bluuebunny/crossref_metadata_2025 huggingface dataset:
Supercritical CO2-Assisted Atomization for Deposition of Cellulose Nanocrystals: An Experimental and Computational Study
Authors: Shariatnia Shadi , Jangale Prajesh , Mishra Rohit , Asadi Amir , Jarrahbashi Dorrin
Published: August 2021

Nanoparticle spray deposition finds numerous applications in pharmaceutical, electronics, manufacturing, and energy industries and has shown great promises in engineering the functional properties of the coated parts. However, current spray deposition systems either lack the required precision in controlling the morphology of the deposited nanostructures or do not have the capacity for large-scale deposition applications. In this study, we introduce a novel spray system that uses supercritical CO2 to assist the atomization process and create uniform micron-size water droplets that are used as cellulose nanocrystal (CNC) carriers. CNCs are selected in this study as they are abundant, possess superior mechanical properties, and contain hydroxyl groups that facilitate interaction with neighboring materials. We fundamentally investigate the effect of different process parameters, such as injection pressure, gas-to-liquid ratio, the axial distance between the nozzle and substrate, and CNC concentration on the final patterns left on the substrate upon evaporation of water droplets. To this end, we show how tuning process parameters control the size of carrier droplets, dynamics of evaporation, and self-assembly of CNCs, which in turn dictate the final architecture of the deposited nanostructures. We will particularly investigate the morphology of the nanostructures deposited after evaporation of micron-size droplets that has not been fully disclosed to date. Different characterization techniques such as laser diffraction, polarized microscopy, and high-resolution profilometry are employed to visualize and quantify the effect of each process parameter. Numerical simulations are employed to inform the design of experiments. Finally, it is shown that the fabricated nanostructures can be engineered based on the size of the carrier droplets controlled by adjusting spray parameters and the concentration of nanoparticles in the injected mixture. Process parameters can be selected such that nanoparticles form a ring, disk, or dome-shaped structure. Moderate operational conditions, simplicity and time efficiency of the process, and use of abundant and biodegradable materials, i.e., water, CNC, and CO2 promote the scalability and sustainability of this method.
Tunnel-redesigned O2-tolerant CO dehydrogenase for removal of CO in real flue gas
Authors: Kim Suk Min , Lee Jinhee , Kang Sung Heuck , Heo Yoonyoung , Hanh Ji Sook , Lee Hyung Ho , Kim Yong Hwan
Published: August 2021

Carbon monoxide dehydrogenase (CODH)-catalyzed oxidation of CO to CO2 provides a promising means of removal of toxic and waste CO from industrial flue gas despite of the lack of active and stable enzymes in the atmosphere. Herein we present rationally and selectively redesigned ChCODH-II (Carboxydothermus hydrogenoformans) variants by engineering gas tunnels in order for O2-tolerant CODHs to catalyze efficient CO oxidation under oxygen (O2). Using the redesigned ChCODH-II A559W and A559H variants showing 42- and 128-fold elevation of O2 tolerance, respectively, complete CO removal was achieved under a near-atmospheric condition. Moreover, these variants efficiently removed CO from industrial flue gas (Linz–Donawiz converter Gas: LDG) discharged from a steel mill despite the high O2 level (13.4%) during successful and repeated reuse after immobilized on Ni-NTA agarose beads. Our study will provide insights into redesigning the transformation of O2-sensitive CODHs into tolerant enzymes for use as workhorses for conversion of toxic or waste gases into safe or value-added chemicals.
A Cost-Effectiveness Analysis of Atezolizumab and Bevacizumab Verses Sorafenib in Patients With Advanced Hepatocellular Carcinoma
Authors: Li Meiyue , Lin Peili , Luo Shaohong , Huang Xiaoting , Huang Xiaojia , Nian Dongni , Lin Shen , Weng Xiuhua
Published: August 2021

Background: Several studies have evaluated the cost-effectiveness of treatment for advanced hepatocellular carcinoma (HCC), but the economics of atezolizumab plus bevacizumab (Ate plus Beva) remains unclear. Method: A three-state Markov model was established to simulate the life-time cost and effectiveness of advanced liver cancer, which included costs and health outcomes. Medical costs were sourced from Red Book, Healthcare Cost and Utilization Project (HCUP) and literatures. Also, the utility values of health state were deprived from references. The primary outcomes were measured by life-years (LYs), quality-adjusted life-years (QALYs), incremental cost-benefit ratio (ICER) and incremental net-health benefit (INHB). The robustness of the model was verified by one-way and probabilistic sensitivity analysis.Results: Ate plus Beva generated a gain of 0.84 QALYs (1.17 LYs ), an additional incremental cost of $242,447.40 per patient as compared with sorafenib, which resulted in the ICER of $288,663.09/QALY ($206,906.76/LY) at the willingness-to-pay (WTP) threshold of $150,000/QALY, and the INHB was -0.78/QALY. The sensitivity analysis demonstrated that the ICER was most affected by the price of atezolizumab.Conclusion: From the U.S. health care payer perspective, compare with sorafenib, Ate plus Beva regimen seems unlikely to be cost-effective in advanced HCC patients at a WTP threshold of 150,000 /QALY. If the price of atezolizumab was reduced by 75%, the probability of atezolizumab being cost-effective was over 50% at the WTP threshold.
Evaluation of an Educational Strategy to Improve Medication Reconciliation in Ambulatory Care
Authors: Jones Laney K , Duboski Vanessa , Romagnoli Katrina M. , Flango Alison , Marks Jami , Graham Jove , Gionfriddo Michael R.
Published: August 2021

Introduction. Improper medication reconciliation can result in inaccurate medication lists which can lead to adverse events including hospitalizations. Interventions targeting medication reconciliation have had varying levels of success. To improve medication reconciliation practices in our ambulatory care clinics, we developed an educational program for clinic personnel. The objective of this study is to describe the educational program, its implementation in a healthcare system, pharmacist and clinic personnel perception of the program, and its impact on clinic personnel knowledge and practice. Methods. Guided by the Conceptual Model of Implementation Research, we conducted an evaluation of a pharmacist-led educational program on evidence-based practices for medication reconciliation by examining implementation outcomes. The implementation outcomes measured include penetration, fidelity, acceptability, appropriateness, feasibility, and adoption. Data was collected through direct observations, administrative data, pre- and post-surveys, and semi-structured interviews. Results. A total of 37/46 (80%) primary care sites implemented the pharmacist delivered medication reconciliation education from April to June 2021 with representation from each of Geisinger’s regions. Ten (27%) clinic sites completed the medication reconciliation educational program as originally designed, with the remainder adapting the program. A total of 296 clinic personnel completed the pre-survey, while 178 completed the post-survey. There were no statistically significant differences in baseline characteristics between clinic personnel who completed the pre- vs. post-survey. Interviews were completed with 11 clinic personnel who attended the educational program and 4 pharmacists who delivered the educational program. All clinic personnel interviewed felt satisfied with the educational program and felt it was appropriate since it directly impacted their job. While clinic personnel felt the educational program was acceptable and appropriate, two major concerns were discussed: lack of patient knowledge about their medications and lack of time to complete the medication reconciliation. We found the adherence rate to the elements of the medication reconciliation which were covered in the education program ranged from 0% to 95% in the 55 observations conducted.Conclusion. An educational program for medication reconciliation was found to be acceptable and appropriate but was often adapted to fit site specific needs. Additional barriers affected adoption of best practices and should be addressed in future studies. Trial registration. N/A
Relationship Between Fluid Therapy Strategies and Mortality Among Sepsis Patients in ICU with high CVP: A Retrospective Analysis of the eICU Database
Authors: Yang Penglei , Tan Rui , Zheng Ruiqiang , Shao Jun , Yuan Jing , Liu Xiaoyun , Chen Hanbing , Wang Jing , Li Xianghui , Yu Jiangquan
Published: August 2021

Objective: It is still debated whether sepsis patients with high CVP (central venous pressure) benefit from it. We performed a retrospective study of sepsis patients with CVP ≥ 12 mmHg to analyze mortality resulting from the different amounts of fluid administered in the fluid therapy at the first 6, 24, and 48 h of the course.Methods: This study included sepsis patients from the eICU database who met the sepsis-3 diagnostic criteria and showed CVP ≥ 12 mmHg on admission. We analyzed the differences between the survivors and the non-survivors at baseline and the difference in fluid balance at 6, 24, and 48 h. Restricted cubic spline (RCS) and logistic regression model were used to identify the association between fluid balance and mortality.Results: Out of the 1150 sepsis patients that showed a high CVP obtained from the eICU database, 847 were survivors and 303 were non-survivors. Compared to survivors, non-survivors had a larger positive fluid balance at 6, 24, and 48 h. The fluid balance and mortality in sepsis patients with high CVP showed an inverted U-type relationship. At 6 h, lower mortality was found in patients who required less than -5 ml/kg fluid therapy. At 24 h, mortality was the lowest at -40~-20 ml/kg. At 48 h, low mortality was observed in patients with < -40 ml/kg fluid balance. In septic shock patients with high CVP, positive balance decrease mortality. In sepsis patients with high CVP without a history of chronic heart failure, and with a history of heart failure negative fluid balance can decrease mortality.Conclusion: In the sepsis group without shock, achieving negative fluid balance possible may significantly improve the prognosis of patients with high CVP, and patients with no history of chronic heart failure and patients with history of chronic heart failure should limit fluid infusion. In patients with septic shock whose CVP ≥ 12 mmHg, positive fluid balance may decrease mortality.
Integrated Bioinformatical Analysis Identified HTRA4 As An Immune-Related Prognostic Biomarker In The Gastric Cancer Microenvironment
Authors: Ji Ce , Dai Jingwei , Wang Zhen , Hu Xiangchen , Kou Youwei
Published: August 2021

HtrA serine peptidase 4 (HTRA4), which belongs to the AB family of proteases/chapterones, participates in multiple signal pathways and plays an important regulatory role in some malignancies; however, its role in the prognosis and immune infiltrates of gastric cancer (GC) remains unclear. HTRA4 expression was thus investigated in tumor tissues, and its association with immune infiltrates was assessed, to determine its prognostic roles in GC patients. Data for patients with GC was collected from three GEO datasets. This study has investigated if high expression levels of HTRA4 are associated with a poor prognosis in GC patients, especially in T2,T3,N1,NI&N2&N3,M1,stage3 and HER2+ subgroups. HTRA4 was positively correlated with CD8+ T cells, CD4+ memory activated T cells, gamma delta T cells, and M2 macrophages in the GC microenvironment. Gene Ontology and Gene set Enrichment Analysis showed that HTRA4 was enriched in some immune-related pathways. High expression levels of HTRA4 were significantly correlated with tumors in the T stage, N stage, and clinical stage, as well as those of histological grade. In summary, HTRA4 was found to play a vital role in the progression of GC and may be a predictive biomarker for the survival of GC patients.
Anti-PD-1 Immunotherapy Combined With Antiangiogenic Therapy as Salvage Therapy in a Patient With Refractory Metastatic Peripheral Primitive Neuroectodermal Tumor: A Case Report and Literature Review
Authors: Chen Qiaoyun , Jin Ronghui , Li Xu , Wu Qifan , An Gaili
Published: August 2021

Background: Peripheral primitive neuroectodermal tumor (pPNET) is a relatively rare malignant neoplasm that usually occurs in children and young adults,associated with poor prognosis. However, standard treatment for refractory pPNET has not been determined.Case presentation: A case of a 38-year-old woman with pPNET on the right shoulder and back,she had gained up to seven-and-a-half years suvival undergoing these comprehensive treatment including surgery, radiotherapy, chemotherapy, antiangiogenic treatment. However, the tumor eventually progressed after receiving multiline treatment.With the patient's strong desire to receive immunotherapy, we finally adjusted the treatment plan to " anti-angiogenic tyrosine kinase inhibitor Lenvatinib combined with PD-1 inhibitor Toripalimab" for 2 cycles.Unfortunately,she developed grade 2-3 immune pneumonia after treatment.Conclusions: To our knowledge, this is the first report of immunotherapy combined with antiangiogenic therapy in pPNET,which provides new ideas for the treatment of refractory pPNET.
Health System Cost of Post-Abortion Care (PAC): A Systematic Review
Authors: Sihaloho Estro Dariatno , Habibie Ibnu , Kamilah Fariza Zahra , Christiani Yodi
Published: August 2021

Background: Despite the increasing trend of Post Abortion Care (PAC) needs and provision, the evidence related to its health system cost is lacking. The study aims to review the health system costs of Post-Abortion Care (PAC) per patient at a national level.Methods: A systematic review of literatures related to PAC cost published in 1994 – October 2020 was performed. Electronic databases such as PubMed, Medline, The Cochrane Library, CINAHL, and PsycINFO were used to search the literature. Following the title and abstract screening, reporting quality was appraised using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. PAC costs were extrapolated into, US dollars ($US) and international dollars ($I), both in 2019. Content analysis was also conducted to synthesize the qualitative findings.Results: Twelve studies met the inclusion criteria. All studies reported direct medical cost per patient in accessing PAC, but only three of them included indirect medical cost. All studies reported either average or range of cost. In terms of range, The highest direct cost of PAC with MVA (Medical Vacuum Aspiration) services can be found in Colombia, between $US50.58-212.47, while the lowest is in Malawi ($US15.2-139.19). The highest direct cost of PAC with D&C (Dilatation and Curettage), services was in El Salvador ($US65.22-240.75), while the lowest is in Bangladesh ($US15.71-103.85). Among two studies providing average indirect cost data, Uganda with $US105.04 is the highest average indirect medical cost, while Rwanda with $US51.44 is the lowest on the cost of indirect medical.Conclusions: Our review shows variability in cost of PAC across countries. This study depicts a clearer picture of how costly it is for women to access PAC service, although it is still seemingly underestimated. When a study compared the use of UE method between MVA and D&C, it is confirmed that MVA treatments tend to have lower costs and potentially reduce a significant cost. Therefore, by looking at both clinical and economic perspective, improving and strengthening the quality and accessibility of PAC with MVA is a priority.
Dual Band Thin Film Infrared Detector Design and Performance Improvement using Plasmonic Nanostructure
Authors: Bashirpour Mohammad , Khankalantary Saeed , Kolahdouz Mohammadreza
Published: August 2021

A new dual band thin film metal-semiconductor-metal infrared photodetector base on InGaAs for wavelength of 1.1–1.7 µm and InSb for wavelength of 3–5 µm is proposed and investigated numerically. One major problem of thin film photodetectors is low quantum efficiency that originates from low optical absorption. The quantum efficiency of proposed structure is improved by locating the array of optimized aluminum nanostructure (Al-NS) between the InGaAs and InSb layers. Using optimized Al-NS between the stack of InGaAs and InSb (InSb/Al-NS/InGaAs) results in plasmon excitation inside the photosensitive layers and so, higher photocarrier generation. Moreover, locating zinc oxide nanorode as an antireflection coating on top of detector reduces the incident light reflection in both spectrum of 1.1–1.7 µm and 3–5 µm. The finite different time domain method is used to investigated the optical properties of proposed structure and optimize the structure. According to the simulation results, designed structure gives rise to 108.1%, 110% and 320% light absorption enhancement at wavelength of 1.33 µm, 1.55 µm and 4 µm, respectively compared to reference conventional structure.
Inflammation drives synucleinopathy propagation
Authors: Kim Tae-Kyung , Bae Eun-Jin , Jung Byung Chul , Choi Minsun , Shin Soo-Jean , Kim Jeong Tae , Jung Min-kyo , Ulusoy Ayse , Song Mi-Young , Lee Jun Sung , Lee He-Jin , Monte Donato Di , Lee Seung-Jae
Published: August 2021

The clinical progression of neurodegenerative diseases correlates with the spread of proteinopathy in the brain. Understanding of the mechanism of the proteinopathy spread is far from complete. Here, we propose that inflammation is fundamental to proteinopathy spread. A sequence variant of α-synuclein (V40G) was much less capable of fibril formation than wild-type α-synuclein (WT-syn) and, when mixed with WT-syn, interfered with its fibrillation. Yet when V40G was injected intracerebrally into mice, it induced aggregate spreading even more effectively than WT-syn. The aggregate spreading was preceded by sustained microgliosis and inflammatory responses, which were more robust with V40G than with WT-syn. Oral administration of an anti-inflammatory agent suppressed aggregate spreading, inflammation, and behavioral deficits in mice. Furthermore, exposure of cells to inflammatory cytokines increased the cell-to-cell propagation of α-synuclein. These results suggest that the inflammatory microenvironment is the major driver of the spread of synucleinopathy in the brain.
Synthesis and Biological Activity of a New Pt(II) Complex Involving 4-bromo-2,6-bis-hydroxymethyl-phenol and Nicotinamide
Authors: Altun Özlen , Yoruç Zeliha , Boz Mesut
Published: August 2021

In the presented study, Pt(II) complex including 4-Bromo-2,6-bis-hydroxymethyl-phenol (BBHMP) and nicotinamide (NA) was synthesized and structurally analyzed by using spectral and thermal analysis methods. The BBHMP and its Pt(II) complex involving BBHMP and NA were investigated for their antimicrobial, cytotoxicity, gen expression and antioxidant properties. The antimicrobial activity results showed that the platinum complex displayed moderate antibacterial and antifungal activities. The cytotoxicity of the BBHMP and platinum complex were determined against human prostate (DU145) and breast (MCF7) cancer cell lines by applying MTT assay. Cytotoxicity results suggest that the Pt(II) complex exhibited moderate cytotoxicity against growth of used cancer cell lines when compared with the reference drug cisplatin. Gen expression results proved that Pt(II) complex is a special bioactive chemical constituent and potential anticancer agent. In addition, the complex demonstrated important antioxidant activity.
Leadership Skills And Quality Health Care For Older Australians
Authors: Dawes Nathan G , Topp Stephanie M
Published: August 2021

BackgroundWith increasing recognition of the quality and safety issues in residential aged care (RAC), there is an urgent need to better understand the role of leadership teams who are often responsible for addressing these concerns. This qualitative study sought to explore the leadership skills that positively influence quality of care within Australian residential aged care facilities (RACFs); and better understand the professional development needs of senior managers to positively influence care within these complex environments. MethodsWe conducted 19 semi-structured interviews with senior managers in 14 RACFs in northern Queensland, Australia. GEN Aged Care Data was reviewed to assist the recruitment of” high performing”, non-government RACFs across different geographical areas of remoteness. Thematic analysis was used, including inductive identification of the leadership skills and strategies employed to promote quality of care. ResultsThe leadership skills reported by senior managers were structured under five domains including: i) communication and relationship management, ii) stewardship, iii) professional development, iv) health care knowledge and v) information technology and finance. A majority of participants highlighted communication and relationship management skills as being influential to RAC quality performance. We found that while most participants recognised the link between leadership skills and quality of care, only managers with a formal health qualification, highlighted the role of health care knowledge as a critical component of their leadership competency.ConclusionsThe skills and strategies employed by leadership and management teams are critical to quality outcomes for organisations and, ultimately, care recipients. With ongoing pressures facing RACFs , more work is needed to identify sector specific professional development (PD) strategies that better prepare RAC senior managers to lead quality health care services within an increasingly complex environment.
The role of lattice dynamics in ferroelectric switching
Authors: Shi Qiwu , Parsonnet Eric , Chen Xiaoxing , Peng Ren-Ci , Fernandez Abel , Fedorova Natalya , Qualls Alexander , Huang Xiaoxi , Chang Xue , Zhang Hongrui , Pesquera David , Das Sujit , Nikonov Dmitri , Young Ian , Chen Long-Qing , Martin Lane , Huang Yen-Lin , Íñiguez Jorge , Ramesh Ramamoorthy
Published: August 2021

Reducing the switching energy of ferroelectric thin films remains an important goal in the pursuit of ultralow power ferroelectric memories and magnetoelectric spin-orbit logic devices. Here, we elucidate the fundamental role of lattice dynamics in ferroelectric switching by combining thermodynamic calculations, experiments, and phase-field simulations on both freestanding BiFeO3 membranes and films clamped to a substrate. We observe a distinct evolution of the ferroelectric domain pattern, from striped, 71° ferroelastic domains (spacing of ~100 nm) in clamped BiFeO3 films, to large (10’s of micrometers) 180° domains or even single domain structures, in freestanding films. Through the use of piezoresponse force microscopy, X-ray diffraction, polarization-electric field hysteresis loops, and high-speed pulsed ferroelectric switching experiments, it is found that removing the constraints imposed by the requirement of macroscopic continuity of deformation (also known as the von Mises criterion in the deformation of solids)[1]–[3] to the substrate, we can realize a ~40% reduction of the switching voltage and a consequent ~60% gain in the switching speed. The work highlights the critical role of mechanics and the clamping effect from the substrate in setting the energetics and dynamics of switching in ferroelectrics.
The Impact of Myosteatosis Percentage on Short-Term Mortality in Patients with Septic Shock
Authors: Kim June-sung , Ha Jiyeon , Kim Youn-Jung , Ko Youn-sun , Park Taeyong , Kim Kyung Won , Kim Won Young
Published: August 2021

Background: The impact of myosteatosis on septic patients has not been fully revealed. This study aimed to evaluate the impact of myosteatosis area and percentage on the 28-day mortality in patients with septic shock.Methods: We conducted a single-center, retrospective study with prospectively collected data from a registry of adult patients with septic shock who presented to the emergency department and performed abdominal computed tomography (CT) from May 2016 to May 2020. Myosteatosis area defined as the sum of the low-attenuation muscle area and intramuscular adipose tissue at the level of the third lumbar vertebra was measured by CT. Myosteatosis percentages were calculated by dividing the myosteatosis area by the total abdominal muscle area. Odds ratios (ORs) and 95% confidence intervals (CIs) for 28-day mortality were estimated using a multivariate logistic regression model.Results: Of the 896 patients, the 28-day mortality was 16.3% and the abnormal myosteatosis areas were commonly detected (81.7%). Among variables of body compositions, non-survivors had relatively lower normal-attenuation muscle area, higher low-attenuation muscle area, higher myosteatosis area, and higher myosteatosis percentage than survivors. Trends in myosteatosis according to age groups were different between the male and female groups. In subgroup analysis with male patients, the multivariate model showed that the myosteatosis percentage (adjusted OR 1.02 [95% CI 1.01–1.03]) was an independent risk factor for 28-day mortality. However, this association was not evident in the female group.Conclusions: Myosteatosis was common and a high myosteatosis percentage was associated with short-term mortality in patients with septic shock. Our results implied that abnormal fatty disposition in the muscle could lead to increased mortality, especially in male patients.
Assessment of Casual Relations, Direct and Indirect Effects of Latent Covariates On CD4 Cell Count Change Among HIV Positive Adults
Authors: Tegegne Awoke Seyoum
Published: August 2021

Background: The use of structural equation modelling and latent variables remains unusual in epidemiology despite its potential usefulness and assessment of casual relations. Measuring direct and indirect effect of latent variables helps for proper intervention and for the ART program to be effective. The main objective of current investigation was to assess casual relations, direct and indirect effect of latent covariates on CD4 cell count change for HIV positive adults under HAART. Methods: Based on the repeated measures of CD4 cell count change data obtained in ART section at Felege Hiwot Teaching and Specialized hospital, AMOS software was employed parameter estimation. The data was conducted on 792 randomly selected HIV positive adults. The data was collected by the health staff for sake of delivering medication adherence. Results: CD4 cell count change was directly and indirectly affected by the latent variables. The powers of effects of observed variables with and without latent variables were a little bit different from each other. Hence, the power effect of observed variables with latent variables was lower as compared to without latent variables. The direct effect of latent variables on the response variable was a little bit greater than indirect effect. Conclusion: The power of effects of observed variables were stronger than their effects with latent variables. Hence, the latent variables had significant contributions for progress of CD4 cell count change. Health related education about the direct and indirect effect of latent variables should be given for patients under HAART.
Harnessing protein folding neural networks for peptide-protein docking
Authors: Tsaban Tomer , Varga Julia , Avraham Orly , Ben-Aharon Ziv , Khramushin Alisa , Schueler-Furman Ora
Published: August 2021

Highly accurate protein structure predictions by the recently published deep neural networks such as AlphaFold2 and RoseTTAFold are truly impressive achievements, and will have a tremendous impact far beyond structural biology. If peptide-protein binding can be seen as a final complementing step in the folding of a protein monomer, we reasoned that these approaches might be applicable to the modeling of such interactions. We present a simple implementation of AlphaFold2 to model the structure of peptide-protein interactions, enabled by linking the peptide sequence to the protein c-terminus via a poly glycine linker. We show on a large non-redundant set of 162 peptide-protein complexes that peptide-protein interactions can indeed be modeled accurately. Importantly, prediction is fast and works without multiple sequence alignment information for the peptide partner. We compare performance on a smaller, representative set to the state-of-the-art peptide docking protocol PIPER-FlexPepDock, and describe in detail specific examples that highlight advantages of the two approaches, pointing to possible further improvements and insights in the modeling of peptide-protein interactions.
Peptide-mediated interactions play important regulatory roles in functional cells. Thus the present advance holds much promise for significant impact, by bringing into reach a wide range of peptide-protein complexes, and providing important starting points for detailed study and manipulation of many specific interactions.
COVID-19: An Opportunity of Systematic Integration for Chagas Disease. Example of A Community-Based Approach within the Bolivian Population in Barcelona
Authors: Prat Jordi Gómez i , Essadek Hakima Ouaarab , Esperalba Juliana , Serrat Francesc Zarzuela , Guiu Isabel Claveria , Goterris Lidia , Zules-Oña Ricardo , Choque Estefa , Pastoret Conxita , Ponce Natàlia Casamitjana , Santos Juan José , Pons Jordi Serrano , Dehousse Aurore , Albajar-Viñas Pedro , Pumarola Tomàs , Campins Magda , Sulleiro Elena
Published: August 2021

As a Neglected Tropical Disease associated to Latin America, Chagas Disease (CD) is little known in non-endemic territories of the Americas, Europe and Western Pacific, making its control challenging, with limited detection rates, healthcare access and consequent epidemiological silence. This is reinforced by its biomedical characteristics - it is usually asymptomatic - and the fact that it mostly affects people with low social and financial resources. Because CD is mainly a chronic infection, which principally causes a cardiomyopathy and can also cause a prothrombotic status, it increases the risk of contracting severe COVID-19.In order to get an accurate picture of CD and COVID-19 overlapping and co-infection, this operational research draws on community-based experience and participative-action-research components. It was conducted during the Bolivian elections in Barcelona on a representative sample of that community. The results show that 55% of the people interviewed had already undergone a previous T. cruzi infection screening - among which 81% were diagnosed in Catalonia and 19% in Bolivia. The prevalence of T. cruzi infection was 18.3% (with 3.3% of discordant results), the SARS-CoV-2 22.3% and the coinfection rate, 6%. The benefits of an integrated approach for COVID-19 and CD were shown, since it only took an average of 25% of additional time per patient and undoubtedly empowered the patients about the co-infection, its detection and care. Finally, the rapid diagnostic test used for COVID-19 showed a sensitivity of 89.5%. This research addresses CD and its co-infection, through an innovative way, an opportunity of systematic integration, during the COVID-19 pandemic.
Association Between Polycyclic Aromatic Hydrocarbons and Urinary Incontinence in U.S. Adult: NHANES 2007-2016
Authors: Zhang Zilong , Jin Kun , Qiu Shi , Huang Xinyi , Hu Dan , Jiang Zhongyuan , Wang Mingda , Yang Lu , Lin Tianhai , Zhou Xianghong , Jin Di , Zhan Yu , Wei Qiang
Published: August 2021

Background: It have been reported that polycyclic aromatic hydrocarbons (PAHs) were associated with a variety of diseases, but it is still unclear that whether PAHs are associated with urinary incontinence (UI). This study aims to assess the association between PAHs and UI.Methods: Data were collected from the National Health and Nutrition Examination Survey (NHANES) from 2007 to 2016. 10 PAHs were detected totally. UI was diagnosed and distinguished into stress UI (SUI), urgency UI (UUI), and mixed UI (MUI) by answers of self-reported questions. Multivariate logistic regression analyses categorizing PAHs as quartiles were performed to detect the correlation between urinary PAHs and all three UI subtypes. Models were adjusted for common epidemiological factors including demographic and living habits factors.Results: A total of 12,393 participants of NHANES with available urine PAHs and UI data were eligible. No significant differences were observed between characteristics of participants with and without UI. Increasing prevalence of UUI was associated with the highest quantiles of 1-hydroxynapthalene (OR=1.208, 95%CI=1.026-1.422, p for trend=0.036), 1-hydroxyphenanthrene (OR=1.203, 95%CI=1.017-1.423, p for trend=0.004), and 1-hydroxypyrene (OR=1.251, 95%CI=1.062-1.475, p for trend=0.013) compared with the lowest quantiles. Increasing rate of SUI was observed in participants with higher exposure of all 9 PAHs (p for trend<0.025) except 3-hydroxyfluorene (OR=1.115, 95%CI=0.929-1.338, p for trend=0.241). Compared with the lowest quantiles, association between MUI and the highest quantiles of 1-hydroxyphenanthrene (OR=1.554, 95%CI=1.244-1.942, p for trend<0.001) and 1-hydroxypyrene (OR=1.307, 95%CI=1.047-1.630, p for trend=0.018) was observed.Conclusion: Our study suggested a positive relationship between U-PAHs and the prevalence of all three types of UI. Almost all PAHs are positively correlated with SUI.
Multiple Tumorous Lesions of The Pituitary Gland
Authors: von Schöning Jannik , Flitsch Jörg , Lüdecke Dieter K , Fahlbusch Rundolph , Buchfelder Michael , Buslei Rof , Knappe Ulrich Johannes , Bergmann Markus , Schulz-Schaeffer W. , Herms Jochen , Glatzel Markus , Saeger Wolfgang
Published: August 2021

Multiple tumorous lesions with an adenoma make up 1.4 % (232 cases) in the large collection of the German Registry of Pituitary Tumors. 2.0% of all PitNETs are associated with a second lesion. Within the selected cases synchronous multiple pituitary neuroendocrine tumors (PitNETs) account for 17,3%, PANCH cases for 14.7%, PitNETs and posterior lobe tumors for 2.2%, PitNETs and metastases for 5.2%, PitNETs and mesenchymal tumors for 2.6%, PitNETs and cysts for 52.2% and PitNETs and primary inflammation for 6.0%. The mean patient age was 53.8 years with a standard deviation of 18.5 years. 55.3% of the patients were female and 44.7% were male. From 1990 to 2018 there was a continuous increase in the number of multiple tumorous lesions.
Sources of Inefficiency in Small-Scale Irrigation in Ethiopia: A Stochastic Frontier Analysis
Authors: Sisha Teshager , Dillie Surafel
Published: August 2021

Increased production, food security, poverty reduction, and rural economic development can be supported by increasing efficiency in the use of scarce resources and technologies. Promoting small-scale irrigation practices may provide opportunities to improve the efficient utilization of land and labor. This paper assesses the extent of technical efficiencies of two household irrigation technologies: rope & washer and pulley practiced by farmers in two pilot areas of rural communities in Ethiopia. Stochastic frontier analysis (SFA) was used to estimate efficiency levels and identify the factors affecting inefficiencies. Labor and land are found to have contributed a greater share in the quantity of production of the crops under study. Plough repetition and experience in irrigation also contributed significantly to increased output. The results obtained from the stochastic frontier analysis indicate that farmers are operating at a significantly lower mean efficiency level of 70%, indicating the existence of room for increased production without additional investment. Distance to the nearest market, female household head, higher dependency ratio and using rope & washer (compared to pulley) increases the likelihood of being inefficient, whereas higher educational attainment of the head of the household and irrigation experience reduces the probability of inefficiency.
Higher rate of covid-19 mortality in patients with type 1 than type 2 diabetes: a nationwide study
Authors: Demirci Ibrahim , Haymana Cem , Tasci Ilker , Satman Ilhan , Atmaca Aysegul , Sahin Mustafa , Ata Naim , Unluturk Ugur , Cakal Erman , Dagdelen Selcuk , Sahin Ibrahim , Celik Osman , Ertugrul Derun , Demir Tevfik , Emral Rifat , Caglayan Murat , Salman Serpil , Birinci Suayip , Sonmez Alper
Published: August 2021

PurposeCOVID-19 disease has a worse prognosis in patients with diabetes, but the comparative data about the course of COVID-19 in patients with type 1 (T1DM) and type 2 diabetes (T2DM) are lacking. The purpose of this study was to find out the relative clinical severity and mortality of COVID-19 patients with T1DM and T2DM.MethodsA nationwide retrospective cohort of patients with conﬁrmed (PCR positive) COVID-19 infection (n=149,671) was investigated. After exclusion of individuals with unspecified diabetes status, the adverse outcomes between patients with T1DM (n=163), T2DM (n=33,478) and the non-diabetics (n=115,108) were compared by using the propensity score matching method. The outcomes were hospitalization, the composite of intensive care unit (ICU) admission and/or mechanical ventilation and mortality.ResultsThe patients with T1DM had higher mortality than the age and gender matched patients with T2DM (n=489) and the non-diabetics (n=489) (p<0.001). After further adjustment for the A1c, microvascular and macrovascular complications, the odds of mortality (OR:3.35, 95% CI:1.41–7.96, p=0.006) and ICU admission and/or mechanical ventilation (OR: 2.95, 95% CI:1.28–6.77, p=0.011) were significantly higher in patients with T1DM compared to those with T2DM. Older age (OR:1.06, 95% CI:1.01–1.12, p=0.028) and lymphopenia (OR:5.13, 95% CI:1.04–25.5, p=0.045) were independently associated with mortality in patients with T1DM.ConclusionAccording to the results, patients with T1DM had poorer COVID-19 prognosis than those with T2DM or the non-diabetics. These patients should be cared diligently until more data will be available about the causes of increased COVID-19 mortality in T1DM.
Complete Home Smoking Ban Survey Analysis: An Opportunity to Improve Health Equity Among Sexual Minority Adults in California, USA
Authors: Boman-Davis Marie , Irvin Veronica L. , Westling Erika
Published: August 2021

Introduction: Increasing the proportion of adults living in smoke-free homes is a US Healthy People 2020 objective. Complete home smoking bans are associated with higher odds of smoking cessation attempts and cessation duration. Sexual minority adults have disproportionality higher rates of smoking. This study investigates correlates of having a complete home smoking ban among sexual minority adults in California. Methods: Secondary data analyses of the California Behavioral Risk Factor Surveillance System (CA BRFSS), 2014-2016. The CA BRFSS telephone survey of adults was conducted in English and Spanish and used random digit dial for landline and cell numbers. Weighted descriptive, bivariate, and multivariable logistic regression analyses were stratified by sexual orientation and biological sex.Results: Sexual minority adults in California had a lower prevalence of complete home smoking bans (Female 76.2%; Male 75.7%), higher prevalence of current cigarette smoking (Female 23.3%; Male 17.4%) and of e-cigarette use (Female 5.8%; Male 6.4%) than their straight counterparts. Sexual minorities that currently smoke “everyday” (Female AOR 0.26, 95% CI 0.11-0.63; Male AOR 0.24, 95% CI 0.01-0.56) or “somedays” (Female AOR 0.28, 95% CI 0.090.90) had lower adjusted odds of having a complete home smoking compared to those who “never smoked”. Conclusions: Currently smoking everyday was the strongest predictor of not having a complete home smoking ban among sexual minority adults. Focused efforts to increase prevalence of complete home smoking bans should address smoking status to improve health equity among sexual minority adults.
Application of deep metric learning to molecular similarity
Authors: Coupry Damien , Pogany Peter
Published: August 2021

Graph based methods are increasingly important in chemistry and drug discovery, with applications ranging from QSAR to molecular generation. Combining graph neural networks and deep metric learning concepts, we expose a framework for quantifying molecular similarity based on learned embeddings separate from any endpoint. Using a minimal definition of similarity, and data from the ZINC database of public compounds, this work demonstrate the properties of the embedding and its suitability for a range of applications, among them a novel reconstruction loss method for training deep molecular auto-encoders. We also compare the performance of the embedding to standard practices, with a focus on known failure points and edge cases.
Induced effect of Ca2+ and Al3+ on chaetominine synthesis by Aspergillus fumigatus CY018 under submerged fermentation
Authors: Liu Changqing , Chen Tianwen , Chen Jijie , Zhou Yuxuan , Deng Lina , Feng Gongneng , Gao Jian , Liang Huixing
Published: August 2021

Chaetominine (CHA), an alkaloid with biological activity produced by Aspergillus fumigatus CY018, has strong anticancer activity against the human leukemia cell. However, its further research for pharmacokinetics is limited by CHA production in submerged fermentation, which is a problem urgently awaiting solutions by effective biological strategies. In this work, Ca2+ and Al3+ exhibited a strong promoting effect on CHA production after multiple metal ions screening. Then, the concentration of Ca2+ and Al3+ and the addition time was optimized. The suitable conditions were 0.5 mM Ca2+ and 0.5 mM Al3+ at 120 h, in which the CHA production reached 58.5 and 49.45 mg/L with optimized condition of Ca2+ and Al3+ respectively. The intermediate metabolites, such as DAHP, chorismate and tryptophan, were increased obviously with addition of Ca2+ and Al3+. The activities of key enzymes of DAHPs, AroAs and TrpCs in CHA biosynthesis pathway were improved by 3.58-, 3.60- and 3.34-folds respectively. Meanwhile, the transcription levels of laeA, dahp, cs, and trpC were upregulated by 3.22-, 12.65-, 5.58- and 6.99-fold respectively by addition of Ca2+ and Al3+. Additionally, the fermentation strategy was successfully scaled up to 5 L reactor, in which CHA production could attain 75.6 mg/L at 336 h. This work demonstrated that Ca2+ and Al3+ co-addition was an effective strategy for increasing CHA production, and the information obtained might be useful to the further improvement of CHA fermentation on large scale.
18F-NOTA-FAPI-04 uptake in metastatic lesions on PET/CT imaging can distinguish different pathological types of lung cancer
Authors: Wei Yuchun , Cheng Kai , Fu Zheng , Zheng Jinsong , Mu Zhengshuai , Zhao Chenglong , Liu Xiaoli , Wang Shijie , Yu Jinming , Yuan Shuanghu
Published: August 2021

Purpose

Radionuclide-labeled fibroblast-activation-protein inhibitor 04 (FAPI-04) as a positron emission tomography (PET) imaging tracer can reveal the localized expression of fibroblast activation protein (FAP), a cell-surface serine protease that is highly upregulated in more than 90% of epithelial carcinomas. In this study, we quantified the 18F-NOTA-FAPI-04 uptake on PET/computed tomography (CT) imaging in different pathological types of lung cancer and metastatic tumors.
Methods

We prospectively enrolled 61 patients with histopathologically proven primary lung cancer with metastases.PET/CT scanning was performed before any antitumor therapy and 1hour after injection of 235.10 ± 3.89 MBq of 18F-NOTA-FAPI-04. Maximum standard uptake values (SUVmax) were calculated for comparison among primary and metastatic lesions.
Results

Sixty-one patients with adenocarcinoma (ADC, n = 30), squamous cell carcinoma (SCC, n = 17), and small cell lung cancer (SCLC, n = 14) were enrolled in this study, and 61 primary tumors and 199 metastases were evaluated. No difference in18F-NOTA-FAPI-04 uptake was observed among primary ADC, SCC, and SCLC tumors (P = 0.198).Additionally, no difference in uptake was found between primary and metastatic lesions of lung cancer with the same pathological type (P > 0.05).However, uptake did differ among metastases of differing pathological type (P < 0.001). The SUVmax of metastatic lymph nodes was highest for SCC, followed by ADC and then SCLC (P < 0.001).The SUVmax of bone metastases also was highest for SCC, followed by ADC and SCLC (P < 0.05), but no difference was observed between ADC and SCLC. The SUVmax of metastases in other organs was higher in SCC cases than in ADC cases, but did not differ between SCC and SCLC or ADC and SCLC. Bone metastases exhibited higher uptake than those of lymph nodes and other organs in SCC and ADC (P < 0.05), but not in SCLC.
Conclusion

18F-NOTA-FAPI-04 PET/CT imaging revealed differences in FAP expression in metastases of lung cancer, with the highest expression specifically in bone metastases, and thus, may be valuable for distinguishing different pathological types of lung cancer.
Hepatitis B Virus Demethylates PD-1 and Modulates the Changes of the Tumor Microenvironment in Hepatocellular Carcinoma Patients
Authors: Lian Weiguang , Lai Ruixue , Wu Jianhua , Zhang Jingjing , Li Shengchao , Peng Li , Guo Zhanjun
Published: August 2021

Background: Hepatitis B virus (HBV) constitutes a major global health burden. Previously study has found the expression of programmed cell death 1 (PD-1) is up-regulated during the chronic HBV infection. However, the mechanism of how HBV infection modulates the expression of PD-1 on CD8+T cells are not well understood. In the present study, we aimed to analyzed the role of DNA methylation in regulating the expression of PD-1 on CD8+T cells during HBV infection, we also aimed to evaluate the HBV induced changes of tumor microenvironment (TME).Methods: The methylation microarray was used to assess the profile changes of gene methylation upon chronic HBV infection. CD8+T cells were separated from peripheral blood of health volunteers and HCC patients including HBV related HCC (HBV-HCC) and non-viral HCC. The immune microenvironments of hepatocellular carcinoma (HCC) was interrogated by using Immunofluorescence staining. The PD-1 expression of CD8+T cells from peripheral blood were examined by western blot and flow cytometry. T cells function was determined by cytokine measurement. Sequenom MassARRAY platform was used to detected the DNA methylation status of PD-1 promoter.Results: HBV could drive 413 genes methylated while 3,023 genes including PD-1 demethylated, the reduced PD-1 expression and increased PD-1 demethylation was proved in HBV-HCC tissue. The subsequent analysis indicate that the expression of PD-1 differed by stages of HBV infection, it reduced on the cell membrane of HBV-transfected CD8+T cells upon transient HBV plasmid transfection which might mimic acute HBV infection, while upregulated on the HBV specific CD8+T cells by demethylation during chronic HBV infection. Interferon-gamma increased in the medium of HBV transfected CD8+T cells and interleukin-10 increased in the blood of chronic HBV infection patients. Increased tumor associated macrophage (TAM) cells and T regulatory cells (Tregs) invasion was identified in HBV-HCC tissue when compared with those from non-viral HCC tissue Conclusion: Our data suggested that the expression of PD-1 varies upon the stage of HBV infection, chronic HBV infection could drove the TME more immunosuppressive through PD-1 demethylation related CD8+T cells exhaustion as well as promotion of invaded Treg and TAM cells thereby to attenuating therapy of immune checkpoint inhibitors.