bluuebunny/crossref_metadata_2025 huggingface dataset:
Biosynthesis of Fluorescent Silver Nanoparticles From Leea Coccinea Leaves and Their Antibacterial Potentialities Against Xanthomonas Phaseoli Pv Phaseoli
Authors: Novelles María del Carmen Travieso , Ortega Annie Rubio , Pita Beatriz Alvarez , López Mylene Corzo , Pérez Lianet Díaz , Medina Emilio Acosta , Pérez Oriela Pino
Published: October 2020

The synthesis of Silver Nanoparticles (SNP) from plants is a simple, fast and environmentally safe route. In the present study, the aqueous extract of fresh leaves from Leea coccinea L. was evaluated as a possible source of reducing and stabilizing agents to obtain SNP. The synthesized SNP were characterized by spectroscopic techniques such as UV-Visible spectrophotometry and Fourier Transform Infrared spectroscopy (FTIR), Scanning Electron and Confocal microscopies and the antimicrobial activity was evaluated against to Xanthomonas phaseoli pv. phaseoli using the agar diffusion methods. The results showed that the evaluated extract was promising for the green synthesis of the SNP, which were visually identified by the formation of a dark brown complex and by the presence of a peak of maximum absorption at 470 nm in a UV-VIS spectrum. FTIR spectrum of SNP showed main characteristic signals of aromatic compounds, carboxylic group between others confirmed through phytochemical screening that evidenced the presence of flavonoids, phenols, leucoanthocyanidins, terpenes and steroids groups. Fluorescents SNP with high degree of agglomeration were visualized by microscopies technical used. A promissory antibacterial activity of SNP was demonstrated by a zone of inhibition of the microbial growing. These results suggest the need to go deeper in the physical-chemical characterization and kinetic studies and the biological evaluation to make possible the use of this vegetable source to future develop of antibacterial formulations to the bean seeds protection.
A neotype nomogram based on accessible clinical indicators to predict the overall survival of esophageal cancer patients underwent radical resection
Authors: Li Xinye , Xu Jinming , Zhu Linhai , Yang Sijia , Yu Li , Lv Wang , Hu Jian
Published: October 2020

Background: Esophageal cancer (EC) is a malignant tumor with dreadful mortality, nomogram is a prognosis tool of great significance in therapeutic guidance and assessment. We aimed to establish a newly-built nomogram for OS prediction of EC patients with radical esophagectomy.Methods: A total of 311 EC patients underwent radical esophagectomy were retrospectively investigated with their survival and demographic and clinicopathological data. Patients were randomly divided into the primary and validation cohorts. The establishment of nomogram was based on Cox hazard regression analysis in primary cohort, the calibration curves and Harrell’s concordance index were performed to verify the predictive accuracy while ROC curves was adopted to reflect the efficacy of nomogram. Kaplan–Meier curves showed the clinical significance of risk classification system and Pearson correlation test was utilized to show the correlation between risk classification system and TNM staging.Results: The median OS and 5-year survival rate are 44 months and 29.8% in primary cohort. In validation cohort, they are 52 months and 27.1%, respectively. In Cox hazard regression analysis, we extracted six independent prognostic factors—age, gender, AGR, PRL, N stage, PNI—to establish the nomogram. The C-index of nomogram is 0.75 in primary cohort and 0.70 in validation cohort. Calibration curves indicated high consistency between accurate and predicted OS in both primary and validation cohorts. ROC curves showed a better efficacy of nomogram compared with AJCC T and N stage. The area under curve (AUC) of primary cohort is 0.801 and 0.727 in validation cohort. Patients in primary cohort were divided into three risk groups according to the nomogram score, the median OS between each group was significantly different. Analogical results were obtained in validation cohort. Furthermore, the risk classification system was strongly correlated to AJCC TNM staging system in total cohort (r2=0.647, P<0.001), and it also demonstrated a better OS prediction efficacy (AUC=0.742).Conclusions: We established a neotype nomogram and a relevant risk classification system with verified accuracy and efficacy in OS prediction of EC patients after radical esophagectomy. They may provide feasible value in prognosis assessment and treatment guidance prospectively.
Analysis of Watershed Characteristics and Spatial Soil Loss Estimation: A case Fincha Watershed, Western Ethiopia
Authors: Debela Seifu Kebede , Fufa Fekadu
Published: October 2020

Characteristics of watershed were not well investigated as global also in Fincha, Ethiopia. Fincha watershed is the most erosion prone area in the highlands of Ethiopia towards to Fincha dam.Therefore, the aim of this study was toanalysisFincha watershed characteristics based on land use/cover, soil type and slope classification and to identify soil erosionpronearea using Arc-GIS and Arc-SWAT model.Accordingly, nine major land use/covers were identified. Those were:- bush land, dominantly cultivated, moderately cultivated, irrigated land, grass land, water bodies, swamp area, urban and woodland open. From these most part of the catchment was under cultivation with 67.677% of the total area. In the same way, the major soil types identified were: - chromic luvisols, chromic vertisols, dystric cambisols, eutric cambisols, eutric nitosols, eutric regosols, haplic phaeozems, humic cambisols and water. Cambisols were covered the highest percentage, 39.98% area of the catchment.Subsequently, average annual values of estimated soil lossfrom the catchment was231.2 ton/ha.The identified prone erosion areas were sub-basins 1, 8, 11, 14, 17 and 20. It was very critical for environmentalists, hydrologists, agricultural experts, watershed managements and concerned decision makers for sustainable water resource projects and environmental protection system. Therefore, further detail investigation and appropriate watershed management practices should be given for these subbasins.
Linaclotide for The Treatment of Refractory Lower Bowel Manifestations of Systemic Sclerosis
Authors: Dein Eric , Wigley Fredrick M. , McMahan Zsuzsanna H.
Published: October 2020

Objective: Lower gastrointestinal tract involvement can affect up to 50% of SSc patients, and may result in malabsorption, pseudo-obstruction, hospitalization, and death. We report our experience with linaclotide, a selective agonist of guanylate cyclase C, for SSc patients with refractory lower GI disease.Methods: We performed a analysis of patients seen at the Johns Hopkins Scleroderma Center and identified patients prescribed linaclotide for refractory lower GI manifestations. Patients had clinical data prospectively collected in our longitudinal database. Linaclotide responders were on medication for at least 12 months with documented effectiveness by the treating physician. Results: Thirty-one patients with SSc were treated with linaclotide. Twenty-three of these patients (74%) had severe GI disease on initiation of linaclotide (Medsger GI score ≥3), as defined by recurrent pseudo-obstruction, malabsorption, and/or need for artificial nutrition. The majority of patients (90.3%; 28/31) had a treatment response, while only three patients (9.7%) reported ineffectiveness or intolerable side effects. Low-dose linaclotide (≤ 145 mcg daily) was used in 18 patients and was effective in 94%. High-dose therapy (>145 mcg daily) was effective in 11 of 13 patients (85%). Common side effects were diarrhea, cramping, or bloating (11/31, 35%). Ineffectiveness, cost, and abdominal pain were complaints cited among those who discontinued therapy. Conclusion: Linaclotide is a well-tolerated and efficacious pro-secretory and pro-motility agent that can be used to manage refractory lower GI manifestations in SSc. We found that low-dose linaclotide is an effective option and may be better tolerated, though a subset of patients may require high dose regimens.
Living on the Edge of the Community: Factors Associated with Discontinuation of Community Living Among People with Cognitive Impairment
Authors: Ura Chiaki , Okamura Tsuyoshi , Sugiyama Mika , Miyamae Fumiko , Yamashita Mari , Nakayama Riko , Edahiro Ayako , Taga Tsutomu , Inagaki Hiroki , Ogawa Madoka , Awata Shuichi
Published: October 2020

BackgroundThe experiences of people with cognitive impairment in the real world have not been fully explored because of methodological difficulties. This study re-accessed people with cognitive impairment identified in a previous epidemiological survey to explore their current situation and the risk factors associated with all-cause discontinuation of community living.MethodsIn 2016, a three-step survey was conducted of 7,614 older residents. In the last step of the survey, a research team visited the homes of 198 participants with a Mini-Mental State Examination score <24. In 2019, we re-accessed these people. We ran a community space in the study area for 3 years to build partnerships with community residents and community workers, and were able to re-access the participants using multiple methods.ResultsWe found that 126 (63.6%) participants had continued living in the same community, but 58 (29.3%) had discontinued community living. Of these, 18 (9.1%) had died, 18 (9.1%) were institutionalized, 9 (4.5%) were hospitalized, and 13 (6.6%) had moved out of the community. A multiple logistic regression analysis identified the following risk factors associated with discontinuation of community living: being certified under long-term insurance, needing housing support, and needing rights protection.ConclusionsThree years after the baseline survey, 29.3% people with cognitive impairment had discontinued community living. Despite having dementia or living alone, older people could continue to live in the community if their needs for housing support and rights protection were met. Both social interventions and medical interventions are important to build age-friendly communities.Trial registration﻿UMIN, UMIN000038189,　Registered 3 October 2019, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000043521
Diagnostic Delays in Vasculitis and Factors Associated With Time to Diagnosis
Authors: Sr Antoine , Cronin Keri , Shaw Dianne , Young Kalen , Burroughs Cristina , Kullman Joyce , Machireddy Kirthi , McAlear Carol , Merkel Peter
Published: October 2020

Background: Patients with vasculitis, a set of rare diseases, encounter delays in obtaining an accurate diagnosis which can lead to substantial morbidity and increased mortality. This study sought to describe the diagnostic journey of patients with vasculitis and identify factors associated with time to diagnosis. Methods: Patients with vasculitis enrolled in an online registry completed a two-stage study: Stage 1: Survey of open-ended questions about patients’ diagnostic journeys and perceived factors associated with rapid or delayed diagnosis; Stage 2: Survey with specific questions based on data from Stage 1 and additional investigator-identified factors. Results: 375 patients with vasculitis participated in Stage 1; 456 patients participated in Stage 2. 85% of patients were seen by a healthcare provider within 3 months of the onset of symptoms. The median time to diagnosis of vasculitis was 7 months. 313/456 (73%) of patients were misdiagnosed initially. 40% of diagnoses were made in a hospital setting; 2% of diagnoses were made at a specialized vasculitis center. 60% of patients had at least 1 visit to an emergency room prior to diagnosis. Unemployment, time to travel to a medical center > 1 hour, initial misdiagnosis, and delays in seeing a specialist were all associated with longer times to diagnosis. 373/456 (82%) of patients reported that a delayed diagnosis had negative consequences on their health.Conclusion: Patients with vasculitis encounter substantial delays in achieving an accurate diagnosis and these delays are associated with negative health consequences. Both patient-related factors and healthcare-related factors are associated with diagnostic delays.
Juvenile Idiopathic Arthritis in South Australia
Authors: Min Ming , Edwards Suzanne , Gibson Catherine , Crotti Tania , Boros Christina
Published: October 2020

Background: Juvenile Idiopathic Arthritis (JIA) is a chronic rheumatic disease that shows variation in subtype distribution by geographic regions. The aim of this study was to create a JIA registry, which could describe the epidemiology and characteristics of JIA patients in South Australia (SA).Methods: Prospectively collected data from JIA patients at the Women’s and Children’s Hospital in Adelaide, between August 2019 and March 2020 were reported. All children and young people diagnosed with JIA according to the International League of Associations for Rheumatology (ILAR) classification criteria were eligible for inclusion. Data including demographics, complications/comorbidities, medications, disease activity as well as patient-reported data using Childhood Health Assessment Questionnaire (CHAQ) were documented. Non-identified data were extracted from this registry and utilised in descriptive analysis and comparative studies.Results: There are currently n=112 JIA patients in this registry, including n=11 incident cases (9.8%), with a predominance of female (n=75, 67.0%). The median disease duration was 3.6 years (interquartile range 1.3-7.6). The most common subtype was persistent oligoarthritis (n=35/112, 31.3%), followed by rheumatoid factor-negative polyarthritis (n=32/112, 28.6%), extended oligoarthritis (n=23/112, 20.5%), enthesitis-related arthritis (ERA; n=12/112, 10.7%), systemic onset arthritis (n=5/112, 4.5%), rheumatoid factor-positive polyarthritis (n=3/112, 2.7%) and psoriatic arthritis (n=2/112, 1.8%). Complications were documented in n=40/112 (35.7%) patients, with n=21/94 (22.3%) observed to have uveitis, and musculoskeletal complications observed in n=10/112 (8.9%). Methotrexate intolerance was present in n=10/79 (12.7%) patients. Forty-nine out of 112 (43.8%) patients had at least one comorbidity, with anxiety/depression (n=5/112, 4.5%) and asthma (n=5/112, 4.5%) being the most common. Around half of patients (n=52/112, 46.4%) had clinically inactive disease at enrolment and most (n=85/112, 75.9%) reported no to low functional disability. Non-steroidal anti-inflammatory drugs have been almost universally used (n=100/112, 89.3%), and n=26/112 (23.2%) have received treatment with biologics.Conclusions: In this JIA registry study, we found that the JIA cohort in SA is female-dominated with persistent oligoarthritis as the most common subtype, consistent with other studies. Most patients have good disease control and report no or mild disability. Further longitudinal work will add to the current description of our JIA cohort and assist improvement of clinical care.
Profiling Basal Forebrain Cholinergic Neurons Reveals a Molecular Basis for Vulnerability Within the Ts65Dn Model of Down Syndrome and Alzheimer’s Disease
Authors: Alldred Melissa J. , Penikalapati Sai C. , Lee Sang Han , Heguy Adriana , Roussos Panos , Ginsberg Stephen
Published: October 2020

Background: Basal forebrain cholinergic neuron (BFCN) degeneration is a hallmark of Down syndrome (DS) and Alzheimer’s disease (AD). Current therapeutics have been unsuccessful in slowing disease progression, likely due to complex pathological interactions and dysregulated pathways that are poorly understood. The Ts65Dn trisomic mouse model recapitulates both cognitive and morphological deficits of DS and AD, including BFCN degeneration. Methods: We utilized Ts65Dn mice to understand mechanisms underlying BFCN degeneration to identify novel targets for therapeutic intervention. We performed high-throughput, single population RNA sequencing (RNA-seq) to interrogate transcriptomic changes within medial septal nucleus (MSN) BFCNs, using laser capture microdissection to individually isolate ~500 choline acetyltransferase-immunopositive neurons in Ts65Dn and normal disomic (2N) mice at 6 months of age (MO). Results: Ts65Dn mice had unique MSN BFCNs transcriptomic profiles at ~6 MO clearly differentiating them from 2N mice. Leveraging Ingenuity Pathway Analysis and KEGG analysis, we linked differentially expressed gene (DEG) changes within MSN BFCNs to several canonical pathways and aberrant physiological functions. The dysregulated transcriptomic profile of trisomic BFCNs provides key information underscoring selective vulnerability within the septohippocampal circuit. Conclusions: We propose both expected and novel therapeutic targets for DS and AD, including specific DEGs within cholinergic, glutamate, GABAergic, and neurotrophin pathways, as well as select targets for repairing oxidative phosphorylation status in neurons. We demonstrate and validate an interrogative quantitative bioinformatic analysis of a key dysregulated neuronal population linking single population transcript changes to an established pathological hallmark associated with cognitive decline for therapeutic development in human DS and AD.
Call to Action – Closing the Gap to Make Patient Blood Management the New Norm(al) as Viewed by Implementors in Diverse Countries
Authors: Hofmann Axel , Spahn Donat R. , Holtorf Anke-Peggy
Published: October 2020

BackgroundMillions of hospitalized patients are anemic. However, anemia is an independent risk factor for adverse outcomes including morbidity and mortality. In combination with blood loss, anemia is the main driver for transfusion, thus adding risk for adverse outcomes. Patient Blood Management (PBM) is a concept to identify and correct anemia and to minimize blood loss. Evidence demonstrates that PBM significantly improves outcomes and safety while reducing cost by macroeconomic magnitudes. Despite its huge potential to improve healthcare systems, PBM is not yet adopted broadly. By gathering the experiences of a diverse group of PBM implementors across countries with different healthcare contexts, we aimed to identify the drivers, barriers, measures, and stakeholders regarding the implementation of PBM. The synthesis of this information should provide a matrix of complementary measures, allowing PBM stakeholders from diverse professional backgrounds to initiate and orchestrate PBM implementation.MethodsSemi-structured interviews were conducted with 1-4 PBM implementors from 12 countries in Asia, Latin America, Australia, Central and Eastern Europe, the Middle East, and Africa. Responses were summarized per country, and key observations extracted. By defining the levels of intervention for PBM implementation and applying the Donabedian Quality Framework, we created and populated a matrix of key measures and outcomes as identified from the interviews.ResultsWe were able to extract a set of structural and procedural PBM implementation measures from interviews with the implementors. We created a matrix addressing six levels of implementation including government, healthcare providers (HCP), funding, research, training/education and patients and identified structural and procedural measures on each level. ConclusionThis matrix helps to decompose the complexity of PBM implementation into concrete measures on each implementation level. It provides guidance for diverse stakeholders to independently initiate and develop strategies to make PBM a national standard of care, thus closing current practice gaps and matching this unmet public health need.
Definition of Acute Respiratory Distress Syndrome in Plateau of Xining,Qinghai: Verification of Berlin Definition Plateau Criteria
Authors: Liu Xiaoqin , Pan Chun , Si Li-Ning , Tong Shijun , Niu Yi , Qiu Haibo , Gan Guifen
Published: October 2020

Background Acute respiratory distress syndrome（ARDS） is a common respiratory critical illness. The high altitude hypoxic environment has a great influence on its occurrence and development. Now we lack clear diagnostic definition of high altitude acute respiratory distress syndrome.To verify the application value of Berlin Definition plateau criteria of Acute Respiratory Distress Syndrome in Xining , Qinghai ( 2261m).Methods Retrospective analysis of the clinical data of ARDS patients admitted to the Department of Critical Care Medicine of the Affiliated Hospital of Qinghai University from January 2018 to December 2018. The severity was divided according to the Berlin definition, the plateau standard, and the Zhang standard, and the differences of three standards were compared.Results In this study, 512 patients with mechanical ventilation were selected. 229 patients who met the criteria of Berlin Definition plateau criteria , including 107 patients with mild ARDS (46.72%), 84 moderate patients (36.68%) and 38 severe ARDS patients (16.59%). Among 253 meet Berlin definition patients , 49(19.77%) were mild,148(58.50%) were moderate,and 56 (22.13%) were severe ARDS. There are 204 patients that meet Zhang criteria, among the 204 enrolled patients, 87(42.65%) were ALI and 117(57.35%) were ARDS. The AUROC of the Berlin Definition, the Plateau criteria and Zhang criteria were 0.6675 (95% CI 0.5866-0.7484), 0.6216 (95%CI 0.5317-0.7116) and 0.6050 (95% CI 0.5084-0.7016).Conclusion For Xining, Qinghai, the Berlin Definition Plateau oxygenation index correction criteria can distinguish the severity of ARDS , but it needs to be enlarged and confirmed by multicenter clinical studies.
Use of Patient Reported Outcome Measures (PROMs) by Orthopedic Surgeons in Saudi Arabia
Authors: Alshehri Fayez , Alarabi Abdulaziz , Alharthi Mohammed , Alanazi Thamer , Alohali Ahmed , Alsaleem Mohammed
Published: October 2020

Background There is increasing literature on the usefulness of patient-reported outcome measures (PROMs), but far fewer studies to determine their use by orthopedic surgeons and the barriers they face in applying PROMs in their daily clinical activity.Methods Cross-sectional study using a questionnaire that was distributed in both soft and hard copy formats to a sample of 262 orthopedic surgeons. Participants included orthopedic surgeons who are employed by the Ministry of Health (MOH) in Riyadh and the Eastern Province, Saudi Arabia. The questionnaire was distributed through onsite visitations to orthopedic departments in MOH hospitals as well as through online correspondence by email, WhatsApp, and social media.Results The study sample included 262 orthopedic surgeons (13.7% females and 86.3% males). Surgeons aged < 34, 35 – 44, and 45 - 54 years old represented 28.66%, 38.9%, and 20.2% of the study sample, respectively. The majority of the included surgeons did not use PROMs (69.1%) and some (17.2%) used it for research purposes. Only 5% used it regularly in daily clinical work.Conclusion The clinical use of PROMs among orthopedic surgeons was negligible, even though an overwhelming majority were interested in using PROMs. The reasons provided included a lack of knowledge on how to use PROMs and the perception that it is too time-consuming to add to regular clinical routine. There should be more effort towards training surgeons on how to use PROMs, whereas increasing compatibility with existing software tools used by MOH hospitals may help offset time-related reservations.
Mid-term Subsidence and Periprosthetic Radiolucency of the AMIStem: A 5-year EBRA-FCA Analysis
Authors: Hasler Julian , Flury Andreas , Dimitriou Dimitris , Holweg Iris , Helmy Naeder , Finsterwald Michael
Published: October 2020

Background: There has been an evolution in cementless total hip arthroplasty (THA) with newer short stem designs aim to preserve metaphyseal bone stock and facilitate implantation through minimally invasive approaches. While early subsidence has been correlated to aseptic loosening in conventional stems, there is a paucity of data regarding short stems. The current study aims to report on stem subsidence and midterm clinical outcomes of a cementless, metaphyseal-anchored short femoral stem, specifically designed for the direct anterior approach (DAA).Methods: 94 consecutive patients (100 hips) with a minimum follow-up of 5 years following cementless THA were included in this single-center retrospective study. Subsidence was evaluated using the “Ein-Bild-Roentgen-Analyse” (EBRA). Periprosthetic radiolucency allocated to the Zones of Charnley and Gruen was assessed. Additionally, demographic and implant-related factors potentially associated with increased subsidence and clinical outcomes were evaluated.Results: At the last follow-up, the average stem subsidence was 1.98 ± 1.20 mm, with 48% of the implants demonstrating subsidence of > 2 mm. Periprosthetic radiolucency of > 2 mm was found in 26% of the implants in Zone 1, and in 9% in Zone 7, respectively. Neither the amount of subsidence nor proximal periprosthetic radiolucency was associated with aseptic loosening or worse clinical outcomes. Conclusions: Comparable to other proximally-fixed short stem designs, the highest subsidence was observed within the first 3 months following implantation. No demographic or implant-related factors were found to have a statistically significant influence on stem subsidence. Periprosthetic radiolucency and subsidence of the AMISstem is not correlated with worse clinical outcomes at 5-years follow-up.
A Prospective and Nutrition-Related Nomogram Model for Prognosis in Colorectal Cancer Survival: A Multicenter Cohort Study in China
Authors: Ruan Guo-Tian , Zhang Kang-Ping , Zhang Qi , Zhang Xi , Tang Meng , Song Meng-Meng , Zhang Xiao-Wei , Ge Yi-Zhong , Yang Ming , Song Chun-Hua , Cong Ming-Hua , Guo Zeng-Qing , Zhu Li-Chen , Braga Marco , Cederholm Tommy E , Xu Hong-Xia , Li Wei , Xiao Chun-Yun , shi hanping
Published: October 2020

BackgroundColorectal cancer (CRC) is a common malignancy with high incidence of malnutrition. Increasing evidence showed that nutritional status could be a prognostic indicator of cancer survival. However, there were few prognostic models involving nutrition-related indicators in CRC. This study aimed to develop a nutrition-related prognostic model for CRC survival.MethodsThis multicenter retrospectively primary cohort data included 1,373 CRC patients, and the external validation cohort enrolled other 108 CRC patients. LASSO and multivariate regression analyses were used to select prognostic indicators and develop the nomogram. We performed C-index, calibration curves, and DCA to assess the discrimination, calibration, and applicability. Finally, the indicators of the nomogram model were used as adjustment factors. Multivariate Cox survival analyses were performed to investigate the benefit of the Patient-Generated Subjective Global Assessment (PG-SGA) and Global Leadership Initiative on Malnutrition (GLIM) malnutrition criteria to CRC prognosis.ResultsFive prognostic indicators (TNM stage, radical resection, reduced food intake, activities and function decline, and low albumin) were chosen to develop the nomogram. C-index of the nomogram was 0.74 (95% CI 0.72-0.77) and 0.72 (95% CI 0.62-0.81) in the primary cohort and validation cohort, which were higher than other models. Calibration plots and DCA showed that the nomogram model has a good consistency and clinical benefit in predicting CRC survival. Multivariate Cox survival analysis suggested moderate (P<0.05, HR 1.32, 95% CI 1.002-1.75) and severe malnutrition (P<0.001, HR 1.69, 95% CI 1.27-2.25) were associated with worse overall survival (OS) in CRC using the PG-SGA criteria. However, there was no prognostic significance in GLIM criteria (all P>0.05). Finally, stratified analysis suggested that malnourished CRC patients with low albumin synergistically increased the death risk of CRC OS both in PG-SGA and GLIM. (P for interaction = 0.007 and 0.004, respectively)ConclusionThis study established a prospective model to predict the OS in CRC patients using nutrition-related indicators. Moreover, we also found that PG-SGA had a better prognostic and predictive efficiency in CRC than GLIM. These findings grant further verification.
Identification of Lipidomic Profiles Associated with Drug-Resistant Prostate Cancer Cells
Authors: Ingram Lishann M. , Mansoura Maryam , Chou Chau-wen , Cummings Brian S.
Published: October 2020

BackgroundThe association of circulating lipids with clinical outcomes of drug-resistant castration-resistant prostate cancer (CRPC) is not fully understood. While it is known that increases in select lipids correlates to decreased survival, neither the mechanisms mediating these alterations nor the correlation of resistance to drug treatments are well characterized.MethodsWe addressed this gap-in-knowledge using in vitro models of non-cancerous, hormone-sensitive, CRPC and drug-resistant cell lines combined with quantitative LC-ESI-Orbitrap-MS lipidomic analysis and subsequent analysis such as Metaboanalyst and Lipid Pathway Enrichment (LIPEA).ResultsThis approach identified several lipid regulatory pathways associated with Docetaxel resistance in PCa. These included those controlling glycerophospholipid metabolism, sphingolipid signaling pathways and ferroptosis. In total, 7,460 features were identified as being dysregulated between the cell lines studied, and 21 lipid species were significantly altered in drug-resistant cell lines as compared to nonresistant cell lines. Docetaxel resistance cells (PC3-Rx and DU145-DR) and had higher levels of phosphatidylcholine (PC), oxidized lipid species, phosphatidylethanolamine (PE), and sphingomyelin (SM) as compared to parent control cells (PC-3 and DU-145). These cells also had higher levels of ceramides release into the media.ConclusionThese data identify lipids whose levels may correlate to Docetaxel sensitivity and progression of prostate cancer.
Pulmonary Embolism: novel corona virus versus tuberculosis
Authors: Dhamecha Nidhi , Nagadiya Qury , Gupta Anurag , Patel Nehal , Thanvi Rashmi , Pandav Ghosha
Published: October 2020

This series describes six paediatric cases who presented as severe acute respiratory illness during the pandemic of covid-19 with high D-dimer levels. All six patients tested negative for novel corona virus. They were diagnosed as having tuberculosis on detailed investigations; High D-dimer levels are one of the most important indicators of the pulmonary embolism. Pulmonary embolism is a rare presentation of tuberculosis and this study emphasizes the need of keeping tuberculosis as an important differential diagnosis of those who present as acute respiratory distress syndrome.
Discovery of LAMP-2A as Potential Biomarkers for Glioblastoma Development by Modulating Apoptosis through N-CoR Degradation
Authors: Wang Yongjie , Zhang Buyi , Wang Jianli , Wu Haijian , Xu Shenbin , Zhang Jianmin , Wang Lin
Published: October 2020

Background: Lysosome-associated membrane protein type 2A (LAMP-2A) is the key component of chaperone-mediated autophagy (CMA), a cargo-selective lysosomal degradation pathway. Aberrant LAMP-2A expression and CMA activation have been demonstrated in various human malignancies. The study focusing on the intrinsic role of LAMP-2A and CMA in glioblastoma (GBM), and downstream mechanism could provide valuable insight into the pathogenesis and novel therapeutic modality of GBM. Methods: The levels of LAMP-2A, nuclear receptor co-repressor (N-CoR), unfolded protein reaction (UPR) and apoptosis were examined in clinical samples. LAMP-2A siRNA and shRNA were constructed to manipulate CMA activation. The role of CMA and downstream mechanism through degradation of N-CoR and arresting UPR mediated apoptosis were explored in GBM cells and nude mouse xenograft model. Results: Elevated LAMP-2A and associated decreased N-CoR expression were observed in GBM as compared with peritumoral region and low-grade glioma. Inhibited UPR and apoptosis were observed in GBM with high LAMP-2A expression. In vitro study demonstrated co-localization and interaction between LAMP-2A and N-CoR. LAMP-2A silencing up-regulated N-CoR and aroused UPR pathway, leading to apoptosis, while N-CoR silencing led to an opposite result. In vivo study further confirmed that LAMP-2A inhibition arrested tumor growth by promoting apoptosis.Conclusions: Our results demonstrated the central role of CMA in mediating N-CoR degradation and protecting GBM cells against UPR and apoptosis, and provided evidence of LAMP-2A as potential biomarker. Further research focusing on CMA with other tumorigenic process is needed and selective modulators of LAMP-2A remain to be investigated to provide a novel therapeutic strategy for GBM.
Applying Implementation and Team Science Principles to Facilitate Cancer Program Implementation in Remote, Under-resourced Areas
Authors: Crabtree-Ide Christina , Sevdalis Nick , Bellohusen Patricia , Constine Louis S. , Fleming Fergal , Holub David , Rizvi Irfan , Rodriguez Jennifer , Sharda Pradeep , Sharda Varsha , Shayne Michelle , Termer Nancy , Tomaszewski Ken , Noyes Katia
Published: October 2020

Background: Failed implementation of health programs is common and may contribute to health disparities in resource-poor communities. We aimed to (1) evaluate barriers and facilitators for implementation of cancer survivorship services in rural communities and to (2) identify optimal strategies for successful implementation of survivorship care programs in these settings. Methods: The study design was guided by the Consolidated Framework for Implementation Research (CFIR) and based on the core principles of effective teamwork. We collected qualitative and quantitative data to assess barriers and facilitators to implementation of rural cancer survivorship care (3 focus groups, size 8, 31, and 77). Data were collected using both in-person and web-based approaches (semi-structured interviews, stakeholder surveys, ThinkTank, project online portal, Google Analytics). Stakeholders included cancer survivors, their families and caregivers, local public services administrators, health providers, and allied health-care professionals from rural and remote communities in Upstate New York. Results: Patients reported preferences for cross-region team-based survivorship care and emphasized the importance of including local providers on regional care teams and networks. Synthesis of results was guided by teamwork principles. Most rural patient stakeholders trusted recommendations received from their local providers (n=6, 86%) and preferred receiving care locally (n=6, 86%). Involvement of rural patient navigators (average rank 1.5 out of 5) and county care managers (1.9) was ranked more favorably than reliance on telemedicine alone (3.3) or visiting practice facilitators (3.3). Rural counties that have existing formal and informal networks involved in cancer care scored higher on the metrics of teamwork and demonstrated more advanced readiness to change in regards to survivorship program implementation. Conclusions: Our analysis identified a unique combination of community socio-economic factors, geographic isolation, and limited provider supply common in rural care settings as barriers to optimal delivery of cancer survivorship care in rural settings. We propose teamwork training and facilitation as an innovative implementation strategy to overcome these barriers and minimize their effect on patient access to care. Merging implementation science and team science frameworks could further assist with program adaptation to minimize implementation failure and improve continuity of care for complex cancer pathway management.
Barriers and facilitators to implementing a mobile intervention with task shifting in the treatment of depressive symptoms in people with diabetes and / or hypertension in Brazil: A study protocol using the CFIR.
Authors: Castro Hellen Carolina Martins , Couto Marcia Thereza , Daley Kate , Rocha Thais Izabel Ugeda , Aschar Suzana Crismanis de Almeida Lopes , Santos Daniela Vera Cruz dos , Claro Heloisa Garcia , Araya Ricardo , Menezes Paulo Rossi
Published: October 2020

Background: Task-shifting and eHealth have been proposed as ways of approaching the mental health treatment gap in low and middle-income countries (LMIC). The Latin America Treatment & Innovation Network in Mental Health (LATIN-MH) developed CONEMO (Emotional Control), a behavioral intervention used to treat depressive symptoms in a sample of patients with diabetes and hypertension in Sao Paulo, Brazil. The intervention uses task shifting and is delivered via a smartphone app. The effectiveness of this intervention was tested in two randomized trials in these countries. Aim: This paper aims to present the protocol for a study that will explore perceived barriers and facilitators to implementing this intervention to help future scale-up. Methods: We will conduct qualitative research with users of the CONEMO intervention and health professionals who participated directly and indirectly in the trial in Brazil. We will use semi-structured interviews, and we will adopt the Consolidated Framework for Implementation Research (CFIR) for data analysis. Discussion: Task-shifting and eHealth are potentially important tools to help decrease the mental health treatment gap in Latin America. This study will increase our understanding of the factors which may facilitate or hinder the implementation of mobile behavioral mental health interventions, using task-shifting, within LMICs. Findings could be used in future design and planning to facilitate successful implementation and treatment. Registration in Clinical Trials (www.clinical.trials.gov) NCT028406662
Anakinra After Corticosteroid and/or Tocilizumab Treatment in Patients with Severe COVID-19 Pneumonia and Moderate Hyperinflammation. A Retrospective Cohort Study.
Authors: Aomar-MIllán Ismael Francisco , Salvatierra Juan , Torres-Parejo Ursula , Faro-Miguez Naya , Callejas-Rubio José Luis , Ceballos-Torres Angel , Cruces-Moreno María Teresa , Gómez-Jimenez Francisco Javier , Vinuesa-García David , Quero José Hernández , Anguita-Santos Francisco
Published: October 2020

Introduction: Little evidence appears to exists for the use of anakinra, a recombinant interleukin-1 receptor antagonist, after non-response to treatment with corticosteroids alone or combined with tocilizumab in patients with severe COVID-19 pneumonia and moderate hyperinflammatory state. Patients and Methods: A retrospective observational cohort study was carried out involving 143 patients with severe COVID-19 pneumonia and moderate hyperinflammation. They received standard therapy along with pulses of methylprednisolone (group 1) or methylprednisolone plus tocilizumab (group 2), with the possibility of receiving anakinra (group 3) according to protocol. The aim of this study was to assess the role of anakinra in the clinical course (death, admission to the intensive care ward) during the first 60 days after the first corticosteroid pulse. Clinical, laboratory, and imaging characteristics as well as infectious complications were also analyzed.Results: 74 patients (51.7%) in group 1, 59 (41.3%) patients in group 2, and 10 patients (7%) in group 3 were included. 8 patients (10.8%) in group 1 died, 6 (10.2%) in group 2, and 0 (0%) in group 3. After adjustment for age and clinical severity indices, treatment with anakinra was associated with a reduced risk of mortality (adjusted hazard ratio 0.518, 95% CI 0.265-0.910; p=0.0437). Patients in group 3 had a lower mean CD4 count after 3 days of treatment. No patients in this group presented infectious complications.Conclusions: In patients with moderate hyperinflammatory state associated with severe COVID-19 pneumonia, treatment with anakinra after non-response to corticosteroids or corticosteroids plus tocilizumab therapy may be an option for the management of these patients, and may improve their prognosis.
A questionnaire-based study to comprehensively assess the status quo of rare disease patients in China
Authors: Li Xuefeng , Liu Meiling , Li Bingzhe , Zhang Xiangyu , Zhang Shu , Lu Zijuan , Zhang Jianyong , Zhou Jincheng , Ou Li
Published: October 2020

Background: There are over 16.8 million rare disease patients in China, representing a large community that should not be neglected. To provide a basis for policy-makers, a comprehensive analysis of the status quo, unmet needs, difficulty caused by the rare disease is essential.Methods: Therefore, a questionnaire-based study of patients and care-givers was performed.Findings: A total of 1,959 patients and care-givers participated, representing 104 rare diseases, such as lysosomal diseases, hemophilia, and muscular dystrophy. The diagnosis was delayed for 1.4 ± 3.0 years, and patients experienced 1.6 ± 3.8 misdiagnoses between 3.2 ± 2.4 hospitals. The hospitals where diagnoses made were highly concentrated in 10 large hospitals (43.8%) and 5 big cities (42.1%), indicating a significant inequality of medical resources. The disease often led to difficulty in social life, education, and employment, as well as financial burden that was seldom covered by medical insurance. A battery of standardized tests, including SF-36, PHQ-9, PHQ-15, GAD-7, and PSQI, demonstrated poor health status, depression, somatization, anxiety, and sleeping issues among both patients and care-givers (p<0.05).To examine the influence of age, disease type, and relationship to patients on the scores in these tests, statistical analysis with a general linear model was conducted. It was also shown that poor health, anxiety, depression, somatization, and sleeping problems were more prevalent in patients than in care-givers, and more prevalent in more severe diseases (e.g., hemophilia, Dravet) or undiagnosed than in other diseases.Interpretations: This study identified the lack of rare disease awareness and legislative support as the major challenge to rare diseases in China, and makes key recommendations for policy-makers, including legislating orphan drug act, raising rare disease awareness, and protecting rights in education and employment.
Atg7 Mediates Metformin Protected Abdominal Aortic Aneurysm by Inducing Autophagy
Authors: Guo Jingjing , Wang Zhu , Xue Ming , Mi Lei , Zhao Mengpeng , Ma Chao , Wu Jian , Han Xinqiang
Published: October 2020

BackgroundAbdominal aortic aneurysm (AAA) is pathologic dilation of the abdominal aorta and is often asymptomatic but has high susceptibility to rupture. Our previous study showed that metformin protected the pathophysiology of AAA by reducing the activation of PI3K/AKT/mTOR pathway. MethodsAngiotensin II (Ang-II) was used to construct the AAA model in vascular smooth muscle cells (VSMCs). The expression of Atg7 and Atg4 was determined by qRT-PCR and Western blot. Atg7 expression was regulated by overexpressed plasmid or siRNA to examine the cell proliferation, cell migration, cell apoptosis and autophagy caused by Ang-II. ResultsAng-II induced the expression of Atg7 and metformin reversed this effect. Suppression of Atg7 inhibited cell proliferation and cell migration, reduced cell apoptosis and autophagy, while overexpression of Atg7 enhanced cell proliferation and cell migration, induced cell apoptosis and autophagy. Moreover, the expression of autophagy related protein was regulated by Atg7 in Ang-II treated VSMCs. We further showed that the Atg7 mediated-autophagy was attenuated by metformin. ConclusionMetformin-reduced autophagy in AAA was mediated by Atg7, suggesting that Atg7 was a potential downstream effector of metformin in protecting the pathophysiology of AAA.
Predictive Social Norms of Physicians’ Intention to Use Liver Cancer Screening: Based on an Extended Theory of Planned Behavior
Authors: Deng Qingwen , Liu Wenbin
Published: October 2020

Background: Globally, liver cancer is one of the most malignant tumors and has become a great concern to public health. The serious context of liver cancer prevention and control urges researchers to find more evidence about liver cancer screening and to expand its use. The purpose of this study was to determine the predictors associated with physicians’ intention to use liver cancer screening. Methods: We took contrast-enhanced ultrasound (CEUS) as an example, and developed the research framework by adding socials norms to the Theory of Planned Behavior (TPB). Data was collected via a cross-sectional questionnaire survey on a sample of 292 physicians randomly selected from Fujian and Jiangxi provinces in China with a high and low incidence of liver cancer, respectively. Due to the multicollinearity problem of the data, ridge regression was applied to determine the influencing factors of physicians’ intention to use CEUS. Results: Most of the participants (87.30%) reported that they were willing to use liver cancer screening in their clinical practice. The scores of TPB variables were generally higher than those of social norms variables. Regression results indicated that the proposed model was explanatory, which has accounted for 72.6% of the total variance in physicians’ intention. Analyses also illustrated the significant role of TPB variables (attitude and perceived behavioral control) and social norms variables (personal norms, organizational norms, and industrial norms) on the physicians’ intention to use CEUS. Conclusions: The study extended the Theory of Planned Behavior (TPB) by including the concepts of social norms, which is not only conducive to expanding the knowledge of factors associated with physicians’ intention to use liver cancer screening, but also provide implications for developing strategies to promote the use of certain health services or products, such as playing the roles of core members, holding the panel meeting, and establishing an information push system.
Lower Starting Dose of Afatinib for the Treatment of Metastatic Lung Adenocarcinoma Harboring Exon 21 and Exon 19 Mutations
Authors: Chen Yi-Chieh , Tsai Ming-Ju , Lee Mei-Hsuan , Kuo Chia-Yu , Shen Mei-Chiou , Tsai Ying-Ming , Chen Huang-Chi , Hung Jen-Yu , Huang Ming-Shyan , Chong Inn-Wen , Yang Chih-Jen
Published: October 2020

BackgroundAfatinib has shown favorable response rates (RRs) and longer progression free survival (PFS) in lung cancer patients harboring EGFR mutations compared with standard platinum-based chemotherapy. However, serious adverse drug reactions (ADRs) limit the clinical application of afatinib. MethodsWe designed a retrospective study, enrolled all patients with metastatic lung adenocarcinoma who were diagnosed and treated with 30 or 40 mg afatinib as their starting dose in three Kaohsiung Medical University-affiliated hospitals in TaiwanResultsA total of 179 patients were enrolled in the study, of which 102 (57%) and 77 (43%) received 30 mg and 40 mg afatinib daily as their initial treatment, respectively. The patients initially using 30 mg afatinib daily had a similar RR (74% vs. 82%, p = 0.1661), median PFS (14.5 months vs. 14.80 months, log-rank p = 0.465) and median OS (34 months vs 25.2 months, log-rank p = 0.5982) compared with those initially using 40 mg afatinib daily. Patients with the lower starting dose had fewer ADRs compared with patients receiving 40 mg as their starting dose. The overall incidence of moderate (49% vs 77%, p=0.002) or severe (7% vs 24%, p<0.0001) ADRs was significantly lower in patients receiving 30 mg afatinib compared with those receiving 40 mg. ConclusionPatients receiving 30 mg afatinib as their starting dose had non-inferior RRs, PFS, OS and significantly fewer serious ADRs compared with those patients who received standard 40 mg afatinib as their starting dose.