bluuebunny/crossref_metadata_2025 huggingface dataset:
Numerical study on the influence of initial ambient temperature on the aerodynamic heating in the tube train system
Authors: Bao Shijie , Hu Xiao , Wang Jukun , Ma Tianhao , Rao Yingyu , Deng Zigang
Published: October 2020

The evacuated tube transportation has great potential in the future because of its advantages of energy saving and environmental protection. The train runs in the closed tube at ultra-high speed. Because the heat quantity generated by aerodynamic heating is not easy to spread to external environment and will accumulate in the tube, the phenomenon that the ambient temperature in the tube will gradually rise will be induced. In this paper, a three-dimensional geometric model and the Shear Stress Transport (SST) κ-ω turbulence model are used to study the influence of initial ambient temperature on the structure of the flow field in the tube. Simulation results show that when the train runs at transonic speed, the supersonic flow region with low temperature and low-pressure is produced in the wake. The structure of the flow field of the wake will change with the initial ambient temperature. And the higher the initial ambient temperature, the shorter the low temperature region in the wake. The larger temperature difference caused by the low temperature region may increase the temperature stress of the tube and affect the equipment inside the tube. Consequently, the temperature inside the tube can be maintained at a reasonable value to reduce the influence of the low temperature region in the wake on the system.
Effects of trees, gardens, and nature trails on heat index and child health: Design and methods of the Green Schoolyards Project
Authors: Lanza Kevin , Alcazar Melody , Hoelscher Deanna M. , Kohl III Harold W.
Published: October 2020

Background: Latinx children in the United States are at high risk for nature-deficit disorder, heat-related illness, and physical inactivity. We developed the Green Schoolyards Project to investigate how green features—trees, gardens, and nature trails—in school parks impact heat index (i.e., air temperature and relative humidity) within parks, and physical activity levels and socioemotional well-being of these children. Herein, we present novel methods for a) observing children’s interaction with green features and b) measuring heat index and children’s behaviors in a natural setting, and a selection of baseline results.Methods: During two September weeks (high temperature) and one November week (moderate temperature) in 2019, we examined three joint-use elementary school parks in Central Texas, United States, serving predominantly low-income Latinx families. To develop thermal profiles for each park, we installed 10 air temperature/relative humidity sensors per park, selecting sites based on land cover, land use, and even spatial coverage. We measured green features within a geographic information system. In a cross-sectional study, we used an adapted version of System for Observing Play and Recreation in Communities (SOPARC) to assess children’s physical activity levels and interactions with green features. In a cohort study, we equipped 30 3rd and 30 4th grade students per school during recess with accelerometers and Global Positioning System devices, and surveyed these students regarding their connection to nature. Baseline analyses included inverse distance weighting for thermal profiles and summing observed counts of children interacting with trees.Results: In September 2019, average daily heat index ranged 2.0°F among park sites, and maximum daily heat index ranged from 103.4°F (air temperature = 33.8°C; relative humidity = 55.2%) under tree canopy to 114.1°F (air temperature = 37.9°C; relative humidity = 45.2%) on an unshaded playground. 10.8% more girls and 25.4% more boys interacted with trees in September than in November.Conclusions: We found extreme heat conditions at select sites within parks, and children positioning themselves under trees during periods of high heat index. These methods can be used by public health researchers and practitioners to inform the redesign of greenspaces in the face of climate change and health inequities.
Carbon ion radiotherapy for prostate cancer with bladder invasion
Authors: Miyasaka Yuhei , Kawamura Hidemasa , Sato Hiro , Kubo Nobuteru , Mizukami Tatsuji , Matsui Hiroshi , Miyazawa Yoshiyuki , Ito Kazuto , Nakano Takashi , Suzuki Kazuhiro , Ohno Tatsuya
Published: October 2020

Background: The optimal management of clinical T4 (cT4) prostate cancer (PC) is still uncertain. At our institution, carbon ion radiotherapy (CIRT) for nonmetastatic PC, including tumors invading the bladder, has been performed since 2010. Since carbon ion beams provide a sharp dose distribution with minimal penumbra and have biological advantages over photon radiotherapy, CIRT may provide a therapeutic benefit for PC with bladder invasion. Hence, we evaluated CIRT for PC with bladder invasion in terms of the safety and efficacy.Methods: Between March 2010 and December 2016, a total of 1,337 patients with nonmetastatic PC received CIRT at a total dose of 57.6 Gy (RBE) in 16 fractions over 4 weeks. Among them, 7 patients who had locally advanced PC with bladder invasion were identified. Long-term androgen-deprivation therapy (ADT) was also administered to these patients. Adverse events were graded according to the Common Terminology Criteria for Adverse Event (CTCAE) version 5.0.Results: At the conclusion of our study, all the patients with cT4 PC were alive with a median follow-up period of 78 months. Grade 2 acute urinary disorders were observed in only 1 patient. Regarding late toxicities, only 1 patient developed grade 2 hematuria and urinary urgency. There was no grade 3 or worse toxicity. Gastrointestinal toxicity was not observed. Six (85.7%) patients had no recurrence or metastasis. One patient had biochemical and local failures 42 and 45 months after CIRT, respectively. However, the recurrent disease has been well controlled by salvage ADT.Conclusions: Seven patients with locally advanced PC invading the bladder treated with CIRT were evaluated. Our findings seem to suggest positive safety and efficacy profiles for CIRT.
Rhodanine-3-Acetamide Derivatives as Aldose and Aldehyde Reductase Inhibitors to Treat Diabetic Complications; Synthesis, Biological Evaluation and Molecular Docking Studies
Authors: Bacha Mohsinul Mulk , Nadeem Humaira , Zaib Sumera , Sarwar Sadia , Imran Aqeel , Rehman Shafiq Ur , Ali Hafiz Saqib , Arif Muazzam , Iqbal Jamshed
Published: October 2020

In diabetes, increased accumulation of sorbitol has been associated with diabetic complications through polyol pathway. Aldose reductase (AR) is one of the key factors involved in reduction of glucose to sorbitol, thereby its inhibition is considered to be important for the management of diabetic complications. In the present study, a series of seven 4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetamide derivatives 3(a-g) were synthesized by the reaction of 5-(4-hydroxy-3-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2a) and 5-(4-methoxybenzylidene)-4-oxo-2-thioxo-1,3-thiazolidin-3-yl acetic acid (2b) with different amines. The synthesized compounds 3(a-g) were investigated for their in vitro aldehyde reductase (ALR1) and aldose reductase (ALR2) enzyme inhibitory potential. Compound 3c, 3d, 3e, and 3f showed ALR1 inhibition at lower micromolar concentration whereas all the compounds were more active than the standard inhibitor valproic acid. Most of the compounds were active against ALR2 but compound 3a and 3f showed higher inhibition than the standard drug sulindac. Overall the most potent compound against aldose reductase was 3f with an inhibitory concentration of 0.12 ± 0.01 µM. In vitro results showed that vanillin derivatives exhibited better activity against both aldehyde reductase and aldose reductase. The molecular docking studies were carried out to investigate the binding affinities of synthesized derivatives with both ALR1 and ALR2. The binding site analysis of potent compounds revealed similar interactions as were found by cognate ligands within the active sites of enzymes.
Influence of inoculated gut bacteria on the development of Bactrocera dorsalis and on its susceptibility to the entomopathogenic fungus, Metarhizium anisopliae
Authors: Gichuhi Joseph , Khamis Fathiya , Berg Johnnie Van den , Mohamed Samira , Ekesi Sunday , Herren Jeremy K.
Published: October 2020

Background: Symbiotic interactions between insects and bacteria have been associated with a vast variety of physiological, ecological and evolutionary consequences for the host. A wide range of bacterial communities have been found in association with the oriental fruit fly, Bactrocera dorsalis (Hendel) (Diptera: Tephritidae), an important pest of cultivated fruit in most regions of the world. We evaluated the diversity of gut bacteria in B. dorsalis specimens from several populations in Kenya and investigated the roles of individual bacterial isolates in the development of axenic (germ-free) B. dorsalis fly lines and their responses to the entomopathogenic fungus, Metarhizium anisopliae. Results: We sequenced 16S rRNA to evaluate microbiomes and coupled this with bacterial culturing. Bacterial isolates were mono-associated with axenic B. dorsalis embryos. The shortest embryonic development period was recorded in flies with an intact gut microbiome while the longest period was recorded in axenic fly lines. Similarly, larval development was shortest in flies with an intact gut microbiome, in addition to flies inoculated with Providencia alcalifaciens. Adult B. dorsalis flies emerging from embryos that had been mono-associated with a strain of Lactococcus lactis had decreased survival when challenged with a standard dosage of M. anisopliae ICIPE69 conidia. However, there were no differences in survival between the germ-free lines and flies with an intact microbiome. Conclusions: These findings will contribute to the selection of probiotics used in artificial diets for B. dorsalis rearing and the development of improved integrated pest management strategies based on entomopathogenic fungi.
Reclassification of Chromobacterium violaceum ATCC 31532 and its Quorum Biosensor Mutant CV026 to Chromobacterium subtsugae
Authors: Harrison Alisha , Soby Scott
Published: October 2020

The precipitous drop in the cost of genomic sequencing and the concomitant availability of computational methods for comparing genome-level data has made the accurate taxonomic placement of bacteria affordable and relatively rapid. Inaccurate taxonomic placement of bacteria has serious implications in clinical, environmental, and regulatory microbiology, but it can also adversely affect interpretation of research results. The quorum biosensor strain CV026 was derived from an isolate of Chromobacterium that was labeled as C. violaceum ATCC 31532, and is catalogued by the ATCC under that species name. Nearly 200 papers have been published that use CV026 as an indicator for quorum sensing activity in many Gram negative bacteria, but the inability of C. violaceum strains to complement the quorum sensing mutation in CV026 has called the taxonomic placement of the parent strain into question. We used molecular phylogeny and a large number of metabolic and phenotypic characters to demonstrate that Chromobacterium strain ATCC 31532 is a member of species Chromobacterium subtsugae.
Transplantation of a Heart Donated After Circulatory Death via Thoraco-Abdominal Normothermic Regional Perfusion. Results from the first Spanish case. 
Authors: Redondo Marina Pérez , Carmona Sara Alcántara , García Susana Villar , Gil Alberto Forteza , Fernández Hector Villanueva , Hernández-Pérez Francisco José , Cruz Jose Luis Campo-Cañaveral de la , Calvo Rocío Velasco , Segovia-Cubero Javier , Menárguez Beatriz Alonso , Gallegos Francisco del Río , Coll Elisabeth , Gonzalez Beatriz Domínguez-Gil , Muñoz Juan José Rubio
Published: October 2020

BackgroundControlled donation after circulatory death (cDCD) has emerged as one of the main strategies for increasing the organ donor pool. Because of the ischemic injury that follows the withdrawal of life-sustaining therapies, hearts from cDCD donors have not been considered for transplantation until recently. The ex-situ perfusion of hearts directly procured from cDCD donors has been used to allow the continuous perfusion of the organ and the assessment of myocardial viability prior to transplantation. Based on our experience with abdominal normothermic regional perfusion in cDCD, we designed a protocol to recover and validate hearts from cDCD donors using thoraco-abdominal normothermic regional perfusion without the utilization of an ex-situ device.Case presentationWe describe the first case of a cDCD heart transplant performed with this approach in Spain. The donor was a 43-year-old asthmatic female diagnosed with severe hypoxic encephalopathy. She was considered a potential cDCD donor and a suitable candidate for multiorgan procurement including the heart via thoraco-abdominal normothermic regional perfusion. The heart recipient was a 60-year-old male diagnosed with amyloid cardiomyopathy. Cold ischemia time was 55 minutes. The surgery was uneventful.ConclusionsThis case report, the first of its kind in Spain, supports the feasibility of evaluating and successfully transplanting cDCD hearts without the need for ex-situ perfusion based on the use of thoraco-abdominal normothermic regional perfusion opening the way for multiorgan donation in cDCD.
In vitro and in vivo evaluation of paclitaxel-induced release of apoptotic biomarker ccCK18 to guide treatment optimization in ovarian cancer 
Authors: Thaye Elien De , Vijver Koen Van de , Dorpe Jo Van , Vermeulen An , Bocxlaer Jan Van , Colin Pieter
Published: October 2020

Background: Cytokeratins hold potential as biomarkers due to their epithelial specificity, abundance and cleavage by caspases during apoptosis. We evaluated paclitaxel-induced circulating caspase-cleaved (cc) cytokeratin 18 (CK18) as potential apoptotic cell-death marker to guide treatment optimization in ovarian cancer.Methods: Six ovarian cancer cell lines (SK-OV-3, SK-OV-3lucIP1, Caov-3, NIH:OVCAR-3, PA-1 and PM-LGSOC-01) were exposed in vitro to paclitaxel (PTX, 0 to 1000 nM) for 24h. Extracellular levels of ccCK18 were measured until 5 days after drug exposure. Cell count and ccCK18 release data were analyzed using a phase-nonspecific pharmacodynamic model implemented in NONMEM®. PA-1 and SK-OV-3lucIP1 xenografted female SCID/Beige mice received a placebo or single dose of 50 mg/kg PTX intraperitoneally. Response to PTX was evaluated in vivo using tumor volume and released ccCK18 levels. Results: In vitro, the correlation between cell count and released ccCK18 levels was present in all cell lines (Spearman’s rank correlation coefficient > 0.64). Tumor volume and ccCK18 longitudinal dynamics were markedly different for controls and PTX-treated PA-1 xenografts with changes in ccCK18 release preceding changes in tumor volume. For SK-OV-3lucIP1 xenografts, no differences were found between controls and PTX-treated mice.Conclusions: An association between PTX-induced ccCK18 release and cell count was demonstrated in vitro. The in vivo study supported the presence of an early-apoptotic peak in ccCK18 levels compared to a later observed effect on tumor volume in PTX-sensitive xenografts. Given the heterogeneous character of ovarian cancer, application and implementation of ccCK18 in a clinical setting to optimize or personalize cancer treatment needs further refinement.
Virulent secondary metabolites of entomopathogenic bacteria genera, Xenorhabdus and Photorhabdus, inhibit phospholipase A2 to suppress host insect immunity
Authors: Mollah Md. Mahi Imam , Kim Yonggyun
Published: October 2020

Background: Xenorhabdus and Photorhabdus are entomopathogenic bacteria that cause septicemia and toxemia in insects. They produce secondary metabolites to induce host immunosuppression. Their metabolite compositions vary among bacterial species. Little is known about the relationship between metabolite compositions and the bacterial pathogenicity. The objective of this study was to compare pathogenicity and production of secondary metabolites of 14 bacterial isolates (species or strains) of Xenorhabdus and Photorhabdus. Results: All bacterial isolates exhibited insecticidal activities after hemocoelic injection to Spodoptera exigua (a lepidopteran insect) larvae, with median lethal doses ranging from 168.8 to 641.3 CFU per larva. Bacterial infection also led to immunosuppression by inhibiting eicosanoid biosynthesis. Bacterial culture broth was fractionated into four different organic extracts. All four organic extracts of each bacterial species exhibited insecticidal activities and resulted in immunosuppression. These organic extracts were subjected to GC-MS analysis which predicted 182 compounds, showing differential compositions for 14 bacteria isolates. There were positive correlations between total number of secondary metabolites produced by each bacterial culture broth and its bacterial pathogenicity based on immunosuppression and insecticidal activity. From these correlation results, 70 virulent compounds were selected from secondary metabolites of high virulent bacterial isolates by deducting those of low virulent bacterial isolates. These selected virulent compounds exhibited significant immunosuppressive activities by inhibiting eicosanoid biosynthesis. They also exhibited relatively high insecticidal activities. Conclusion: Virulence variation between Xenorhabdus and Photorhabdus is determined by their different compositions of secondary metabolites, of which PLA2 inhibitors play a crucial role.
Serum alkaline phosphatase levels and the risk of new-onset diabetes in hypertensive adults
Authors: Zhang Yuanyuan , Zhou Chun , Li Jianping , Zhang Yan , Xie Di , Liang Min , Wang Binyan , Song Yun , Wang Xiaobin , Huo Yong , Hou Fan Fan , Xu Xiping , Qin Xianhui
Published: October 2020

Background: The association between alkaline phosphatase (ALP) and incident diabetes remains uncertain. Our study aimed to investigate the prospective relation of serum ALP with the risk of new-onset diabetes, and explore possible effect modifiers, in hypertensive adults.Methods: A total 14,393 hypertensive patients with available ALP measurements and without diabetes and liver disease at baseline were included from the China Stroke Primary Prevention Trial (CSPPT). The primary outcome was new-onset diabetes, defined as physician-diagnosed diabetes or use of glucose-lowering drugs during follow-up, or fasting glucose ≥7.0mmol/L at the exit visit. The secondary study outcome was new-onset impaired fasting glucose (IFG), defined as FG <6.1mmol/L at baseline and ≥6.1 but <7.0mmol/L at the exit visit.Results: Over a median of 4.5 years follow-up, 1,549 (10.8%) participants developed diabetes. Overall, there was a positive relation of serum ALP and the risk of new-onset diabetes (per SD increment, adjusted OR, 1.07; 95%CI: 1.01, 1.14) and new-onset IFG (per SD increment, adjusted OR, 1.07; 95%CI: 1.02, 1.14). Moreover, a stronger positive association between baseline ALP (per SD increment) with new-onset diabetes was found in participants with total homocysteine (tHcy) <10μmol/L (adjusted OR, 1.24; 95%CI: 1.10, 1.40 vs. ≥10μmol/L: adjusted OR, 1.03; 95%CI: 0.96, 1.10; P-interaction=0.007) or FG ≥5.9mmol/L (adjusted OR, 1.16; 95%CI: 1.07, 1.27 vs. <5.9mmol/L: adjusted OR, 1.00; 95%CI: 0.93, 1.08; P-interaction =0.009)Conclusions: In this non-diabetic, hypertensive population, higher serum ALP was significantly associated with the increased risk of new-onset diabetes, especially in those with lower tHcy or higher FG levels.Clinical Trial Registration-URL: Trial registration: NCT00794885 (clinicaltrials.gov). Retrospectively registered November 20, 2008.
Efficacy of the Self-Mutual-Group model targeting quality of life improvement among empty-nest elderly: An intervention study
Authors: Zhang Chichen , Xue Yaqing , Cai Yuan , Lu Jiao , Zheng Xiao , Yuan Wenpei , Qian Yi
Published: October 2020

BackgroundThe “empty nest” family is becoming the main family pattern in China. Meanwhile, the health-related quality of life of empty-nest elderly is an increasing public health concern. This research aims to examine the effectiveness of Self-Mutual-Group (SMG) model in improving quality of life of the empty-nest elderly to provide a scientific evidence for improving their health.MethodsA prospective intervention study was conducted among empty-nest elderly in Taiyuan, Shanxi. Participants who met the inclusion criteria were assigned randomly to the intervention or control group. The intervention group received a seven-month SMG-based intervention. A participant’s quality of life was measured at the baseline and seven months after using the Short Form 36-Item Health Survey (SF-36).ResultsNo significant difference was found between the intervention and control groups in terms of participant characteristics at baseline (P > 0.05). After the intervention, participants’ scores on Mental Component Summary (MCS), Physical Component Summary (PCS), role emotional (RE), vitality (VT), social function (SF), mental health (MH) and general health (GH) increased significantly in the intervention group. Additionally, these scores differed significantly from those in the control group (P < 0.05).ConclusionThis study showed that the SMG-based health management is effective in improving quality of life among empty-nest elderly after seven months.Trial registrationStudy on the ‘SMG’ Health Management Model Based on Community Organization Theory among empty-nest elderly (ChiCTR1800015884). Registration date: 26-04-2018. Retrospectively registered.
Melatonin as an endogenous hormone to slow down the exhaustion of ovarian follicle reserve in mice–a novel insight into its roles in early folliculogenesis and ovarian aging
Authors: Yang Chan , Liu Qinghua , Chen Yingjun , Wang Xiaodong , Ran Zaohong , Fang Fang , Xiong Jiajun , Liu Guoshi , Li Xiang , Yang Liguo , Changjiu He
Published: October 2020

Previous studies have shown that long-term intake of exogenous melatonin can effectively delay ovarian aging, but the mechanism has not been fully elucidated. We observed that SNAT, the rate-limiting enzyme in the melatonin synthetic pathway, is localized in primordial and early follicle, and that granulosa cells isolated from follicle can synthesize melatonin. In vitro cultured neonatal mice ovaries with melatonin inhibited primordial follicle activation and early follicle growth. In vivo experiments further indicated that daily injections of melatonin to neonatal mice during the primordial follicle activation phase can reduce the number of activated follicles by inhibiting the PI3K-AKT-FOXO3 pathway; during the early follicle growth phase, injections of melatonin significantly suppressed early follicle growth and atresia, and transcriptome data showed that multiple pathways involved in folliculogenesis, including PI3K-AKT, were suppressed. Further, SNAT knockout in mice resulted in a significant increase in follicle activation and atresia, and eventually accelerated ovarian aging. We also demonstrated that prolonged high-dose melatonin intake had no obvious adverse effect on the health condition of mice. This study confirms that endogenous melatonin is involved in the regulation of ovarian aging, and reveals that melatonin delays ovarian aging by inhibiting primordial follicle activation, early follicle growth and atresia.
Identification and Characterization of TUBBY genes in developmental stages of Zea mays
Authors: Mejia Sendi , Shah Suhani , Abdelsalam Yara , Nimra Ali , Bhatt Munzir , Borges Daniela , Chen Joey , Dwamena George , Elcock Angel , Firrello Jason , Foster Anordia , James Josephine , Jenkins Delivrance , Khan Maheen , Lewis Adwoa , Manzanilla Ana , Morataya Melisa , Pendleton Shedonna , Quill Deanni , Zayas Orlando Rivera , Rosengarden Shannon , Scott Mornette , Suriel Meliss , Toussaint Wildine , Valencia Paula , Wadhwani Pragya , Zaib Arshia , Marco Cristina Fernandez , Monaco Marcela K. , Ware Doreen , Noutsos Christos
Published: October 2020

In this paper, we studied the organization and function of TUBBY Transcription Factor gene family in maize. Initially, using comparative approach, we discovered the Arabidopsis thaliana orthologs in Zea mays. We found in total 13 genes, 12 of which are orthologs and a unique paralog that exhibits the highest activity in maize. We studied the role of TUBBY gene family across different developmental stages using existing expression data, and discovered the binding motifs present in the promoter region of the genes.
Extensive genomic plasticity identified by anti-cancer Huaier therapy
Authors: Tanaka Manami , Tanaka Tomoo , Teng Fei , Lin Hong , Xu Chenying , Li Ning , Luo Zhu , Wei Ding , Lu Zhengxin
Published: October 2020

Clinical significance of anti-cancer effects of Huaier has been emphasized recently. We have proved that a broad spectrum of Huaier effects was based on the rescue of the disrupted Hippo signalling pathway, especially through the rescue of transcriptional dysregulation. We initiated clinical research for thorough understanding of mode of action by total RNA- and small non-coding RNA-sequencing. Here we provide the surprising genomic plasticity by Huaier observed in the time course of recovery from cancer. The extensive changes in RNA editing events were first observed, such as average 92,427 SNP variances per individual (22,688 in normal control). The subsequent changes in the process of translation and transcription resulted in the drastic changes in number of up/down-regulated transcripts. The ratio of the changes at maximum was 85% (23,210/27,447). With the advent of many novel sequences found in small nuclear RNAs and the consequent gene-silencing derived from miRNA-mediated post-transcriptional control, quantitative and qualitative changes of expression in transcriptional factors (mean 1,115/person) contributed to rescue dysregulated functions occurred in almost all required physiological functions for cancer recovery. The transcription control was demonstrated as functional lineage map between the core transcriptional factor and functionally linked transcripts, and the recovery could be clearly shown as the silencing of those massive changes in the end. The genetic alterations, especially related to the inhibition of NFκB and TGF-β signalling pathways showed significant effects on the improvement of prognosis. Thus, Huaier therapy contributes to cancer cell death with damaged tissue regeneration by extensive and systematic genomic modulations.
Multiple Endocrine Neoplasia Type 1 Combined With Papillary Thyroid Carcinoma and Nodular Goiter: A Case Report and Review of The Literature
Authors: Xu Jialu , Dong Su , Han Zhe , Sun Lele , Liu Jia
Published: October 2020

Introduction: This is the first report of multiple endocrine neoplasia type 1 (MEN1) combined with papillary thyroid carcinoma (PTC) and nodular goiter in China. MEN1 is a rare hereditary tumor syndrome inherited in an autosomal dominant manner and presenting mostly as tumors of the parathyroid, endocrine pancreas (such as gastrinoma) and anterior pituitary. However, PTC and nodular goiter were not previously regarded as components.Patient concerns: We present a 35-year-old woman with MEN1 accompanied with coinstantaneous PTC and nodular goiter.Diagnosis: The pathological diagnosis was PTC with cervical lymph node metastasis, nodular goiter, parathyroid cyst and adenomatoid hyperplasia. Genetic analysis was performed and a germ-line MEN1 gene mutation was detected.Interventions: The patient underwent unilateral lobectomy of the thyroid gland and surgical removal of the parathyroid tumors.Outcomes: After 6 months of follow-up, ultrasonic examination of the patient’s neck showed no abnormality. Serum calcium and parathyroid hormone levels were normal.Conclusion: This is the first experience of a case of MEN1 combined with PTC and nodular goiter in China. MEN1 syndrome may have predisposed the present patient to PTC and nodular goiter. PTC and/or nodular goiter may be new components of MEN1. More cases are required to confirm this association.
Establishment of A Rapid and Stable Infected System by Agrobacterium-Mediated Transformation of Germination Seeds in Diploid Strawberry.
Authors: Xu Peng-Hao , Gu Xiao-Jiao , Shen Yuan-Yue
Published: October 2020

Background Strawberry (Fragaria) is regarded as a model plant for both Rosaceae and non-climacteric fruit ripening. Although much progress has been made in identification of gene function using stable and transient genetic transformation systems in strawberry, the limitation is, more or less, are present. To this end, development of a rapid, efficient, and stable transformation system is required for strawberry research and breeding. Results Here, using diploid Hawaii-4 (Fragaria vesca) seeds and a reporter gene of CHLH (the H subunit of magnesium chelatase magnesium chelatase) key to chlorophyll synthesis, we first develop a rapid, efficient, and stable infected system by the Agrobacterium-mediated seed infection to silence the reporter gene, reaching an infection frequency with 28.3% through a series of optimization elements, including seed full imbibition and initial germination, shaking infection for 24 h, dark cultivation on MS medium for 3 d at 24 ℃, light culture on MS-Tim medium for 1 week at 24 ℃, and vector construction tagged with fluorescence label. Taken together, radicle-emergence germination seeds, appropriate Agrobacterium concentration and infection time are critical for successful infection, finally obtaining the infected kanamycin-resistant seedlings of T1 generation by infected wild seeds within 1 month and T2 generation-infected plants within 4 months. Conclusions The Agrobacterium-mediated infection of germinating seeds (AMTGS) in diploid strawberry (F. vesca) is first established, providing a useful tool for gene function identification and improved agronomic traits in strawberry.
Predictors of Radiographic Erosion and Joint Space Narrowing Progression in Patients with Early Rheumatoid Arthritis: A Cohort Study
Authors: Rydell Emil Per , Forslind Kristina , Nilsson Jan-Åke , Karlsson Magnus , Åkesson Kristina E , Jacobsson Lennart TH , Turesson Carl
Published: October 2020

Background Radiographic damage in rheumatoid arthritis (RA) includes erosions and joint space narrowing (JSN). Different mechanisms may underlie their development. The objective of this study was to evaluate predictors of these entities separately. Methods Consecutive early RA patients (symptom duration ≤12 months) from a defined area (Malmö, Sweden) recruited during 1995–2005 were investigated. Radiographs of hands and feet were scored by a trained reader according to the modified Sharp-van der Heijde score. Fat mass and lean mass distribution were measured at baseline using dual energy x-ray absorptiometry. Potential predictors of erosion- and JSN progression from inclusion to the 5-year follow-up were evaluated.Results Two hundred and thirty-three patients were included. Radiographs at baseline and 5 years were available for 162 patients. The median (interquartile) progression of erosion and JSN scores were 4 (0-8) and 8 (1-16), respectively. Rheumatoid factor (RF) was a robust significant predictor of both erosion- and JSN score progression. In adjusted analyses, anti-CCP antibodies predicted erosions while the erythrocyte sedimentation rate was predictive of both outcomes. Smoking, high levels of cartilage oligomeric matrix protein (>12 U/L) and high baseline disease activity (DAS28 >5.1) predicted progression of erosions. Baseline erosion score was associated with progression of both erosion- and JSN progression, while baseline JSN score was predictive only of the progression of JSN. Overweight/obesity (BMI ≥25kg/m2) was a significant negative predictor of JSN score progression (ß= -0.14, p= 0.018, adjusted for RF, age, baseline JSN score) also when additionally adjusting for ever smoking (p= 0.041). Among female patients, this effect was observed in those of estimated post-menopausal age (>51 years), but not in younger women. The truncal: peripheral fat ratio was associated with less JSN score progression in women, but not in men. Conclusions Overweight RA patients had less JSN progression, independent of smoking status. This effect was seen in particular among older women (mainly post-menopausal), but not younger. Truncal fat was associated with less JSN progression in female patients. Smoking predicted erosion progression, and erosions may precede JSN. BMI and fat distribution may influence cartilage damage in early RA and might be related to hormonal factors.
In Vivo Assessment of Glutamine Anaplerosis into the TCA Cycle in Human Pre-malignant and Malignant Clonal Plasma Cells
Authors: Gonsalves Wilson , Jang Jin Sung , Jessen Erik , Hitosugi Taro , Evans Laura , Jevremovic Dragan , Petterson Xuan-Mai , Bush Alexander Graham , Gransee Jaimee , Anderson Emilie I , Kumar Shaji K , Sreekumaran K.
Published: October 2020

BackgroundOverexpression of c-Myc is required for the progression of pre-malignant plasma cells in monoclonal gammopathy of undetermined significance (MGUS) to malignant plasma cells in multiple myeloma (MM). c-Myc also increases glutamine anaplerosis into the tricarboxylic acid (TCA) cycle within cancer cells. Whether increased glutamine anaplerosis is associated with the progression of pre-malignant to malignant plasma cells is unknown.MethodsHuman volunteers (N = 7) and patients with MGUS (N = 11) and MM (N = 12) were prospectively recruited to undergo an intravenous infusion of 13C-labelled glutamine followed by a bone marrow aspiration to obtain bone marrow cells and plasma.ResultsDespite notable heterogeneity, stable isotope resolved metabolomics (SIRM) revealed that the mean 13C-labelled glutamine anaplerosis into the TCA cycle was higher in malignant compared to pre-malignant bone marrow plasma cells relative to the remainder of their paired bone marrow mononuclear cells. RNA sequencing demonstrated a higher relative mRNA expression of c-Myc and glutamine transporters such as ASCT2 and SN2 in malignant compared to pre-malignant bone marrow plasma cells. Finally, higher quantitative levels of TCA cycle intermediates in the bone marrow plasma differentiated MM from MGUS patients.ConclusionMeasurement of the in vivo activity of glutamine anaplerosis into the TCA cycle provides novel insight into the metabolic changes associated with the transformation of pre-malignant plasma cells in MGUS to malignant plasma cells in MM.
Few-Layer Graphene Induces Both Primary and Secondary Genotoxicity in in Vitro Alveolar Barrier Models
Authors: Burgum Michael John , Cl Martin JD , Evans Stephen J , Hondow Nicole , Tarat Afshin , Jenkins Gareth J , Doak Shareen H
Published: October 2020

Background: Toxicological evaluation of engineered nanomaterials (ENMs) is essential for occupational health and safety, particularly where bulk manufactured ENMs such as few-layer graphene (FLG) are concerned. Additionally, there is a necessity to develop advanced in vitro models when testing ENMs to provide a physiologically relevant alternative to invasive animal experimentation. The aim of this study was to determine the genotoxicity of non-functionalised (neutral), amine- and carboxyl-functionalised FLG upon both human-transformed type-I (TT1) alveolar epithelial cell monocultures, as well as co-cultures of TT1 and differentiated THP-1 monocytes (d.THP-1 (macrophages)). Results: In monocultures, TT1 and d.THP-1 macrophages showed a statistically significant (p<0.05) cytotoxic response with each ENM following 24-hour exposures. Monoculture genotoxicity measured by the in vitro cytokinesis blocked micronucleus (CBMN) assay revealed significant (p<0.05) micronuclei induction at 8µg/ml for amine- and carboxyl-FLG. Transmission electron microscopy (TEM) revealed ENMs were internalised by TT1 cells within membrane-bound vesicles. In the co-cultures, ENMs induced genotoxicity in the absence of cytotoxic effects. Co-cultures pre-exposed to 1.5mM N-acetylcysteine (NAC), showed baseline levels of micronuclei induction, indicating that the genotoxicity observed was driven by oxidative stress. Conclusions: Therefore, FLG genotoxicity when examined in monocultures, results in primary-indirect DNA damage; whereas co-cultured cells reveal secondary mechanisms of DNA damage.
A Bayesian Latent Class Mixture Model With Censoring for Correlation Analysis in Antimicrobial Resistance Across Populations
Authors: Zhang Min , Wang Chong , O'Connor Annette
Published: October 2020

Background: The emergence of antimicrobial resistance across populations is a global threat to public health. Surveillance programs often monitor human and animal populations to evaluate trends of emergence in these populations. Many national level antibiotic resistance surveillance programs quantify the proportion of resistant bacteria as a means of monitoring emergence and control measures. The reason for monitoring these different populations are many, including interest in similar changes in resistance which might provide insight into emergence and control options. Methods: In this research, we developed a method to quantify the correlation in antimicrobial resistance across populations, for the conventionally unnoticed mean shift of the susceptible bacteria. With the proposed Bayesian latent class mixture model with censoring and multivariate normal hierarchy, we address several challenges associated with analyzing the minimum inhibitory concentration data. Results: Application of this approach to the surveillance data from National Antimicrobial Resistance Monitoring System led to a detection of positive correlation in the central tendency of azithromycin resistance of the susceptible populations from Salmonella serotype Typhimurium across food animal and human populations. Conclusions: Our proposed approach has been shown to be accurate and superior to the naïve frequentist estimation by simulation studies. Further implementation of this Bayesian model could serve as a useful tool to indicate the co-existence of antimicrobial resistance, and potentially a need of clinical intervention.
Mental Health and Sleep Habits/Problems in Children at 3–4 Years of Age: A General Population Study
Authors: Horiuchi Fumie , Kawabe Kentaro , Oka Yasunori , Nakachi Kiwamu , Hosokawa Rie , Ueno Shu-ichi
Published: October 2020

Background: Sleep is essential for mental health at all ages, but few studies have investigated the importance of sleep for mental health in early childhood. Therefore, this study examined the association between mental health and sleep habits/problems in children at 3-4 years of age. Methods: Children aged 3 to 4 years who were living in the community (n = 415; 211/204 boys/girls) were recruited in this study. Their mental health was assessed using the Strengths and Difficulties Questionnaire (SDQ), and their sleep habits/problems were evaluated using the Child and Adolescent Sleep Checklist. Results: Based on the total difficulties score of the SDQ, the children were divided into two groups: a poor mental health group (n = 76) and a control group (n = 339). In terms of sleep habits, which included total sleep time, bedtime, wake time, and nap conditions, there were no differences between the two groups. Regarding sleep-related problems, however, anxiety before going to sleep (p = 0.026), abnormality in the circadian rhythm (p = 0.014), and sleepiness during classes outside of naptimes (p = 0.031) were significantly higher in the poor mental health group than in the control group. Multiple regression analysis showed that poor mental health status was significantly associated with sleepiness and snoring (p = 0.017 and p = 0.018, respectively). Conclusions: The mental health status of 3-year-old children is associated with sleep-related problems, namely sleepiness and snoring. Healthcare providers should pay attention to children’s irregular sleep-wake patterns; moreover, interventions for appropriate sleep hygiene will reduce the psychological burden on both children and their families.
Identification of a Prognostic Signature of Malignant Melanoma Based on Tumor Immune Microenvironment Exploration
Authors: yuan lingyan , Bing Zhitong , Wang Jianshu , Li Jing , Jin Xiaodong , Li Rui , Wang Caiyun , Sun Xueqiang , Yang Lei , Yang Kuhu
Published: October 2020

Background: In contrast to identification of well-defined oncogenic alterations like BRAF mutations for malignant melanoma (MM) patient stratification, effective selection of predictive biomarkers remains a challenge in the era of checkpoint blockade.Methods: The differentially expressed genes (DEGs) related to the TME were identified using The Cancer Genome Atlas (TCGA) dataset by Wilcoxon rank sum test. The prognostic effects of immune-related genes (IRGs) were analyzed using univariate Cox regression. Next, the prognostic model was constructed by step multivariate Cox regression and risk score of each sample was calculated. Then, survival and Receiver Operating Characteristic (ROC) analyses were conducted to validate the model using TCGA and the Gene Expression Omnibus (GEO) datasets, respectively. Finally, the overall immune status, tumor purity of high- and low-risk groups was further analyzed to reveal the potential mechanisms of prognostic effects of the model.Results: Twenty eight IRGs were identified, the univariate cox analysis indicated the hazard ratio ranged from 0.796 to 2.621 (p-value < 0.05). 6 genes (SLPI, S100A7, LYZ, CCL19, CXCR4 and CD79A) were screened out by step multivariate cox regression and a 6-IRGs, which can be used as an independent prognostic factor, was constructed. The MM patients in both training (TCGA) and testing (GEO) datasets can be well stratified as high-risk and low-risk groups with the 6-IRGs signature, and the 3-year and 5-year area under curve (AUC) of ROC curves of GEO set were 0.681 and 0.678 (GSE19234). Conclusions: In sum, we identified and constructed a 6-IRGs , which can be used to predict the prognosis of metastasis in MM patients.
Point-of-care Cerebrospinal Fluid Gram Stain For the Management of Acute Meningitis in Adults: A Retrospective Observational Study
Authors: Taniguchi Tomohiro , Tsuha Sanefumi , Shiiki Soichi , Narita Masashi
Published: October 2020

Background: Gram staining of cerebrospinal fluid (CSF) is widely used in the diagnosis of acute meningitis, but is often conducted in the laboratory, as only some hospitals have access to point-of-care Gram stain (PCGS). The purpose of this study was to demonstrate the clinical impact and utility of PCGS in diagnosing and treating both bacterial and aseptic meningitis in adults. Methods: This was a hospital-based, retrospective observational study at a referral center in Okinawa, Japan. We reviewed the records of all patients aged 15 years or older who were admitted to the Division of Infectious Diseases between 1995 and 2015 and finally diagnosed with bacterial (n=34) or aseptic meningitis (n=97). For bacterial meningitis, we compared the treatments that were actually selected based on PCGS with simulated treatments that would have been based on the Japanese guidelines. For aseptic meningitis, we compared the rates of antibiotic use between real cases where PCGS was available and real cases where it was not. Results: PCGS was the most precise predictor for differentiating between bacterial and aseptic meningitis (sensitivity 91.2%, specificity 98.9%), being superior in this regard to medical histories, vital signs and physical examinations, and laboratory data available in the emergency room. In bacterial meningitis, PCGS reduced the frequency of meropenem use (1/34=3.0%) compared with simulated cases in which PCGS was not available (19/34=55.9%) (p=0.000). In real aseptic meningitis cases, the rate of antibiotic administration was lower when PCGS was used (38/97=39.2%) than when it was not (45/74=60.8%) (p=0.006). Conclusions: PCGS of CSF distinguishes between bacterial and aseptic meningitis more accurately than other predictors available in the ER. Patients are more likely to receive narrower-spectrum antimicrobials when PCGS is used than when it is not. PCGS of CSF thus can potentially suppress the empiric use of antimicrobials for aseptic meningitis.
Treatment of Acute Acquired Concomitant Esotropia
Authors: Shi Minghua , Zhou Yuanxiang , Qin Aijiao , Chen Jing , Ren Hongxing
Published: October 2020

Background: The treatment efficacy of botulinum toxin bilateral medial rectus injections for acute acquired concomitant esotropia (AACE) in adult is not clear. We characterize the effects of botulinum toxin injection in the treatment of AACE, especially in patients over 14 years old,and compared it with surgical treatment.Methods: In this prospective, nonrandomized, controlled clinical study, patients with AACE in our hospital from March 2017 to March 2020 elected to receive bilateral medial rectus injections of botulinum toxin or to undergo extraocular muscle surgery. Ocular position and stereopsis were evaluated before and after treatment.Results: A total of 60 patients were treated: 40 patients in the botulinum toxin group, and 20 patients in the surgery group. The botulinum toxin group included 31 cases ≥14 years of age and 9 cases <14 years of age. After 1–3 botulinum injections, the cumulative initial success rate was 95% (38/40), and the recurrence rate was 22.5% (9/40). Nine children <14 years of age were treated successfully, without recurrence. In the surgery group, the initial success rate after surgery was 75% (17/20), and the recurrence rate was 20% (4/20). There was no significant difference between groups in the rate of success rate or the rate of recurrence (P>0.05).Conclusion: The injection of botulinum toxin has a good effect on AACE in adults with minimal squinting and in children. The outcomes achieved with injected botulinum toxin are similar to those achieved with surgery.Trial registration: ChiCTR, ChiCTR2000032544. Registered May 2, 2020，Retrospectively registered, http://www.chictr.org.cn/showproj.aspx?proj=52349
Primary Gastroduodenal Tuberculosis Complicated With Acute Pancreatitis: A Rare Case Report and Literature Review
Authors: Li Yuanhua , Liao Suhuan , Zuo Haijun , Yang Wei , Jiang Di
Published: October 2020

Background: Tuberculosis (TB) is a major health problem worldwide. Even in highly prevalent countries, primary gastroduodenal tuberculosis is a rare manifestation of extrapulmonary tuberculosis. In recent years, as the incidence of tuberculosis has increased year by year, the occur of gastroduodenal tuberculosis has also increased. Endoscopy is an important tool for diagnosing gastroduodenal tuberculosis. The performance of gastroduodenal tuberculosis under endoscopy is often non-specific, which may imitate other benign or malignant gastroduodenal diseases. Diagnosis of gastroduodenal tuberculosis relies on a combination of endoscopy and guided biopsy. Case presentation: Here, we report a rare and interesting case of gastroduodenal tuberculosis with acute pancreatitis. The case initially mimicked gastroduodenal ulcers in morphology and appeared in a middle-aged person with normal immunity but with prolonged fever and abdominal pain. The disease was diagnosed through endoscopy and guided biopsy, and it responded well to antituberculosis drugs. Conclusions: Clinicians must remember that even in the absence of immunodeficiency, as in this case, tuberculosis can affect any part of the gastrointestinal tract.