bluuebunny/crossref_metadata_2025 huggingface dataset:
Evidence That the Etiology of Congenital Hypopituitarism Has a Major Genetic Component but Is Infrequently Monogenic
Authors: Jee Youn Hee , Gangat Mariam , Yeliosof Olga , Temnycky Adrian G. , Vanapruks Selena , Whalen Philip , Gourgari Evgenia , Bleach Cortney , Yu Christine H. , Marshall Ian , Yanovski Jack A. , Link Kathleen , Ten Svetlana , Baron Jeffrey , Radovick Sally
Published: August 2021

Purpose

Congenital hypopituitarism usually occurs sporadically. In most patients, the etiology remains unknown.

Methods

We studied 13 children with sporadic congenital hypopituitarism. Children with non-endocrine, non-familial idiopathic short stature (NFSS) (n= 19) served as a control group. Exome sequencing was performed in probands and both unaffected parents. A burden testing approach was used to compare the number of candidate variants in the two groups.

Results

First, we assessed the frequency of rare, predicted-pathogenic variants in 42 genes previously reported to be associated with pituitary gland development. The average number of variants per individual was greater in probands with congenital hypopituitarism than those with NFSS (1.1 vs. 0.21, mean variants/proband,P= 0.03). The number of probands with at least 1 variant in a pituitary-associated gene was greater in congenital hypopituitarism than in NFSS (62% vs. 21%,P= 0.03). Second, we assessed the frequency of rare, predicted-pathogenic variants in the exome (to capture undiscovered causes) that were inherited in a fashion that could explain the sporadic occurrence of the proband’s condition with a monogenic etiology (de novomutation, autosomal recessive, or X-linked recessive) with complete penetrance. There were fewer monogenic candidates in the probands with congenital hypopituitarism than those with NFSS (1.3 vs. 2.5 candidate variants/proband,P= 0.024). We did not find any candidate variants (0 of 13 probands) in genes previously reported to explain the phenotype in congenital hypopituitarism, unlike NFSS (8 of 19 probands,P= 0.01).

Conclusion

Our findings provide evidence that the etiology of sporadic congenital hypopituitarism has a major genetic component but may be infrequently monogenic with full penetrance, suggesting a more complex etiology.
High-Throughput Sequencing-Based Identification of miRNAs and Their Target mRNAs in Wheat Variety Qing Mai 6 Under Salt Stress Condition
Authors: He Xiaoyan , Han Zhen , Yin Huayan , Chen Fan , Dong Yihuan , Zhang Lufei , Lu Xiaoqing , Zeng Jianbin , Ma Wujun , Mu Ping
Published: August 2021

Soil salinization is one of the major abiotic stresses that adversely affect the yield and quality of crops such as wheat, a leading cereal crop worldwide. Excavating the salt-tolerant genes and exploring the salt tolerance mechanism can help breeding salt-tolerant wheat varieties. Thus, it is essential to identify salt-tolerant wheat germplasm resources. In this study, we carried out a salt stress experiment using Qing Mai 6 (QM6), a salt-tolerant wheat variety, and sequenced the miRNAs and mRNAs. The differentially expressed miRNAs and mRNAs in salt stress conditions were compared with the control. As results, a total of eight salt-tolerance-related miRNAs and their corresponding 11 target mRNAs were identified. Further analysis revealed that QM6 enhances salt tolerance through increasing the expression level of genes related to stress resistance, antioxidation, nutrient absorption, and lipid metabolism balance, and the expression of these genes was regulated by the identified miRNAs. The resulting data provides a theoretical basis for future research studies on miRNAs and novel genes related to salt tolerance in wheat in order to develop genetically improved salt-tolerant wheat varieties.
Interferon-Induced Transmembrane Protein 3 Shapes an Inflamed Tumor Microenvironment and Identifies Immuno-Hot Tumors
Authors: Cai Yun , Ji Wenfei , Sun Chuan , Xu Rui , Chen Xuechun , Deng Yifan , Pan Jiadong , Yang Jiayue , Zhu Hongjun , Mei Jie
Published: August 2021

Interferon-induced transmembrane protein 3 (IFITM3) is an interferon-induced membrane protein, which has been identified as a functional gene in multiple human cancers. The role of IFITM3 in cancer has been preliminarily summarized, but its relationship to antitumor immunity is still unclear. A pancancer analysis was conducted to investigate the expression pattern and immunological role of IFITM3 based on transcriptomic data downloaded from The Cancer Genome Atlas (TCGA) database. Next, correlations between IFITM3 and immunological features in the bladder cancer (BLCA) tumor microenvironment (TME) were assessed. In addition, the role of IFITM3 in estimating the clinical characteristics and the response to various therapies in BLCA was also evaluated. These results were next confirmed in the IMvigor210 cohort and a recruited cohort. In addition, correlations between IFITM3 and emerging immunobiomarkers, such as microbiota and N6-methyladenosine (m6A) genes, were assessed. IFITM3 was enhanced in most tumor tissues in comparison with adjacent tissues. IFITM3 was positively correlated with immunomodulators, tumor-infiltrating immune cells (TIICs), cancer immunity cycles, and inhibitory immune checkpoints. In addition, IFITM3 was associated with an inflamed phenotype and several established molecular subtypes. IFITM3 expression also predicted a notably higher response to chemotherapy, anti-EGFR therapy, and immunotherapy but a low response to anti-ERBB2, anti-ERBB4, and antiangiogenic therapy. In addition, IFITM3 was correlated with immune-related microbiota and m6A genes. In addition to BLCA, IFITM3 is expected to be a marker of high immunogenicity in most human cancers. In conclusion, IFITM3 expression can be used to identify immuno-hot tumors in most cancers, and IFITM3 may be a promising pancancer biomarker to estimate the immunological features of tumors.
G6pd-Deficient Mice Are Protected From Experimental Cerebral Malaria and Liver Injury by Suppressing Proinflammatory Response in the Early Stage of Plasmodium berghei Infection
Authors: Yi Haoan , Jiang Weiyang , Yang Fang , Li Fan , Li Yirong , Zhu Wenjing , Li Qing , Fakhar Syed Hassam , Cao Yaming , Luo Lan , Zhang Wen , He Yongshu
Published: August 2021

Epidemiological studies provide compelling evidence that glucose-6-phosphate dehydrogenase (G6PD) deficiency individuals are relatively protected against Plasmodium parasite infection. However, the animal model studies on this subject are lacking. Plus, the underlying mechanism in vivo is poorly known. In this study, we used a G6pd-deficient mice infected with the rodent parasite Plasmodium berghei (P.berghei) to set up a malaria model in mice. We analyzed the pathological progression of experimental cerebral malaria (ECM) and acute liver injury in mice with different G6pd activity infected with P.berghei. We performed dual RNA-seq for host-parasite transcriptomics and validated the changes of proinflammatory response in the murine model. G6pd-deficient mice exhibited a survival advantage, less severe ECM and mild liver injury compared to the wild type mice. Analysis based on dual RNA-seq suggests that G6pd-deficient mice are protected from ECM and acute liver injury were related to proinflammatory responses. Th1 differentiation and dendritic cell maturation in the liver and spleen were inhibited in G6pd-deficient mice. The levels of proinflammatory cytokines were reduced, chemokines and vascular adhesion molecules in the brain were significantly down-regulated, these led to decreased cerebral microvascular obstruction in G6pd-deficient mice. We generated the result that G6pd-deficiency mediated protection against ECM and acute liver injury were driven by the regulatory proinflammatory responses. Furthermore, bioinformatics analyses showed that P.berghei might occur ribosome loss in G6pd-deficient mice. Our findings provide a novel perspective of the underlying mechanism of G6PD deficiency mediated protection against malaria in vivo.
Methods for Identifying Species Complexes Using a Novel Suite of Multivariate Approaches and Multiple Data Sources: A Case Study With Gulf of Alaska Rockfish
Authors: Omori Kristen L. , Tribuzio Cindy A. , Babcock Elizabeth A. , Hoenig John M.
Published: August 2021

International and national laws governing the management of living marine resources generally require specification of harvest limits. To assist with the management of data-limited species, stocks are often grouped into complexes and assessed and managed as a single unit. The species that comprise a complex should have similar life history, susceptibility to the fishing gear, and spatial distribution, such that common management measures will likely lead to sustainable harvest of all species in the complex. However, forming complexes to meet these standards is difficult due to the lack of basic biological or fisheries data to inform estimates of biological vulnerability and fishery susceptibility. A variety of cluster and ordination techniques are applied to bycatch rockfish species in the Gulf of Alaska (GOA) as a case study to demonstrate how groupings may differ based on the multivariate techniques used and the availability and reliability of life history, fishery independent survey, and fishery catch data. For GOA rockfish, our results demonstrate that fishing gear primarily defined differences in species composition, and we suggest that these species be grouped by susceptibility to the main fishing gears while monitoring those species with high vulnerabilities to overfishing. Current GOA rockfish complex delineations (i.e., Other Rockfish and Demersal Shelf Rockfish) are consistent with the results of this study, but should be expanded across the entire GOA. Differences observed across species groupings for the variety of data types and multivariate approaches utilized demonstrate the importance of exploring a diversity of methods. As best practice in identifying species complexes, we suggest using a productivity-susceptibility analysis or expert judgment to begin groupings. Then a variety of multivariate techniques and data sources should be used to identify complexes, while balancing an appropriate number of manageable groups. Thus, optimal species complex groupings should be determined by commonality and consistency among a variety of multivariate methods and datasets.
A Standard Criterion for Measuring Turbulence Quantities Using the Four-Receiver Acoustic Doppler Velocimetry
Authors: Park Hyoungchul , Hwang Jin Hwan
Published: August 2021

Acoustic Doppler velocimetry (ADV) enables three-dimensional turbulent flow fields to be obtained with high spatial and temporal resolutions in the laboratory, rivers, and oceans. Although such advantages have led ADV to become a typical approach for analyzing various fluid dynamics mechanisms, the vagueness of ADV system operation methods has reduced its accuracy and efficiency. Accordingly, the present work suggests a proper measurement strategy for a four-receiver ADV system to obtain reliable turbulence quantities by performing laboratory experiments under two flow conditions. Firstly, in still water, the magnitude of noises was evaluated and a proper operation method was developed to obtain the Reynolds stress with lower noises. Secondly, in channel flows, an optimal sampling period was determined based on the integral time scale by applying the bootstrap sampling method and reverse arrangement test. The results reveal that the noises of the streamwise and transverse velocity components are an order of magnitude larger than those of the vertical velocity components. The orthogonally paired receivers enable the estimation of almost-error-free Reynolds stresses and the optimal sampling period is 150–200 times the integral time scale, regardless of the measurement conditions.
Confronting Complex Accountability in Conservation With Communities
Authors: Crosman Katherine M. , Singh Gerald G. , Lang Sabine
Published: August 2021

Increasingly, conservation organizations are conducting conservation activities with local communities. Many conservation organizations now position their work as contributing to sustainable development initiatives, and local involvement in conservation is understood to increase conservation and sustainability success. Aside from communities, however, conservation organizations are accountable to funders and partners, and values and priorities vary across actor type. Mismatched goals combine with power imbalances between conservation actors, and create decision-making conflict throughout conservation processes, from objective setting through implementation and evaluation. As a result, communities may lose local decision-making power or face new negative consequences, trust in organizational/community partnerships may be undermined, and conservation organizations’ reputations (and the reputation of the sector as whole) may suffer. In this commentary we point out processes and conditions that can lead conservation organizations to privilege accountability to funders and others over accountability to communities, thereby undermining community-level success. We follow with suggestions for how funders, conservation organizations and others may improve community engagement and community-level outcomes, and improve their reputations in general and in their work with communities, by actively leveraging accountability to the community and involving local community members in decision-making.
Pan-Cancer Analysis of Genomic and Prognostic Characteristics Associated With Coronavirus Disease 2019 Regulators
Authors: Zhang Jian , Jiang Huali , Du Kunpeng , Xie Tao , Wang Baiyao , Chen Chengcong , Cen Bohong , Yuan Yawei , Ye Jiacai
Published: August 2021

Background: Cancer patients are alleged to have poor coronavirus disease 2019 (COVID-19) outcomes. However, no systematic or comprehensive analyses of the role and mechanisms of COVID-19 receptor-related regulators in cancer are available.

Methods: We comprehensively evaluated the genomic alterations and their clinical relevance of six COVID-19 receptor-related regulators [transmembrane serine protease 2 (TMPRSS2), angiotensinogen (AGT), angiotensin-converting enzyme 1 (ACE1), solute carrier family 6 member 19 (SLC6A19), angiotensin-converting enzyme 2 (ACE2), and angiotensin II receptor type 2 (AGTR2)] across a broad spectrum of solid tumors. RNA-seq data, single nucleotide variation data, copy number variation data, methylation data, and miRNA–mRNA interaction network data from The Cancer Genome Atlas (TCGA) of 33 solid tumors were analyzed. We assessed the sensitivities of drugs targeting COVID-19 receptor-related regulators, using information from the Cancer Therapeutics Response Portal database.

Results: We found that there are widespread genetic alterations of COVID-19 regulators and that their expression levels were significantly correlated with the activity of cancer hallmark-related pathways. Moreover, COVID-19 receptor-related regulators may be used as prognostic biomarkers. By mining the genomics of drug sensitivities in cancer databases, we discovered a number of potential drugs that may target COVID-19 receptor-related regulators.

Conclusion: This study revealed the genomic alterations and clinical characteristics of COVID-19 receptor-related regulators across 33 cancers, which may clarify the potential mechanism between COVID-19 receptor-related regulators and tumorigenesis and provide a novel approach for cancer treatments.
Evaluation of Short-Chain Antimicrobial Peptides With Combined Antimicrobial and Anti-inflammatory Bioactivities for the Treatment of Zoonotic Skin Pathogens From Canines
Authors: Tang Qiyu , Yang Chunyi , Li Weitian , Zhang Yuhang , Wang Xinying , Wang Weixin , Ma Zhiling , Zhang Di , Jin Yipeng , Lin Degui
Published: August 2021

The incidence of zoonotic Staphylococcus pseudintermedius and Microsporum canis infections is rapidly growing worldwide in the context of an increasing frequency of close contact between animals and humans, presenting challenges in both human and veterinary medicine. Moreover, the development of microbial resistance and emergence of recalcitrant biofilms, accompanied by the insufficiency of new antimicrobial agents, have become major obstacles in treating superficial skin infections caused by various microbes including S. pseudintermedius and M. canis. Over recent years, the prospects of antimicrobial peptides as emerging antimicrobials to combat microbial infections have been demonstrated. In our study, two novel short-chain peptides, namely, allomyrinasin and andricin B, produced by Allomyrina dichotoma and Andrias davidianus, were revealed to exhibit potent antimicrobial efficacy against clinical isolates of S. pseudintermedius and M. canis with remarkable and rapid fungicidal and bactericidal effects, while allomyrinasin exhibited inhibition of biofilm formation and eradication of mature biofilm. These peptides displayed synergistic activity when combined with amoxicillin and terbinafine against S. pseudintermedius and M. canis. Cytoplasmic leakage via cytomembrane permeabilization serves as a mechanism of action. Extremely low hemolytic activity and serum stability in vitro, as well as superior anti-infective efficacy in reducing bacterial counts and relieving the inflammatory response in vivo, were detected. The potent antibacterial, antifungal, and anti-inflammatory activities of allomyrinasin and andricin B might indicate promising anti-infective alternatives for the treatment of S. pseudintermedius and M. canis infections in the context of human and veterinary medicine.
Interspecific Niche Competition Increases Morphological Diversity in Multi-Species Microbial Communities
Authors: Chu Xiao-Lin , Zhang Quan-Guo , Buckling Angus , Castledine Meaghan
Published: August 2021

Intraspecific competition for limited niches has been recognized as a driving force for adaptive radiation, but results for the role of interspecific competition have been mixed. Here, we report the adaptive diversification of the model bacteriaPseudomonas fluorescensin the presence of different numbers and combinations of four competing bacterial species. Increasing the diversity of competitive community increased the morphological diversity of focal species, which is caused by impeding the domination of a single morphotype. Specifically, this pattern was driven by more diverse communities being more likely to contain key species that occupy the same niche as otherwise competitively superior morphotype, and thus preventing competitive exclusion within the focal species. Our results suggest that sympatric adaptive radiation is driven by the presence or absence of niche-specific competitors.
The Phage T4 Antiholin RI Has a Cleavable Signal Peptide, Not a SAR Domain
Authors: Mehner-Breitfeld Denise , Schwarzkopf Jan Michel Frederik , Young Ry , Kondabagil Kiran , Brüser Thomas
Published: August 2021

Holin/endolysin-mediated lysis of phage T4 of Escherichia coli is tightly regulated by the antiholins RI and RIII. While regulation by the cytoplasmic RIII plays a minor role, the periplasmic antiholin RI binds tightly to the holin T and is believed to directly sense periplasmic phage DNA from superinfections as a trigger for the inhibition of lysis. RI has been reported to contain a non-cleavable signal peptide that anchors the protein to the membrane. Lysis is believed to be induced at some stage by a membrane depolarization that causes a release of RI into the periplasm without cleavage of the signal anchor. For the current model of phage lysis induction, it is thus a fundamental assumption that the N-terminal trans-membrane domain (TMD) of RI is such a signal anchor release (SAR) domain. Here we show that, in contrast to previous reports, this domain of RI is a cleavable signal peptide. RI is processed and released into the periplasm as a mature protein, and inactivation of its signal peptidase cleavage site blocks processing and membrane release. The signal peptide of RI can also mediate the normal translocation of a well-characterized Sec substrate, PhoA, into the periplasm. This simplifies the current view of phage lysis regulation and suggests a fundamentally different interpretation of the recently published structure of the soluble domains of the RI–T complex.
Meta-Analysis of the Diagnostic Value of Cell-free DNA for Renal Cancer
Authors: Xu Yipeng , Jiang Yingjun , Yu Mingke , Lou Jianmin , Song Mei , Xu Han , Cui Yingying , Zeng Xiaowei , Wang Qibo , Ma Hanyun , Wang Zongping , Zhu Shaoxing , Li Guorong , Zhao An
Published: August 2021

Cell-free DNA (cf-DNA) has been reported to represent a suitable material for liquid biopsy in the diagnosis and prognosis of various cancers. We performed a meta-analysis of published data to investigate the diagnostic value of cf-DNA for renal cancer (RCa). Systematic searches were conducted using Pubmed, Embase databases, Web of Science, Medline and Cochrane Library to identify relevant publications until the 31st March 2021. For all patients, we evaluated the true diagnostic value of cf-DNA by calculating the number of true positive, false positive, true negative, and false negative, diagnoses by extracting specificity and sensitivity data from the selected literature. In total, 8 studies, featuring 754 RCa patients, and 355 healthy controls, met our inclusion criteria. The overall diagnostic sensitivity and specificity for cf-DNA was 0.71 (95% confidence interval (CI), 0.55–0.83) and 0.79 (95% CI, 0.66–0.88), respectively. The pooled positive likelihood ratio and pooled negative likelihood ratio were 3.42 (95% CI, 2.04–5.72) and 0.36 (95% CI, 0.23–0.58), respectively. The area under the summary receiver operating characteristic curve was 0.82 (95% CI, 0.79–0.85), and the diagnostic odds ratio was 7.80 (95% CI, 4.40–13.85). Collectively, our data demonstrate that cf-DNA has high specificity and sensitivity for diagnosing RCa. Therefore, cf-DNA is a useful biomarker for the diagnosis of RCa.
Motor Dysfunction Questionnaire and Dopamine Transporter Imaging Composite Scale Improve Differentiating Dementia With Lewy Bodies From Alzheimer's Disease With Motor Dysfunction
Authors: Chiu Pai-Yi , Wei Cheng-Yu , Hung Guang-Uei , Wu Shey-Lin
Published: August 2021

Objective: Characteristic parkinsonism is the major comorbidity of dementia with Lewy bodies (DLB). We aimed to differentiate DLB from Alzheimer's disease (AD) with motor dysfunction using a composite scale with a characteristic motor dysfunction questionnaire (MDQ) and dopamine transporter (DAT) imaging. It could help detect DLB easily in healthcare settings without movement disorder specialists.

Methods: This is a two-phase study. In the design phase, seven questions were selected and composed of a novel MDQ. In the test phase, all participants with DLB, AD, or non-dementia (ND) control completed dementia and parkinsonism survey, the novel designed questionnaire, DAT imaging, and composite scales of MDQ and DAT. The cutoff scores of the MDQ, semiquantitative analysis of the striatal–background ratio (SBR) and visual rating of DAT, and the composite scale of MDQ and DAT for discriminating DLB from AD or ND were derived and compared.

Results: A total of 277 participants were included in this study (126 with DLB, 86 with AD, and 65 with ND). Compared with the AD or ND groups, the DLB group showed a significantly higher frequency in all seven items in the MDQ and a significantly lower SBR. For discrimination of DLB from non-DLB with MDQ, SBR, and composite scale, the cutoff scores of 3/2, 1.37/1.38, and 6/5 were suggested for the diagnosis of DLB with the sensitivities/specificities of 0.91/0.72, 0.91/0.80, and 0.87/0.93, respectively. The composite scale significantly improved the accuracy of discrimination compared with either the MDQ or SBR.

Conclusion: This study showed that the novel designed simple questionnaire was a practical screening tool and had similar power to DAT scanning to detect DLB. The questionnaire can be applied in clinical practice and population studies for screening DLB. In addition, the composite scale of MDQ and DAT imaging further improved the diagnostic accuracy, indicating the superiority of the dual-model diagnostic tool.
Astrocyte Heterogeneity in Multiple Sclerosis: Current Understanding and Technical Challenges
Authors: Lo Chih Hung , Skarica Mario , Mansoor Mohammad , Bhandarkar Shaan , Toro Steven , Pitt David
Published: August 2021

The emergence of single cell technologies provides the opportunity to characterize complex immune/central nervous system cell assemblies in multiple sclerosis (MS) and to study their cell population structures, network activation and dynamics at unprecedented depths. In this review, we summarize the current knowledge of astrocyte subpopulations in MS tissue and discuss the challenges associated with resolving astrocyte heterogeneity with single-nucleus RNA-sequencing (snRNA-seq). We further discuss multiplexed imaging techniques as tools for defining population clusters within a spatial context. Finally, we will provide an outlook on how these technologies may aid in answering unresolved questions in MS, such as the glial phenotypes that drive MS progression and/or neuropathological differences between different clinical MS subtypes.
Evaluation of Kappa Index as a Tool in the Diagnosis of Multiple Sclerosis: Implementation in Routine Screening Procedure
Authors: Sanz Diaz Carmen Teresa , de las Heras Flórez Silvia , Carretero Perez Mercedes , Hernández Pérez Miguel Ángel , Martín García Vicente
Published: August 2021

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system. Previous studies have shown that cerebrospinal fluid (CSF) kappa free light chains (K-FLCs) may have a role in MS diagnosis. In this regard, the kappa index (K-Index) has demonstrated higher sensitivity, and slightly lower specificity than oligoclonal bands (OCBs), the gold standard for the detection of intrathecal immunoglobulin synthesis, a feature of MS. Here, we evaluated the performance of the K-Index (K-Index = CSF/serum K-FLC divided by CSF/serum albumin) for the differential diagnosis of MS in a cohort of patients with suspected MS. K-FLCs were quantitatively measured in parallel serum and CSF samples by turbidimetry (Freelite Mx reagent on an Optilite system, The Binding Site Group Ltd). From 160 (63.4%) of a total of 252 patients who had K-FLC in CSF <0.03 mg/dl, below the sensitivity limit of the technique, only one had a diagnosis of MS. However, the absence of OCB in this same patient suggested no synthesis of intrathecal immunoglobulin. Globally, MS patients presented significantly higher K-Index levels than patients without an MS diagnosis (66.96 vs. 0.025, respectively; p < 0.0001). In agreement, patients with positive OCB testing also exhibited higher K-Index levels than patients negative for OCB (65.02 vs. 0.024, respectively; p < 0.0001). An optimal K-Index cutoff of 3.045 was defined by receiver operating characteristic (ROC) analysis for screening suspected MS, achieving a higher diagnostic sensitivity and slightly lower specificity than OCB (Sens. 0.9778 and Spec. 0.8629 vs. Sens. 0.8889 and Spec. 0.9086, respectively). A previously reported K-Index cutoff of 6.6 also showed good diagnostic performance (Sens. 0.9333; Spec. 0.8731), validating its power as a diagnostic biomarker for MS. Finally, a time- and cost-effective algorithm for MS screening is proposed that would offer an initial rapid evaluation of the intrathecal immunoglobulin synthesis through the K-FLC in CSF and K-Index analysis, followed by reflexing OCB testing that may be ordered more selectively.
Serum mBDNF and ProBDNF Expression Levels as Diagnosis Clue for Early Stage Parkinson's Disease
Authors: Yi Xu , Yang Yujia , Zhao Zhengfan , Xu Manyu , Zhang Yuan , Sheng Yingying , Tian Junying , Xu Zhiqiang
Published: August 2021

Parkinson's disease (PD) is one of the most common chronic, progressive, and neurodegenerative diseases characterized clinically by resting tremor, bradykinesia, rigidity, and postural instability. As this disease is usually detected in the later stages, the cure is often delayed, ultimately leading to disability due to the lack of early diagnostic techniques. Therefore, it is of great importance to identify reliable biomarkers with high sensitivity and specificity for the early diagnosis of PD. In this study, we aimed to investigate whether serum expressions of mature brain-derived neurotrophic factor (mBDNF) and proBDNF can serve as biomarkers for the diagnosis of PD at early stage. One hundred and fifty-six patients with limb tremor and/or bradykinesia meeting the inclusion criteria were assigned to either ex-PD group (PD cases) or ex-NPD group (non-PD cases) and then reassigned to either po-PD group (with PD) or po-NPD group (without PD) at 1-year follow-up based on the results of the rediagnoses as performed in accordance with MDS Parkinson's diagnostic criteria. To improve early diagnostic accuracy, grouping (PD group and non-PD group) at initial visit and follow-up was performed differently and independently. Serum mBDNF and proBDNF levels were measured by enzyme-linked immunosorbent assays. The results demonstrated that serum levels of mBDNF and mBDNF/proBDNF were significantly lower in the ex-PD group (19.73 ± 7.31 and 0.09 ± 0.05 ng/ml) as compared with the ex-NPD group (23.47 ± 8.21 and 0.15 ± 0.12 ng/ml) (p < 0.01 for both) and in the po-PD group (19.24 ± 7.20 and 0.09 ± 0.05 ng/ml) as compared with the po-NPD group (25.05 ± 7.67 and 0.16 ± 0.14 ng/ml) (p < 0.01 for both). However, a significantly higher serum level of proBDNF was noted in the ex-PD group (235.49 ± 60.75 ng/ml) as compared with the ex-NPD group (191.75 ± 66.12 ng/ml) (p < 0.01) and in the po-PD group (235.56 ± 60.80 ng/ml) as compared with the po-NPD group (188.42 ± 65.08 ng/ml) (p < 0.01). In conclusion, mBDNF/proBDNF can be used as biomarkers for early stage Parkinson's disease; in addition, mBDNF plus proBDNF has better diagnostic value than mBDNF alone in the diagnosis of PD.
The Learning Styles Neuromyth Is Still Thriving in Medical Education
Authors: Newton Philip M. , Najabat-Lattif Hannah Farukh , Santiago Gabriella , Salvi Atharva
Published: August 2021

Learning Styles theory promises improved academic performance based on the identification of a personal, sensory preference for informational processing. This promise is not supported by evidence, and is in contrast to our current understanding of the neuroscience of learning. Despite this lack of evidence, prior research shows that that belief in the Learning Styles “neuromyth” remains high amongst educators of all levels, around the world. This perspective article is a follow up on prior research aimed at understanding why belief in the neuromyth of Learning Styles remains so high. We evaluated current research papers from the field of health professions education, to characterize the perspective that an educator would be given, should they search for evidence on Learning Styles. As in earlier research on Higher Education, we found that the use of Learning Style frameworks persist in education research for the health professions; 91% of 112 recent research papers published on Learning Styles are based upon the premise that Learning Styles are a useful approach to education. This is in sharp contrast to the fundamental principle of evidence-based practice within these professions. Thus any educator who sought out the research evidence on Learning Styles would be given a consistent but inaccurate endorsement of the value of a teaching technique that is not evidence based, possibly then propagating the belief in Learning Styles. Here we offer perspectives from both research and student about this apparent mismatch between educational practice and clinical practice, along with recommendations and considerations for the future.
The Roles of Magnetic Resonance-Guided Focused Ultrasound in Pain Relief in Patients With Bone Metastases: A Systemic Review and Meta-Analysis
Authors: Han Xiaying , Huang Runzhi , Meng Tong , Yin Huabin , Song Dianwen
Published: August 2021

Objective

Cancer pain, the most common skeleton-related event of bone metastases, significantly disturbs patients’ life. MRI-guided focused ultrasound (MRgFUS) is a therapeutic option to relieve pain; however, its efficacy and safety have not been fully explored. Therefore, we aim to conduct a meta-analysis on studies reporting MRgFUS for patients with bone metastases.

Methods

Randomized controlled trials (RCT) and non-RCTs on MRgFUS treatment for patients with bone metastases were collected using PubMed, MEDLINE In-Process (US National Library of Medicine), National Institutes of Health (US National Library of Medicine), Embase (Elsevier), Web of Science, CINAHL, and the Cochrane Library between August 2007 and September 2019. Data on quantitative pain assessment before/after MRgFUS, response rate, and complication were extracted and analyzed.

Results

Fifteen eligible studies with 362 patients were selected in this meta-analysis. The average pain score was 6.74 (95% CI: 6.30–7.18) at baseline, 4.15 (95% CI: 3.31–4.99) at 0–1 week, 3.09 (95% CI: 2.46–3.72) at 1–5 weeks, and 2.28 (95% CI: 1.37–3.19) at 5–14 weeks. Compared with baseline, the pain improvement at 0–1 week was 2.54 (95% CI: 1.92–3.16, p < 0.01), at 1–5 weeks was 3.56 (95% CI: 3.11–4.02, p < 0.01), and at 5–14 weeks was 4.22 (95% CI: 3.68–4.76, p < 0.01). Change from baseline in OMEDD at 2 weeks after treatment was −15.11 (95% CI: −34.73, 4.50), at 1 month after treatment was −10.87 (95% CI: −26.32, 4.58), and at 3 months after treatment was −5.53 (95% CI: −20.44, 9.38). The overall CR rate was 0.36 (95% CI: 0.24–0.48), PR rate was 0.47 (95% CI: 0.36–0.58), and NR rate was 0.23 (95% CI: 0.13–0.34). Among 14 studies including 352 patients, 93 (26.4%) patients with minor complications and 5 (1.42%) patients with major complications were recorded.

Conclusion

This meta-analysis identifies MRgFUS as a reliable therapeutic option to relieve cancer pain for patients with metastatic bone tumors with controllable related complications.
Impact of Surgical Approach on Surgical Resection Quality in Mid- and Low Rectal Cancer, A Bayesian Network Meta-Analysis
Authors: Wang Xiaojie , Zheng Zhifang , Yu Qian , Ghareeb Waleed M. , Lu Xingrong , Huang Ying , Huang Shenghui , Lin Shuangming , Chi Pan
Published: August 2021

Aim

To evaluate the evidence concerning the quality of surgical resection in laparoscopic (LapTME), robotic (RobTME) and transanal (TaTME) total mesorectal excision for mid-/low rectal cancer.

Methods

A systematic literature search of the PubMed, EMBASE and Cochrane Central Register of Controlled Trials databases was performed. A Bayesian network meta-analysis was utilized to compare surgical resection involved in these 3 surgical techniques by using ADDIS software. Rates of positive circumferential resection margins (CRMs) were the primary endpoint.

Results

A total of 34 articles, 2 randomized clinical trials (RCTs) and 32 non-RCTs, were included in this meta-analysis. Pooled data showed CRM positivity in 114 of 1763 LapTME procedures (6.5%), 54 of 1051 RobTME procedures (5.1%) and 60 of 1276 TaTME procedures (4.7%). There was no statistically significant difference among these 3 surgical approaches in terms of CRM involvement rates and all other surgical resection quality outcomes. The incomplete mesorectal excision rates were 9.6% (69/720) in the LapTME group, 1.9% (11/584) in the RobTME group and 5.6% (45/797) in the TaTME group. Pooled network analysis observed a higher but not statistically significant risk of incomplete mesorectum when comparing both LapTME with RobTME (OR = 1.99; 95% CI = 0.48-11.17) and LapTME with TaTME (OR = 1.90; 95% CI = 0.99-5.25). By comparison, RobTME was most likely to be ranked the best or second best in terms of CRM involvement, complete mesorectal excision, rate of distal resection margin (DRM) involvement and length of DRMs. In addition, RobTME achieved a greater mean tumor distance to the CRM than TaTME. It is worth noting that TaTME was most likely to be ranked the worst in terms of CRM involvement for intersphincteric resection of low rectal cancer.

Conclusion

Overall, RobTME was most likely to be ranked the best in terms of the quality of surgical resection for the treatment of mid-/low rectal cancer. TaTME should be performed with caution in the treatment of low rectal cancer.
Fatty Acid Metabolism-Related lncRNAs Are Potential Biomarkers for Predicting the Overall Survival of Patients With Colorectal Cancer
Authors: Peng Yurui , Xu Chenxin , Wen Jun , Zhang Yuanchuan , Wang Meng , Liu Xiaoxiao , Zhao Kang , Wang Zheng , Liu Yanjun , Zhang Tongtong
Published: August 2021

Abnormal metabolism, including abnormal fatty acid metabolism, is an emerging hallmark of cancer. The current study sought to investigate the potential prognostic value of fatty acid metabolism-related long noncoding RNAs (lncRNAs) in colorectal cancer (CRC). To this end, we obtained the gene expression data and clinical data of patients with CRC from The Cancer Genome Atlas (TCGA) database. Through gene set variation analysis (GSVA), we found that the fatty acid metabolism pathway was related to the clinical stage and prognosis of patients with CRC. After screening differentially expressed RNAs, we constructed a fatty acid metabolism-related competing endogenous RNA (ceRNA) network based on the miRTarBase, miRDB, TargetScan, and StarBase databases. Next, eight fatty acid metabolism-related lncRNAs included in the ceRNA network were identified to build a prognostic signature with Cox and least absolute shrinkage and selection operator (LASSO) regression analyses, and a nomogram was established based on the lncRNA signature and clinical variables. The signature and nomogram were further validated by Kaplan–Meier survival analysis, Cox regression analysis, calibration plots, receiver operating characteristic (ROC) curves, decision curve analysis (DCA). Besides, the TCGA internal and the quantitative real-time polymerase chain reaction (qRT-PCR) external cohorts were applied to successfully validate the robustness of the signature and nomogram. Finally, in vitro assays showed that knockdown of prognostic lncRNA TSPEAR-AS2 decreased the triglyceride (TG) content and the expressions of fatty acid synthase (FASN) and acetyl-CoA carboxylase 1 (ACC1) in CRC cells, which indicated the important role of lncRNA TSPEAR-AS2 in modulating fatty acid metabolism of CRC. The result of Oil Red O staining showed that the lipid content in lncRNA TSPEAR-AS2 high expression group was higher than that in lncRNA TSPEAR-AS2 low expression group. Our study may provide helpful information for fatty acid metabolism targeting therapies in CRC.
Transcriptomic Analyses of the Adenoma-Carcinoma Sequence Identify Hallmarks Associated With the Onset of Colorectal Cancer
Authors: Hong Qin , Li Bing , Cai Xiumei , Lv Zhengtao , Cai Shilun , Zhong Yunshi , Wen Bo
Published: August 2021

The concept of the adenoma-carcinoma sequence in colorectal cancer (CRC) is widely accepted. However, the relationship between the characteristics of the transcriptome and the adenoma-carcinoma sequence in CRC remains unclear. Here, the transcriptome profiles of 15 tissue samples from five CRC patients were generated by RNAseq. Six specific dynamic expression patterns of differentially expressed genes (DEGs) were generated by mFuzz. Weighted correlation network analysis showed that DEGs in cluster 4 were associated with carcinoma tissues, and those in cluster 6 were associated with non-normal tissues. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses identified metabolic dysregulation as a consistent finding throughout the transition process, whereas downregulation of the immune response occurred during normal to adenoma transition, and the upregulation of canonical pathways was associated with adenoma to carcinoma transition. Overall survival analysis of patients in cluster 6 identified TPD52L1 as a marker of poor prognosis, and cell proliferation, colony formation, wound healing, and Transwell invasion assays showed that high expression levels of TPD52L1 promoted malignant behaviors. In total, 70 proteins were identified as potential partners of hD53 by mass spectrometry. CRC formation was associated with three cancer hallmarks: dysregulation of metabolism, inactivation of the immune response, and activation of canonical cancer pathways. The TPD52L1 gene was identified as a potential marker to track tumor formation in CRC and as an indicator of poor patient prognosis.
Identifying Motor Control Strategies and Their Role in Low Back Pain: A Cross-Disciplinary Approach Bridging Neurosciences With Movement Biomechanics
Authors: Schmid Stefan , Bangerter Christian , Schweinhardt Petra , Meier Michael L.
Published: August 2021

Persistent low back pain (LBP) is a major health issue, and its treatment remains challenging due to a lack of pathophysiological understanding. A better understanding of LBP pathophysiology has been recognized as a research priority, however research on contributing mechanisms to LBP is often limited by siloed research within different disciplines. Novel cross-disciplinary approaches are necessary to fill important knowledge gaps in LBP research. This becomes particularly apparent when considering new theories about a potential role of changes in movement behavior (motor control) in the development and persistence of LBP. First evidence points toward the existence of different motor control strategy phenotypes, which are suggested to have pain-provoking effects in some individuals driven by interactions between neuroplastic, psychological and biomechanical factors. Yet, these phenotypes and their role in LBP need further validation, which can be systematically tested using an appropriate cross-disciplinary approach. Therefore, we propose a novel approach, connecting methods from neuroscience and biomechanics research including state-of-the-art optical motion capture, musculoskeletal modeling, functional magnetic resonance imaging and assessments of psychological factors. Ultimately, this cross-disciplinary approach might lead to the identification of different motor control strategy phenotypes with the potential to translate into clinical research for better treatment options.
Effects of Family Intervention on Physical Activity and Sedentary Behavior in Children Aged 2.5–12 Years: A Meta-Analysis
Authors: Huang Ting , Zhao Guanggao , Tan Haoyuan , Wu Hua , Fu Jinmei , Sun Shunli , Lv Wendi , He Zihao , Hu Qiming , Quan Minghui
Published: August 2021

Introduction: To use a quantitative approach to examine the effects of family interventions on physical activity (PA) and sedentary behavior (SB) in children aged 2. 5–12 years.

Methods: PubMed, OVID, Web of Science, and others were searched from their inception to May 2020. Intervention studies that examined the effects of family interventions on PA among children aged 2.5–12 years were included in this meta-analysis. Lastly, subgroup analyses were conducted to examine the potential modifying effects of family intervention's characteristics and study quality.

Results: Eleven articles met the inclusion criteria for this review. Studies investigated a range of PA outcomes, including moderate-to-vigorous PA (MVPA), total PA (TPA), daily steps, and SB levels. Meta-analysis showed that family intervention had a significant effect on PA [standardized mean difference (SMD) = 0.10; 95% CI = 0.01–0.19], especially for daily steps [weight means difference (WMD) = 1,006; 95% CI = 209–1,803], but not for SB (WMD = −0.38; 95% CI = −7.21–6.46). Subgroup analyses indicated the improvements in PA occurred when children were 6–12 years old, intervention focused on PA only, intervention duration ≤ 10 weeks, and “low risk of bias” study performed.

Conclusions: Family intervention may be a promising way to promote children's PA levels, especially for daily steps.

Trial Registration: Meta-analysis protocol was registered on PROSPERO: CRD42020193667.
Isovitexin Inhibits Ginkgolic Acids-Induced Inflammation Through Downregulating SHP2 Activation
Authors: Zhang Yiwei , Qi Zhipeng , Wang Wenjie , Wang Lei , Cao Fuliang , Zhao Linguo , Fang Xianying
Published: August 2021

It has been reported that Celtis sinensis Pers. is employed as a folk medicine for the treatment of inflammatory diseases. But the mechanism supporting its use as anti-inflammatory remains unclear. To investigate the anti-inflammatory of Celtis sinensis Pers. ICR mice were provided Celtis sinensis Pers. leaf extract (CLE) at 100, 200 mg/kg after ginkgolic acids (GA) sensitization. Our data showed that CLE and the main flavonoid isovitexin in CLE could ameliorate GA-induced contact dermatitis in mice. Ear swelling, inflammatory cell infiltration and splenomegaly were inhibited significantly by isovitexin, while the weight loss of mice in the isovitexin-treated group was much better than that in the dexamethasone-treated group (positive control drug). It has been reported in previous research that GA-induced inflammation is closely related to the T cell response. Therefore, T cells were the focus of the anti-inflammatory effect of isovitexin in this paper. The in vivo results showed that isovitexin (10, 20 mg/kg) inhibited the expression of proinflammatory cytokines (TNF-α, IFN-γ, IL-2 and IL-17A) in lymph nodes, inhibited the secretion of cytokines into the serum from mice with contact dermatitis and promoted the expression of apoptosis-related proteins. In vitro, isovitexin also induced apoptosis and inhibited proinflammatory cytokine expression in Con A-activated T cells. Further study showed that the MAPK and STAT signaling pathways and the phosphorylation of SHP2 were inhibited by isovitexin. Both molecular docking and biological experiments indicated that SHP2 may be an anti-inflammatory target of isovitexin in T cells. Taken together, isovitexin can serve as a potential natural agent for the treatment or prevention of GA-induced inflammatory problems.
Screening of Quality Markers During the Processing of Reynoutria multiflora Based on the UHPLC-Q-Exactive Plus Orbitrap MS/MS Metabolomic Method
Authors: Bai Junqi , Su He , Liang Youling , Shi Xuhua , Huang Juan , Xu Wen , Zhang Jing , Gong Lu , Huang Zhihai , Qiu Xiaohui
Published: August 2021

The root of Reynoutria multiflora (Thunb.) Moldenke (syn: Polygonum multiflorum Thunb.) is a distinguished herb that has been popularly used in traditional Chinese medicine. The raw Reynoutria multiflora (RRM) should be processed by steaming before use, and the processing time is not specified in the processing specification. Our previous studies showed that the efficacy and toxicity of processed Reynoutria multiflora (PRM) at different processing times were inconsistent. A comprehensive identification method was established in this study to find a quality marker of raw Reynoutria multiflora (RRM) and processed Reynoutria multiflora (PRM) with different processing times. Metabolomics based on ultra-high-performance liquid chromatography tandem quadrupole/electrostatic field orbitrap high-resolution mass spectrometry (UHPLC-Q-Exactive plus orbitrap MS/MS) was used in this study. Using the CD.2 software processed database, multivariate statistical analysis methods coupled with cluster analysis and heatmap were implemented to distinguish between RRMs and PRMs with different processing times. The results showed that RRM and PRMs processed for 4, 8, 12, and 18 h cluster into group 1, and PRM processed for 24 and 32 h into group 2, indicating that it can effectively distinguish between the two groups and twenty potential markers, made the highest contributions to the observed chemical differences between two groups. Among them, tetrahydroxystilbene-O-hexoside-O-galloyl and sucrose can be used to identify PRM processed for 24 h. Therefore, the properties of RRM changed after 24 h of processing, and the quality markers were screened to distinguish RRM and PPM. It can also be used as an important control technology for the processing of RM, which has wide application prospects.