bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamic Analysis of QTLs on Plant Height with Single Segment Substitution Lines in Rice
Authors: Fu Yu , Zhao Hongyuan , Huang Jiongkai , Zhu Haitao , Luan Xin , Bu Suhong , Liu Zupei , Meng Lijun , Liu Guifu , Zhang Guiquan , Wang Shaokui
Published: October 2021

Dynamic regulation of QTLs remains mysterious. Single segment substitution lines (SSSLs) and conditional QTL mapping and functional QTL mappings are ideal materials and methods to explore dynamics of QTLs for complex traits. This paper analyzed the dynamics of QTLs on plant height with SSSLs in rice. Five SSSLs were verified with plant height QTLs first. All five QTLs had significant positive effects at one or more developmental stages except QTL1. They interacted each other, with negative effects before 72 d after transplanting and positive effects since then. The five QTLs selectively expressed in specific periods, mainly in the periods from 35 to 42 d and from 49 to 56 d after transplanting. Expressions of epistasis were dispersedly in various periods, negative effects appearing mainly before 35 d. The five QTLs brought the inflexion point ahead of schedule, accelerated growth and degradation, and changed the peak plant height, while their interactions had the opposite effects. The information will be helpful to understand the genetic mechanism for developmental traits.
ZNF384 Gene Rearrangement in Acute Lymphocytic Leukemia with Kidney Involvement as the First Manifestation is Associated with Poor Prognosis: A Case Report
Authors: Ma Jinlong , Guan Jiaheng , Chen Baoan
Published: October 2021

Background: Novel fusion genes such as ZNF384 have been identified in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) in recent years. Patients harboring ZNF384 rearrangement have a distinctive immunophenotype with weak CD10 and aberrant CD13 and/or CD33 expression, which makes ZNF384-rearranged ALL a unique subtype of BCP-ALL. However, research on the prognostic significance of ZNF384 rearrangement has been limited to date.Case presentation: We described a 17-year-old young woman who was diagnosed with ALL and had kidney involvement as the first manifestation, which was very rare in the existing studies. FISH analysis indicated a rearrangement of ZNF384 according to its probe. The patient had a typical characteristic immunophenotype of ZNF384 rearrangement with CD10 being negative but CD13 and CD33 being positive. She had an unfavorable prognosis since she responded poorly to chemotherapy and developed a relapse shortly after reaching CR.Conclusion: The importance of the ZNF384 gene rearrangement in terms of prognosis remains unclear. We reported a young woman harboring ZNF384 rearrangement in ALL with kidney involvement. She experienced different treatments, but her prognosis remained poor. Since ZNF384 rearrangement may act as a negative prognostic predictor, early detection based on its characteristic immunophenotype is of great necessity.
Identification of Potentially Functional Circular RNAs hsa_circ_0070934 and hsa_circ_0004315 as Prognostic Factor of Hepatocellular Carcinoma by Integrated Bioinformatics Analysis
Authors: Morovat Pejman , Morovat Saman , Ashrafi Arash M. , Teimourian Shahram
Published: October 2021

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide, which has a high mortality rate and poor treatment outcomes with yet unknown molecular basis. It seems that gene expression plays a pivotal role in the pathogenesis of the disease. Circular RNAs (circRNAs) can interact with microRNAs (miRNAs) to regulate gene expression in various malignancies by acting as competitive endogenous RNAs (ceRNAs). However, the potential pathogenesis roles of the ceRNA network among circRNA/miRNA/mRNA in HCC are unclear. In this study, first, the HCC circRNA expression data were obtained from three Gene Expression Omnibus microarray datasets (GSE164803, GSE94508, GSE97332), and the differentially expressed circRNAs (DECs) were identified using R limma package. Also, the liver hepatocellular carcinoma (LIHC) miRNA and mRNA sequence data were retrieved from TCGA, and differentially expressed miRNAs (DEMIs) and mRNAs (DEGs) were determined using the R DESeq2 package. Second, CSCD website was used to uncover the binding sites of miRNAs on DECs. The DECs' potential target miRNAs were revealed by conducting an intersection between predicted miRNAs from CSCD and downregulated DEMIs. Third, some related genes were uncovered by intersecting targeted genes predicted by miRWalk and targetscan online tools with upregulated DEGs. The ceRNA network was then built using the Cytoscape software. The functional enrichment and the overall survival time of these potential targeted genes were analyzed, and a PPI network was constructed in the STRING database. Network visualization was performed by Cytoscape, and ten hub genes were detected using the CytoHubba plugin tool. Four DECs (hsa_circ_0000520, hsa_circ_0008616, hsa_circ_0070934, hsa_circ_0004315) were obtained and six miRNAs (hsa-miR-542-5p, hsa-miR-326, hsa-miR-511-5p, hsa-miR-195-5p, hsa-miR-214-3p, and hsa-miR-424-5p) which are regulated by the above DECs were identified. Then 543 overlapped genes regulated by six miRNAs mentioned above were predicted. Functional enrichment analysis showed that these genes are mostly associated with cancer regulation functions. Ten hub genes (TTK،AURKB, KIF20A، KIF23، CEP55، CDC6، DTL، NCAPG، CENPF، PLK4) have been screened from the PPI network of the 204 survival-related genes. KIF20A, NCAPG, TTK, PLK4, and CDC6 were selected for the highest significant p-values. In the end, a circRNA-miRNA-mRNA regulatory axis was established for five final selected hub genes. This study implies the potential pathogenesis of the obtained network and proposes that the two DECs (has_circ_0070934 and has_circ_0004315) may be important prognostic factor for HCC.
Epidermal Microbiomes of Triakis Semifasciata Are Consistent Across Captive and Wild Environments
Authors: Goodman Asha , Papudeshi Bhavya , Doane Michael P. , Johnson Colton , Mora Maria , Kerr Emma , Torres Melissa , Nero Jennifer , Lima Laís , Nosel Andrew P. , Dinsdale Elizabeth A.
Published: October 2021

Background: Characterizations of sharks-microbe systems in wild environments have outlined patterns of species-specific microbiomes; however, whether captivity affects these trends has yet to be determined. We used high-throughput shotgun sequencing to assess the epidermal microbiome belonging to leopard sharks (Triakis semifasciata) in captive (Birch Aquarium, La Jolla California), semi-captive (<1 year in captivity; Scripps Institute of Oceanography, California) and wild environments (Moss Landing and La Jolla, California). Results: Here we report captive environments do not drive microbiome composition of T. semifasciata to significantly diverge from wild counterparts as life-long captive sharks maintain a species-specific epidermal microbiome resembling those associated with semi-captive and wild populations. Major taxonomic composition shifts observed were inverse changes of top taxonomic contributors across captive duration, specifically an increase of Pseudoalteromonadaceae and consequent decrease of Pseudomonadaceae relative abundance as T. semifasciata increased duration in captive conditions. Moreover, we show captivity did not lead to significant losses in microbial α-diversity of shark epidermal communities. Finally, we present a novel association between T. semifasciata and the Muricauda genus as MAGs revealed a consistent relationship across captive, semi-captive, and wild populations. Conclusions: Our report illustrates the importance of conservation programs for coastal fishes as epidermally-associated microbes of near-shore shark species do not suffer detrimental impacts from long or short-term captivity. Our findings also expand on current understanding of shark epidermal microbiomes, explore the effects of ecologically different scenarios on benthic shark microbe associations, and highlight novel microbial associations that are consistent across captive gradients.
Real-Time Monitoring and Alarm System in Underground Coal Mines Using Smart Helmets (A Case Study: Tabas Coal Mine)
Authors: Ghadyani Daniyal , Badraddini Amirhossein , Kazemi Mohammad Mirzehi Kalateh , Sarfarazi Vahab , Mostofi Sohrab Naser , Khodabandeloo Vahid
Published: October 2021

Regarding the hazard-prone working conditions in underground mines, synchronous monitoring and alarm system is vital to increase the safety. By analyzing the accidents in underground mines in Iran, it can be deduced that most fatalities are related to harmful gas leakage, objects drop off on the head, and not using helmets by the staff. Therefore, a smart helmet with the capability of measuring harmful gasses (regarding the type of the mine), detection of the existence of the helmet on the head, temperature and humidity measurement, and detection of blow on the head is designed and fabricated to eliminate the present dangers and problems. This system displays the evaluated data on a developed software through wireless data transmission hardware. The data transmission hardware is the primary link between the intelligent safety helmet and the software. To follow the idea, practical experiments have been performed in Parvadeh four and East Parvadeh of Tabas coal mine to confirm the validity of data transmission that culminated in successful results. The results were altered by the complexity of the design of the underground spaces so that in a straight direction, data transmission was held until 430 meters. However, further progress was not possible due to tunnel limitations. Data transmission was reduced to 190 meters in access horizons with curvatures or tilts. According to present standards, some thresholds are defined for each of the mentioned cases such that alarm protocol is activated by exceeding these thresholds in critical circumstances. Then the helmet user and the software’s operator will be informed of the occurred danger and will settle the problem.
Gene Expression Profiles in Sporadic ALS Fibroblasts Define Disease Subtypes and The Metabolic Effects of the Investigational Drug EH301
Authors: Fels Jasmine A. , Casalena Gabriella , Konrad Csaba , Holmes Holly , Dellinger Ryan W. , Manfredi Giovanni
Published: October 2021

Background: Majority of ALS cases are sporadic (sALS), as they lack defined genetic causes. Metabolic alterations shared between the nervous system and skin fibroblasts have emerged in ALS. Recently, we found that a subgroup of sALS fibroblasts (sALS1) is characterized by metabolic profiles (metabotype) distinct from other sALS cases (sALS2) and controls, suggesting that metabolic therapies could be effective in sALS. The metabolic modulators nicotinamide riboside and pterostilbene (EH301) are under clinical development for the treatment of ALS. Here, we studied the metabolome and transcriptome of sALS cells to understand the molecular bases of sALS metabotypes and the impact of EH301.Methods: Six fibroblast cell lines (3 male and 3 female subjects of similar ages) were used for each group (sALS1, sALS2, and controls). Metabolomics and transcriptomics were investigated at baseline and after EH301 treatment. Differential gene expression (DEGs) and metabolite abundance were assessed by a Wald Test and ANOVA, respectively, with FDR correction, and pathway analyses were performed. EH301 protection against metabolic stress was tested by thiol depletion. Weighted gene co-expression network analysis (WGCNA) was used to investigate the association of metabolic and clinical features and was also performed on the Answer ALS dataset from induced motor neurons (iMN). A machine learning model based on DEGs was tested as a sALS disease progression predictor. Results: We found that the sALS1 transcriptome is distinct from sALS2 and that EH301 modifies gene expression differently in sALS1, sALS2, and controls. Furthermore, EH301 had strong protective effects against metabolic stress, which is linked to anti-inflammatory and antioxidant pathways. WGCNA revealed that ALS functional rating scale and metabotypes are associated with gene modules enriched for cell cycle, immunity, autophagy, and metabolism terms, which are modified by EH301. Meta-analysis of publicly available transcriptomics data from iMNs confirmed functional associations of genes correlated with disease traits. A small subset of genes differentially expressed in sALS fibroblasts could be used in a machine learning model to predict disease progression.Conclusions: Multi-omics analyses of patient-derived fibroblasts highlighted differential metabolic and transcriptomic profiles in sALS metabotypes, which translate into differential responses to the investigational drug EH301.
Predicting Retinal Sensitivity Using Optical Coherence Tomography Parameters in Central Serous Chorioretinopathy
Authors: Kanda Satoru , Zhou Han Peng , Inoue Tatsuya , Fujino Ryosuke , Sugiura Aya , Aoyama Yurika , Kadonosono Kazuaki , Maruyama-Inoue Maiko , Obata Ryo , Asaoka Ryo
Published: October 2021

Purpose
To predict the change of retinal sensitivity using optical coherence tomography (OCT) parameters in eyes with central serous chorioretinopathy (CSC).
Methods
Twenty-three eyes of 23 patients with CSC were enrolled. Retinal sensitivity was measured twice with a microperimetry in all examined eyes. OCT measurement was simultaneously conducted. The relationship between retinal sensitivities and the thicknesses of i) retinal nerve fiver layer + ganglion cell layer (RNFL+GCL), ii) inner nuclear layer (INL) iii) outer nuclear layer (ONL) and iV) serous retinal detachment height (SRDH) were investigated in a point-wise manner. We also investigated the association between the change of retinal sensitivity and OCT parameters at baseline.
Results
The mean age of participants was 49.8 ± 10.7 years. The mean SRDH was significantly lower (p<0.001) and the mean retinal sensitivity (p<0.001) was significantly higher in the 2nd examination compared to the 1st measurements, however LogMAR visual acuity (VA) was not significantly different between the two measurements (p=0.063). LogMAR VA was associated with retinal sensitivity both in the 1st and 2nd measurements (p<0.001). The retinal sensitivity in the 2nd examination was significantly correlated with retinal sensitivity, RNFL+GCL, INL, ONL, SRDH in the 1st examination and the improvement of SRDH.
Conclusions
Retinal sensitivity was associated with retinal structure in eyes with CSC; these parameters were useful to predict the change of visual function before the treatment.
Being A Safe Place: A Qualitative Study Exploring Perceptions As To How A Rural Community Hospice Could Respond To Enactment of Voluntary Assisted Dying Legislation
Authors: Auret Kirsten , Pikora Terri , Gersbach Kate
Published: October 2021

Background: There is a lack of research to guide the implementation of voluntary assisted dying legislation within a hospice setting. Furthermore, there is limited published information related to the expectations of the community and staff to assist decision making regarding voluntary assisted dying in a community hospice. The aim of this study was to explore the expectations of staff, volunteers and members of the community as how a rural community hospice could respond in relation to enactment of Voluntary Assisted Dying legislation. Methods: A total of 63 Hospice staff and volunteers and community members participated in 11 workshops. This qualitative study used a grounded theory approach to analyse the workshop transcripts. Results: While there was not a consensus view on community expectation, there was agreement among the participants for respect for a patient’s individuality and choices. Furthermore, care offered in hospice needs to remain non-judgemental and patient focused regardless of whether voluntary assisted dying policy was implemented or not. Both opportunities and risks associated with implementation were identified by the participants. Conclusion: There was common ground around the respect for the dying person and the ideal of a “safe place” despite opposing views on what this may mean in practice. There is a need for clarity in organisational responses around policy, risk management, education, and staff support.
Multiple Context Learning Networks for Visual Question Answering
Authors: Zhang Pufen , Lan Hong
Published: October 2021

In recently years, some visual question answering (VQA) methods that emphasize the simultaneous understanding of both the context of image and question have been proposed. Despite the effectiveness of these methods, they fail to explore a more comprehensive and generalized context learning tactics. To address this issue, we propose a novel Multiple Context Learning Networks (MCLN) to model the multiple contexts for VQA. Three kinds of contexts are investigated, namely visual context, textual context and a special visual-textual context that ignored by previous methods. Moreover, three corresponding context learning modules are proposed. These modules endow image and text representations with context-aware information based on a uniform context learning strategy. And they work together to form a multiple context learning layer (MCL). Such MCL can be stacked in depth and which describe high-level context information by associating intra-modal contexts with inter-modal context. On the VQA v2.0 datasets, the proposed model achieves 71.05% and 71.48% on test-dev set and test-std set respectively, and gains better performance than the previous state-of-the-art methods. In addition, extensive ablation studies have been carried out to examine the effectiveness of the proposed method.
Comparing occlusal contact quality after aligner and fixed appliance treatment using computerized occlusal analysis during 6 months of retention
Authors: Cohen-Lévy Julia , Boulos Colette , Rompré Pierre , Montpetit Andrée , Kerstein Robert Barry
Published: October 2021

Objective

Less than ideal contacts have been reported following aligner therapy, which is believed will resolve with settling, despite settling improving occlusal balance has not been scientifically confirmed. The aim of this study was to compare the outcome quality of occlusal contacts in patients treated with fixed appliances or clear aligners.
Methods

39 orthodontic patients (14 treated with aligners; 25 with fixed appliances) were evaluated with a digital occlusal analysis system (T-scan10 ™), assessing Maximum Intercuspation contact simultaneity, symmetry, and relative force distribution. The Occlusion Time, the Right/Left force percentage (%R/L), the Anterior/Posterior contact ratio (RAP), and the anteroposterior Center of Force (COF) locations were recorded at treatment completion, and 3 and 6 months after.
Results

No significant differences in measured occlusal contact quality parameter were found between groups at treatment completion or follow-up (OT, %R, RAP nor COF position). The COF moved posteriorly and remained stable after 3 months, near to the first molar, but was located more anterior in females (p= 0.01). 10 patients finished treatment with marked asymmetry, (%R/L > 50±10%), especially in the fixed appliance group (9/25 =3 6%) versus the aligner group (1/14 = 7%). 1/3 of all patients (both groups combined) after 6 months retention had %R/L imbalances > 50±10%.
Conclusions

Occlusal contacts were comparable at completion of treatment with aligners or brackets and after 3-6 months of retention. Contacts increased in the posterior region with time, but settling did not improve marked asymmetry in all patients.
Relationship Between Rotator Cuff Tears and Scapular Morphology
Authors: Nakamura Yoshihiro , Yokoya Shin , Matsubara Yuki , Harada Yohei , Adachi Nobuo
Published: October 2021

Background

The purpose of this study was to identify differences in the morphology of the scapula according to the presence or absence of a rotator cuff tear (RCT).
Methods

One hundred and three shoulders with and 87 shoulders without RCTs were included in this study. The critical shoulder angle (CSA) and lateral acromion angle in the frontal view and the acromial coverage angle (ACA) and coracoid and scapular spine angle (CSSA) in the lateral view were evaluated using three-dimensional computed tomography. The glenoid anterior tilt, anterior acromial projection angle (AAPA), coracoid process angle, scapular spine angle (SSA) and inferior angle angle (IAA) with respect to the scapular plane were measured in the lateral view. The morphological parameters of the scapula associated with RCT were statistically analysed using a multivariate logistic regression analysis.
Results

In univariate logistic regression analysis, CSA, ACA, CSSA, AAPA, SSA and IAA were significantly different between shoulders with and without RCTs. In multivariate logistic regression analysis, CSA and IAA were greater in shoulders with RCT and were significantly associated with this condition.
Conclusion

To the best of our knowledge, this is the first study to focus on the relationship between RCT and the scapular body. RCT cases were characterised by a greater curvature of the scapular body in addition to CSA.
Genome-Wide Transcriptome Profiling of Human Trabecular Meshwork Cells Treated with TGF-β2.
Authors: Callaghan Breedge , Lester Karen , Lane Brian , Fan Xiaochen , Goljanek-Whysall Katarzyna , Simpson David A. , Sheridan Carl , Willoughby Colin E.
Published: October 2021

Glaucoma is a complex neurodegenerative disease resulting in progressive optic neuropathy and is a leading cause of irreversible blindness worldwide. Primary open angle glaucoma (POAG) is the predominant form affecting 65.5 million people globally. Despite the prevalence of POAG and the identification of over 120 glaucoma related genetic loci, the underlaying molecular mechanisms are still poorly understood. The transforming growth factor beta (TGF-β) signalling pathway is implicated in the molecular pathology of POAG. To gain a better understanding of the role TGF-β2 plays in the glaucomatous changes to the molecular pathology in the trabecular meshwork, we employed RNA-Seq to delineate the TGF-β2 induced changes in the transcriptome of normal primary human trabecular meshwork cells (HTM). We identified a significant number of differentially expressed genes and associated pathways that contribute to the pathogenesis of POAG. The differentially expressed genes were predominantly enriched in ECM regulation, TGF-β signalling, proliferation/apoptosis, inflammation/wound healing, MAPK signalling, oxidative stress and RHO signalling. Canonical pathway analysis confirmed the enrichment of RhoA signalling, inflammatory-related processes, ECM and cytoskeletal organisation in HTM cells in response to TGF-β2. We also identified novel genes and pathways that were affected after TGF-β2 treatment in the HTM, suggesting additional pathways are activated, including Nrf2, PI3K-Akt, MAPK and HIPPO signalling pathways. The identification and characterisation of TGF-β2 dependent differentially expressed genes and pathways in HTM cells is essential to understand the patho-physiology of glaucoma and to develop new therapeutic agents.
Shedding Light Into The Black Box of Out-of-Hospital Respiratory Emergencies – A Retrospective Cohort Analysis of Discharge Diagnoses, Prehospital Diagnostic Accuracy, And Predictors of Mortality
Authors: Spörl Patrick , Beckers Stefan K. , Rossaint Rolf , Felzen Marc , Schröder Hanna
Published: October 2021

Background: Respiratory distress is one of the most common complaints of patients requiring out-of-hospital emergency services. Determining the precise discharge diagnosis in these circumstances can be challenging due to the wide range of suspected diagnoses. Moreover, these patients appear to have particularly high mortality, but little is currently known about the exact mortality rates associated with specific discharge diagnoses. Our study, therefore, aimed to determine how accurately correct diagnoses are made by EMS physicians in the out-of-hospital setting, identify examination findings that correlate with discharge diagnoses, investigate hospital mortality, and identify mortality-associated predictors.Methods: This retrospective observational study examined emergency medical service (EMS) encounters between December 2015 and May 2016 in the city of Aachen, Germany, in which an EMS physician was present at the scene. Adult patients were included if the EMS physician initially detected dyspnea, low oxygen saturation, or pathological auscultation findings at the scene (n = 719). By linking out-of-hospital data to hospital records, including initial blood gas analysis, a discharge diagnosis was assigned to each EMS encounter, and the outcome was analyzed. Binary logistic regressions were used to search for associations between pathological findings and discharge diagnoses, as well as predictors of hospital mortality.Results: The overall diagnostic accuracy was 69.9% (485/694). The highest diagnostic accuracies were observed in asthma (15/15 ≙ 100%), hypertensive crisis (28/33 ≙ 84.4%), and COPD exacerbation (114/138 ≙ 82.6%), and the lowest accuracies were observed in urinary tract infection (14/35 ≙ 40%), pulmonary embolism (8/18 ≙ 44.4%), and pneumonia (70/142 ≙ 49.3%). The overall hospital mortality rate was 13.8% (99/719). The highest hospital mortality rates were seen in pneumonia (44/142 ≙ 31%) and urinary tract infection (7/35 ≙ 20%). Potential risk factors for hospital mortality identified in this study were reduced vigilance, low oxygen saturation, increasing age, blood gas analysis (BGA) results associated with metabolic acidosis, and an incorrect out-of-hospital diagnosis by the EMS physician.Conclusions: Our data highlight the diagnostic uncertainties and high mortality in out-of-hospital emergency patients presenting with respiratory distress. The identified predictors could help in early detection of patients at risk in the future.
SNAP25 Is a Potential Prognostic Biomarker for Prostate Cancer
Authors: Di Longjiang , Gu Maoli , Wu Yan , Liu Guoqiang , Zhang Lishuo , Li Yifei , Zhang Wenjing
Published: October 2021

Background Prostate cancer is one of the most lethal cancers in male individuals. The Synaptosome associated protein 25 (SNAP25) gene is a key mediator of multiple biological functions in tumours. However, its significant impact on the prognosis in prostate cancer remains to be elucidated.Methods We performed a comprehensive analysis of the Cancer Genome Atlas dataset (TCGA) to identify the differentially expressed genes between prostate cancer and normal prostate tissue. We subjected the differentially expressed genes to gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional analysis, and constructed a protein-protein interaction network. We then screened for pivotal genes to identify the hub genes of prognostic significance by performing Cox regression analysis. We identified SNAP25 as one such gene and analysed the relationship between its expression in prostate cancer to poor prognosis using Studio R. Results TCGA database demonstrated that SNAP25 was significantly downregulated in prostate cancer, and that its expression was significantly correlated with the Gleason score and pathological TNM stage of patients. The association between SNAP25 expression and tumour-infiltrating immune cells was evaluated using the Tumour Immune Estimation Resource site. Gene set enrichment and gene ontology analyses were used to analyse the function of SNAP25. We found that SNAP25 expression strongly correlated with overall survival in the Gleason score. In addition, SNAP25 was involved in the activation, differentiation, and migration of immune cells, and its expression was positively correlated with immune infiltration, including of B cells, CD8+ T cells, CD4+ T cells, neutrophils, dendritic cells, macrophages, and natural killer cells. SNAP25 expression was also positively correlated with chemokines/chemokine receptors, suggesting that SNAP25 might regulate the migration of immune cells. These molecular experiment results validate the low expression of SNAP25 seen in prostate cancer cells.Conclusion Our findings indicate a relationship between SNAP25 expression and prostate cancer, demonstrating that SNAP25 is a potential prognostic biomarker due to its vital role in immune infiltration.
Donor Site Evaluation after Full-Width Metatarsal Transfer for Metacarpal Reconstruction in Severe Thumb Hypoplasia: A Clinical Retrospective Study
Authors: Bai Fan , Liu Lu , Li Qiuya , Xue Yunhao , Yang Chen , Chen Shanlin
Published: October 2021

Background: Pollicization remains the default treatment for severe thumb hypoplasia, while the metatarsal transfer is an effective choice for metacarpal reconstruction, with competitive outcome of reconstructed thumb. However, rare researches focused on the outcome of donor foot of the metatarsal transfer. The purpose of this study was to evaluate the short-term outcome of donor foot after full-width metatarsal transfer for Manske Type IIIB and IV thumb hypoplasia.Methods: Fourteen patients with Manske Type IIIB and IV thumb hypoplasia were enrolled in the study. A full-width metatarsal graft (vascularised, from the second metatarsal or non-vascularised, from the fourth metatarsal) was harvested; an adjacent half-width graft from the third metatarsal was transposed horizontally to replace the donor defect. Objective and subjective evaluations were performed at least 12 months postoperatively. The appearances of the toes and the radiographic findings of the metatarsals were evaluated by two authors, the length and width of the metatarsals were measured on digital anteroposterior radiographs using a paired sample t test. The parental satisfaction was evaluated using a self-administered questionnaire. Results: Among these 14 patients (eight type ⅢB and six type Ⅳ thumbs), there were ten male and four female patients. The mean age at operation was 34.2 months (range: 14 to 127 months), and the mean follow-up was 16.1 months (range: 12 to 30 months). Toe lengthening, toe overriding, and synostosis between the metatarsals were observed in two, two and two patients; toe shortening, toe deviation, metatarsal lengthening and metatarsal angulation were observed in one, one, one and one patient. The lengths of third and fourth metatarsals in donor site were significantly larger than those in contralateral side, while the widths of third and fourth metatarsals were not significantly different between donor and contralateral sides. The mean score in the parental satisfaction questionnaire (full score, 30) was 27.2, (range: 17 to 30), which rated as “good”. Conclusions: Following full-width metatarsal transfer for Type IIIB and IV thumb hypoplasia, transposition of the adjacent half-width metatarsal for donor reconstruction results in minor donor deficit and overall parenteral satisfaction. Level of evidence: Ⅳ
Sexual Dimorphism in Testosterone Programming of Cardiomyocyte Development in Sheep
Authors: Ghnenis Adel , Padmanabhan Vasantha , Vyas Arpita
Published: October 2021

Perturbed in-utero hormone milieu leads to intrauterine growth retardation (IUGR), a known risk factor for left ventricular (LV) dysfunction later in life. Gestational testosterone (T) excess predisposes offspring to IUGR and leads to LV myocardial disarray and hypertension in adult females. However, the early impact of T excess on LV programming and if it is female-specific is unknown. LV tissues were obtained at day 90 gestation from days 30-90 T-treated or control fetuses (n=6/group/sex) and morphometric and molecular analyses were conducted. Gestational T treatment increased cardiomyocyte number only in female fetuses. T excess up-regulated receptor expression of insulin and insulin-like growth factor. Furthermore, in a sex-specific manner, T increased expression of Phosphatidylinositol 3-kinase (PI3K) while down regulating phosphorylated mammalian target of rapamycin (pmTOR) /mTOR ratio suggestive of compensatory response. T excess 1) upregulated atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), markers of stress and cardiac hypertrophy 2) upregulated estrogen receptors1 (ESR1) and 2 (ESR2) but not in androgen receptor (AR). Thus, gestational T excess upregulated markers of cardiac stress and hypertrophy in both sexes while inducing cardiomyocyte hyperplasia only in females, likely mediated via insulin and estrogenic programming.
Effect of Radiotherapy Sequence on Long-term Outcome in Patients With Node-positive Breast Cancer: a Retrospective Study
Authors: Woo Joohyun , Moon Byung-In , Kwon Hyungju , Lim Woosung
Published: October 2021

The optimal sequence of chemotherapy (CT) and radiotherapy (RT) after surgery in breast cancer patients is unclear. There is a lack of literature on RT given between anthracycline and taxane administration. We evaluated the effect of RT sequence on long-term outcome in breast cancer. Two hundred patients who underwent surgery between January 2009 and December 2012 for node-positive breast cancers were evaluated retrospectively. All patients were treated with doxorubicin and cyclophosphamide (AC) followed by taxane. Sandwich RT group that received RT between AC and taxane was compared to the group that received RT after CT. The mean follow-up period was 105.4 months. The locoregional recurrence (LRR) rate was lower in sandwich RT group (P=0.012) and there was no significant difference in distant metastasis between the two groups. The RT sequence was an important predictor for LRR in multivariable analysis (P=0.017). For luminal A subtype, disease-free survival (DFS) was better in sandwich RT group than in CT followed by RT group (P=0.001). The overall survival did not correlated with RT sequence regardless of subtype. Sandwich RT can offer DFS benefit in luminal A subtype breast cancer. A tailored approach of sequencing chemotherapy and radiotherapy would be needed considering the factors that can influence outcome.
Title Evaluation of the Integration of Social Accountability Values into Medical Education using a Problem-Based Learning Curriculum
Authors: Dash Nihar Ranjan , Taha Mohamed H. , Shorbagi Sarra , Aballa Mohamed Elhassan
Published: October 2021

BackgroundMedical schools have the obligation to direct their education toward addressing the priority health concerns of the societies that they serve. The purpose of this study was to evaluate the integration of the concepts and values of social accountability into the case scenarios that are used in a problem-based learning (PBL) curriculum at a medical school in the United Arab Emirates (UAE). Methods A validated “social accountability inventory for PBL” was used for examining 70 case scenarios in a problem-based learning (PBL) medical curriculum.ResultsThe findings of the study indicate that the majority of the case scenarios integrated the social accountably values in addressing the following: the major health problems or social health concerns of the UAE (73%), the social determinants of health (70%), the contextual integration of medical professionalism (87%), the evolving roles of doctors in the health system (79%), the healthcare referral system based on the case complexity (73%), the involvement of different stakeholders in healthcare (87%) and the psychosocial issues rather than only the disease-oriented issues (80%). However, the case scenarios were deficient in integrating other social accountability values that related to the importance of a multidisciplinary approach to patient management (29%), issues regarding the management of the health system (49%), the values of health promotion/prevention (59%), consideration of the underserved, disadvantaged or vulnerable populations in the society (62%), the socioeconomic statuses of patients (54%), ethnicity (54%) and cost-effectiveness (65%). There was variability in integrating the social accountability values in case scenarios across different units which are based on organ system. ConclusionMedical educators can use this valuable data to calibrate their curriculum content, especially when using a problem-based learning curriculum to integrate the values of social accountability such as relevance, quality, equity and cost-effectiveness to train the future generation of healthcare providers to be ready to address the ever-changing and diverse needs of the societies.
Molecular and Clinical Characteristics Associated with Elevated TREM1 and its Emergence as a Prognostic Biomarker in Gliomas
Authors: Zhang Lin , Xu Yangyang , Qu Xun
Published: October 2021

Background: Monotherapy with immune checkpoint blockade for most gliomas does not seem to induce durable antitumor responses, which drive us to explore potential immunological targets in glioma. Triggering receptor expressed on myeloid cells-1 (TREM1) has been reported to be associated with immune-related inflammatory disorders. However, to date, there has rarely been studied in glioma.Methods: The data included clinicopathological characteristics and transcriptome data of patients with glioma obtained from publicly available genomic databases. Bioinformatics methods were employed to identify TREM1 expression pattern, prognostic value, biological function, and immune characteristics by R language, SPSS 19 and GraphPad Prism 8 softwareResults: In this study, it was observed that TERM1 expression was increased significantly in GBM compared with other types and was associated with poor outcome. Increased TREM1 accompanied distinct mutation and amplification of driver oncogenes. Moreover, gene ontology and KEGG analyses showed that TREM1 may play a role in the immunobiology of gliomas. TREM1 may participate in the immunosuppressive microenvironment by inhibiting T cell antitumor immunity functions. Additionally, through correlation analysis, TREM1 was found to be tightly correlated with immune checkpoint molecules.Conclusion: TREM1 may be a novel and attractive immune target and may provide new avenues to overcome the low response rate of glioma patients to current immunotherapies.
Qufeng Xuanbi Formula ameliorates airway remodeling in asthmatic mice by suppressing airway smooth muscle cells proliferation through MEK/ERK signaling pathway
Authors: Wang Bohan , Tang Lingling , Shi Suofang , Yang Ying , Sun Xianhong , Zhang Xiaona , Liu Chunyang , Liu Li
Published: October 2021

BackgroundAsthma is a common chronic respiratory disease. Qufeng Xuanbi Formula (QFXBF), a Chinese herbal decoction, has shown efficiency for the management of asthma. The purpose of current study is to investigate the potential therapeutic effects of QFXBF for the treatment of asthma both in vitro and in vivo. MethodsPDGF-induced ASMCs proliferation model and MTT assay have been applied for exploring the effects of QFXBF on the proliferation of ASMCs. Moreover, 40 female BALB/c mice were randomly divided into five groups: control group, OVA group, High QFXBF group, Low QFXBF group, and dexamethasone (DEX) group (n = 8 per group). The mouse allergic asthma model has been established by intranasally administered ovalbumin (OVA) sensitization method. Morphological changes of the lung tissue have been examined by hematoxylin and eosin (H&E) staining and Masson’s staining. Finally, the protein expressions of α-SMA, PCNA, p-MEK1/2, MEK1/2, p-ERK1/2, and ERK1/2 in ASMCs and lung tissue were determined by western blotting and immunofluorescent staining assays. ResultsPDGF induced significant increase in viability of ASMCs. Compared with mice in control group, the airway walls and airway smooth muscle of mice in OVA group mice thickened, and the inflammatory cells around the bronchus increased significantly. Moreover, administration of QFXBF markedly inhibited the proliferation of ASMCs and alleviated the pathologic changes induced by OVA. Furthermore, the protein expressions of p-ERK1/2, p-MEK1/2, PCNA, and α-SMA were significantly increased in OVA-treated mice and PDGF-treated ASMCs. Finally, treatment of QFXBF also significantly decreased the protein expression of p-ERK1/2, p-MEK1/2, α-SMA and PCNA. ConclusionQFXBF can inhibit the proliferation of ASMCs via suppressing the MEK/ERK signaling in PDGF-induced ASMCs and OVA-induced mice.
Two Pulse Intrusive Events of the Pliocene Tanigawa-Dake Granites Revealed from Zircon U-Pb Dating.
Authors: Minami Saki , Nagata Mitsuhiro , Sueoka Shigeru , Fukuda Shoma , Kajita Yuya , Ogita Yasuhiro , Kagami Saya , Yokoyama Tatsunori , Tagami Takahiro
Published: October 2021

We performed zircon U–Pb dating on the Pliocene Tanigawa-dake granites (Makihata and Tanigawa bodies) and the Cretaceous Minakami quartzdiorite, Northeast Japan Arc. Concordia ages were estimated to be 3.95 ± 0.11 Ma (± 2 sigma) for the Makihata body, 3.18 ± 0.13 Ma and 3.32 ± 0.15 Ma for the Tanigawa body, and 109.4 ± 2.2 Ma for the Minakami quartzdiorite. The Minakami quartzdiorite is possibly correlated to the bedrock in the Ashio belt because the age of the Minakami quartzdiorite is consistent with the zircon U–Pb ages of the earliest Tadamigawa granites (107–62 Ma) which are distributed to the northeast of the Tanigawa-dake region and belong to the Ashio belt. All the zircon U-Pb ages of the Tanigawa-dake granites are older than the previously reported cooling ages, i.e., K–Ar ages and zircon fission-track ages, being consistent with their difference in closure temperature. On the basis of these results, we concluded that the intrusive ages of the Tanigawa-dake granites are ~4–3 Ma, which are among the youngest exposed plutons on Earth. The U–Pb ages of the Makihata body and the Tanigawa body are different significantly in the 2 sigma error range. Thus, the Tanigawa body intruded later than the Makihata body by ~0.7 Myr.
Traditional Chinese Medicine Syndromes Classification Associates with Tumor Cell and Microenvironment Heterogeneity in Colorectal Cancer: a Single Cell RNA Sequencing Analysis
Authors: Lu Yiyu , Zhou Chungen , Zhu Meidong , Fu Zhiliang , Shi Yong , Li Min , Wang Wenhai , Zhu Shibo , Jiang Bin , Luo Yunquan , Shibing Su
Published: October 2021

Background: Colorectal cancer (CRC) is one of the common gastrointestinal malignancies, tumor heterogeneity is the main cause of refractory CRC. Syndrome differentiation is the premise of individualized treatment of traditional Chinese medicine (TCM), but TCM syndrome lacks objective identification in CRC. Methods: In this study, we using scRNA-seq technology, investigate the significance of tumor heterogeneity in TCM syndromes classification on CRC. Results: The results showed that 662 cells isolated from 11 primary CRC tumors are divided into 14 different cell clusters, and each cell subtype and its genes have different functions and signal transduction pathways, indicating significant heterogeneity. CRC tumor cell clusters have different proportions in Excess, Deficiency and Deficiency-Excess syndromes, and have their own characteristic genes, gene co-expression networks, gene functional interpretations as well as monocle functional evolution. Moreover, there were significant differences between the high expressions of MUC2, REG4, COL1A2, POSTN, SDPR, GPX1, ELF3, KRT8, KRT18, KRT19, FN1, SERPINE1, TCF4 and ZEB1 genes and Excess and Deficiency syndrome classification in CRC (P<0.01). Conclusions: The study suggested that the Excess and Deficiency syndromes classification of CRC may be related to tumor heterogeneity and its microenvironment.
Isorhamnetin Protects Zearalenone-induced Damage via the PI3K/Akt Signaling Pathway in Porcine Granulosa Cells
Authors: Li Xiaoya , Chen Huali , Zhang Zelin , Li Xiaodi , Duan Jiaxin , Hua Rongmao , Yang Li , Cheng Jianyong , Li Qingwang
Published: October 2021

Background: Zearalenone (ZEA) is widely derived from moldy cereal grain, which has adverse effects on animal reproduction. In particular, pigs are more sensitive to ZEA-induced toxicity than other animals. Isorhamnetin, a flavonoid has extensive of pharmacological activities. However, little is known about the effects of isorhamnetin on reproduction. Thus, it would be interesting to clarify the effect and the underlying molecular mechanism of isorhamnetin involvement in ZEA-induced cytotoxicity in porcine granulosa cells.Results: Our findings showed that isorhamnetin suppressed ZEA-induced apoptosis by regulating Bcl-2 and Bax protein changes. Changes in intracellular Ca2+ levels and CHOP, ATF6, GRP78 indicated that isorhamnetin rescued ZEA-induced endoplasmic reticulum stress (ERS). Furthermore, isorhamnetin prevented ZEA-induced reactive oxygen species (ROS) via P38 signaling pathway. Mechanistically, isorhamnetin stimulated the expression of PCNA and CyclinD, thereby raising the ratio of S phases cells in response to ZEA-induced apoptosis via PI3K/Akt signaling pathway. Isorhamnetin also recovered ZEA-induced steroidogenesis disorder by regulating steroidogenic enzyme gene and proteins (FSH-R, CYP19A1). Conclusions: Collectively, these findings show that isorhamnetin protects granulosa cells from ZEA-induced damage via the PI3K/Akt signaling pathway, which promotes proliferation, alleviates steroidogenesis disorder, ERS and oxidative stress.
The pattern of alternative splicing in lung adenocarcinoma shows novel events correlated with tumorigenesis and immune microenvironment
Authors: Qiu Wensheng
Published: October 2021

Lung adenocarcinoma (LUAD) is the leading cause of cancer deaths worldwide due to the lack of early diagnostic markers and specific drugs. Previous studies have shown the association of LUAD growth with aberrant alternative splicing (AS). Herein, clinical data of 535 tumor tissues and 59 normal tissues were extracted from the TCGA database. Each sample was analyzed using the ESTIMATE algorithm; a comparison between higher and lower score groups (stromal or immune) was made to determine the overall- and progression-free survival-related differentially expressed AS (DEAS) events. We then performed unsupervised clustering of these DEASs, followed by determining their relationship with survival rate, immune cells, and the tumor microenvironment (TME). Next, two prognostic signatures were developed using bioinformatics tools to explore the prognosis of cases with LUAD. Five OS- and six PFS-associated DEAS events were implemented to establish a prognostic risk score model. When compared to the high-risk group (HRG), the PFS and OS of the low-risk group (LRG) were found to be considerable. Additionally, a better prognosis was found considerably associated with the ESTIMATE score of the patients as well as immune cells infiltration. Our analysis of AS events in LUAD not only helps to clarify the tumorigenesis mechanism of AS, but also provides ideas for revealing potential prognostic biomarkers and therapeutic targets.