bluuebunny/crossref_metadata_2025 huggingface dataset:
From Measuring User Satisfaction to Improving Quality of Care: Community Verifications and Performance-Based Financing in District Hospitals in Mali
Authors: Zitti Tony , Coulibaly Abdourahmane , Ridde Valéry
Published: June 2022

Context: User satisfaction in health facilities is increasingly taken into account to improve the quality of care. In Mali, performance-based financing (PBF) aims to improve the quality of care by increasing the motivation, responsibility, and accountability of health workers. Community verification (CV) is one of the main functions of the PBF. CV makes it possible to monitor the effectiveness of the services reported by the health facilities and to conduct satisfaction surveys of the users who have received care. This paper aims to analyze the CV process during the implementation of the PBF in the Koulikoro region of Mali.Methods: We adopted a qualitative approach based on a multiple case study design corresponding to the district hospitals (DH) and stakeholder groups. We conducted thirty-nine semi-structured interviews with investigators, patients, and health workers in three of the ten DHs in the Koulikoro region. We designed three interview guides and inductively analyzed our data.Results: The CV process was well perceived and welcomed. However, the vast majority of interviewers reported difficulties locating some patients in the community for several reasons: incorrect spelling of names, illegible cards, lack of telephone contact information and incomplete information on the cards, and cases of homonymity. All of this was due to poor record-keeping at the health facilities. Some investigators fraudulently filled out forms without investigating users in the communities. They justified this by the lack of time available to them to conduct the CV. No feedback on the results of the CV was possible from the health workers.Conclusion: The CV is an essential component of PBF implementation. The validity, reliability, and efficiency of the measurement instruments must be considered in user-satisfaction surveys. In addition, emphasis should be placed on data analysis and the use of CV results.
Determination and Evapotranspiration of different Agro-climatic regions of India by Artificial Neural Network
Authors: Abraham Markutty , Mohan Sankaralingam
Published: June 2022

Climate change has a tremendous effect on the evapotranspiration (ET) process worldwide and the computation of ET for various climatic regions is essential for efficient water management. ET was estimated using Artificial Neural Network models for 10 stations falling under different agro-climatic regions of India. Although the Penman–Monteith ET model has superior predictive ability than the other methods, owing to the need for a large number of climatic variables, it is difficult to use in data-short conditions and it is necessary to determine the most important climatic variables for the agro-climatic regions. Most sensitive climatic variables were identified from the Principal Component Analysis (PCA) for all the stations. Sensitivity analysis showed that the overall average change in ET0 values for 25% change in the climatic variables were 18%, 16%, 14%, 7%, 5%, 4% respectively for Tmax, RHmean, Rn, Wind speed, Tmin and sunshine hours. New ET models were developed for each station, both with all climatic variables and with the important climatic variables identified by PCA, using the ANN model and compared the performance with Penman–Monteith ET estimates. Net radiation, high and low temperatures, usual relative humidity, wind velocity, and the ratio of daily sunshine hours are all input variables to the model, with ET0 values as an output. Several neurons in the hidden layer for each station for the best model performance were found. PCA variables guaranteed the most reliable estimation of potential evapotranspiration (PET) accounting for 98% of the variability. The average values of coefficient of determination (R2), standard error of estimate (SEE), and percentage efficiency (%) were observed as 0.96, 0.24, 94% respectively. There was no significant difference between the ANN model with all climatic variables and with the PCA variables identified indicating that the ANN model with variables resulting from PCA can be preferred for practical applications.
Study of manufacturing defects on compressive deformation of 3D printed polymeric lattices
Authors: Amirpour Maedeh , Battley Mark
Published: June 2022

This paper studies theoretical, numerical and experimental studies on static compression behaviour of Polyamide 12 Body-Centred Cube (BCC) lattices manufactured using the Selective Laser Sintering (SLS) method. In the analytical formulation, the influence of imperfections that happened during 3D printing such as material overlapping in the vicinity of filament joints is considered to provide predictions of mechanical properties of a macro lattice structure. Finite Element (FE) models of the BCC lattices are performed to predict the compressive behaviour and deformation localisation of filaments. In order to determine a material model and input parameters for FE simulation of the lattice cubes, an individual 3D printed filament is subjected to transverse compressive loading utilising a custom-made filament compression rig. Then, true experimental stress and strain data are generated that are imported into an inverse calibration technique using MCalibration software to determine the material parameters for the FE simulation. A series of BCC lattice cubes were printed using the SLS method. Compression experiments were conducted utilising digital image correlation (DIC) techniques in order to determine localisation of deformations and strains and validate the material properties obtained by the analytical modelling and numerical simulations. Good agreements are observed among the analytical, numerical and experimental results. The results show that effect of filament defects should be taken into account to find the accurate responses in analytical model and FE simulation.
Enhanced hemocompatibility of Lysine grafted polyacrylonitrile electrospun nanofiber membranes as a potential bilirubin adsorption in hemoperfusion
Authors: Liu Muhua , Zhang Wen , Li Hao , Zhan Jinjie , Zhao Wenjun , Mei Xi
Published: June 2022

Hyperbilirubinemia is one of most severe clinical diseases, which is caused by the accumulation of unconjugated bilirubin. Electrospun nanofiber membranes used as highly efficient bilirubin adsorbents have been applied to remove the extra bilirubin in hemoperfusion for their high surface area and easy functionalized properties. In this work, Lysine (Lys) grafted polyacrylonitrile (PAN) electrospun nanofiber membranes doped with organic Hectorite (OHec) (Lys-HPAN@OHec) have been fabricated via a series of modified process, including pore forming, alkaline hydrolysis and grafting reaction. The obtained Lys-HPAN@OHec nanofiber membranes have been analyzed in detail and investigated the adsorption capacity for bilirubin. Compared with original PNA membranes, Lys-HPAN@OHec nanofiber membranes show an excellent bilirubin adsorption capacity and more stable rejection rate of bovine serum albumin (BSA). The maximum adsorption capacity of Lys-HPAN@OHec membranes for bilirubin is 64 mg/g, the adsorption process of Lys-HPAN@OHec membranes matched the Langmuir model well. In addition, dynamic adsorption reveals that the adsorption equilibrium time of Lys-HPAN@OHec membranes is about 2 h. Significantly, Lys-HPAN@OHec membranes have excellent biocompatibility and hemocompatibility. This study demonstrates that the novel Lys-HPAN@OHec membranes may provide a new way to treat hyperbilirubinemia.
Machinability analysis and optimisation of EDM in AA6082/ 3 wt. % BN/1wt. % MoS2 hybrid composites using entropy method weights integrated with Complex Proportional Assessment (COPRAS) method
Authors: G karthik pandiyan , D Jafrey Daniel James , Sivalingam Vinothkumar , D Arjun , S Gowtham , P Gokul Kannan , K Bhuvaneshwar , R Ramkumar , Chandran Mohanraj
Published: June 2022

An investigation was made on composites containing AA6082 as matrix and boron nitride/molybdenum disulphide (BN/MoS2) used as reinforcement, which was 3 wt. % of BN and 1% MoS2 hybrid composite materials were fabricated by stir casting methodology. Using electrical discharge machining (EDM) equipment, machinability studies were examined to achieve an optimal condition of process parameters. Taguchi (L27 orthogonal array) based design of experiments was employed for experiments to examine the influence of process parameters like pulse on time (Ton), peak current (IP) and gap voltage (V) on material removal rate (MRR), circularity (CIRC), electrode wear rate (EWR), and cylindricity (CYLD) were investigated. Multi Criteria Decision Making (MCDM) methodology was employed for the process parameters while machining AA6082/ 3 wt. % BN/1% MoS2 hybrid composites. An entropy-based objective weights method was integrated with the complex proportional assessment (COPRAS) approach to assess the most excellent optimal level of process parameters. The entropy (Wj) weights were 0.1285, 0.1002, 0.5707 and 0.2005 for MRR, EWR, CIRC, and CYLD. The optimal conditions are obtained from the COPRAS method of relative significance score, and quantitative utility assessment score in the nineteenth experiment having the 15 A, 50 µs and 30 V with the relative significance score of 0.0735 with a higher quantitative utility score of 100% is achieved. Using an SEM, the machined surface is analysed for the micro-structural examination. At higher peak current (IP), micro-voids and craters with poor surface finish were achieved.
Thermally-stable threshold selector based on CuAg alloy for energy-efficient memory and neuromorphic computing applications
Authors: Zhou Xi , Zhao Liang , Yan Chu , Zhen Weili , Lin Yinyue , Li Le , Du Guanlin , Lu Linfeng , Zhang Shan-Ting , Lu Zhichao , Li Dongdong
Published: June 2022

As a promising candidate for high-density data storage and neuromorphic computing, cross-point memory arrays provide a platform to overcome the von-Neumann bottleneck and accelerate neural network computation. In order to suppress the sneak-path current problem that limits their scalability and read accuracy, a two-terminal selector can be integrated at each cross-point to form the one-selector-one-memristor (1S1R) stack. In this work, we demonstrate a CuAg alloy-based, thermally-stable and electroforming-free selector device with tunable threshold voltage and over 7 orders of magnitude ON/OFF ratio. A vertically-stacked 64 × 64 1S1R cross-point array is further implemented by integrating the selector with SiO2-based memristors. The 1S1R devices exhibit extremely low leakage currents and proper switching characteristics, which are suitable for both storage class memory and synaptic weight storage. Finally, a selector-based leaky-integrate-and-fire neuron is designed and experimentally implemented, which expands the application prospect of CuAg alloy selectors from synapses to neurons.
Pollen Morphological and Molecular identification, and deposition of Ocimum species
Authors: Alex ASHA MONICA.A , S Senthilkumar
Published: June 2022

Ocimum species is an exceptionally exchanged and broadly utilized species of Ayurvedic medication inferable from its colossal helpful potential, which has prompted defilement of the two definitions as well as exchanged crude medications. To fulfill the guideline worldwide market necessities, fast and proficient strategies for confirmation are required which can stay up with the rising interest in the spice. In 2019, four Ocimum species were collected from the Tiruchirappalli districts and identified based on morphological and molecular levels. Pollen morphological studies were carried out using Scanning electron Microscopy. The shape of the studied, plants are prolate, oblate-spherical and percolate Morphological characters are identified based on the physical characters tod the herbarium sheet was submitted in St Joseph’s College. Molecular identification is carried out by PCR with help of three primers rbcL, trnH-psbA, and trnL-F. The conserved region is identified and constructed in a phylogenetic tree based on interspecific and intraspecific molecular markers with help of The Molecular Evolutionary Genetics Analysis (MEGA) software. Finally, sequences are submitted to NCBI and got an accession number from Genbank.
Cellulose in secondary xylem of Cactaceae: chemical composition and anatomical distribution
Authors: Maceda Agustín , Soto-Hernández Marcos , Terrazas Teresa
Published: June 2022

Cellulose is the main polymer that gives strength to the cell wall and consists of crystalline-microfibrils and amorphous-matrix cellulose located in the primary and secondary cell walls of the plants. In the Cactaceae family, there are studies on the composition of lignin but not on the composition of cellulose. Therefore, the objective of his work is to analyze the chemical composition and distribution of cellulose in the cells of the xylem tissue. Twenty-five species of Cactaceae were collected, dried, and milled. The extractables were removed until obtaining extractive-free wood. Subsequently, cellulose was purified, readings with Fourier transform infrared spectroscopy were made, and the crystallinity indexes were calculated. In addition, for the anatomical analysis of wood, stem sections for each plant were fixed, cut, and stained with safranin O / fast green to observe them under the epifluorescence microscope with three excitation and emission bands. The results showed that crystalline cellulose percentages were different between non-fibrous and fibrous species. In non-fibrous species, the values for crystalline cellulose were above 60%. The fluorescence emission of cellulose in all species was red, the distribution of cellulose in non-fibrous species was in the primary wall; while in the fibrous species, the distribution was in the internal walls and the pits. The high percentages of crystalline cellulose may be related to its distribution in the non-lignified parenchyma and primary walls of tracheary elements with helical or annular thickenings of non-fibrous species, possibly offering structural rigidity and as part of the defense system against pathogens.
Shikonin triggers GSDME-mediated pyroptosis in tumours by regulating autophagy via the ROS–MAPK14/p38α axis
Authors: Ju Xiaoli , Wang Jiayou , Wang Jin , Guo Lanfang , Zhang Heng , Wang Qiang
Published: June 2022

Shikonin (SK), a botanical drug extracted from Lithospermum erythrorhizon, has been shown to inhibit tumour growth through apoptosis and necrosis. However, whether SK induces pyroptosis in cancer cells is still unknown. Here, we demonstrated that SK treatment induced gasdermin E (GSDME)-dependent pyroptosis in tumour cells. The activation of BAX/caspase-3 signalling was essential for GSDME-mediated pyroptosis by SK. Mechanistically, the intracellular reactive oxygen species (ROS) generation induced by SK treatment initiated GSDME-dependent pyroptosis. SK stimulation induced protective autophagy in a ROS-dependent manner, and repressed autophagy significantly enhanced SK-induced pyroptosis. Moreover, MAPK14/p38α, a ROS sensor, modulated SK-induced autophagy and ultimately affected GSDME-dependent pyroptosis. This study demonstrated that SK initiates ROS signalling to drive pyroptosis in cancer cells and implicates SK as having an anticancer effect by inducing tumour cell death.
A query interface for clinical research with Chinese electronic health record using Natural Language Processing
Authors: Li Mengyang , Cai Hailing , Chen Yani , Lu Xudong , Duan Huilong
Published: June 2022

Background: The recruitment of clinical trials is a challenging task. Traditionally, the time-consuming task is accomplished manually or assisted by form-based tools. Electronic health record (EHR) contains comprehensive information which can speed up the process. The development of natural language processing (NLP) makes it possible to reduce manual effort. To our knowledge, there are almost no query interfaces based on NLP techniques for Chinese EHR.Methods: A query interface based on NLP was developed. Firstly, we collected and annotated eligibility criteria(EC) from the Chinese Clinical Trial Registry. Then, an information extraction(IE) system was developed to parse them including named entity recognition(NER), relation classification(RC), and concept matching(CM). Next, the extracted information was post-processed(PP) to generate formal queries. Finally, we built a natural language query interface based on the system.Results: 4691 stroke-related EC were collected for annotation. 91.23% F1 score was achieved for the NER task. For the RC task, 92.75% F1 score was achieved. For the CM task, 90.78% accuracy was achieved and an evaluation result showed 42.42% of entities from NER results can be matched with EHR. And a natural language query interface has been implemented and applied in clinical research about stroke. Conclusions: We build a query interface for Chinese EHR based on NLP techniques. The proposed information extraction pipeline can support medical professionals to reduce the information gap with minimal human effort when interacting with Chinese EHR.
Convolutional Neural Networks for Approximating Electrical and Thermal Conductivities of Cu-CNT Composites
Authors: Ejaz Faizan , Hwang Leslie K , Son Jangyup , Kim Jin-Sang , Lee Dong Su , Kwon Beomjin
Published: June 2022

This article explores the deep learning approach towards approximating the effective electrical and thermal conductivities of copper (Cu)-carbon nanotube (CNT) composites with CNTs aligned to the field direction. Convolutional neural networks (CNN) are trained to map the two-dimensional images of stochastic Cu-CNT networks to corresponding conductivities. The CNN model learns to estimate the Cu-CNT composite conductivities for various CNT volume fractions, interfacial electrical resistances, Rc = 20 Ω − 20 kΩ, and interfacial thermal resistances, R”t,c = 10− 10 m2K/W − 10− 7 m2K/W. For training the CNNs, we optimize the hyperparameters such as learning rate, minibatch size, and hidden layer neurons. Without iteratively solving the physical governing equations, the trained CNN model approximates the electrical and thermal conductivities within a second with an accuracy greater than 98%, which may take longer than 100 minutes for a convectional numerical simulation. This work demonstrates the potential of the deep learning surrogate model for the complex transport processes in composite materials.
Coding and noncoding genes involved in atrophy and compensatory muscle growth in Nile Tilapia
Authors: Ali Ali R. , Shaalan Walaa M. , Al-Tobasei Rafet , Salem Mohamed
Published: June 2022

Improvements in growth-related traits reduce fish time and production costs to reach market size. Feed deprivation and refeeding cycles have been introduced to maximize aquaculture profits through compensatory growth. However, the molecular compensatory growth signature is still uncertain in Nile tilapia. In this study, fish were subjected to two weeks of fasting followed by two weeks of refeeding. The growth curve in refed tilapia was suggestive of a partial compensatory response. Transcriptome profiling of starved and refed fish was conducted to identify genes regulating muscle atrophy and compensatory growth. Pairwise comparisons revealed 5,009 and 478 differentially expressed (DE) transcripts during muscle atrophy and recovery, respectively. Muscle atrophy appears to be mediated by the ubiquitin-proteasome and autophagy/lysosome systems. Autophagy-related 2A, F-box and WD repeat domain containing 7, F-box only protein 32, miR-137, and miR-153 showed exceptional high expression suggesting them as master regulators of muscle atrophy. On the other hand, the muscle compensatory growth response appears to be mediated by the continuous stimulation of muscle hypertrophy which exceeded normal levels found in control fish. For instance, genes promoting ribosome biogenesis or enhancing the efficiency of translational machinery were upregulated in compensatory muscle growth. Additionally, myogenic microRNAs (e.g., miR-1 and miR-206), and hypertrophy-associated microRNAs (e.g., miR-27a-3p, miR-29c, and miR-29c) were reciprocally expressed to favor hypertrophy during muscle recovery. Overall, the present study provided insights into the molecular mechanisms regulating muscle mass in fish. The study pinpoints extensive growth-related gene networks that could be used to inform breeding programs and also serve as valuable genomic resources for future mechanistic studies.
Safety and outcomes of combined immune checkpoint inhibitor and radiation therapy for patients with melanoma brain metastases
Authors: Desagneaux Andréa , Charles Julie , Kastler Adrian , Dols Anne -Marie , Leccia Marie-Thérèse , Elhalawani Hesham , Aizer Ayal , Flandin Isabelle , Verry Camille
Published: June 2022

INTRODUCTION:
In spite of the promising results of systemic treatment in melanoma, the development of brain metastases remains a common issue, often prompting use of Radiation Therapy (RT). The purpose of this study is to assess the safety and outcomes of Immune Checkpoint Inhibitor (ICI) and brain RT with a focus on timing of both treatments.
METHODS
This retrospective study included all consecutive patients treated for a brain metastatic melanoma with an ICI (anti – CTLA4 or anti – PD1 or both) and brain RT from December 1, 2010 and April 30, 2018. The concurrent group was defined by an ICI performed within 4 weeks before or after RT. Primary endpoint was neurological adverse events graded with Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
RESULTS
Fifty - three consecutive patients were included. A total of 81 RT courses were performed: 23 with whole brain radiotherapy (WBRT) and 58 with stereotactic radiotherapy (SRT). The majority of RT (63%, n = 51) was delivered with concurrent ICI. Acute neurological Adverse Events (AE) ≥ grade 3 occurred for 12.3% of RT course, with no difference between concurrent and non – concurrent groups. The median OS after RT was 11.5 months for the entire cohort with 15.9 months for SRT in comparison to 2.7 months for WBRT. The objective response rate was significantly better for concurrent ICI – SRT group at 66.7% compared to 40% for non-– concurrent group (p = 0.04). One-year LC probability was higher in the concurrent group than in the non-concurrent group, respectively 72. % vs 38.5% (p = 0.007).
CONCLUSIONS
Combined RT and ICI is well tolerated with acceptable neurological adverse events. Stereotactic radiation therapy delivered concurrently with ICI is associated with improved local control.
Distribution characteristics and clinical significance of circulating CD8 + CD28 - regulatory T cells in the peripheral blood of patients with pulmonary tuberculosis
Authors: Yu Xin , Lin Yao , Chen Hui , Huang Li-Na , Song Yi-Yan , Gu Bin-Bin , Ye Zhi-Jian , Xu Ping , Zhang Jian-Ping , Xu Jun-Chi
Published: June 2022

Background: Regulatory T cells (Treg cells) in the peripheral blood of patients with pulmonary tuberculosis (PTB) may be closely related to the progression of PTB. In this study, the distribution characteristics and clinical importance of CD8+CD28- Treg cells in patients with tuberculosis were systematically analyzed, and the role and importance of CD8+CD28- Treg cells in influencing the immune response and progression of tuberculosis were discussed, which will provide immunological indices and reference values for the clinical diagnosis of tuberculosis.Methods: Flow cytometry, sputum smears and CT imaging were used to analyze the distribution characteristics of CD8+CD28- Treg cells in the peripheral blood of patients with PTB and the correlation between CD8+CD28- Treg cells and clinical and immune indices.Results: Compared with those in the healthy control (HCs) group, the percentages of CD4+CD25high and CD8+CD28- Treg cells in the peripheral blood of patients with PTB increased significantly. Further analysis showed that compared with that in the HCs group, the percentage of CD4+CD25high Treg cells in the Stage II group increased significantly. The percentages of CD4+CD25high and CD8+CD28- Treg cells increased significantly in patients in the Stage II group. The proportion of CD8+CD28-Treg cells was directly proportional to the positive degree of sputum smears, while CD4+CD25high Treg cells did not show this effect.The correlations between the percentage of CD4+CD25high and CD8+CD28- Treg cells and the percentage of lymphocyte subsets were examined. CD8+CD28-Treg cells were negatively correlated with CD4+T cells and positively correlated with the CD8+T cell ratio in the HCs and PTB groups. CD4+CD25highTreg cells were positively correlated with CD4+T cells only in the PTB group.Conclusions: This study was the first to show that the proportion of CD8+CD28- Treg cells in the peripheral blood of patients with PTB was significantly increased, and the increase in CD8+CD28-Treg cells was related to the progression of PTB, which may affect the proportion of immune cell subsets by inhibiting the immune response, resulting in the progression of PTB.
Multi-phased ASM evolution and rainfall response during Heinrich Stadial 5
Authors: Liu Dianbing , Mi Xiang , Liu Shushuang , Wang Yongjin
Published: June 2022

Changes in Asian summer monsoon (ASM) circulation and regional precipitation were reconstructed from stalagmite δ 18 O and trace element records from Wulu Cave in southern China, covering Chinese Interstadial (CIS) 13 to Heinrich Stadial (HS) 5. During HS 5, the evolution of δ 18 O-based ASM can be divided into four stages, i.e., an abrupt onset/termination and unstable mid-HS 5 (a slow ASM decline followed by a stepwise ASM strengthening). The extent of ASM weakening in mid-HS 5, relative to the mean δ 18 O value, reaches 58% of the total magnitude of HS 5. In contrast, multi-stage variability is less clear in element-inferred rainfall variations, which feature a stadial/interstadial pattern. During CIS 13, large-amplitude element oscillations are accompanied by a rapid decline at the onset of HS 5, with a limited range of variability in HS 5. The rainfall reduction in mid-HS 5, in comparison with the mean level, approximates 33% of the full event, practically equivalent to that during Chinese Stadial (CS) 14. It suggests a pronounced sensitivity of ASM and an inertial precipitation response to HSs. During HS 5, a cooling in the eastern tropical Pacific could favor a formation of La Niña state and a wetting in southern China. The timing of HS 5 in our record (48.53±0.12 ka, 47.19±0.12 ka) agrees well with the central age of spatially-separated cave records (48.72±0.14 ka, 47.35±0.24 ka). At the onset of HS 5, Asian hydroclimate changes are coeval with bipolar ice-core records, but lead the Greenland warming by 300 years at the termination or are synchronous with Greenland records via atmospheric CH 4 constraints. This at least implicates that the monsoonal rainfall is less sensitive to climate perturbations during HS 5.
Surface protein modification of living bacteria: a promising antitumor therapeutic strategy
Authors: He Zhongming , Chen Kun , An Yu , He Jie , Zhang Xiaoli , Tang Lannan , Sun Fa , Jiang Kehua
Published: June 2022

Objective: Validating the feasibility of surface modification of Escherichia coli (E. coli) with bovine serum albumin (BSA), and propose a approach of protein modification on living bacterial surface to to develop a new antitumor therapeutic strategy. Methods: Based on the advantages of live bacteria and albumin in drug delivery and antitumor therapy, E. coli and BSA were used as the live bacteria and target protein, respectively. Through the bridging action of biotin and streptavidin, the surface of E. coli was modified by BSA. To enhance the chemotaxis ability, tumor adhesion and targeting ability of E. coli vector, we report a new method of using living bacterial surface protein modification as a tool to develop a promising antitumor therapeutic strategy. Results: BSA modification on the surface of E. coli was feasible and enhanced the tumor targeting ability and adhesion capacity of E. coli to tumor cells. Conclusion: Protein modification on the surface of living bacteria was effective and easy, and the novel strategy would enable the development of a new model of live bacteria as anti-tumor therapy.
Multi-cancer early detection with a spectroscopic liquid biopsy platform
Authors: Cameron James M. , Sala Alexandra , Antoniou Georgios , Brennan Paul M. , Butler Holly J. , Conn Justin J.A. , Connal Siobhan , Curran Tom , Hegarty Mark G. , McHardy Rose , Orringer Daniel , Palmer David S. , Smith Benjamin R. , Baker Matthew J.
Published: June 2022

A rapid, low-cost, sensitive, multi-cancer early detection (MCED) test would be transformational in the diagnostics field. Earlier cancer detection can increase survival rates and quality of life of patients. An effective test must accurately identify the small proportion of patients with typically non-specific symptoms who have cancer. Such symptoms do not easily segregate by organ system, necessitating a multi-cancer approach. In this large-scale study (n = 2094 patients) we applied the Dxcover® Cancer Liquid Biopsy to differentiate cancer against non-cancer patients, as well as organ specific tests to identify cancers of the brain, breast, colorectal, kidney, lung, ovary, pancreas, and prostate. The test uses Fourier transform infrared (FTIR) spectroscopy to analyze all macromolecules in a minute volume of patient serum, and machine learning algorithms to build a classifier of the resultant spectral profiles to detect cancer. This approach can be fine-tuned to maximize either sensitivity or specificity depending on the requirements from different healthcare systems and cancer diagnostic pathways. The cancer v asymptomatic non-cancer classification detected 64% of stage I cancers when specificity was 99% (overall sensitivity 56%). When tuned for higher sensitivity, this model identified 99% of stage I cancers (while specificity was 58%). When examining cancer against all non-cancer (including symptomatic patients), the sensitivity-tuned model enabled 90% sensitivity with 61% specificity, with detection rates of 93% for stage I, 84% for stage II, 92% for stage III and 95% for stage IV. For organ specific cancer classifiers, area under the receiver operating characteristic (ROC) curve values were calculated for all cancers: brain (0.90), breast (0.75), colorectal (0.91), kidney (0.91), lung (0.91), ovarian (0.86), pancreatic (0.85) and prostate (0.86). Cancer treatment is more effective when given earlier and this low-cost strategy can facilitate the requisite earlier diagnosis.
The prevalence of gastrointestinal symptoms and cobalamin deficiency in patients with chronic urticaria.
Authors: Abadeh Armin , Herman Sari M , Abdalian Rupert
Published: June 2022

BackgroundThere is a paucity of studies reporting the presence of systemic symptoms and micronutrient deficiency in patients with chronic urticaria, and these data are lacking in a Canadian population.Objective To report the prevalence of gastrointestinal symptoms and cobalamin deficiency in a Canadian patient population diagnosed with chronic urticaria. MethodsA retrospective chart review of 100 adult patients with chronic urticaria was conducted. Demographic characteristics, medications, presence of gastrointestinal symptoms, and laboratory findings were abstracted from electronic medical records. ResultsSeventy percent of patients with chronic urticaria reported experiencing gastrointestinal symptoms. The most common symptom identified was gastroesophageal reflux (42%). Cobalamin deficiency, defined as serum B12 ≤250 pmol/L, was identified in 31.7% of the patients. Among those patients with urticaria and B12-deficiency, 68% reported gastrointestinal symptoms. ConclusionsThis is the first study to provide data on the high prevalence of gastrointestinal symptoms and cobalamin deficiency in a Canadian population diagnosed with chronic urticaria. Early recognition and management of systemic symptoms and micronutrient deficiency may lead to a more comprehensive approach to management of these patients.
Analysis of outcome indicators of cancer-related fatigue treated with Chinese medicine
Authors: Li Zhonghui , Zhang Xinwei , Weng Yueyan , Zhou Lei , Wang Fang
Published: June 2022

Objective
In the direction of evaluating the current status of outcome indicators and control group selection in randomized controlled studies of Chinese herbal compounding for cancer-caused fatigue, and to provide a reference for clinical studies of Chinese herbal compounding for cancer-caused fatigue.
Methods
Randomized controlled studies of Chinese herbal medicine for cancer-caused fatigue in the midst of 2012 and 2022 were searched in CNKI, PubMed, and EMBASE databases on the China Knowledge Network. Two researchers independently conducted the literature review, and then the studies that met the criteria were grouped and analyzed adopting qualitative analysis of outcome indicators and control groups.
Results
A total of 70 randomized controlled studies that met the requirements were included, and after doing statistical analysis, it can draw to the conclusion that the risk of bias in the included studies was high, at the same time, the Traditional Chinese Medicine(TCM)evidence score scale, objective indicators, and safety indicators were underutilized, additionally, there were no uniform standards for the fatigue scale, and the selection of control groups lacked balance and consistency.
Conclusion
The outcome indicators of TCM compound treatment of cancer-caused fatigue should be on the basis of the principle of "diagnosis and treatment" in TCM, the proportion of objective indicators should be exaggerated, as well as the interventions in the control group should be unified.
Efficacy of combination therapy with lenvatinib, programmed cell death 1 inhibitors and transarterial therapy: a propensity score-matching cohort study
Authors: Lang Mengran , Gan Leijuan , Ren Shaohua , Ma Xiaochen , Li Guangtao , Li Huikai , Zhang Ti , Wu Qiang , Cui Yunlong , Zhang Wei , Fang Feng , Li Qiang , Lu Wei , Song Tianqiang
Published: June 2022

Purpose Few studies have investigated the efficacy of triple combination therapy with lenvatinib, programmed cell death 1 (PD-1) inhibitors and transarterial therapy in patients with intermediate/advanced hepatocellular carcinoma (HCC). Patients and methods We retrospectively analyzed patients with intermediate/advanced HCC treated at Tianjin Cancer Hospital from December 2018 to October 2020 and compared outcomes of lenvatinib plus PD-1 inhibitors and transarterial therapy (LEN-PD1-TH) versus lenvatinib and PD-1 inhibitors (LENPD1). Propensity score-matching was used. The primary study endpoint was progression-free survival (PFS). Secondary endpoints were overall survival (OS) and overall response rate (ORR) assessed using modified RECIST. The Cox proportional hazards model was used to identify factors that affected prognosis. Results In total, 152 patients were included. Propensity score matching led to 35 matched patients in each group. The median follow-up time was 14 months (95% CI, 10.1-17.9) as of May 2021. The LEN-PD1-TH group had a longer median PFS and OS versus the LEN-PD1 group (15 vs. 9 months; P=0.004 and 14 months vs. NA; P<0.001, respectively). The ORR was significantly higher in the LEN-PD1-TH group versus the LEN-PD1 group (42.9 vs. 20.1%; P=0.039). In multivariate analysis, all triple therapy regimens were associated with improved PFS (hazard ratio [HR]=0.362; 95% CI, 0.185-0.771; P=0.003) and OS (HR=0.143; 95% CI, 0.053-0.383; P<0.001). Child-Pugh class B and Barcelona clinic liver cancer stage (BCLC) C disease were identified as risk factors for PFS, and large tumor size was a risk factor for OS. Patients with extrahepatic metastases, no vascular invasion, tumor diameter <10 cm, tumor number >3, BCLC stage C, and alpha-fetoprotein ≤400 ng/ml showed a tendency to benefit from the triple therapy regimen. The addition of transarterial therapy to lenvatinib and PD-1 inhibitors did not significantly increase adverse reactions. Conclusions LEN-PD1-TH improved survival outcomes for patients with intermediate to advanced HCC compared to LEN-PD1.
Association between Sensitivity to Thyroid Hormones and Risk of Arrhythmia in Patients with Coronary Heart Disease: A RCSCD-TCM study in China
Authors: Liu Fanfan , Liu Yijia , Li Zhu , Yu Lu , Li Lin , Ma Mei , Lai Ziqin , Li JiaYing , Wang Xianliang , Yang Rongrong , Yu ChunQuan
Published: June 2022

BackgroundThyroid dysfunction is closely related to arrhythmia. However, the relationship between sensitivity to thyroid hormone and risk of arrhythmia remains unknown. This study aimed to investigate the association between the thyroid system complex index and risk of arrhythmia in patients with coronary heart disease (CHD).MethodsThis large, multi-center study included 28,413 patients with CHD. Central sensitivity to thyroid hormone was assessed by calculating the thyroid feedback quantile-based index (TFQI). Logistic regression was used to analyze the relationship between sensitivity to thyroid hormone and risk of arrhythmia. This study also assessed the relationship between sensitivity to thyroid hormone and risk of arrhythmia in different sexes, ages, and glucose regulation and blood lipid states.ResultsOf the 28,413 participants, 8,935 (31.4%) patients with CHD had arrhythmia. There was a remarkable association between TFQI and risk of arrhythmia (odds ratio [OR]: 0.783; 95% confidence interval [CI], 0.735–0.836). Furthermore, the association between the TFQI and risk of arrhythmia in women (OR: 0.731; 95% CI: 0.667–0.802) was stronger than that in men (OR: 0.894; 95% CI: 0.816–0.910), as well as higher in elder (OR: 0.779; 95% CI: 0.721–0.843) than middle-aged (OR: 0.789; 95% CI: 0.703–0.886) patients. Furthermore, the association was stronge in the state of diabetes (OR: 0.635; 95% 0.569–0.709) and dyslipidemia (OR: 0.706; 95% CI: 0.644–0.774).ConclusionThere is a remarkable association between sensitivity to thyroid hormone and risk of arrhythmia in patients with CHD, which is more pronounced among women and the elderly. The association is also stronger in patients with dyslipidemia or diabetes.
Rebaudioside B attenuates lung ischemia-reperfusion injury associated apoptosis and inflammation
Authors: Huang Jian , Yang Jianbao , Zhang Rongzhi , Wang Shixiong , Cheng Xingdong , Li Jian , Li Yongnan , Gao Bingren
Published: June 2022

Currently no proven effective treatment exists for lung ischemia-reperfusion injury (LIRI). Natural compounds represent a source of new drugs for the treatment of different diseases. The present study aims to investigate Rebaudioside B (Reb B) as a potential compound to the treatment of LIRI in vivo and in vitro. The present study includes the human pulmonary alveolar cells line with epithelial type II A549 under oxygen-glucose deprivation/recovery (OGD/R) to high-throughput in vitro cell viability screening to identify the most promising compound tested candidates. Moreover, an in vivo rat model of lung ischemia-reperfusion was used to assess the potential protective effect of Reb B. Reb B was identified as the most promising compound among the natural compounds tested, being identified by high-throughput screening. Reb B enhances cell viability by reducing apoptosis in A549 OGD/R models. In the in vivo model of LIRI, preconditioning with Reb B significantly reduced apoptotic cells, perivascular edema, and neutrophil infiltration in lung tissues. In addition, Reb B inhibits LIRI lung inflammation mainly by increasing IL-10 levels, while decreasing IL-1β and IL-8 levels. The overall results suggest that Reb B has a promising protective effect in LIRI caused by the inhibition of the mitochondrial apoptotic pathway and by decreasing the inflammatory response.
Virtual classroom proficiency-based progression for robotic surgery training (VROBOT): a randomised, prospective, cross-over, effectiveness study
Authors: Nathan Arjun , Patel Sonam , Georgi Maria , Fricker Monty , Asif Aqua , Ng Alexander , Mullins William , Hang Man Kien , Light Alexander , Nathan Senthil , Francis Nader , Kelly John , Collins Justin , Srid Ashwin
Published: June 2022

IntroductionRobotic surgery training has lacked evidence-based standardisation. We aimed to determine the effectiveness of adjunctive interactive virtual classroom training (VCT) in concordance with the self-directed Fundamentals of Robotic Surgery (FRS) curriculum.MethodsThe virtual classroom is comprised of a studio with multiple audio-visual inputs to which participants can connect remotely via the BARCO weConnect platform. 11 novice surgical trainees were randomly allocated to two training groups (A and B). In week one, both groups completed a robotic skills induction. In week two, Group A received training with the FRS curriculum and adjunctive VCT; Group B only received access to the FRS curriculum. In week three, the groups received the alternate intervention.The primary outcome was measured using the validated robotic-objective structured assessment of technical skills (R-OSAT) at the end of week two (timepoint 1) and three (timepoint 2).ResultsAll participants completed the training curriculum and were included in the final analyses. At timepoint 1, Group A achieved a statistically significant greater mean proficiency score compared to Group B (44.80vs35.33 points, p=0.006). At timepoint 2, there was no significant difference in mean proficiency score in Group A from timepoint 1. In contrast, Group B, who received further adjunctive VCT showed significant improvement in mean proficiency by 9.67 points from timepoint 1 (95% CI 5.18-14.15, p=0.003).ConclusionVCT is an effective, accessible training adjunct to self-directed robotic skills training. With the steep learning curve in robotic surgery training, VCT offers interactive, expert-led learning and can increase training effectiveness and accessibility.
Deeper Insights into the Biochemical, Hematological and Histological Changes Induced by Bisphenol A Exposure in Adult Male African Catfish (Clarias gariepinus)
Authors: Asenuga Ebunoluwa R. , Olajuyigbe Folasade M , Akinmoladun Afolabi C. , Fasakin Emmanuel A.
Published: June 2022

Exposure to Bisphenol A (BPA) has been associated with several health challenges in humans and animals. This study investigated the effect of BPA toxicity on African catfish (Clarias gariepinus) with emphasis on biochemical, hematological and histological changes. Seventy healthy adult male fish were used for the study. Fish were divided into seven groups in duplicates. Group A was the water control group, and Group B served as the solvent control group. In contrast, Groups C, D, E, F and G were exposed to BPA at varying concentrations (10 mg/L, 15 mg/L, 20 mg/L, 25 mg/L, and 50 mg/L of water, respectively) for 96 h. Results showed that the lethal concentration (LC50) of BPA was 26.9 mg/L. Physicochemical parameters assessment of water showed a significant increase in the conductivity level and total dissolved solids. Markers of hepatorenal dysfunction (alanine aminotransferase, aspartate aminotransferase, alkaline phosphate, blood urea nitrogen, creatinine, total protein, albumin and globulin) increased with BPA concentration. A significant decrease in hematocrit (HCT), hemoglobin (Hb), red blood cell (RBC) was observed. A significant increase in mean corpuscular volume (MCV), white blood cell (WBC), and lymphocyte counts were also observed in C. gariepinus exposed to BPA. Histological examination showed centrilobular hepatocellular atrophy in the liver, lamellae atrophy and fusion of the gills, atrophy and vacuolation of goblet and club cells of the skin tissue. Findings from this study provide deeper insights into the effects of BPA exposure on hepatorenal functions, hematological profile and histology of selected tissues of adult male C. gariepinus.
Evaluation of the Eeffectiveness of Two Surgical Methods of Tension-free Vaginal Tape (Transversal and Longitudinal Incision of the Vagina) in Women with Stress Urinary Incontinence
Authors: Bartani Zohreh , Mousavi Seyedeh Roqayeh
Published: June 2022

The aim of this study was to determine the effectiveness of two surgical methods of Tension-free Vaginal Tape (TVT) (transversal and longitudinal incision of the vagina) on stress urinary incontinence in women referred to Imam Reza Hospital during 2012–2019. The present study was a clinical trial study which was conducted on 138 women with stress urinary incontinence. TVT surgery. Patients were randomly divided into two groups with transversal (n = 69) and longitudinal incision (n = 69) based on purposive sampling. All patients before surgery underwent cystoscopy, Marshall test and cough stress test, urinary tract mobility test and, if necessary, urodynamic test, pelvic examination and post-void residual (PVR) urine test and completed the incontinence impact questionnaire-7 (IIQ-7). Then, mesh survival at 60 months after surgery was assessed by trans-libial ultrasonography. Statistical analysis was conducted by SPSS 24 (Chi-square test, Fisher's exact test).There was no statistically significant difference between the two groups with longitudinal and transverse incisions in terms of mean age, duration of surgery and the amount of urine remaining in the bladder before and after surgery (P-Value > 0.05). The recovery rate was higher in the transverse incision group compared to the longitudinal incision group and this difference was statistically significant (P-Value = 0.023). Also, the mesh retention rate was higher in the middle position of the duct in the transverse incision group .TVT surgery with transversal incision of the vagina can be effective and safe in treating stress urinary incontinence of women.
Extracranial arteriovenous malformations demonstrate dysregulated TGF-β/BMP signaling and increased circulating TGF-β1
Authors: Wei Ting , Richter Gresham T. , Zhang Haihong , BE Ravi Sun , Smith Conor , Strub Graham
Published: June 2022

Background: Extracranial arteriovenous malformations (AVMs) are characterized by anomalous arterial-to-venous connections, aberrant angiogenesis, local inflammation and hypoxia, and disorganized histological architecture; however, the precise molecular perturbations leading to this phenotype remain elusive. We hypothesized that extracranial AVM tissue would demonstrate deregulation of the TGF-β/BMP signaling pathway, which may serve as a potential target in the development of molecular-based therapies for AVMs. Methods: AVM tissue was harvested during resection from 10 patients with AVMs and compared to control tissue. Blood was collected from 14 AVM patients and 10 patients without AVMs as controls. Expression of TGF-β/BMP pathway components was analyzed using RT-PCR, western blotting, and immunohistochemistry. Circulating levels of TGF-β1 were analyzed by ELISA. Paired t tests were utilized to perform statistical analysis. Results: The mRNA levels of TGF-β1, ALK1, Endoglin (ENG), Smad6, Smad7, and Smad8 were significantly elevated in AVM tissue when compared to controls. Protein levels of TGF-β1 and Smad3 were elevated in AVM tissue while protein levels of BMP-9, ALK1, Smad1, Smad6, and Smad8 were significantly decreased in AVMs. Immunohistochemistry demonstrated significantly increased TGF-β1 in the perivascular cells of AVMs compared to normal controls, and circulating levels of TGF-β1 were significantly higher in AVM patients.Conclusions: Patients with AVMs demonstrate aberrant TGF-β/BMP expression in AVM tissue and blood compared to controls. Targeting aberrantly expressed components of the TGF-β/BMP pathway in extracranial AVMs may be a viable approach in the development of novel molecular therapies, and monitoring circulating TGF-β1 levels may be a useful indicator of treatment success.