bluuebunny/crossref_metadata_2025 huggingface dataset:
Estimating the tolerance of Brachial Plexus to hypofractionated Stereotactic Body Radiotherapy – A modelling-based approach from clinical experience.
Authors: Kapitanova Irina , Biswas Sharmi , Divekar Sabrina , Kemmerer Eric J , Rostock Robert A , Forster Kenneth M , Grimm Rachel J , Scofield Carla J , Grimm Jimm , Emami Bahman , Mahadevan Anand
Published: February 2021

Background: Brachial plexopathy (BP) is a potentially serious complication from stereotactic body radiation therapy (SBRT) that has not been widely studied. Therefore, we compared datasets from two different institutions and generated a brachial plexus dose-response model, to quantify what dose constraints would be needed to minimize the effect on normal tissue while still enabling potent therapy for the tumor.Methods: Two published SBRT datasets were pooled and modeled from patients at Indiana University and the Richard L. Roudebush Veterans Administration Medical Center from 1998 to 2007, as well as the Karolinska Institute from 2008 to 2013. All patients in both studies were treated with SBRT for apically located lung tumors localized superior to the aortic arch. Toxicities were graded according to Common Terminology Criteria for Adverse Events (CTCAE) and a probit dose response model was created with maximum likelihood parameter fitting.Results: This analysis includes a total of 89 brachial plexus Dmax values from both institutions. Among the 14 patients who developed BP, the most common complications were grade 2, comprising 7 patients. The median follow-up was 30 months (range 6.1-72.2) in the Karolinska dataset, and Indiana had a median of 13 months (range 1-71). Both studies had a median range of 3 fractions, but in the Indiana dataset 9 patients were treated in 4 fractions and the paper did not differentiate which ones were which, so our analysis is considered to be in 3-4 fractions, which is one of the main limitations. The probit model showed that the risk of BP with Dmax of 26 Gy in 3-4 fractions is 10%, and 50% with Dmax of 70 Gy in 3 -4 fractions.Conclusions: This analysis is only a preliminary result because more details are needed, and more comprehensive datasets are needed from a much broader cross-section of clinical practices. When more institutions join the QUANTEC and HyTEC methodology of reporting sufficient details to enable data pooling, our field will finally reach an improved understanding of human dose tolerance.
Medium-chain fatty acids accelerate the incorporation of eicosapentaenoic acid into lung tissue
Authors: Beermann Christopher , Fussbroich Daniela , Schubert Ralf
Published: February 2021

Long-chain polyunsaturated fatty acids (LCPUFAs) are reported to resolve chronic inflammation in asthma and other lung diseases. This study aimed to accelerate the incorporation of eicosapentaenoic acid (EPA) into lung tissue through the coapplication of medium-chain fatty acids (MCFAs) which enhance the fat-metabolic rate. Female C57BL/6 mice were supplemented with either 1363,6 mg EPA or 1363,6 mg EPA and MCFAs at 30% of the total fat per kg body weight per day for 28 days (each group size: n=21). The resorption of EPA into the peripheral blood and lung tissue was monitored over 63 days including the wash-out phase. In the peripheral blood plasma and clots the supplementation with EPA always led to higher EPA concentrations than the administration of EPA with MCFAs pointing to a preferred EPA incorporation into tissues induced by MCFAs (EPA in plasma at day 26: EPA 12.33 wt% ± 1.41; EPA and MCFAs 3.91 wt% ± 0.32; Δ 8.42; p< 0.001; EPA in clots at day 26: EPA 16.44 wt% ± 1.82; EPA and MCFAs 4.47 wt% ± 1.26; Δ 11.97; p< 0.001). In the lung tissue the EPA-incorporation at day 26 was increased by MCFAs compared to the EPA-administration alone (EPA in lung tissue at day 26: EPA 1.28 wt% ± 0.18; EPA and MCFAs 1.83 wt% ± 0.17; Δ 0.55; p< 0.01). The present study recommends the use of dietary LCPUFA supplementation with MCFAs to support their incorporation into lung tissues.
Glucagon-like peptide-2 receptor is a receptor for tick-borne encephalitis virus to infect nerve cells
Authors: Chen Xinwen , Yang Qi , Chen Jizheng , Pei Rongjuan , Wang Yun , Yang Min , Tang Jielin , Zhou Yuan , Zhao He , Chen Jiekai , He Jun , Xiong Xiaoli , Shi Pei-Yong
Published: February 2021

Tick-borne encephalitis virus (TBEV) is a tick-borne flavivirus that causes severe encephalitis disease1,2. Host proteins required for TBEV entry remain largely unknown3. Here we performed a genome-wide CRISPR-Cas9 knockout screen and identified G-protein-coupled receptor glucagon-like peptide-2 receptor (GLP2R) as a receptor for TBEV to infect nerve cells. Knockdown or knockout of GLP2R reduced TBEV infection of different nerve cells; trans supply of GLP2R restored viral infection. GLP2R directly binds to viral envelope domain III through its extracellular loop 1 (ECL1). TBEV infection can be blocked by the ECL1 peptide, a functional ligand to GLP2R, or GLP2R antibodies. GLP2R-deficient mice were generated to validate the role of GLP2R in TBEV infection and pathogenesis. Wild-type mice succumbed to TBEV infection and developed >107 TCID50 (median tissue culture infectious dose) virus per gram of brain tissue. In contrast, all GLP2R-deficient mice survived TBEV infection without detectable infectious virus in brain. Altogether, our results support GLP2R as a receptor for TBEV to infect nerve cells.
Airway Pseudomonas aeruginosa Density in Mechanically Ventilated Patients: Clinical Impact and Relation to Therapeutic Efficacy of Antibiotics
Authors: Migiyama Yohei , Sakata Shinya , Iyama Shinji , Tokunaga Kentaro , Saruwatari Koichi , Tomita Yusuke , Saeki Sho , Okamoto Shinichiro , Ichiyasu Hidenori , Sakagami Takuro
Published: February 2021

Background: The bacterial density of Pseudomonas aeruginosa is closely related to its pathogenicity. We evaluated the effect of airway P. aeruginosa density on the clinical course of mechanically ventilated patients and the therapeutic efficacy of antibiotics.Methods: We retrospectively analyzed data of mechanically ventilated ICU patients with P. aeruginosa isolated from endotracheal aspirates. Patients were divided into three groups according to the peak P. aeruginosa density during ICU stay: low (≤104 cfu/mL), moderate (105‒106 cfu/mL), and high (≥107 cfu/mL) peak density groups. The relationship between peak P. aeruginosa density and weaning from mechanical ventilation, risk factors for isolation of high peak density of P. aeruginosa, and antibiotic efficacy were investigated using multivariate and propensity score-matched analyses.Results: Four-hundred-and-sixty-one patients were enrolled. Patients with high peak density of P. aeruginosa had higher inflammation and developed more severe respiratory infections. High peak density of P. aeruginosa was independently associated with few ventilator-free days on day 28 (P < 0.01) and increased ICU mortality (P = 0.047). Risk factors for high peak density of P. aeruginosa were prolonged mechanical ventilation (odd ratio [OR] 3.07 95% confidence interval [CI] 1.35‒6.97), non-antipseudomonal cephalosporins (OR 2.17, 95% CI 1.35‒3.49), hyperglycemia (OR 2.01, 95% CI 1.26‒3.22) during ICU stay, and respiratory diseases (OR 1.9, 95% CI 1.12‒3.23). Isolation of commensal colonizer was associated with lower risks of high peak density of P. aeruginosa (OR 0.43, 95% CI 0.26‒0.73). Propensity score-matched analysis revealed that antibiotic therapy for patients with ventilator-associated tracheobronchitis improved weaning from mechanical ventilation only in the high peak P. aeruginosa group.Conclusions: Patients with high peak density of P. aeruginosa had worse ventilator outcome and ICU mortality. In patients with ventilator-associated tracheobronchitis, antibiotic therapy was associated with favorable ventilator weaning only in the high peak P. aeruginosa density group, and bacterial density could be a good therapeutic indicator for ventilator-associated tracheobronchitis due to P. aeruginosa.
Impact of seasonality and malaria control interventions on Anopheles density and species composition from three areas of Uganda with differing malaria endemicity.
Authors: Mawejje Henry , Kilama Maxwell , Kigozi Simon P. , Musiime Alex K. , Kamya Moses , Lines Jo , Lindsay Steven W. , Smith David , Dorsey Grant , Donnelly Martin J. , Staedke Sarah G.
Published: February 2021

Background Long lasting insecticidal nets (LLINs) and indoor residual spraying (IRS) are malaria control interventions primarily responsible for reductions in transmission intensity across sub-Saharan Africa. These interventions, however, may have differential impact on Anopheles species composition and density. Here, we studied the changing pattern of Anopheles species in three areas of Uganda with markedly different transmission intensities and different levels of vector control. Methods From October 2011 to June 2016 mosquitoes were collected monthly using CDC light traps from 100 randomly selected households in three areas: Walukuba (low transmission), Kihihi (moderate transmission) and Nagongera (high transmission). LLINs were distributed in November 2013 in Walukuba and Nagongera and in June 2014 in Kihihi. IRS was implemented only in Nagongera, with three rounds of bendiocarb delivered between December 2014 and June 2015. Mosquito species were identified morphologically and by PCR (Polymerase Chain Reaction). Results In Walukuba, LLIN distribution was associated with a decline in Anopheles funestus vector density (0.07 vs 0.02 mosquitoes per house per night, density ratio [DR] 0.34, 95% CI: 0.18-0.65, p=0.001), but not An. gambiae s.s. nor An. arabiensis. In Kihihi, over 98% of mosquitoes were An. gambiae s.s. and LLIN distribution was associated with a decline in An. gambiae s.s. vector density (4.00 vs 2.46, DR 0.68, 95% CI: 0.49-0.94, p=0.02). In Nagongera, the combination of LLINs and multiple rounds of IRS was associated with almost complete elimination of An. gambiae s.s. (28.0 vs 0.17, DR 0.004, 95% CI: 0.002-0.009, p<0.001), and An. funestus s.l. (3.90 vs 0.006, DR 0.001, 95% CI: 0.0005-0.004, p<0.001), with a less pronounced decline in An. arabiensis (9.18 vs 2.00, DR 0.15 95% CI: 0.07-0.33, p<0.001). Conclusions LLIN distribution was associated with reductions in An. funestus s.l. in the lowest transmission site and An. gambiae s.s. in the moderate transmission site. In the highest transmission site, a combination of LLINs and multiple rounds of IRS was associated with the near collapse of An. gambiae s.s. and An. funestus s.l. Following IRS, An. arabiensis, a behaviorally resilient vector, became the predominant species, which may have implications for malaria vector control activities. Development of interventions targeted at outdoor biting remains a priority.
Performance of liver stiffness measurements obtained with FibroScan is affected by glucose metabolism in patients with nonalcoholic fatty liver disease
Authors: Yang Xinyu , Chang Xinxia , Wu Shengdi , Sun Xiaoyang , Zhu Xiaopeng , Wang Liu , Xu Yushan , Yao Xiuzhong , Rao Shengxiang , Hu Xiqi , Xia Mingfeng , Bian Hua , Yan Hong-Mei , Gao Xin
Published: February 2021

Background: The performance of liver stiffness measurements (LSMs) obtained using FibroScan can be affected by several factors, and cut-off values are different for fibrosis caused by various aetiologies. The study aims to evaluate the diagnostic accuracy of LSM in nonalcoholic fatty liver disease (NAFLD) patients with abnormal glucose metabolism and investigate whether the LSM value would be affected by metabolic indicators.Methods: The study involved 91 NAFLD patients with abnormal glucose metabolism who underwent liver biopsy. The diagnostic accuracy of LSM value was evaluated by the receiver operator characteristic (ROC) curves, with the biopsy results taken as the gold standard. Multivariate linear regression and subgroup analysis were performed to determine the correlated indicators.Results: The areas under the ROC curves (AUROCs) of LSM values for detecting fibrosis stage ≥1, 2, 3 and 4 were 0.793 (95% confidence interval [CI]: 0.695-0.871), 0.764 (95% CI: 0.663-0.846), 0.837 (95% CI: 0.744-0.906) and 0.902 (95% CI: 0.822-0.955), with cut-off values of 6.3, 7.6, 8.3 and 13.8 kPa, respectively. Multivariate linear regression demonstrated that haemoglobin A1c (HbA1c, β = 0.200, P = 0.038) and aspartate aminotransferase (AST, β = 0.200, P = 0.044) were independently associated with the LSM value after adjustment for fibrosis stage, ballooning and inflammation grade from liver biopsy. Subgroup analysis demonstrated that LSM values were slightly higher in patients with HbA1c ≥7% than in those with HbA1c <7% and in patients with body mass index (BMI) ≥30 kg/m2 than in those with BMI <30 kg/m2.Conclusions: FibroScan was valuable for the evaluation of liver fibrosis in NAFLD patients with abnormal glucose metabolism. FibroScan is recommended to evaluate severe fibrosis, especially to exclude advanced fibrosis. Glucose metabolism state may affect LSM values.
High expression of CDCA7 predicts poor prognosis for clear cell renal cell carcinoma and explores its associations with immunity
Authors: Liu Shouyong , Wang Yi , Miao Chenkui , Xing Qianwei , Wang Zengjun
Published: February 2021

Background: Cell division cycle-associated 7 (CDCA7), as a member of the cell division cycle associated family, was reported to be aberrantly expressed in both solid tumors and hematological tumors, suggesting its essential role in promoting tumorigenesis. Hence, we aimed to explore its comprehensive roles of overall survival (OS) in clear cell renal cell carcinoma (ccRCC) and emphasize its associations with immunity.Methods: The RNA sequencing data and corresponding clinical information were downloaded from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was adopted to explore CDCA7 associated signaling pathways. Univariate and multivariate Cox regression analyses were carried out to assess independent prognostic factors. Furthermore, roles of CDCA7 in human immunity were also investigated.Results: Our results suggested that CDCA7 was overexpressed in ccRCC and its elevated expression was related to shorter OS (P<0.01). Univariate and multivariate Cox regression analyses identified CDCA7 as an independent prognostic factor (both P<0.05). The prognostic nomogram integrating CDCA7 expression level and clinicopathologic variables was constructed to predict 1-, 3- and 5-year OS. GSEA indicated that high CDCA7 expression was related to the apoptosis pathway, cell cycle pathway, JAK-STAT pathway, NOD like receptor pathway, P53 pathway, T cell receptor pathway and toll like receptor pathway, etc. Moreover, CDCA7 was significantly related to microsatellite instability (MSI, P<0.001) and tumor mutational burden (TMB, P<0.001). As for immunity, CDCA7 was remarkably associated with immune infiltration, tumor microenvironment, immune checkpoint molecules and immune pathways.Conclusions: CDCA7 could serve as an independent prognostic factor for ccRCC and it was closely related to MSI, TMB, and immunity.
Extra Large Sequence Transformer Model for Chinese Word Segment
Authors: Shen Dezhou
Published: February 2021

Chinese word segment is widely studied in document analysis.
The accuracy of the current popular word segment model, LSTM+CRF, is still not satisfactory.
Models trained by the popular dataset often fails in the out-domain situation.
In this paper, combining the Transformer-XL layer, the Fully-Connect layer, and the Conditional Random Field layer, the proposed model improved 3.23% in the macro-F1 score, comparing to the BERT+CRF model, on the MSR2005 Chinese word segment test dataset.
Effect of adding hydrochlorothiazide to usual treatment of patients with acute decompensated heart failure: a randomized clinical trial
Authors: Piardi Diogo , Butzke Mauricio , Mazzuca Ana Carolina , Gomes Bruna , Alves Sofia , Kotzian Bruno , Ghisleni Eduarda , Giaretta Vanessa , Bellaver Priscila , Varaschin Gabrielle , Garbin Arthur , Beck-da-Silva Luís
Published: February 2021

Introduction:
Acute decompensated heart failure (ADHF) is the leading cause of hospitalization in patients aged 65 years or older, and most of them present with congestion. The use of hydrochlorothiazide (HCTZ) may increase the response to loop diuretics.
Objective
To evaluate the effect of adding HCTZ to furosemide on congestion and symptoms in patients with ADHF.
Methods
This randomized clinical trial compared HCTZ 50 mg versus placebo for 3 days in patients with ADHF and signs of congestion. The primary outcome of the study was daily weight reduction. Secondary outcomes were change in creatinine, need for vasoactive drugs, change in natriuretic peptides, congestion score, dyspnea, thirst, and length of stay.
Results
Fifty-one patients were randomized — 26 to the HCTZ group and 25 to the placebo group. There was a trend towards additional weight reduction in the HCTZ group (HCTZ: -1.78 ± 1.08 kg/day vs placebo: -1.05 ± 1.51 kg/day; p = 0.062). In post hoc analysis, the HCTZ group demonstrated significant weight reduction for every 40 mg of intravenous furosemide (HCTZ: -0.74 ± 0.47 kg/40 mg vs placebo: -0.33 ± 0.80 kg/40 mg; p = 0.032). There was a trend to increase in creatinine in the HCTZ group (HCTZ: 0.50 ± 0.37 vs placebo: 0.27 ± 0.40; p = 0.05) but no significant difference in onset of acute renal failure (HCTZ: 58% vs placebo: 41%; p = 0.38). No differences were found in the remaining outcomes.
Conclusion
There was a trend towards greater daily weight reduction in the HCTZ group. In analysis adjusted to the dose of intravenous furosemide, adding HCTZ 50 mg to furosemide resulted in a significant synergistic effect on weight loss.
Chloroplast phylogenomics and the dynamic evolution of Santalum (Santalaceae)
Authors: Liu Xiaojin , Xu Daping , Hong Zhou , Zhang Ningnan , Cui Zhiyi
Published: February 2021

Background

Santalum (Santalaceae, sandalwood) is a hemiparasitic genus including approximately 15 extant species. It is known for its aromatic heartwood oil, which is used in incense and perfume. Demand for sandalwood-based products has led to drastic over-harvesting, and wild Santalum populations are now threatened. Knowledge of the phylogenetic relationships and genetic diversity will be critical for the conservation and proper management of this genus. Here, we sequenced the chloroplast genome of 11 Santalum species. The data were then used to investigate the chloroplast genome evolutionary dynamics and relationships and divergence time within Santalum and related species.
Results

The Santalum chloroplast genome contains the typical quadripartite structures, ranging from 143,291 to 144,263 bp. The chloroplast genome contains 124 genes. The whole set of ndh genes and the infA gene were found to lose their function. Between 17 and 31 SSRs were found in the Santalum chloroplast genome, and mononucleotide simple sequence repeats (SSRs) were the major type. The P-distance among the Santalum species was 0.0003 to 0.00828. Three mutation hotspot regions, 14 small inversions, and 460 indels events were discovered in the Santalum chloroplast genome. Our phylogenomic assessment provides improved resolution compared to past analyses. Our divergence time analysis shows that the crown age of Santalum was 8.46 Mya, the first divergence occurred around 6.97 Mya, and diversification was complete within approximately 1 Mya.
Conclusions

By sequencing the 12 chloroplast genomes of Santalum, we gain insight into the evolution of its chloroplast genomes. The chloroplast genome sequences had sufficient polymorphic information to elucidate the evolutionary history of Santalum.
Coughing Children in Family Practice and Primary Care – A Systematic Review On Prevalence, Aetiology and Prognosis
Authors: Bergmann Milena , Haasenritter Jörg , Beidatsch Dominik , Schwarm Sonja , Bartsch Kaja , Bösner Stefan , Grevenrath Paula , Schmidt Laura , Viniol Annika , Donner-Banzhoff Norbert , Becker Annette
Published: February 2021

Background: For evidence-based decision-making general practitioners need setting specific knowledge on the pre-test probabilities of underlying diseases and a symptom’s course. We performed a systematic review on symptom evaluating studies in primary care to give evidence on the prevalence, aetiologies and prognosis of coughing children who consult primary care settings. Methods: Following a pre-defined algorithm and independent double reviewer ratings we searched MEDLINE and EMBASE. We included data from all quantitative original research articles in English, French or German assessing unselected study populations of children consulting for cough in primary care. We used the random effects model for meta-analysis in eligible subgroups if comprehensive in terms of heterogeneity. Results: We identified 14 eligible studies on prevalence, five on aetiology and one on prognosis. Prevalence estimates varied between 4.7% and 23.3% of all reasons for encounter or up to estimates of 60% when related to patients or consultations. Cough in children is more frequent than in adults with lowest prevalences in adolescents and in summer. Acute cough is mostly caused by upper respiratory tract infections (62.4%) and bronchitis (33.3%); subacute or chronic cough by recurrent respiratory tract infection (27.7%), asthma (3% in cough of all durations to 50.4% in more than 3 weeks cough), and pertussis (37.2%). Potentially serious diseases like croup, pneumonia or tuberculosis are scarce. In children with subacute and chronic cough the total duration of cough ranged from 24 to 192 days. About 62.3% of children suffering from prolonged cough are still coughing two months after the beginning of symptoms. We found strong heterogeneity across studies and only five studies with an overall low risk of bias. Conclusion: Cough is one of the most frequent reasons of encounter in primary care. Our findings on aetiologies and prognosis fit in with current guideline recommendations supporting a thoughtful wait-and-see approach in acute cough and a special awareness of asthma in chronic cough. There is a remarkable high pre-test probability of pertusssis in children with cough of more than two weeks’ duration. To develop primary-care cough guidelines symptom-evaluating studies assessing setting and age specific aetiologies and prognosis of cough are needed.
Effects of Consumption Frequency of 10 Food Groups on Activities of Daily Living in Elderly Japanese Women: A Longitudinal Cohort Study
Authors: Kojima Narumi , Kim Miji , Saito Kyoko , Yoshida Yuko , Hirano Hirohiko , Obuchi Shuichi , Shimada Hiroyuki , Suzuki Takao , Iwasa Hajime , Kim Hunkyung
Published: February 2021

Background

This study aimed to examine the effects of the consumption frequency of 10 food groups on activities of daily living (ADL) in elderly Japanese women.
Methods

This was a four-year longitudinal cohort study conducted in Itabashi Ward, Tokyo. Participants were 1,111 community-dwelling elderly women aged 75 to 85 years, without baseline ADL disability or missing values. The main outcome measures were the relationship between the baseline consumption frequency of 10 food groups and future incidence of ADL disability. The relationship between baseline consumption frequency of 10 food groups and change in ADL status was analyzed through logistic regression analyses.
Results

The incidence rate of ADL disability was 7.6%. The trend tests show that less-frequent consumption of soy products, colored vegetables, and fats/oils leads to a significantly higher odds ratio of ADL disability incidence whether adjusted or not (p < 0.005, p = 0.03, and p = 0.02, respectively, when adjusted).
Conclusions

Our results suggest that in community-dwelling elderly Japanese women, lower consumption frequency of soy products, colored vegetables, or fats/oils are risk factors for future incidence of ADL disability.
Influences of Tumor Size and Pleural Layer Invasion on the Prognosis of Patients with Stage IB Lung Adenocarcinoma
Authors: Sui Qihai , Liang Jiaqi , Hu Zhengyang , Xu Xinming , Chen Zhencong , Huang Yiwei , Zhao Mengnan , Bi Guoshu , Zhan Cheng , Lin Zongwu , Wang Qun , Wang Lin
Published: February 2021

Backgroud: Lung adenocarcinoma (ADC) at stage IB has its own prognostic characteristics. This study aimed to investigate the clinical factors that may affect the prognosis of patients with stage IB ADC.Methods: The data of ADC cases were selected from the Surveillance, Epidemiology, and End Results (SEER) database (2010-2016) and patients in Zhongshan Hospital Affliated to Fudan University (Department of Thoracic Surgery, 2015-2016). Kaplan-Meier method was used to obtain the overall survival (OS). Factors that significantly related to the prognosis were evaluated by univariate and multivariate analysis (UVA, MVA) using the Cox model. A nomogram was developed and validated to predict the 3-year OSs of those patients.Results: 7605 patients with stage IB ADC were included ultimately and were divided into 2 groups, a training cohort (n = 5,324) and a test cohort (n = 2,281). Besides, there was a validation cohort (n = 272) for the verification of the nomogram model. Those with significantly older age, male, the white race, lower grades of tumor differentiation, larger tumor size (31-40mm) without pleural layer (PL) invasion as well as receiving sublobectomy suffered from poorer survival (P < 0.001), which were identified as independent factors for stage IB ADC (P < 0.001), and according to which, a nomogram model was created.Conclusion: Age, sex, race, histological grade, surgery to the primary site, and tumor size combined with PL invasion were independent risk factors for stage IB ADC, based on which a nomogram was constructed to predict the prognosis.
Different Concentrations of C5a Affect Human Dental Pulp Mesenchymal Stem Cells Differentiation
Authors: Liu Jie , Wei Xiaoling , Hu Junlong , Tan Xiaohan , Kang Xiaocui , Gao Li , Li Ning , Shi Xin , Yuan Mengtong , Hu Weiping , Liu Mingyue
Published: February 2021

Background During the process of deep decay, when decay approaches the pulp, an immune response is triggered inside the pulp, which activates the complement cascade. The effect of complement component 5a (C5a) on the differentiation of dental pulp mesenchymal stem cells (DPSCs) is related to dentin reparation. The aim of the present study was to stimulate DPSCs with different concentrations of C5a and evaluate the differentiation of odontoblasts using dentin sialoprotein (DSP). Methods DPSCs were divided into the following six groups: i) Control; ii) DPSCs treated with 50 ng/ml C5a; iii) DPSCs treated with 100 ng/ml C5a; iv) DPSCs treated with 200 ng/ml C5a; v) DPSCs treated with 300 ng/ml C5a; and vi) DPSCs treated with 400 ng/ml C5a. Flow cytometry and multilineage differentiation potential were used to identify DPSCs. Mineralization induction, Real-time PCR and Western blot were conducted to evaluate the differentiation of odontoblast in the 6 groups.Result DPSCs can express mesenchymal stem cell markers, including CD105, CD90, CD73 and, a less common marker, mesenchymal stromal cell antigen-1. In addition, DPSCs can differentiate into adipocytes, neurocytes and osteoblasts. All six groups formed mineralized nodules after 28 days of culture. Reverse transcription-quantitative PCR and western blotting indicated that the high concentration C5a groups expressed higher DSP levels and promoted DPSC differentiation, whereas the low concentration C5a groups displayed an inhibitory effect.Conclusion In this study, the increasing concentration of C5a, which accompanies the immune process in the dental pulp, has demonstrated an enhancing effect on odontoblast differentiation at higher C5a concentrations in vitro.
Analysis of Spatial Distribution Characteristics of Human Echinococcosis at the Township Level in Sichuan Province, China
Authors: He Wei , Yu Wen-jie , Zhang Guang-jia , Liao Sha , Wang Qi , Li Rui-rui , Zhong Bo , Yang Liu , Yao Ren-xin , Liu Yang , Zeli Dan-ba , Qin Sheng-chao , Wang Shi-an , Wang Yan-xia , Huang Yan , Wang Qian
Published: February 2021

BackgroundEchinococcosis is a global zoonotic parasitic disease caused by the larvae of Echinococcus, which affects both humans and animals. In China, this disease is highly endemic in Sichuan Province. In this study, we investigated the prevalence and spatial distribution characteristics of human echinococcosis at the township level in Sichuan province, so as to provide a reference for the development of precise prevention and control strategies in the future.MethodsWe explored the prevalence of echinococcosis using the B-ultrasonography diagnostic method in Sichuan province between 2016 and 2019, where patients and transmission conditions had been identified in the past. All data were inputted using Epi-Info software, while SPSS software was used for statistical analysis. We then employed ArcGIS software to draw the spatial distribution map and perform trend surface analysis. Finally, Geoda software was used to analyze spatial autocorrelation and draw Lisa clustering map.ResultsA total of 2 542 135 people from 649 towns in 35 counties of Sichuan province were screened for echinococcosis, of which 11 743 echinococcosis patients were detected. The prevalence of echinococcosis in humans was 0.462%, among which the occurrence of cystic echinococcosis [CE] was 0.221%, while that of alveolar echinococcosis [AE] was 0.244%. We also observed that the predominance of echinococcosis in humans decreased gradually from west to east and from north to south based on the results of the spatial distribution map and trend surface analysis. The Global Moran's I index was 0.77 (Z = 32.07, P < 0.05), which indicated that the prevalence of echinococcosis in humans was spatially clustered, exhibiting a significant spatial positive correlation. Further, the findings of local spatial autocorrelation analysis revealed that the “high-high” concentration areas were primarily located in some townships in the northwest of Sichuan province. On the other hand, the “low-low” concentration areas were predominantly located in some townships in the southeast of Sichuan province. Conclusion﻿Our findings demonstrated that the prevalence of echinococcosis in humans of Sichuan province is following a downward trend, implying that the current prevention and control work has achieved some substantial outcomes. However, the prevalence in humans at the township level is widely distributed and differs greatly, with a clear clustering in space. Therefore in the future, precise prevention and control strategies should be formulated for clusters, particularly strengthening the “high-high” clusters at the township level.
Telocytes Reduce Oxidative Stress by Downregulating DUOX2 Expression in Inflamed Lungs of Mice
Authors: Liang Tao , Zhang Nu , Ju Huihui , Zhou Yile , Yang Yajie , Tang Haihong , Song Dongli , Fang Hao
Published: February 2021

Background: Telocytes (TCs), a newly identified interstitial cell type, have been found to participate in tissue protection and repair. This study investigated the antioxidative effects of TCs in inflamed lungs of mice.Methods: Acute respiratory distress syndrome mice were used as model of inflamed lungs of mice. Gene sequencing was used to screen for differentially expressed miRNAs in TCs after lipopolysaccharide (LPS) stimulation. AntagomiR-146a-5p-pretreated TCs were first injected into mice, and the antioxidant activity of TCs was estimated. TCs, RAW264.7 cells, and MLE-12 cells were collected for mRNA, miRNA, and protein measurements after LPS stimulation. Silencing miRNAs were delivered to examine the involved signaling pathways in the experiments. Oxidative stress was examined in cultured cells, supernatants, and lung tissue by measuring malondialdehyde (MDA) levels.Results: MiR-146a-5p and miR-21a-3p were upregulated in TCs after LPS stimulation. Compared with ARDS mice, TC-preinfused ARDS mice had reduced lung tissue injury scores, lung wet-dry ratios, white blood cell counts in alveolar lavage fluid and MDA concentrations in lung tissue. However, ARDS mice preinfused with antagomiR-146a-5p TCs did not exhibit any of the corresponding changes. DUOX2 was downregulated in TCs at both the gene and protein levels, and the concentration of MDA was decreased in TCs and their culture medium after LPS stimulation. DUOX2 expression was restored when TCs were treated with antagomiR-146a-5p. CREB1 was downregulated by miR-146a-5p, as confirmed by a dual-luciferase reporter assay, and the protein expression of DUOX2 was downregulated by CREB1, which was further confirmed by treating TCs with a specific CREB1 inhibitor.Conclusion: LPS stimulation increases miRNA-146a-5p expression in TCs, which downregulates the CREB1/DUOX2 pathway, resulting in a decrease in oxidative stress in cultured TCs. TCs reduce LPS-induced oxidative stress by decreasing DUOX2 expression in inflamed lungs of mice.
The Gut Microbiome as a Promising Biomarker of Cancer Progression Among Female Never-smokers With Lung Adenocarcinoma
Authors: Otoshi Takehiro , Nagano Tatsuya , Park Jonguk , Hosomi Koji , Yamashita Tomoya , Tachihara Motoko , Tabata Tokiko , Sekiya Reina , Tanaka Yugo , Kobayashi Kazuyuki , Mizuguchi Kenji , Itoh Tomoo , Maniwa Yoshimasa , Kunisawa Jun , Nishimura Yoshihiro
Published: February 2021

Background: The gut microbiome plays an important role in the immune system and has attracted attention as a new biomarker of various diseases, including cancer. As such, in this study, we examined the relationship between the gut microbiome and lung cancer progression. In addition, we assessed the correlation between the gut microbiome and epidermal growth factor receptor (EGFR) mutation status.Methods: Female never-smokers diagnosed with lung adenocarcinoma were consecutively enrolled between May 2018 and August 2019. Fecal samples were collected within 1 month before or after diagnosis and before administration of any lung cancer treatment. Principal coordinate analyses were performed using Bray-Curtis distance matrices to investigate the effects of clinical variables (age, body mass index, Tumor-Node-Metastasis stage, T category, N category, M category, primary tumor size, performance status, and EGFR mutation status) on the gut microbial community. A correlation analysis was also performed to determine the strength of association between the dominant taxonomy (comprising ≥1% of the relative abundance of bacterial DNA sequences) and clinical variables.Results: A total of 37 patients were enrolled. T category and primary tumor size were significantly correlated with the gut microbial community (p=0.018 and 0.041, respectively). At the genus level, a significant positive correlation was observed between the relative abundance of Faecalibacterium and both T category (correlation coefficient, R=0.51, p=0.0013) and primary tumor size (R=0.37, p=0.024), whereas a significant negative correlation was observed between the relative abundances of Fusicatenibacter and Bacteroides and T category (R=−0.35, p=0.034 and R=−0.32, p=0.05, respectively) and primary tumor size (R=−0.36, p=0.029 and R=−0.41, p=0.012, respectively). EGFR mutation status had no statistically significant effect on the gut microbial community (p=0.11). However, the relative abundances of Bifidobacterium and Faecalibacterium were significantly higher in EGFR mutation–negative patients than EGFR mutation–positive patients (p=0.012 and 0.041), whereas the relative abundance of Blautia was significantly lower in EGFR mutation–negative patients (p=0.036).Conclusions: This is the first study identifying the gut microbiome as a promising biomarker of lung cancer progression. Further elucidation of the role of the gut microbiome in lung cancer progression could facilitate development of new treatments for lung cancer.
Genome-wide Association Study of Individual Sugar Content and Sugar Conversion in Fruit of Japanese Pear (Pyrus spp.)
Authors: Nishio Sogo , Hayashi Takeshi , Shirasawa Kenta , Saito Toshihiro , Terakami Shingo , Takada Norio , Takeuchi Yukie , Moriya Shigeki , Itai Akihiko
Published: February 2021

Background: Sweetness is one of the most important traits determining fruit quality. Sweetness is controlled not only by the total sugar content but also by the contents of individual sugars. The major sugars in mature Rosaceae fruits are sucrose, fructose, glucose, and sorbitol, which have different levels of sweetness. Among these, sucrose and fructose have high sweetness, whereas glucose and sorbitol have low sweetness. The objective of this study was to identify the quantitative trait loci (QTLs) associated with fruit traits including individual sugar accumulation and conversion, to infer the candidate genes underlying the QTLs, and to assess the potential of genomic selection for breeding pear fruit traits.Results: We evaluated 10 fruit traits and conducted genome-wide association studies (GWAS) for 106 cultivars and 17 breeding populations (1112 F1 individuals) using 3484 tag single-nucleotide polymorphisms (SNPs) genotyped by double-digest restriction-site associated DNA sequencing (ddRAD-Seq). By implementing a mixed linear model and a Bayesian multiple-QTL model in GWAS, 56 SNPs associated with fruit traits were identified. Four loci were presumed to be associated with sugar conversion because the SNPs were significant for more than one individual sugar and the individual sugar contents associated with each SNP genotype were negatively correlated. In particular, a SNP located close to acid invertase gene PPAIV3 on chromosome 7 and a newly identified SNP on chromosome 11 had quite large effects on sugar conversion. We used ‘Golden Delicious’ doubled haploid (GDDH) 13, an apple reference genome to infer the candidate genes for the identified SNPs. In the region flanking the SNP on chromosome 11, there is a tandem repeat of early responsive to dehydration (ERD6)-like sugar transporter genes which might play a role in the phenotypes observed.Conclusions: SNPs associated with sugar accumulation and conversion were newly identified at several loci, and candidate genes underlying QTLs were inferred using advanced apple genome information. Several QTLs showed clear effects with more than 10% of phenotypic variance explained by those SNPs in the breeding populations. By combining the effects of multiple QTLs, breeders would be able to select seedlings that will later bear fruit with high sucrose and fructose content.
The value of D-dimer, ESR and CRP in the Diagnosis of Deep Vein Thrombosis of Lower Limbs After Hip and Knee Joint Replacement
Authors: Fan Xinchao , Zhang Kai , Sun Xilong , Duan Xiangrui , Wan Dadi , Yuan Ye , Zhou Yibin , Qiu Changmao , Li Wenyi , Li Xicheng
Published: February 2021

Objective: To investigate the diagnostic value of D-dimer, ESR and CRP in deep vein thrombosis (DVT) of lower extremity after hip and knee replacement.Methods: Clinical data of 216 patients who underwent hip and knee replacement in our hospital from January 2018 to November 2020 were retrospectively analyzed. Among them, there were 86 patients with lower extremity deep vein thrombosis and 130 patients without lower extremity deep vein thrombosis. Preoperative blood D-dimer, prothrombin time, fibrinogen content, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), albumin and hemoglobin levels were collected. Chi-square test was used to compare the rate of deep vein thrombosis in lower limbs. The PSM propensity score matching method was used to select 86 patients from 130 patients without lower extremity deep vein thrombosis (DVT) as control group. The levels of D-dimer, albumin and hemoglobin in 172 patients were compared, and the diagnostic efficacy of D-dimer, ESR and CRP in the diagnosis of lower extremity deep vein thrombosis after hip and knee replacement was analyzed by ROC curve.Results: ROC curve analysis results showed that: The optimal cut-off values of D-dimer, prothrombin time, ESR, CRP and age for the diagnosis of DVT of lower extremity after hip replacement were 1.745mg/L, 10.850s, 15.500mm/h, 2.375mg/L and 72 years old, respectively. The sensitivity was 71.8%, 66.7%, 61.5%, 94.9%, 71.8%, the specificity was 74.1%, 66.7%, 70.4%, 33.3%, 100%, and the area under the curve was 0.746, 0.683, 0.658, 0.651, 0.869. The optimal truncation value of D-dimer for the diagnosis of DVT of lower extremity after knee replacement was 0.285mg/L, the sensitivity was 78.7%, the specificity was 44.1%, and the area under the curve was 0.622.Conclusion: The diagnostic value of D-dimer in the formation of lower extremity DVT after knee arthroplasty is higher than that after hip arthroplasty, but the diagnostic value of prothrombin time, ESR, CRP and age in the formation of lower extremity DVT after hip arthroplasty is higher than that after knee arthroplasty.
CD4+ CD8αα+ T Cells in the Gastric epithelium Mediate Chronic Inflammation Induced by Helicobacter Felis
Authors: Ruan Guojing , Huang An , Hu Chupeng , Xu Ningyin , Fan Menghui , Zhang Zhenxing , Wang Yue , Xing Yingying
Published: February 2021

CD4+ CD8αα+ double-positive intraepithelial T lymphocytes (DP T cells), a newly characterized subset of intraepithelial T cell, has been reported to contribute to local immunosuppression. However, whether DP T cells are present in Helicobacter. pylori-induced gastritis, and their relationship with disease prognosis remain to be elucidated. In this study, We established chronic gastritis models through Helicobacter felis (H. felis) infection. Gastric infiltrating lymphocytes were isolated from H. felis-induced gastritis mice and analyzed by flow cytometry. Our results suggest that DP T cells frequency in H. felis-induced gastritis mice was higher than the uninfected mice. Gastric DP T cells derived from lamina propria cells, which distributed in the gastric epithelial layer. We found that DP T cells exhibited anti-inflammatory function. In vitro, DP T cells inhibited the maturation of dendritic cells and the proliferation of CD4+ T cell. The elimination of CD4+CD8αα+ T cells in vivo resulted in severe gastritis and a reduction of H. felis load. Additionally, vaccine with silk fibroin as delivery systems enhanced vaccine efficacy by reducing DP T cells. We demonstrated that DP T cells performed an immunosuppressive role in Helicobacter felis-induced gastritis. These findings revealed that DP T cells may affect the prognosis of the disease and the vaccine efficacy.
Redefining the Risk of Surgery for Clinical Stage IIIA (N2) Non-Small Cell Lung Cancer: A Pooled Analysis of the STS GTSD and ESTS Registry
Authors: Arndt Andrew T , Brunelli Alessandro , Cicconi Silvia , Falcoz Pierre-Emmanuel , Salati Michele , Kozower Benjamin , Liptay Michael J. , Rocco Gaetano , Karush Justin M. , Geissen Nicole , Basu Sanjib , Seder Christopher W.
Published: February 2021

BackgroundManagement of clinical stage IIIA-N2 (cIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. We evaluated treatment strategies and outcomes in cIIIA-N2 NSCLC patients who underwent pulmonary resection in The Society of Thoracic Surgeons General Thoracic Surgery Database (STS GTSD) and the European Society of Thoracic Surgeons (ESTS) Registry.MethodsThe STS GTSD and ESTS Registry were queried for patients who underwent pulmonary resection for cIIIA-N2 NSCLC between 2012 and 2016. Demographic variables, treatment strategies, and outcome measures were collected and analyzed. Significance of differences was determined using the X2 test for categorical variables and the Wilcoxon rank sum test for continuous variables.ResultsPulmonary resection was performed in 4279 cIIIA-N2 NSCLC patients (2928 STS GTSD; 1351 ESTS). Induction therapy was administered to 49%. Lobectomy was performed in 67.1% and pneumonectomy in 13%. Lobectomy was associated with 19.2% major morbidity and 1.6% operative mortality, while pneumonectomy was associated with 34.1% and 5%, respectively. Induction therapy was associated with a higher rate of major morbidity or mortality than upfront surgery (23.2% vs. 19.5%, p=0.004), driven by pneumonectomy (40.7% vs. 30.3%, p=0.012) rather than lobectomy (20.3% vs. 18.8%, p=0.31).ConclusionsPulmonary resection for cIIIA-N2 NSCLC is associated with low rates of operative morbidity and mortality, with lobectomy having lower morbidity and mortality than pneumonectomy. Induction therapy, particularly chemoradiotherapy, is associated with a higher rate of composite morbidity or mortality than upfront surgery in pneumonectomy patients but not lobectomy patients.
Selective Intra-Arterial 177Lu-PSMA Therapy for Castration Resistant Prostate Cancer: Preliminary Results of a Pilot Study
Authors: Sayman Haluk , Gulsen Fatih , Sager Sait , Akgun Elife , Yeyin Nami , Bilgic Seckin , Toplutas Kubra N. , Beytur Fatih , Oklu Rahmi , Aras Omer
Published: February 2021

Purpose177Lu-PSMA is a promising therapy for patients with metastatic castration resistant prostate cancer patients (mCRPC). To our knowledge, no study has compared the pharmacokinetic profiles of 177Lu-PSMA therapy delivered intra-arterially. We aimed to compare the feasibility and safety of selective intra-arterial (IA) administration vs conventional intravenous (IV) administration of 177Lu-PSMA in mCRPC. MethodsIn this within-patient pilot study, four patients (median age, 62.5; range, 53-72) with mCRPC who were referred to our clinic between January 2018 and September 2019 for treatment with 177Lu-PSMA. Patients were treated in two visits; in each visit receiving half of the total empiric therapeutic dose of 200 mCi, IV at the first visit and IA at the second visit. They were followed upto 8 weeks using routine parameters such as hematological status, renal function, and serum PSA levels. For each patient, organ biodistribution in lesions, kidneys, liver, bone marrow, prostate, and whole body was calculated for both administration routes according to the Medical Internal Radiation Dose (MIRD) schema. Mean absorbed doses (MAD) across all patients were compared between both administration routes. ResultsThe MAD of all metastatic lesions was significantly higher by IA vs IV administration (1.59 vs 1.20 MGy/MBq; p=0.024). The prostate gland had a lower MAD between IA and IV administrations, but the difference was not significant (0.27 vs 0.36 MGy/MBq; p=0.22). Patients tolerated IA administration very well without unexpected side effects. ConclusionThese preliminary results of an ongoing study showed that IA 177Lu-PSMA therapy is feasible and safe to treat metastatic lesions, potentially having a higher delivery efficacy compared to IV administration.This study is approved by Cerrahpasa Medical Faculty ethics committee on March 5, 2019 and retrospectively registered with file no: 83045809-604.01.02.