bluuebunny/crossref_metadata_2025 huggingface dataset:
Polygenic Risk Score is a Predictor of Adenomatous Polyps at Screening Colonoscopy 
Authors: Northcutt Michael , Shi Zhuqing , Zijlstra Michael , Shah Ayush , Zheng Siqun , Yen Eugene , Khan Omar , Beig Mohammad Imran , Imas Polina , Vanderloo Adam , Ansari Obaid , Xu Jianfeng , Goldstein Jay
Published: September 2020

Background: SNP-based polygenic risk scoring is predictive of colorectal cancer (CRC) risk. However, few studies have investigated the association of genetic risk score (GRS) with detection of adenomatous polyps at screening colonoscopy. Methods: We randomly selected 1,769 Caucasian subjects who underwent screening colonoscopy from the Genomic Health Initiative (GHI), a biobank of NorthShore University HealthSystem. Outcomes from initial screening colonoscopy were recorded. Twenty-two CRC risk-associated SNPs were obtained from the Affymetrix™ SNP array and used to calculate an odds ratio (OR)-weighted and population-standardized GRS. Subjects with GRS of <0.5, 0.5-1.5, and >1.5 were categorized as low, average and elevated risk.Results: Among 1,769 subjects, 520 (29%) had 1 or more adenomatous polyps. GRS was significantly higher in subjects with adenomatous polyps than those without; mean (95% confidence interval) was 1.02 (1.00-1.05) and 0.97 (0.95-0.99), respectively, p<0.001. The association remained significant after adjusting for age, gender, body mass index, and family history, p<0.001. The detection rate of adenomatous polyps was 10.8%, 29.0% and 39.7% in subjects with low, average and elevated GRS, respectively, p-trend <0.001. Higher GRS was also associated with early age diagnosis of adenomatous polyps, p<0.001. In contrast, positive family history was not associated with risk and age of adenomatous polyps.Conclusions: GRS was significantly associated with adenomatous polyps in subjects undergoing screening colonoscopy. This result may help in stratifying average risk patients and facilitating personalized colonoscopy screening strategies.
Medication Adherence Support of an in-home Electronic Medication Dispensing System for Individuals Living With Chronic Conditions: A Randomized Controlled Trial
Authors: Arain Mubashir , Ahmad Armghan , Chiu Venus , Kembel Lorena
Published: September 2020

Background: Medication adherence is challenging for older adults due to factors, such as the number of medications, dosing schedule, and the duration of drug therapy. The objective of this study was to examine the effectiveness of an in-home electronic medication dispensing system (MDS) on improving medication adherence and health perception in older adults with chronic conditions.Methods: A Randomized Controlled Trial (RCT) was conducted using a two-arm parallel assignment model. The intervention group used an MDS as their medication management method. The control group continued to use their current methods of medication management. Block randomization was used to assign participants into the intervention or control group. The inclusion criteria included 1) English speaking 2) age 50 and over 3) diagnosed with one or more chronic condition(s) 4) currently taking five or more oral medications 5) City of Calgary resident. Participants were recruited from a primary care clinic in Alberta, Canada. The study was open label where knowledge about group assigned to participants after randomization was not withheld. Medication adherence was captured over a continuous, six-month period and analyzed using Intention-to-Treat (ITT) analysis.Results: A total of 91 participants were assessed for eligibility and 50 were randomized into the two groups. The number of participants analyzed for ITT was 23 and 25 in the intervention and control group, respectively. Most of the demographic characteristics were comparable in the two groups except mean age of the intervention group, which was higher compared to the control group (63.96±7.86 versus 59.52±5.93, p-value=0.03). The average recorded adherence over 26 weeks was significantly higher in the intervention group than the control group (98.35%±2.15% versus 91.17%±9.76%, p<0.01). The self-rated medication adherence in the intervention group also showed a significant increase from baseline to 6-month (7.63±1.63 versus 9.13±0.81, p<0.01). The control group showed a non-significant increase (7.20±1.74 versus 8.27±2.09, p=0.07).Conclusion: MDS can be an effective, long-term solution to medication non-adherence in older adults experiencing chronic conditions and taking multiple medications. The technology induces better consistency and improvement in medication taking behaviour than simple, non-technological intervention.Trial Registration: Registered with ClinicalTrials.gov on April 09, 2020 with identifier NCT04339296.
Helicobacter pylori regulates ILK signaling pathways to influence autophagy in gastric epithelial cells
Authors: Xu Zheng , Du Yunqiu , Zhang Ruiqing , Tong Xiaohan , Li Boqing , Wu Yulong , Ji Xiaofei , Zhang Ying
Published: September 2020

BackgroundThe ability of Helicobacter pylori to manipulate host autophagy is an important pathogenic mechanism.ResultsWe found a negative correlation between the expression of ILK and the autophagy marker protein LC3B in H. pylori-positive human samples and in H. pylori-infected GES-1 cell lines. There was a significant accumulation of autophagosomes in ILK-knockdown GES-1 cells, and the expression levels of both LC3B and p62 were also increased. Here, we showed the activities of Rac1 and RhoA were decreased in H. pylori-infected GES-1 cells and ILK-knockdown GES-1 cells. Inhibition of Rac1 and RhoA increased LC3B levels and autophagosome formation in GES-1 cells after H. pylori infection. Simultaneously, H. pylori infection activated downstream signal molecules of Rac1 (PAK1, LIMK1 and cofilin) and RhoA (ROCK1, ROCK2 and LIMK1 and cofilin).ConclusionsOur results demonstrated that H. pylori regulated autophagy through ILK/Rac1 and ILK/RhoA signaling pathways in gastric epithelial cells.
Prognostic value of ST2 for MACEs and all-cause mortality in patients with coronary artery disease during a long-term follow up
Authors: Li Man , Duan Lei , Cai Yulun , Hao Benchuan , Chen Jianqiao , Li Huiying , Liu Hongbin
Published: September 2020

Background: Suppression of tumorigenesis-2 is implicated in the myocardial overload and it was long been recognized as an inflammation marker related to heart failure and acute coronary syndromes, but the data on prognostic value of suppression of tumorigenesis-2 on patients with coronary artery disease remains limited. The study ought to investigate the prognostic value of suppression of tumorigenesis-2 in patients with established coronary artery disease.Methods: In this prospective cohort study, a total of 3641 consecutive patients were included. The primary end point was major adverse cardiovascular events. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). The secondary end point was all-cause death. The association between suppression of tumorigenesis-2 and outcomes was investigated using multivariable COX regression.Results: During a median follow up of 6.4 years, there were 775 patients had the occurrence of major adverse cardiovascular events and 275 patients died. Kaplan-Meier survival estimates indicated that the patients with higher levels of ST2 (ST2> 19 ng/ml) had a significantly increased risk of MACEs (log-rank p＜0.001) and all-cause death (log-rank p＜0.001). Multiple COX regression models showed that higher level of suppression of tumorigenesis-2 was an independent predictor in developing major adverse cardiovascular events (HR=1.36, 95% CI 1.17-1.56, p＜0.001) and all-cause death (HR=2.01, 95%CI 1.56-2.59, p＜0.001). The addition of suppression of tumorigenesis-2 to established risk factors significantly improved risk prediction of the composite outcome of major adverse cardiovascular events and all-cause death (c-statistic, net reclassification index, and integrated discrimination improvement, all p＜0.05).Conclusions: Higher level of suppression of tumorigenesis-2 is significantly associated with long-term all-cause death and major adverse cardiovascular events. Suppression of tumorigenesis-2 may provide incremental prognostic value beyond traditional risk factors.
Dietary Protein is the Strong Predictor of Coronary Artery Disease; A Data Mining Approach
Authors: Soflaei Sara Saffar , Shamsara Elham , Sahranavard Toktam , Esmaily Habibollah , Moohebati Mohsen , Shabani Niloofar , Asadi Zahra , Tajfard Mohammad , Ferns Gordon A , Mobarhan Majid Ghayour
Published: September 2020

Backgrounds and aims: Coronary artery disease (CAD) is the major cause of mortality and morbidity globally. Diet is known to contribute to CAD risk, and the dietary intake of specific macro- or micro-nutrients might be potential predictors of CAD risk. Machine learning methods may be helpful in the analysis of the contribution of several parameters in dietary including macro- and micro-nutrients to CAD risk. Here we aimed to determine the most important dietary factors for predicting CAD.Methods: Total 273 cases with more than 50% obstruction in at least one coronary artery and 443 healthy controls who completed a food frequency questionnaire (FFQ) were entered into the study. All dietary intakes were adjusted for energy intake. QUEST method was applied to determine the diagnosis pattern of CAD.Results: Total 34 dietary variables obtained from FFQ were entered the study that 23 of these variables were significantly associated with CAD according to t-test. Out of 23 dietary input variables adjusted protein, manganese, biotin, zinc and cholesterol remained in the model. According to our tree, only protein intake could identify the patients with coronary artery stenosis according to angiography from healthy participant up to 80%. Manganese dietary intake was the second important variable after protein. The accuracy of the tree was 84.36% for training dataset and 82.94% for testing dataset.Conclusion: Among different macro- and micro-nutrients in the dietary, a combination of protein, manganese, biotin, zinc and cholesterol could predict the presence of CAD.
Structural basis for the mechanisms of human presequence protease conformational switch and substrate recognition
Authors: Liang Wenguang , wijaya Juwina , Wei Hui , Noble Alex , Mo Swansea , Lee David , Mancl Jordan , King John Lin , Pan Man , Liu chang , Koehler Carla , Zhao Minglei , Potter Clinton , Carragher Bridget , Li Sheng , Tang Wei-Jen
Published: September 2020

Presequence protease (PreP), a 117 kDa mitochondrial M16C metalloprotease vital for mitochondrial proteostasis, degrades presequence peptides cleaved off from nuclear-encoded proteins and other aggregation-prone peptides, such as amyloid β (Aβ). PreP structures have only been determined in a closed conformation; thus, the mechanisms of substrate binding and selectivity remain elusive. Here, we leverage advanced vitrification techniques to overcome the preferential denaturation of one of two ~55 kDa homologous domains of PreP caused by air-water interface adsorption, and thereby elucidate cryoEM structures of three apo-PreP open states along with Aβ- and citrate synthase presequence-bound PreP at 3.3 Å-4.6 Å resolution. Together with integrative biophysical and pharmacological approaches, these structures reveal the key stages of the PreP catalytic cycle and how the binding of substrates or PreP inhibitor drives the rigid body motion of the protein for substrate binding and catalysis. Together, our studies provide key mechanistic insights into M16C metalloproteases for future therapeutic innovations.
Serum tRNA-derived small RNAs as potential novel diagnostic biomarkers for Pancreatic Ductal Adenocarcinoma
Authors: Xue Meilin , Shi Minmin , Xie Junjie , Zhang Jun , Jiang Lingxi , Deng Xiaxing , Peng Chenghong , Shen Baiyong , Xu Hong , Chen Hao
Published: September 2020

Background Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal common cancer because of late diagnosis. tRNA-derived small RNAs (tsRNAs) are novel small RNAs might serve as biomarkers for cancer diagnosis and participate in diverse physiological and pathological process. We investigated whether the expression of tsRNAs in serum could be a noninvasive method in the early diagnosis of PDAC.Methods Blood sample of PDAC patients and healthy controls were collected from Ruijin Hospital, Shanghai, China. Tumor and adjacent normal pancreas tissues were collected from 51 patients with PDAC undergoing therapeutic surgery. The testing cohort comprised 6 PDAC patients and 6 healthy controls and the expression of small RNAs in serum was analyzed by small RNA sequence. We verified the diagnostic performance of serum tsRNAs by qPCR in validation cohort including 110 PDAC patients and 100 healthy controls. Expression level of tsRNAs in tissue was also verified in another independent cohort including 51 tumor and 51 adjacent normal pancreas tissues. Unpaired t-test and paired t-test are used for comparing depending on whether the samples are paired. Receiver operating characteristic (ROC) area under the curve (AUC) was used to determine diagnostic accuracy.Results There were 45 tsRNAs expressed at remarkably higher levels, 6 tsRNAs expressed at lower levels in PDAC patients, respectively, compared with healthy volunteers. tsRNA-ValTAC-41, tsRNA-MetCAT-37 and tsRNA-ThrTGT-23 expressed significant highly (P<0.05) in serum of PDAC patients in validation cohort. tsRNA-ValTAC-41 or tsRNA-MetCAT-37 combined with CA19-9 could increase the AUC of PDAC prediction (AUC=0.947 and 0.949 respectively), relative to CA19-9 test alone. Besides, tsRNA-ValTAC-41 expressed at remarkably higher level in tumor tissue, and it was obviously associated with tumor staging both in serum and tissue.Conclusions We provide tsRNAs profiles observed by small RNA sequencing. The diagnostic accuracy of tsRNA-ValTAC-41 and tsRNA-MetCAT-37 in serum of PDAC patients were verified. Further studies for tsRNA-ValTAC-41 are needed to confirm the findings. These tsRNAs may be promising and effective candidates in the development of highly sensitive, noninvasive biomarkers for PDAC diagnosis.
Determinants of growth monitoring and promotion service utilization among children 0-23 months of age in Northern Ethiopia: Unmatched case control study
Authors: Chanie Samuel Dagne , Yimam Jemal Aliyu , Antigegn Yonatan Menber , Mengistie Yosef Wassihun , Bayabel Netsanet Fentahun
Published: September 2020

Back groundChild malnutrition is one of the world’s public health problems. Promotion of child growth and development is one of the health priorities to control child mortality and poverty reduction. One of the strategies to promote child health is growth monitoring and promotion services. But, there is limited information on determinants of Growth Monitoring and Promotion service utilization.ObjectiveTo identify determinants of growth monitoring and promotion (GMP) service utilization among children 0–23 months of age in Legambo district, South Wollo zone, Northern Ethiopia, 2020.MethodsCommunity based un-matched case control study was conducted on 363 (91 cases and 272 controls) study participants from March 15 to April 15, 2020.. Multi-stage sampling technique was employed to select the study participants.. Data were collected by using interviewer administered questionnaire and entered in to Epi data and exported to SPSS version 23 for analysis. Bivariable and multivariable logistic regressions were performed and adjusted odds ratio with 95% confidence intervals was estimated to identify determinants of GMP service utilization.ResultsGood maternal knowledge (AOR) = 2.42; 95% CI: 1.23, 4.75), mother with favorable attitude (AOR = 2.45; 95% CI; 1.20, 4.98), counseling on GMP (AOR = 2.34; 95% CI; 1.19, 4.56), Attending ante natal care services (AOR = 2.46; 95% CI: 1.18, 5.16), index child age 12–17 months(AOR = 3.45; 95% CI: 1.26, 9.41) and 18–23 months (AOR = 4.38; 95% CI: 1.53, 12.49), and short distance to health facilities (AOR = 4.53; 95% CI; 1.99, 10.28) were determinants of GMP service utilization.Conclusions and recommendationIndex child age, good knowledge, favorable attitude, attending ante natal care services, receiving nutritional counseling and short distance to health facility were determinants of GMP service utilization. Nutritional interventions should emphasis nutritional counseling, utilization of ANC service and accessibility of growth monitoring and promotion service to improve growth monitoring and promotion service utilization and reduce malnutrition in EthiopiaTrial registrationNo applicable
Respiratory microbiome profiles differ by recent hospitalization and nursing home residence in patients on mechanical ventilation
Authors: Baek Min-gyung , Woo Seongji , Kim Nam-Eun , Baek Chaeyun , Won Sungho , Kim Youngmi , Lee Jae Jun , Yi Hana , Hong Ji Young
Published: September 2020

Background: Healthcare-associated pneumonia (HCAP) is a heterogeneous disease. We redefined nursing-home- and hospital-associated infections (NHAI) group by revising existing HCAP risk factors. The NHAI group comprised nursing home residents with a poor functional status, or recent (past 90 days) hospitalization or recent (past 180 days) antibiotic therapy. Our aim was to determine whether respiratory microbiota profiles are related to newly defined NHAI group in critically ill patients on mechanical ventilation.Methods: The 180 endotracheal aspirates (ETAs) from 60 mechanically ventilated ICU patients (NHAI group, n = 24; non-NHAI group, n = 36) were prospectively collected on days 1, 3 and 7 in a university hospital. The bacterial community profiles of the ETAs were explored by 16S rRNA gene sequencing. A phylogenetic-tree-based microbiome association test (TMAT), generalized linear mixed models (GLMMs), the Wilcoxon test and the reference frame method were used to analyze the association between microbiome abundance and disease phenotype.Results: The relative abundance of the genus Corynebacterium was significantly higher in the pneumonia than in the non-pneumonia group. The microbiome analysis revealed significantly lower α-diversity in the NHAI group than in the non-NHAI group. In the analysis of β-diversity, the structure of the microbiome also differed significantly between the two groups (weighted UniFrac distance, Adonis, P <0.001). The abundance of Corynebacterium was significantly higher, and the relative abundances of Granulicatella, Staphylococcus, Streptococcus and Veillonella were significantly lower, in the NHAI group than in the non-NHAI group. Conclusions: The microbiota signature of the ETAs distinguished between patients with and without risk factors for NHAI. The lung microbiome may serve as a therapeutic target for NHAI group.
Photosynthetic analysis of mid-vein and leaf lamina in high-yield hybrid rice in fields during senescence
Authors: Gao Zhiping , Xu Minli , Zhang Haizi , Chen Guoxiang
Published: September 2020

Previous studies on rice (Oryza sativa L.) have shown that different components of the photosynthetic apparatus are not uniformly synthesized or degraded during senescence. However, most of these senescence-related studies focused on leaf lamina, while few have addressed functional aspects on chloroplasts or leaf physiology. Here, we investigated the photosynthetic properties of the mid-vein and leaf lamina in a super high-yield hybrid rice (LYP9) during senescence. We found that assimilation and transpiration decreased more slowly in the mid-vein than in the lamina during senescence, suggesting more sustained photosynthesis in the mid-vein, as well as stronger heat dissipation. Two-dimensional gel electrophoresis revealed that the mid-vein had a higher abundance of proteins involved with energy and lower levels of disease or defense-related proteins, suggesting that photosynthesis and energy metabolism were less affected by senescence in the mid-vein than in leaf lamina. In late senescence stage, the excess energy dissipation in the mid-vein through the xanthophyll cycle had a higher active photosynthetic capacity than in the leaf lamina, and we inferred that the mid-vein and leaf lamina of LYP9 rice aged heterogeneously. Taken together, these results provide new insights into the underlying mechanisms of senescence and associated physiology of the rice mid-vein.
An Assessment of Wastewater Inventory and its Energy Potential: Bangladesh Perspective
Authors: Islam A K M Khabirul
Published: September 2020

Background: Everyday considerable amount of wastewater is produced by each one of us. Developed country produce more wastewater than developing country. But disposing this wastewater into the environment is an expensive task and need heavy initial investment for that reason developing country only focus on water supply not on wastewater treatment considering it’s a burden and threatening the human health environment and climate change. Research shows that wastewater contain considerable amount kinetic and biochemical energy. But tapping energy from wastewater, proper inventory of national wastewater including type and characteristics of both industrial and municipal wastewater is essential which is presently absent in Bangladesh. In this paper, efforts have been taken firstly to estimate yearly total domestic as well as industrial wastewater production in Bangladesh based on reliable secondary data and monthly per capita income. Secondly, common, and emerging energy recovery technologies ideal for tapping energy from wastewater have been reviewed systematically and identified which are anaerobic digestion (AD) micro hydro powerplant (MHP), microbial electrolysis cell (MEC) and microbial fuel cell (MFC). Finally, energy potential has been estimated basing on previous research outputs and with empirical formula. At the end barrier and overcoming strategy with important recommendation has been proposed for researchers and decision makers.Results: Estimated yearly domestic and industrial wastewater is 4.874 billion and 0.452 billion tons respectively. For energy estimation,10%-50% total wastewater has been considered. Calculation shows that, 10% wastewater can produce 2.41, 1829.09 and 1.97 GW energy yearly through AD, MHP, MEC and MFC technologies, respectively whereas 50% total wastewater can generate 9145.94 GW energy yearly by MHP only.Conclusion: Estimated quantity of produced wastewater and energy potentials from wastewater is based on secondary data. For more reliable estimation feasibility study may be conducted by the researchers supported by stakeholders. Both wastewater producers and treatment plant owners should have noble desire backed by governmental organizations will facilitate the process. Outcomes are very significant and optimistic and it is expected that this findings not only inspired researcher, wastewater operators and policy makers of Bangladesh but also other developing countries around the globe.
Young Woman With Sudden-onset Neck Pain and Quadriplegia: A Case Report
Authors: Ota Koshi , Ogawa Shoji , Fujii Kensuke , Oishi Yasuo , Oka Masahiro , Onishi Naoya , Ota Kanna , Sano Yohei , Yokoyama Hiroki , Takasu Akira
Published: September 2020

Introduction: Sudden-onset quadriplegia is a neurologic emergency that requires immediate management. Anterior spinal artery syndrome (ASAS) is rare, but can cause sudden-onset quadriplegia. Magnetic resonance imaging (MRI) is an essential imaging modality for diagnosing ASAS.Case presentation: A 31-year-old woman without previous medical history was transferred to our facility for further workup of sudden-onset neck pain with quadriplegia. Diffusion-weighted imaging (DWI) revealed hyperintense signals predominantly in grey matter with a decreased apparent diffusion coefficient (ADC). These findings strongly suggested ASAS with spinal cord infarction. Edaravone, heparin, and aspirin with steroid pulse therapy was immediately initiated. Twelve days in an intensive care unit was required for dyspnea. Symptoms gradually resolved with rehabilitation, but the patient was wheelchair-bound without bladder control and was transferred to a rehabilitation facility on hospital day 48.Conclusion: A combination of DWI with ADC mapping of the spine should proceed as soon as possible to ensure appropriate management. Early treatment with edaravone, aspirin and steroid pulse therapy may prove beneficial for ASAS.
Characterization and genetic diversity of Helicobacter pylori type IV secretion system components, CagI and CagN and its association with clinical outcomes among Iranian patients
Authors: Azizimoghaddam Yasaman , Kermanpour Sadaf , Mirzaei Nasrin , Houri Hamidreza , Yadegar Abbas , Kumar Navin , Aghdaei Hamid Asadzadeh , Zali Mohammad Reza
Published: September 2020

Background

A number of cagPAI genes in H. pylori genome was proposed to be the most probably evolved under a diversifying selection and evolutionary pressure. Among them, CagI and CagN are described as a part of the two different-operon of cagPAI that are involved in the T4SS, but the definite association of these factors with clinical manifestations is unclear.
Methods

A total of 70 H. pylori isolates were obtained from different gastroduodenal pateints. All isolates were examined for the presence of primary H. pylori virulence genes by PCR analysis. Direct DNA sequence analysis was performed for the cagI and cagN genes. The results were compared with reference strain.
Results

The cagI, cagN, cagA, cagL, vacA s1m1, vacA s1m2, vacA s2m2, babA2, sabA and dupA genotypes were detected in 80%, 91.4%, 84%, 91.4%, 32.8%, 42.8%, 24.4%, 97.1%, 84.3%, and 84.3% of the total isolates, respectively. The most variable codon usage in cagI was observed at residues 20 to 25, 55 to 60, 94, 181 to 199, 213 to 221, 241 to 268, and 319 to 320, while the most variable codon usage in CagN hypervariable motif (CagNHM) was observed at residues 53 to 63. This CagNHM region is postulated to contain GDEEITEEEKK sequence in the P12 reference strain. Sequencing data analysis of cagN revealed a conserved hypothetical hexapeptide repeat (EAKDEN/K) in residues of 278–283 among six H. pylori isolates, which needs further studies to evaluate its putative function.
Conclusion

The present study demonstrated a high prevalence of cagI and cagN genes among Iranian H. pylori isolates with gastroduodenal diseases. Furthermore, no significant correlation between cagI and cagN variants and clinical outcomes was observed. However, all patients had high prevalence of cagPAI genes including cagI, cagN, cagA and cagL that indicates more potential role of these genes in disease outcome.
The role of intermittent negative pressure wound therapy combined with a mesh incision in the salvage of perforator flap with venous congestion, a case report
Authors: Li Zhaoyue , Xie Kun , He Rui , Li Qiang , Zhou Changqing , Qi Xin , Jiang Shan , Shen Yimeng , Wen Bing
Published: September 2020

Background: The application of perforator flap is becoming wide. The most common postoperative complication is venous congestion but traditional treatments’ effect is limited. A new method called negative pressure wound therapy(NPWT) was introduced to improve wound healing. Many scholars have tried this method with continuous mode and achieved good outcomes. In this paper, we tried a different mode(intermittent) of negative pressure wound therapy on congested perforator flaps after a mesh incision, and we expected this paper could provide information for follow-up clinical research.Case presentation: A retrospective research of 6 patients (6 perforator flaps) who had been suffered from venous congestion from June, 2016 to June, 2019 was performed. All flaps were treated by intermittent negative pressure wound therapy after a mesh incision. Among 6 flaps, 4 of them were totally survived while the other 2 of them were mostly survived.Conclusions: Intermittent negative pressure wound therapy combined with a mesh incision can be a safe option to rescue perforator flaps with venous congestion. This technique has a certain success rate and clinical application value.
Linkage between Financial Development and Income Inequality in India
Authors: Sharma Rajesh , Dahiya Suman
Published: September 2020

The authors have requested that this preprint be removed from Research Square.
Impact of Diabetes Mellitus on the Early-Phase Arterial Healing After Drug-Eluting Stent Implantation
Authors: Ishihara Takayuki , Sotomi Yohei , Tsujimura Takuya , Iida Osamu , Kobayashi Tomoaki , Hamanaka Yuma , Omatsu Takashi , Sakata Yasushi , Higuchi Yoshiharu , Mano Toshiaki
Published: September 2020

Background: Early arterial healing after drug-eluting stent (DES) implantation may enable short dual-antiplatelet therapy (DAPT) strategy. The impact of diabetes mellitus (DM) on this healing has not been elucidated. We used coronary angioscopy (CAS) to compare intravascular status of DM and non-DM patients in the early phase after DES implantation.Methods: This study was a multicenter retrospective observational study. We analyzed CAS findings of 337 lesions from 270 patients evaluated 3-5 months after DES implantation. We divided the lesion into two groups: DM (n=149) and non-DM (n=188). We assessed neointimal coverage (NIC) grades (dominant, maximum and minimum), thrombus adhesion and maximum yellow color grade. NIC was graded as follows: grade 0, stent struts were not covered; grade 1, stent struts were covered by thin layer; grade 2, stent struts were buried under neointima. Yellow color was graded as grade 0, white; grade 1, light yellow; grade 2, yellow; grade 3, intensive yellow.Results: Minimum NIC grade was significantly lower in DM than in non-DM groups (p=0.002), whereas dominant and maximum NIC grades were similar between them (p=0.59 and p=0.94, respectively), as were thrombus adhesion (44.3% vs. 38.8%, p=0.32) and maximum yellow color grade (p=0.78). A multivariate analysis demonstrated that DM was an independent predictor of minimum NIC of grade 0 (odds ratio: 2.14, 95% confidence interval: 1.19-3.86, p=0.011).Conclusion: DM patients showed more uncovered struts than non-DM patients 3-5 months after DES implantation, suggesting that the recent ultra-short DAPT strategy might not be easily applied to DM patients.
Use of a novel Screen–Enrich–Combine(-biomaterials) Circulating System for filling of a 3D-printed open Ti6Al4V frame with mesenchymal stem cells/β-tricalcium phosphate to repair complex anatomical bone defects in load-bearing areas
Authors: Chu Wenxiang , Liu Zhiqing , Gan Yaokai , Chang Yongyun , Jiao Xin , Jiang Wenbo , Dai Kerong
Published: September 2020

Background: Repairing complex anatomical load-bearing bone defects is difficult because it requires restoration of load-bearing function, reconstruction of anatomical shape and repair by regenerated bone. We previously developed a Screen–Enrich–Combine(-biomaterials) Circulating System (SECCS) for rapid intraoperative enrichment of autologous bone marrow mesenchymal stem cells (MSCs) to enhance the osteogenic ability of porous bone substitutes. In this study, we prepared a 3D-printed Ti6A14V macroporous frame matching the defect shape to provide early load-bearing support and evaluated the efficacy of filling the frame with SECCS-processed MSCs/beta tricalcium phosphate (β-TCP) for long-term bone growth. Method: Mechanical testing of the cylindrical Ti6Al4V frame identified optimal 3D printing parameters. The lateral part of a goat distal femur was used as the defect model, and a matching electron beam melting technology-prepared (EBM) Ti6Al4V frame was fitted. Three frames filled with nothing, pure porous β-TCP or SECCS-processed MSCs/β-TCP were fixed onto the defect site. Repair efficacy was evaluated by X-ray radiography, computed tomography, histology and histomorphology. Results: In the basic regular hexagon printing unit, the combined side width (w) and inscribed circle diameter (d) determines the printing frame’s mechanical strength. The compressive load was significantly higher for w = 1.9 mm, d = 4.4 mm than for w = 1.7 mm, d = 4.0 mm or w = 2.0 mm, d = 5.0 mm (P < 0.05). The EBM-prepared Ti6Al4V defect-matched frame was well maintained 9 months after implantation. The MSCs successfully adhered to the wall of the porous β-TCP in the SECCS-processed group and had spread fully in the test samples. Each goat in the MSCs/β-TCP–filling group had approximately 31,321.7 ± 22,554.7 MSCs and a larger area of new bone growth inside the frame than the areas in the control and blank groups.Conclusion: Filling the 3D-printed Ti6Al4V large-aperture frame with osteogenic materials achieved biological reconstruction over a larger area of regenerated bone for repair of complex anatomical weight-bearing bone defects under the condition of early frame-supported load bearing. MSCs/β-TCP prepared by SECCS can be used as a filling material for this type of bone defect to obtain more efficacious bone repair.
Prognostic Significance of SQSTM1 in Breast Cancer: A Comprehensive Analysis
Authors: Liu Yang , Du Qian , Sun Dan , Han Ruiying , Teng Mengmeng , Zhang Ying , Dong Yuzhu , Chen Siying , You Haisheng , Dong Yalin
Published: September 2020

Background: SQSTM1 (Sequestosome 1, p62) is degraded by activated autophagy and involved in the progression of in various types of cancers. However, the prognostic role and underlying regulation mechanism of SQSTM1 in the progression and development of breast cancer remain unclear.Methods: In this study, 1336 samples with available mRNA data from Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) database and 27 formalin fixation and paraffin embedding (FFPE) tissue samples from the First Affiliated Hospital of Xi’an Jiaotong University were collected to evaluate SQSTM1 expression in mRNA and protein levels. Kaplan–Meier and Cox regression were used for revealing prognostic value in three independent breast cancer independent datasets. Tumor Immune Estimation Resource (TIMER) database and Gene Set Variation Analysis (GSVA) was used to explore the relationship of SQSTM1 mRNA expression and immune infiltration level in breast cancer. Dysregulation mechanisms of SQSTM1 were also explored including copy number variation (CNV), somatic mutation, epigenetic alterations and other transcription and post-transcription level using multiple datasets. Finally, Gene Set Enrichment Analysis (GSEA) was constructed to elucidate functional regulating performance of SQSTM1 in breast cancer.Results: The results showed that mRNA and protein level of SQSTM1 were significantly elevated in breast cancer and receiver operating characteristic (ROC) curve showed that p62 may act as diagnostic biomarker. Lower expression of SQSTM1 predicted better outcome through multiple datasets. It was also found that SQSTM1 correlated with immune infiltrates in breast cancer. Moreover, CNV and methylation of SQSTM1 DNA was correlated with SQSTM1 dysregulation and act as prognostic factors for breast cancer patients. Yet, somatic mutation status of SQSTM1 didn’t show any prognostic relevance. We also identified diverse transcription factors that directly bound to SQSTM1 DNA and the miRNAs which may regulate SQSTM1 mRNA. Finally, functional enrichment analysis revealed that SQSTM1 is related to cell signal transduction, oxidative stress and autophagy in breast cancer.Conclusion: Our findings revealed that SQSTM1 plays a key role in the progression of breast cancer and might be a promising biomarker for the diagnosis and personalized treatment of breast cancer patients.
Differential Metabolites in Chinese Autistic Children: A Multi-Centre Study Based on Urinary 1H-NMR Metabolomics Analysis
Authors: Ma Yu , Zhou Hao , Li Chunpei , Zou Xiaobing , Luo Xuerong , Wu Lijie , Li Tingyu , Chen Xiang , Mao Meng , Huang Yi , Li Erzhen , An Yanpeng , Zhang Lili , Wang Tianqi , Xu Xiu , Yan Weili , Jiang Yonghui , Wang Yi
Published: September 2020

Background: Autism spectrum disorder (ASD) is a group of early-onset neurodevelopmental disorders. However, there is no valuable biomarker for the early diagnosis of ASD. Our large-scale and multi-centre study aims to identify metabolic variations between ASD and healthy children and to investigate differential metabolites and associated pathogenic mechanisms.Methods: 117 autistic children and 119 healthy children were recruited from research centres of 7 cities. Urine samples were assayed by 1H-NMR metabolomics analysis to detect metabolic variations. Multivariate statistical analysis, including principal component analysis (PCA) and orthogonal projection to latent structure discriminant analysis (OPLS-DA), as well as univariate analysis were used to assess differential metabolites between the ASD and control groups. The differential metabolites were further analysed by receiver operating characteristics (ROC) curve analysis and metabolic pathways analysis.Results: Compared with the control group, the ASD group showed higher levels of glycine, guanidinoacetic acid, creatine, hydroxyphenylacetylglycine, phenylacetylglycine and formate and lower levels of 3-aminoisobutanoic acid, alanine, taurine, creatinine, hypoxanthine and N-methylnicotinamide. ROC curve showed relatively significant diagnostic values for hypoxanthine (area under the curve (AUC) = 0.657, 95% CI 0.588 to 0.726), creatinine (AUC = 0.639, 95% CI 0.569 to 0.709), creatine (AUC = 0.623, 95% CI 0.552 to 0.694), N-methylnicotinamide (AUC = 0.595, 95% CI 0.523 to 0.668) and guanidinoacetic acid (AUC = 0.574, 95% CI 0.501 to 0.647) in the ASD group. Combining the metabolites creatine, creatinine and hypoxanthine, the AUC of the ROC curve reached 0.720 (95% CI 0.659 to 0.777). Significantly altered metabolite pathways associated with differential metabolites were glycine, serine and threonine metabolism, arginine and proline metabolism, and taurine and hypotaurine metabolism.Limitations: Due to the restriction of research centres, inconsistent urine collection times may have affected the quality of metabolic analyses. Moreover, it is necessary to compare metabolite levels that vary with ASD severity to better clarify the pathogenesis of ASD.Conclusions: Urinary amino acid metabolites significantly altered in children with ASD. Amino acid metabolic pathways might play important roles in the pathogenic mechanisms of ASD.Clinical Trial registration: National Study on Autism Spectrum Disorder in China (NCT02200679). Registered July 24, 2014. https://www.clinicaltrials.gov/ct2/show/NCT02200679
Acute Miliary Tuberculosis in Pregnancy After in Vitro Fertilization and Embryo Transfer: Report of Seven Cases and Systemic Review
Authors: Gai Xiaoyan , Chi Hongbin , Cao Wenli , Zeng Lin , Chen Lixue , Zhang Weixia , Song Donghong , Wang Ying , Liu Ping , Li Rong , Sun Yongchang
Published: September 2020

BackgroundWhile miliary tuberculosis (TB) in pregnancy is rare after in vitro fertilization and embryo transfer (IVF-ET), it poses a serious threat to the health of pregnant women and their fetuses. The present study aimed to describe the clinical features of miliary TB and pregnancy outcomes of patients after IVF-ET.MethodsData of infertile patients who received IVF-ET at Peking University Third Hospital between January 2012 to December 2017 were retrospectively analyzed. Patients who developed miliary TB during pregnancy were identified, and clinical characteristics of miliary TB were described. The keywords “infertility,” “in vitro fertilization and embryo transfer,” and “tuberculosis” were used to search for articles published from 1980 to 2019 in PubMed, Medline, and EMBASE databases.ResultsOf 62,755 enrolled women, 7137 (11.4%) showed signs of prior pulmonary TB on chest X-ray (CXR). Seven patients aged 28–35 years had miliary TB during pregnancy, with two patients complicated by TB meningitis. All of these patients presented with fever. Notably, old TB lesions were detected on CXR in six patients before IVF-ET; nevertheless, no anti-TB therapy was administered. Furthermore, salpingography revealed oviduct obstruction in all patients (7/7). Patients received anti-TB therapy following a diagnosis of miliary TB and were clinically cured. However, pregnancy was terminated due to spontaneous (4/7) and induced (3/7) abortion. Previous literature indicates that signs of prior TB on CXR and oviduct obstruction on laparoscopy are risk factors for TB reactivation during pregnancy, which displayed a trend for hematogenous dissemination.ConclusionsTB reactivation, mostly as miliary TB and TB meningitis, is severe in pregnant women after IVF-ET and deleterious to pregnancy outcomes. The coexistence of primary infertility, untreated prior pulmonary TB, and fallopian tube obstruction is a risk factor for TB dissemination.
Modification of N-Terminal α-Amine of Proteins via Biomimetic ortho-quinone-mediated Oxidation
Authors: Wang Ping , Wang Siyao , Zhou Qingqing , Li Yunxue , Chen Xiaoping , Luo Rong-Hua , Yang Liu-Meng , Zheng Yong-Tang
Published: September 2020

Naturally abundant quinones are important molecules, which play essential roles in various biological processes due to their reduction potential. In contrast to their universality, the reactions between quinones and proteins remain sparse. Herein, we report the development of unprecedented strategy to protein modification via a biomimetic quinone-mediated oxidation at the N-terminus. By exploiting unique reactivity of an ortho-quinone reagent, the α-amine of protein N-terminus was oxidized to generate aldo or keto handle for orthogonal conjugation. Its applications have been demonstrated using a range of proteins, including myoglobin and ubiquitin. The effect of this method was further highlighted via the preparation of a series of 17 MIP-1β analogs, followed by preliminary anti-HIV activity and cell viability assays, respectively. This method offers a fast, efficient and complementary approach to existing strategies for protein N-terminus modification.
Putative Risk Factors of Prostate Cancer in Unscreened Ghanaian Men
Authors: Gyamfi Michael Adu , Anto Enoch Odame , Acheampong Emmanuel , Obirikorang Christian , Obirikorang Yaa
Published: September 2020

African countries with weak health systems and infrastructure are at risk of high incidence and mortality of prostate cancer. The absence of specific causative agents for prostate cancer calls for early detection strategies and the identification of susceptible factors. We undertook a community-based prostate-specific antigen screening of Ghanaian men to ascertain the association between putative risk factors and prostate cancer. Using an adjusted PSA cut-off we found a prostate cancer prevalence of 12.5% with most men diagnosed between 62–77 years (Mean; 69.50 ± 8.46). We found no statitsically significant association between putative risk factors such as obesity, hypertension, intake of alcohol, and smoking with prostate cancer. However, we observed a significant association between age and occupation, and prostate cancer. Prostate cancer is a growing challenge in Ghanaian men. Detection with PSA offers diagnostic significance and may help in reducing the burden in men. Differences in genetic and environmental differences between populations call for a population-specific assessment of risk factors.
Metagenomic analyses and genetic diversity of Tomato leaf curl virus complex affecting tomato plants in Kenya
Authors: Avedi Edith Khamonya , Adediji Adedapo Olutola , Kilalo Dora Chao , Olubayo Florence Mmogi , Macharia Isaac , Ateka Elijah Miinda , Machuka Eunice Magoma , Mutuku Josiah Musembi
Published: September 2020

Background
Tomato production is threatened worldwide by the occurrence of begomoviruses which are associated with tomato leaf curl diseases. There is little information on the molecular properties of tomato begomoviruses in Kenya, hence we investigated the population and genetic diversity of begomoviruses associated with tomato leaf curl in Kenya.
Methods
In 2018, we obtained tomato leaf samples with virus-like symptoms from farmers’ fields across Kenya and used Illumina sequencing to identify associated begomoviruses. Using the sequences, we determined the genetic diversity of begomoviruses. Additionally, selection pressure and recombinant isolates within the population were evaluated.
Results
Twelve complete begomovirus genomes were obtained from our samples with an average coverage of 99.9%. The sequences showed 95.7–99.7% identity among each other and 95.9–98.9% similarities with a Tomato leaf curl virus Arusha virus (ToLCArV) isolate from Tanzania. When we analyzed the amino acid sequences, we detected the highest identities in the regions coding for the coat protein gene (98.5–100%) within the isolates, and with the C4 gene of ToLCArV (97.1–100%). Phylogenetic algorithms clustered all Kenyan isolates in the same clades with ToLCArV, thus confirming the isolates to be a variant of the virus. Recombination analyses identified four putative events (P ≤ 0.05) among the isolates. Estimation of selection pressure within the virus population revealed the occurrence of negative or purifying selection in 5 out of the 6 coding regions.
Conclusions
The begomovirus associated with tomato leaf curl diseases in Kenya is a variant of ToLCArV possibly originating from Tanzania. Recombinant virus strains were detected within the population and there are divergence evolutionary events within the coding regions of the virus in Kenya. This information is useful in the development of appropriate management strategies for the disease.
Excretion of urine extracellular vesicles bearing markers of activated immune cells and calcium/phosphorus physiology differ between calcium kidney stone formers and non-stone formers
Authors: Zhang Jiqing , Kumar Sanjay , Jayachandran Muthuvel , Wang Stanley , Wilson Elena M. , Lieske John C.
Published: September 2020

Backgrounds:
Previous studies have demonstrated that excretion of urinary extracellular vesicles (EVs) from different nephron segments differs between kidney stone formers and non-stone formers (NSFs), and could reflect pathogenic mechanisms of urinary stone disease. In this study we quantified selected populations of specific urinary EVs carrying protein markers of immune cells and calcium/phosphorus physiology in calcium stone formers (CSFs) compared to non-stone formers (NSFs).
Methods
Incident CSFs (n = 24) and age- and sex- matched NSFs (n = 21) were studied. Clinical data were abstracted and biobanked cell-free urine samples were used to quantify specific urinary EV populations. EVs carrying proteins related to renal calcium/phosphorus physiology (phosphorus transporters (PiT1 and PiT2), Klotho, and fibroblast growth factor 23 (FGF23)); markers associated with EV generation (anoctamin-4 (ANO4) and Huntington interacting protein 1 (HIP1)), and markers shed from activated immune cells were quantified by standardized and published method of digital flow cytometry.
Results
The urine pH of CSFs was lower than NSFs (P < 0.05), whereas urine excretion of calcium, phosphorus, and calcium oxalate and uric acid supersaturation (SS) were significantly higher in CSFs compared to NSFs (P < 0.05). Urinary excretion of EVs with markers of total leukocytes (CD45), neutrophils (CD15), macrophages (CD68), Klotho, FGF23, PiT1, PiT2, and ANO4 were each markedly lower in CSFs than NSFs (P < 0.05) whereas excretion of those with markers of monocytes (CD14), T-Lymphocytes (CD3), B-Lymphocytes (CD19), plasma cells (CD138 plus CD319 positive ) were not different between the groups. Urinary excretion of EVs expressing PiT1 and PiT2 negatively (P < 0.05) correlated with urinary phosphorus excretion whereas excretion of EVs expressing FGF23 correlated negatively (P < 0.05) with both urinary calcium and phosphorus excretion.
Conclusions
Urinary excretion of EVs derived from specific types of activated immune cells and EVs with proteins related to calcium/phosphorus regulation were different between CSFs and NSFs. Thus, further validation of these and other populations of urinary EVs could identify biomarkers that elucidate novel pathogenic mechanisms of calcium stone formation in specific subsets of patients.