulating the expression of immune checkpoint proteins, tuning the secretion of inflammation-associated factors, modulating the differentiation of immune cells in the tumor microenvironment, and promoting cancer resistance to immunotherapies. Careful consideration of the role of mRNA translation in the tumor-immune ecosystem could suggest more effective therapeutic strategies and may eventually change the current paradigm of cancer immunotherapy. In this review, we discuss recent advances in understanding the relationship between mRNA translation and tumor-associated immunity, the potential mechanisms of immunotherapy resistance in cancers linked to translational reprogramming, and therapeutic perspectives and potential challenges of modulating translational regulation in cancer immunotherapy.
The Landmark Discovery That Paved the Way to a Mechanistic Understanding of P53 Gain of Function and Personalized Medicine
Authors: Napoli Marco , Deshpande Avani A. , Flores Elsa R.
Published: September 2021

In 1990, Baker and colleagues reported their seminal findings in Cancer Research focusing on the transition from adenoma to carcinoma of the colon. By sequencing the TP53 locus in 58 colorectal tumors (25 adenomas and 33 carcinomas) and measuring its allelic deletions, they discovered that this transition requires the loss of one TP53 allele and the mutation of the other one. Here, we discuss how this landmark discovery shed a new light on p53 mutations, prompting the generation of novel mouse models that definitively proved the mutant p53 gain-of-function hypothesis suggested by these results. Finally, we evaluate the implications that the Vogelstein model of cancer progression had on numerous aspects of cancer biology and cancer care, including the characterization of tumor evolution and the response to therapy, and how it ultimately contributed to the wider adoption of early detection screenings and personalized medicine.

See related article by Baker and colleagues, Cancer Res 1990;50:7717–22
Lowering mTORC1 Drives CAR T-Cells Home in Acute Myeloid Leukemia
Authors: Maiti Abhishek , Daver Naval G.
Published: September 2021

Cellular therapies have demonstrated limited efficacy thus far in acute myeloid leukemia (AML). A recent study shows that mTOR complex 1 activation downregulated CXCR4 reducing marrow infiltration of EpCAM-targeting chimeric antigen receptor (CAR) T-cells in AML. Abrogating mTOR signaling by cotreatment with mTOR inhibitors during IL2-mediated ex vivo expansion upregulated CXCR4 and bolstered bone marrow migration and AML elimination by CAR T-cells.

See related article by Nian et al., p. 6026
Secreted Frizzled-Related Protein 5 Ameliorates Vascular Calcification in a Rat Model of Chronic Kidney Disease through the Wnt/β-Catenin Pathway
Authors: Deng Dai , Han Xue , Diao Zongli , Liu Wenhu
Published: September 2021

Introduction: Vascular calcification (VC) is highly prevalent and a major cardiovascular risk factor in chronic kidney disease (CKD) patients. Secreted frizzled-related protein 5 (SFRP5), an inhibitor of the Wnt pathway, is an adipokine with a positive effect on metabolic and cardiovascular diseases. Our previous in vitro study showed that SFRP5 attenuates high phosphate-induced calcification in vascular smooth muscle cells by inhibiting the Wnt/β-catenin pathway. Therefore, we hypothesized that SFRP5 may protect against CKD-associated VC (CKD-VC) through the same signalling. Methods: The rat model of CKD with VC was induced by 0.75% adenine combined with 1.8% high phosphate diet, which were administered with adenovirus vectors of SFRP5. We evaluated the SFRP5 effect on VC by von Kossa staining and calcium content analysis and osteogenic markers by immunohistochemistry and Western blot. The components of Wnt/ß-catenin signalling were also evaluated. Results: SFRP5 local and serum levels were significantly decreased in the CKD-VC rat model compared with the control group. Adenovirus-mediated overexpression of SFRP5 significantly inhibited VC, which was due to suppression of CKD-induced expression of calcification and osteoblastic markers. Additionally, SFRP5 abrogated activation of the Wnt/β-catenin pathway that plays a major role in the pathogenesis of VC. The specificity of SFRP5 for inhibition of VC was confirmed using an empty adenovirus as a control. Conclusion: Our results suggest that SFRP5 ameliorates VC of CKD rats by inhibiting the expression of calcification and osteoblastic markers as well as the Wnt/β-catenin pathway. Collectively, this study suggests that SFRP5 is a potential therapeutic target in CKD-VC.
Variation of Hair Follicle Counts among Different Scalp Areas: A Quantitative Histopathological Study
Authors: Rutnin Suthinee , Chanprapaph Kumutnart , Pakornphadungsit Kallapan , Leerunyakul Kanchana , Visessiri Yingluck , Srisont Smith , Suchonwanit Poonkiat
Published: September 2021

Introduction: Scalp biopsy is a standard method for the definitive diagnosis of alopecia. The hair count parameters of each scalp area remain unclear. This study aimed to determine hair count values at different scalp locations from histopathology and to establish reference values for each part of the scalp. Methods: We obtained biopsy specimens from the frontal, vertex, temporoparietal, and occipital areas of the scalps of normal deceased subjects. All specimens were evaluated for the number of follicular units, hair counts, hair types, and stages of the hair cycle. Results: In total, 240 specimens were collected from 60 cadavers. Across all scalp sites, the temporoparietal area showed the lowest mean hair count, number of follicular units, terminal and vellus hairs, and terminal-to-vellus hair ratio. The average anagen-to-telogen hair ratio was comparable across all scalp sites. This study did not observe a significant association of hair parameters with gender differences or increasing age in all scalp areas. Conclusions: The present study revealed the diversity of the hair index among different scalp areas and suggested that normal hair count values should be separately standardized on each scalp region. Our findings may provide useful reference values for the histopathological evaluation of hair disorders in Asians.
Genetic Variant Score and Arrhythmogenic Right Ventricular Cardiomyopathy Phenotype in Plakophilin-2 Mutation Carriers
Authors: Svensson Anneli , Platonov Pyotr G. , Haugaa Kristina H. , Zareba Wojciech , Jensen Henrik Kjærulf , Bundgaard Henning , Gilljam Thomas , Madsen Trine , Hansen Jim , Dejgaard Lars A. , Karlsson Lars O. , Gréen Anna , Polonsky Bronislava , Edvardsen Thor , Svendsen Jesper Hastrup , Gunnarsson Cecilia
Published: September 2021

Introduction: Whether detailed genetic information contributes to risk stratification of patients with arrhythmogenic right ventricular cardiomyopathy (ARVC) remains uncertain. Pathogenic genetic variants in some genes seem to carry a higher risk for arrhythmia and earlier disease onset than others, but comparisons between variants in the same gene have not been done. Combined Annotation Dependent Depletion (CADD) score is a bioinformatics tool that measures the pathogenicity of each genetic variant. We hypothesized that a higher CADD score is associated with arrhythmic events and earlier age at ARVC manifestations in individuals carrying pathogenic or likely pathogenic genetic variants in plakophilin-2 (PKP2). Methods: CADD scores were calculated using the data from pooled Scandinavian and North American ARVC cohorts, and their association with cardiac events defined as ventricular tachycardia/ventricular fibrillation (VT/VF) or syncope and age at definite ARVC diagnosis were assessed. Results: In total, 33 unique genetic variants were reported in 179 patients (90 males, 71 probands, 96 with definite ARVC diagnosis at a median age of 35 years). Cardiac events were reported in 76 individuals (43%), of whom 53 had sustained VT/VF (35%). The CADD score was neither associated with age at cardiac events (HR 1.002, 95% CI: 0.953–1.054, p = 0.933) nor with age at definite ARVC diagnosis (HR 0.992, 95% CI: 0.947–1.039, p = 0.731). Conclusion: No correlation was found between CADD scores and clinical manifestations of ARVC, indicating that the score has no additional risk stratification value among carriers of pathogenic or likely pathogenic PKP2 genetic variants.
Contemporary Patients With Congenital Heart Disease
Authors: Brouwer Charlotte , Hebe Joachim , Lukac Peter , Nürnberg Jan-Hendrik , Cosedis Nielsen Jens , de Riva Silva Marta , Blom Nico , Hazekamp Mark , Zeppenfeld Katja
Published: September 2021

Background:

Poor outcome after atrial tachycardia (AT) radiofrequency catheter ablation (RFCA) in repaired congenital heart disease (CHD) has been attributed to CHD complexity. This may not apply to contemporary patients. The objective of our study was to assess outcome after RFCA for AT in contemporary patients with CHD according to prior atrial surgery and predefined procedural endpoints.

Methods:

Patients with CHD referred for AT RFCA to 3 European centers were classified as no atrial surgery/cannulation only, limited or extensive prior atrial surgery. Procedural success was predefined as termination and nonreinducibility for focal AT and bidirectional block across ablation lines for intra-atrial reentrant tachycardia and after empirical substrate ablation for noninducible patients. Patients were followed for AT recurrence and mortality.

Results:

Ablation was performed in 290 patients (41±17 years, 59% male; 3-dimensional mapping 89%, irrigated tip catheters 90%, transbaffle access 15%). In 197, 233 AT were targeted (196 intra-atrial reentrant tachycardia [64% cavotricuspid (mitral) isthmus–dependent, 33% systemic-venous incision–dependent] and 37 focal AT). In 93 noninducible patients, empirical substrate ablation was performed. Procedural success was achieved in 209 (84%) patients. AT recurred in 148 (54%) 10 (interquartile range, 0–25) months after RFCA. AT-free survival was significantly better in patients with no atrial repair/cannulation only and in patients with complete procedural success independently of CHD complexity. From 94 patients undergoing reablation, the initially targeted substrate had recovered in 64%.

Conclusions:

In contemporary patients with CHD, outcome after AT ablation is associated with presence of prior atrial surgery and achievement of predefined procedural endpoints rather than CHD complexity. Techniques to improve lesion durability are likely to further improve long-term outcome.
Human RyR2 (Ryanodine Receptor 2) Loss-of-Function Mutations
Authors: Li Yanhui , Wei Jinhong , Guo Wenting , Sun Bo , Estillore John Paul , Wang Ruiwu , Yoruk Ayhan , Roston Thomas M. , Sanatani Shubhayan , Wilde Arthur A.M. , Gollob Michael H. , Roberts Jason D. , Tseng Zian H. , Jensen Henrik K. , Chen S.R. Wayne
Published: September 2021

Background:

The overall objective of the present study is to extend our understanding of the clinical phenotype and underlying mechanism of a newly discovered cardiac arrhythmia syndrome through a multicenter study. Gain-of-function mutations in the cardiac Ca
2+
release channel (RyR2 [ryanodine receptor 2]) cause catecholaminergic polymorphic ventricular tachycardia, whereas loss-of-function RyR2 mutations are linked to a new cardiac arrhythmia disorder termed Ca
2+
-release deficiency syndrome (CRDS). Catecholaminergic polymorphic ventricular tachycardia is an inherited arrhythmia disorder characterized by stress-induced bidirectional and polymorphic ventricular tachyarrhythmias and is routinely diagnosed by using exercise stress testing. Conversely, RyR2-CRDS is characterized by ventricular arrhythmias and sudden cardiac death but a negative exercise stress testing for catecholaminergic polymorphic ventricular tachycardia. There are currently no clinical diagnostic tests for CRDS and affected patients may manifest with sudden cardiac death as their first symptom. In the absence of effective clinical diagnostic tools, in vitro functional characterization of associated RyR2 mutations provides an alternative means to identify potential cases of CRDS.

Methods:

We searched for patients presenting with phenotypes compatible with CRDS that have RyR2 mutations and performed in vitro functional characterization.

Results:

We found that 3 novel (G570D, R4147K, and A4203V) and 2 previously reported (M4109R and A4204V) RyR2 mutations associated with CRDS phenotypes markedly reduced caffeine-induced Ca
2+
release and store overload-induced Ca
2+
release. We also characterized 2 additional loss-of-function RyR2 mutations previously reported (Q3925E and L4769S) that are located in the central and channel pore-forming domains critical for Ca
2+
activation and channel gating. Q3925E was identified through postmortem genetic testing in an individual who died suddenly, while L4769S is a variant of uncertain significance reported in ClinVar, suggesting that RyR2 CRDS may be under detected.

Conclusions:

These findings provide further support for the existence of an emerging RyR2 loss-of-function associated arrhythmia syndrome (CRDS) and shed new insights into the disease mechanism.
Atrial Fibrillation in Spontaneous Intracerebral Hemorrhage, Dijon Stroke Registry (2006–2017)
Authors: Gabet Amélie , Olié Valérie , Béjot Yannick
Published: September 2021

Background

Atrial fibrillation (AF) represents a major indication for oral anticoagulants (OAC) that contribute to spontaneous intracerebral hemorrhage (ICH). This study evaluated AF prevalence among patients with ICH, temporal trends, and early functional outcomes and death of patients.

Methods and Results

Patients with first‐ever ICH were prospectively recorded in the population‐based stroke registry of Dijon, France, (2006–2017). Association between AF and early outcome of patients with ICH (ordinal modified Rankin Scale score and death at discharge) were analyzed using ordinal and logistic regressions. Among 444 patients with ICH, 97 (21.9%) had AF, including 65 (14.6%) with previously known AF treated with OAC, and 13 (2.9%) with newly diagnosed AF. AF prevalence rose from 17.2% (2006–2011) to 25.8% (2012–2017) (
P
‐trend=0.05). An increase in the proportion of AF treated with OAC (11.3% to 17.5%,
P
‐trend=0.09) and newly diagnosed AF (1.5% to 4.2%,
P
‐trend=0.11) was observed. In multivariable analyses, after adjustment for premorbid OAC, AF was not significantly associated with ordinal modified Rankin Scale score (odds ratio [OR], 1.29; 95% CI, 0.69–2.42) or death (OR, 0.89; 95% CI, 0.40–1.96) in patients with ICH. Nevertheless, adjusted premorbid OAC use remained highly associated with a higher probability of death (OR, 2.53; 95% CI, 1.11–5.78).

Conclusions

AF prevalence and use of OAC among patients with ICH increased over time. Premorbid use of OAC was associated with poor outcome after ICH, thus suggesting a need to better identify ICH risk before initiating or pursuing OAC therapy in patients with AF, and to develop acute treatment and secondary prevention strategies after ICH in patients with AF.
Investigating Rurality as a Risk Factor for State and Trait Hopelessness in Hospitalized Patients With Ischemic Heart Disease
Authors: Bomgaars Deb , Jensen Gwenneth A. , White Lynn L. , Van De Griend Kristin M. , Visser Angela K. , Goodyke Madison P. , Luong Anna , Tintle Nathan L. , Dunn Susan L.
Published: September 2021

Background

Rurality and hopelessness are each associated with increased mortality in adults with ischemic heart disease (IHD), yet there is no known research examining rurality as a risk factor for hopelessness in patients with IHD. This study evaluated rurality as a risk factor for state and trait hopelessness in adults hospitalized with IHD in samples drawn from the Great Lakes and Great Plains regions of the United States.

Methods and Results

A descriptive cross‐sectional design was used. Data were collected from 628 patients hospitalized for IHD in the Great Lakes (n=516) and Great Plains (n=112). Rural–Urban Commuting Area codes were used to stratify study participants by level of rurality. Levels of state hopelessness (measured by the State‐Trait Hopelessness Scale) were higher in rural patients (58.8% versus 48.8%; odds ratio [OR], 1.50; 95% CI, 1.03–2.18), a difference that remained statistically significant after adjusting for demographics, depression severity (measured by the Patient Health Questionnaire–8), and physical functioning (measured by the Duke Activity Status Index; OR, 1.59; 95% CI, 1.06–2.40;
P
=0.026). There was evidence of an interaction between marital status and rurality on state hopelessness after accounting for covariates (
P
=0.02). Nonmarried individuals had an increased prevalence of state hopelessness (nonmarried 72.0% versus married 52.0%) in rural areas (
P
=0.03).

Conclusions

Rural patients with IHD, particularly those who are nonmarried, may be at higher risk for state hopelessness compared with patients with IHD living in urban settings. Understanding rurality differences is important in identifying subgroups most at risk for hopelessness.

Registration

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT04498975.
Towards mobile learning deployment in higher learning institutions: a report on the qualitative inquiries conducted in four universities in Tanzania
Authors: Ghasia Mohamed A. , De Smet Egbert , Machumu Haruni , Musabila Albogast
Published: September 2021

Over the past two decades, mobile learning (m-learning) has been a purposeful area of research among educational technologists, educators and instructional designers whereby doubts and controversies over its relevancy and applicability have been keenly addressed. This paper explores stakeholders’ perceptions of m-learning deployment in Higher Learning Institutions (HLIs). Specifically, we examine the potential of m-learning for HLIs in Tanzania and the challenges that hinder successful m-learning deployment. We adopt a comparative qualitative case study design in which four HLIs in Tanzania were purposefully selected. The study uses a combination of design science research approach and qualitative methods including grounded theory, document reviews, and observation. The respondents included university lecturers, students and ICT experts, who were selected for the interviews through theoretical sampling. The transcripts were loaded, coded and analyzed in NVIVO software. The results indicate that mobiles (smartphone, tablets, laptops, feature-phones etc.) are widely used in the HLIs. Stakeholders perceive that m-learning deployment is important and useful because it improves the quality of the learning experience. The results further indicate that there are financial, pedagogical, technological, infrastructural, individuals – and policy – related challenges that hinder successful deployment of m-learning in HLIs in Tanzania, such as limited network coverage, some students´ inability to afford mobiles, lack of qualified staff for preparation of mobile content and administration, gaps in the existing policies, and faulty course design. However, our results show that participants are optimistic about the potential of m-learning in the HLIs of Tanzania. They expect that m-learning will improve access to learning resources, teacher-student and student-student interaction without being restricted by time or place. Thus, m-learning is considered to have the potential to address issues of crowded classrooms, expertise, access to learning materials, flexibility of the learners as well as remote connectivity.

We recommend that HLIs should prioritize m-learning and commit resources to the success of the related projects. We also recommend that the governments and stakeholders provide policy interventions, subsidize mobile technologies, expand network coverage, build capacity within and outside HLIs, and improve digital literacy by integrating ICT education at all levels of education.
Litotetothrips Priesner (Thysanoptera, Phlaeothripinae); an Asian genus newly recorded from Australia with two new species and one new combination
Authors: MOUND LAURENCE A. , TREE DESLEY J.
Published: September 2021

Relationships are discussed among the five genera related to Liothrips in which species have antennal segment VIII long and slender. Litotetothrips is the oldest of these generic names and is used here for three species newly recorded from Australia: L. caledonensis (Bournier) comb.n., L. gallicola sp.n. and L. tareei sp.n.
A tiny new species of Microhyla Tschudi, 1838 (Amphibia: Anura: Microhylidae) from Belitung Island and Southeastern Sumatra, Indonesia
Authors: EPRILURAHMAN RURY , GARG SONALI , ATMAJA VESTIDHIA Y. , ALHADI FARITS , MUNIR MISBAHUL , UBAIDILLAH ROSICHON , ARISURYANTI TUTY , BIJU S. D. , SMITH ERIC N. , HAMIDY AMIR
Published: September 2021

A tiny new species of narrow-mouthed frog of the genus Microhyla is described from the island of Belitung and southeastern Sumatra, Indonesia. The most distinctive feature of the new frog is its diminutive adult size, snout-vent length ranging only from 12.3 to 15.8 mm in adult males. Phylogenetic analyses based a fragment of the mitochondrial 16S rRNA gene, along with detailed morphological and acoustic comparison differentiate the new taxon from all known congeners. The new species, formally described as Microhyla sriwijaya sp. nov., is a member of the M. achatina species group and the sister taxon to M. orientalis. It is diagnosable from other congeners by a combination of characters: (1) smaller male snout-vent size < 16 mm; (2) snout obtusely rounded in dorsal view; (3) absence of mid-dorsal line and skin fold; (4) first finger reduced (finger I length less than half of finger II length); (5) dorsum with a prominent dark median mark extending posteriorly, narrow anteriorly near the level of the shoulder and expanding dorsolaterally up to the vent; margins of the dorsal marking concave with broad reddish-brown or orange colouration on either side; (6) foot webbing rudimentary, reaching just up to the first subarticular tubercle on all toes; (7) dorsal skin with prominent tubercles, especially in life; (8) tibiotarsal articulation of adpressed limb reaching beyond the snout tip; and (9) males produce a single type of call with pulsatile temporal structure, calls of relatively short duration ranging between 31.8–62.8 s, with two to three pulses delivered at a rate ranging between 32.2–36.0 pulses per second, and the mean overall dominant frequency of 4.3 kHz. The uncorrected pairwise genetic distances between Microhyla sriwijaya sp. nov. and all other known congeners are > 3.8% for the studied 16S gene fragment. The new species was discovered from wayside rural areas with oil palm plantations at four localities in the small island of Belitung (type locality), and from coffee plantation and secondary forest at Lampung in southeastern Sumatra. It is not known from any protected area and appears to be threatened due to tin mining activity, intensive logging, oil palm, and other commonly practiced agriculture activities.
Review of the genus Larnaca Walker, 1869 from China (Orthoptera: Gryllacrididae: Gryllacridinae)
Authors: YIN ZI-XU , MENG LING-XIN
Published: September 2021

The Chinese species of Larnaca are reviewed. A new species, Larnaca (Larnaca) walle sp. nov. is described from China. Female of Larnaca (Larnaca) emarginata Bian, Guo & Shi, 2015 is described for the first time. The type specimen is deposited in Museum of Biology, East China Normal University.
Methicillin-Resistant Staphylococcus aureus (MRSA): Prevalence, Antimicrobial Susceptibility Pattern, and Detection of mecA Gene among Cardiac Patients from a Tertiary Care Heart Center in Kathmandu, Nepal
Authors: Dhungel Sajina , Rijal Komal Raj , Yadav Bindeshwar , Dhungel Binod , Adhikari Nabaraj , Shrestha Upendra Thapa , Adhikari Bipin , Banjara Megha Raj , Ghimire Prakash
Published: September 2021

Background:

Methicillin Resistant Staphylococcus aureus (MRSA) is a significant human pathogen associated with nosocomial infections. mecA in the S. aureus is a marker of MRSA. The main objective of this study was to detect mecA and vanA genes conferring resistance in S. aureus among cardiac patients attending Sahid Gangalal National Heart Centre (SGNHC), Kathmandu, Nepal between May and November 2019.

Methods:

A total of 524 clinical samples (blood, urine, sputum) were collected and processed. Bacterial isolates were tested for antimicrobial susceptibility test (AST) and screening for MRSA was carried out by cefoxitin disc diffusion method. Minimum inhibitory concentration (MIC) of vancomycin for MRSA was established by agar dilution method and chromosomal DNA was extracted and used in polymerase chain reaction targeting the mecA and vanA genes.

Results:

Out of 524 specimens, 27.5% (144/524) showed bacterial growth. Among 144 culture positive isolates, S. aureus (27.1%; 39/144) was the predominant bacteria. Among 39 S. aureus isolates, all isolates were found resistant to penicillin followed by erythromycin (94.9%; 37/39), gentamicin (94.9%; 37/39) and cefoxitin (87.2%; 34/39). Out of 39 S. aureus, 87.2% (34/39) were MRSA. Among 34 MRSA, 8.8% (3/34) were vancomycin intermediate S. aureus (VISA). None of the MRSA was resistant to vancomycin. All of the 3 VISA isolates were obtained from inpatients. Of 39 S. aureus, 82.1% (32/39) harbored mecA gene. Similarly, the entire VISA isolates and 94.1% (32/34) of the MRSA isolates were tested positive for mecA gene.

Conclusions:

High prevalence of MRSA among the cardiac patients indicates the increasing burden of drug resistance among bacterial isolates. Since infection control is the crucial step in coping with the burgeoning antimicrobial resistance in the country, augmentation of diagnostic facilities with routine monitoring of drug resistance is recommended.
Exportin-T: A Novel Prognostic Predictor and Potential Therapeutic Target for Neuroblastoma
Authors: Pan Li-Jia , Chen Jian-Lei , Wu Zhi-Xiang , Wu Ye-Ming
Published: September 2021

Exportins as the key mediators of nucleocytoplasmic transport have been identified as the controllers of the passage of numerous types of crucial cancer-related proteins. Targeting exportins in cancer cells might represent an emerging strategy in cancer intervention with the potential to affect clinical outcomes. Here, we focused on the prognostic and therapeutic values of Exportin-T (XPOT) in neuroblastoma. The correlation between the expression and prognostic values of XPOT in patients with neuroblastoma was investigated based on both published transcriptome data and our clinical data. Then, decision curve analysis (DCA) was implemented to identify a XPOT risk prediction model. In addition, RNA inference was performed to silence the expression of XPOT to further investigate the specific roles of XPOT in the progression of neuroblastoma in vitro. Overexpression of XPOT mRNA was associated with poor clinical characteristics, such as age at diagnosis more than 18 months, amplification of MYCN, and advanced International Neuroblastoma Staging System (INSS) stage, and XPOT expression was identified as an independent poor prognosis factor for neuroblastoma using Cox proportional hazards model ( P < .001). DCA suggested that neuroblastoma patients could benefit from XPOT risk prediction model-guided interventions (status of MYCN  +  INSS stage  +  XPOT). Experimentally, knockdown of XPOT by small interfering RNA inhibited the proliferation and migration in neuroblastoma cells. XPOT is identified as a novel prognostic predictor and potential therapeutic target for neuroblastoma patients. Further investigation should focus on the profound molecular mechanism underlying the tumor inhibition activity of XPOT inhibitors.
Thermessaite-(NH4), (NH4)2AlF3(SO4), a new fumarole mineral from La Fossa crater at Vulcano, Aeolian Islands, Italy
Authors: Garavelli Anna , Pinto Daniela , Mitolo Donatella , Kolitsch Uwe
Published: September 2021

Thermessaite-(NH4), ideally (NH4)2AlF3(SO4), is a new mineral found as a medium- to high-temperature (~250–300°C) fumarole encrustation at the rim of La Fossa crater, Vulcano, Aeolian Islands, Italy. The mineral deposited as aggregates of minute (<0.2 mm) sharp prismatic crystals on the surface of a pyroclastic breccia in association with thermessaite, sulfur, arcanite, mascagnite, and intermediate members of the arcanite–mascagnite series.

The new mineral is colourless to white, transparent, non-fluorescent, has a vitreous lustre, and a white streak. The calculated density is 2.185 g/cm3. Thermessaite-(NH4) is orthorhombic, space group Pbcn, with a = 11.3005(3) Å, b = 8.6125(3) Å, c = 6.8501(2) Å, V = 666.69(4) Å3 and Z = 4. The eight strongest reflections in the powder X-ray diffraction data [d in Å (I)(hkl)] are: 5.65 (100)(200), 4.84 (89)(111), 6.85 (74)(110), 3.06 (56)(112), 3.06 (53)(221), 3.08 (47)(311), 2.68 (28)(022) and 2.78 (26)(130). The average chemical composition, determined by quantitative SEM-EDS (N by difference), is (wt.%): K2O 3.38, Al2O3 25.35, SO3 36.58, F 26.12, (NH4)2O 22.47, O = F –11.00, total 102.90. The empirical chemical formula, calculated on the basis of 7 anions per formula unit, is [(NH4)1.85K0.15]Σ2.00Al1.06F2.94S0.98O3.06. The crystal structure, determined from single-crystal X-ray diffraction data [R(F) = 0.0367], is characterised by corner-sharing AlF4O2 octahedra which form [001] octahedral chains by sharing two trans fluoride atoms [Al–F2 = 1.8394(6) Å]. Non-bridging Al–F1 distances are shorter [1.756(1) Å]. The two trans oxygen atoms [Al–O = 1.920(2) Å] are from SO4 tetrahedra. NH4+ ions occur in layers parallel to (100) which alternate regularly with (100) layers containing ribbons of corner-sharing AlF4O2 octahedra and associated SO4 groups. The NH4+ ions are surrounded by five oxygen atoms and by four fluorine atoms. The mineral is named as the (NH4)-analogue of thermessaite, K2AlF3(SO4), and corresponds to an anthropogenic phase found in the burning Anna I coal dump of the Anna mine, Aachen, Germany. Both mineral and mineral name have been approved by the International Mineralogical Association Commission on New Minerals, Nomenclature and Classification (IMA2011-077).
Targeting pediatric leukemia-propagating cells with anti-CD200 antibody therapy
Authors: Diamanti Paraskevi , Cox Charlotte V. , Ede Benjamin C. , Uger Robert A. , Moppett John P. , Blair Allison
Published: September 2021

Treating refractory pediatric acute lymphoblastic leukemia (ALL) remains a challenge despite impressive remission rates (>90%) achieved in the last decade. The use of innovative immunotherapeutic approaches such as anti-CD19 chimeric antigen receptor T cells does not ensure durable remissions, because leukemia-propagating cells (LPCs) that lack expression of CD19 can cause relapse, which signifies the need to identify new markers of ALL. Here we investigated expression of CD58, CD97, and CD200, which were previously shown to be overexpressed in B-cell precursor ALL (BCP-ALL) in CD34+/CD19+, CD34+/CD19–, CD34–/CD19+, and CD34–/CD19– LPCs, to assess their potential as therapeutic targets. Whole-genome microarray and flow cytometric analyses showed significant overexpression of these molecules compared with normal controls. CD58 and CD97 were mainly co-expressed with CD19 and were not a prerequisite for leukemia engraftment in immune deficient mice. In contrast, expression of CD200 was essential for engraftment and serial transplantation of cells in measurable residual disease (MRD) low-risk patients. Moreover, these CD200+ LPCs could be targeted by using the monoclonal antibody TTI-CD200 in vitro and in vivo. Treating mice with established disease significantly reduced disease burden and extended survival. These findings demonstrate that CD200 could be an attractive target for treating low-risk ALL, with minimal off-tumor effects that beset current immunotherapeutic approaches.
Pathophysiology of pulmonary function anomalies in COVID-19 survivors
Authors: Laveneziana Pierantonio , Sesé Lucile , Gille Thomas
Published: September 2021

Coronavirus disease 2019 (COVID-19) is a disease caused by a new coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-​2), and the predisposing and protecting factors have not been fully elucidated. COVID-19 primarily impacts the respiratory system, and can result in mild illness or serious disease leading to critical illness requiring admission to the intensive care unit due to respiratory failure. After hospital discharge, the more commonly described pulmonary function anomalies are alterations in diffusing capacity and the loss of lung volume. Reduction of inspiratory muscle contraction may also be underestimated. This article will focus on the pathophysiology of pulmonary function anomalies in COVID-19 survivors. We will discuss current advances and provide future directions and also present our perspective on this field.
Defining obstructive sleep apnoea syndrome: a failure of semantic rules
Authors: Riha Renata L.
Published: September 2021

Obstructive sleep apnoea syndrome (OSAS) is one of the most ubiquitous medical conditions in industrialised society. Since the recognition that symptoms of excessive daytime somnolence, problems with concentration, mood and cognitive impairment, as well as cardiometabolic abnormalities can arise as a consequence of obstructed breathing during sleep, it has been subject to variation in its definition. Over the past five decades, attempts have been made to standardise the definitions and scoring criteria used for apnoeas and hypopnoea, which are the hallmarks of obstructive sleep apnoea (OSA). However, applying these definitions in clinical and research practice has resulted in over- and under-estimation of the severity and prevalence of OSAS. Furthermore, the definitions may eventually become redundant in the context of rapid technological advances in breathing measurement and other signal acquisition. Increased efforts towards precision medicine have led to a focus on the pathophysiology of obstructed breathing during sleep. However, the same degree of effort has not been focused on how and why the latter does or does not result in diurnal symptoms, integral to the definition of OSAS. This review focuses on OSAS in adults and discusses some of the difficulties with current definitions and the possible reasons behind them.