bluuebunny/crossref_metadata_2025 huggingface dataset:
Psychometric Properties and Hidden Dimensionality of the Sinhala Version of End Stage Renal Disease Adherence Questionnaire (SINESRD-AQ) Among Patients Receiving Haemodialysis in a Selected Hospital in Sri Lanka
Authors: Lasanthika Chalani , Wanigasuriya Kamani , Hettiaratchi Usha , Amarasekara Thamara Dilhani , Goonewardena Christine Sampatha Evangeline
Published: February 2022

ObjectiveThe purpose of this study was to evaluate the psychometric properties of Sinhala translated version of End Stage Renal Disease Adherence Questionnaire (SINESRD-AQ). ResultsA total of 150 patients with mean age of 54.08±10.78 (±SD) years were included. Majority were males (72.7%). Excellent face and content validity of SINESRD-AQ was reported with an average I-CVI of 0.93. The Confirmatory Factor Analysis of two subscales of ESRD-AQ demonstrated barely acceptable model fit (SRMR=0.120, CFI=0.913, GFI=0.997, AGFI=0.996, NNFI=0.896). Subsequent Non-linear Principal Component Analysis (CATPCA), O’Connor parallel analysis and Cattell’s Scree plot revealed new dimensionality with five components of SINESRD-AQ explaining 74% of the total variance. Acceptable level of Cronbach’s Alpha and composite reliability confirmed the internal consistency reliability of new dimensionality. Convergent validity of new dimensionality was confirmed with Composite Reliability (CR) and Average Variance Extracted (AVE) with the values greater than 0.7 and 0.5 respectively. According to the Fornell Larcker criterion (1971), the square root of AVEs of components were greater than the inter component correlations and heterotrait-monotrait values were less than the threshold of 0.85 demonstrated the discriminant validity of new dimensionality.
The complete chloroplast genome sequence of wax gourd (Benincasa hispida), and comparative analyses with related species revealing evolutionary dynamics within Benincaseae
Authors: Song Weicai , Chen Zimeng , He Li , Qi Feng , Zhang Hongrui , Shi Chao , Wang Shuo
Published: February 2022

Benincasa hispida (wax gourd) is a crucial important crop of Cucurbitaceae with enormous economic and medicinal importance. Here, we first report the de novo assembled and completely annotated the chloroplast genome of wax gourd with 156,758 bp in total that comprises of a large single copy (LSC) region with 86,538 bp and a small single copy (SSC) region with 18,060 bp, separated by a pair of inverted repeats (IRa and IRb) with 26,080 bp each. The chloroplast genome contains 131 genes, including 86 protein-coding genes, 37 tRNAs and 8 rRNAs. Comparison analyses among B. hispida and three other species from Benincaseae presented a great extent of conversation regarding nucleotide content, genome structure, codon usage, synonymous and non-synonymous substitutions, putative RNA editing sites, microsatellites, and oligonucleotide repeats. LSC and SSC regions were detected to be much more variety than IR regions through divergent analysis among species within Benincaseae. Notable IR contraction and expansions were observed, causing the difference in genome size and gene duplication, deletion and the presence of pseudogenes. Intronic gene sequences such as trnR-UCU – atpA, atpH – atpI were observed as high divergent regions and genes namely ycf1, accD, ccsA and matK presented more various than other genes. Two types of phylogenetic analysis based on complete cp genome and 72 genes suggested the sister relationships of B. hispida with genus Citrullus, Lagenaria and Cucumis. The cp genome of B. hispida provide valuable genetic resource for the detection of molecular marker, research of the taxonomic discrepancies and the inference of phylogenetic relationships among species within Cucurbitaceae.
Self-resistance electric heating of shaped CFRP laminates: temperature distribution optimization and validation
Authors: Shen Yingxiang , Lu Yong , Liu Shuting , Liu Qiangqiang , Tao Shuangquan , Hao Xiaozhong
Published: February 2022

The Self-Resistance Electrical (SRE) heating method to cure carbon fiber reinforced polymer (CFRP) part possesses the advantages of rapid and volumetric heating, low energy consumption, and low asset investment. But the current SRE heating methods are difficult to uniformly cure the shaped CFRP parts due to the non-uniformly distributed Joule heat power in the parts with a varying cross-sectional area. In this paper, an optimized multi-zone SRE heating method is proposed, in which the uniform heating and curing process of the shaped CFRP part is firstly achieved. By optimizing the orientation of the rectangular zones, the local overheating caused by the voltage gradient and current diffusion between different zones is notably suppressed. Combined with the electro-thermal numerical analysis, the influence of the positional offset of electrodes in two adjacent zones on the temperature uniformity is investigated. Based on this, an automated zoning algorithm and the prioritizing method of the zone orientation are established. The proposed method is numerically and experimentally validated with the typical shaped CFRP parts, and the results are compared with that of the existing SRE heating method. The proposed method realizes that the maximum in-plane temperature difference of shaped CFRP parts is reduced by more than 80%. This method significantly improves the temperature uniformity of shaped CFRP parts during the multi-zone SRE heating process, which provides a potential solution for high-quality and efficient curing of CFRP parts.
Barriers And Facilitators For Therapeutic Drug Monitoring Of Beta-Lactams And Ciprofloxacin In The ICU: A Nationwide Cross-Sectional Study
Authors: Ewoldt Tim M.J. , Abdulla Alan , Broek Puck van den , Hunfeld Nicole , Bahmany Soma , Muller Anouk E. , Gommers Diederik , Polinder Suzanne , Endeman Henrik , Spronk Inge , Koch Birgit C.P.
Published: February 2022

Background: Recent studies demonstrated that failure of achieving pharmacodynamic targets of commonly used antibiotics is common in critically ill patients. Therapeutic drug monitoring (TDM) can contribute to optimize the exposure of beta-lactams and ciprofloxacin. While evidence for TDM of these antibiotics is growing, translation into clinical implementation remains limited. Therefore, perceived barriers and facilitators are important for implementing TDM in this population. The primary aim of this study was to identify healthcare professionals’ barriers and facilitators for the implementation of TDM of beta-lactams and ciprofloxacin in Dutch intensive care units (ICU).Methods: We conducted a nationwide cross-sectional online survey among healthcare professionals (HCPs) involved in antibiotic treatment of ICU patients. An adapted version of the Measurement Instrument for Determinants of Innovations was sent out. Items were considered barriers when ≥ 20% of participants responded with a negative answer. If ≥ 80% of the participants responded with a positive answer, the item was considered a facilitator.Results: Sixty-four HCPs completed the survey, of which 14 were from academic hospitals, 25 from general hospitals, and 25 from teaching hospitals. Most participants were hospital pharmacists (59%) or medical specialists (23%). Eleven barriers and four facilitators for implementation of TDM of beta-lactams were identified; 17 barriers for TDM of ciprofloxacin and no facilitators. The most important barriers were a lack of conclusive evidence, organizational support, and low availability of assays. Additional barriers were a lack of consensus on which specific patients to apply TDM and which pharmacodynamic targets to use. Identified facilitators for beta-lactam TDM implementation are low complexity and high task perception, combined with the perception that TDM is important to prevent side effects and to adequate treat infections. Twenty-eight percent of participants reported that flucloxacillin could be analyzed in their hospital. Availability of other beta-lactams and ciprofloxacin varied (3-17%).Conclusion: Several barriers were identified that could obstruct the implementation of TDM of beta-lactams and ciprofloxacin in the ICU. In particular, education, clear guidelines, and organizational support in particular should be considered when creating tailored implementation strategies. Finally, evidence of beneficial clinical outcomes on TDM of beta-lactams and ciprofloxacin can enhance further implementation.
Baseline composition and microbial quality assessment of raw milk from endemic small ruminants and Maghrebi camels in the oasis area of Tunisia
Authors: Khaldi Zahran , Nafti Mounir , Jilani Mohamed Tabarek
Published: February 2022

The milk quality and characteristics of the local Gharbi sheep and autochthonous goat population were studied and compared to those of the local Maghrebi camel. Milk samples from 378 lactating animals raised in the Tunisian oasis region were obtained and processed for various physicochemical compositions (pH, density, acidity, dry matter, fat, protein, lactose, casein, ash, and casein-protein ratio), mineral concentrations (Ca, P, Na, and K), and bacteriological properties (total mesophilic aerobic bacteria (TMAB), total coliform count (TCC), lactic acid bacteria (LAB), sulfite-reducing Clostridium (CSR), yeast and molds (Y/M), Staphylococcus aureus (S. aureus), Escherichia coli (E. coli), and Salmonella) using standard methods. Milk from sheep breeds had a higher average of all physical parameters (pH, density, and dornic acidity) than milk from goat species. The sheep population produced milk with a similar pH to the camel population, but with a higher density and acidity content. The pH and acidity were higher in Neggas than in goat species, while density was similar in both. For chemical composition, the results showed significant heterogeneity in milk content across all species. Except for the casein-protein ratio, which favors goat species, the analysis indicates that sheep species were superior to populations of goats and camels in all chemical compositions. The present results showed considerable variation in the mineral content of milk from different species. The levels of calcium and phosphorus are higher in sheep than in goat and camel milk. Compared to small ruminants, milk from camels is the richest in Na and K. Additionally, more calcium is present in the milk of camels than that of goats. Goat milk, the lowest in Ca and Na, contains more P than camel milk and more K than sheep's milk on average. The poorest microbial quality was that of camel milk for all bacterial counts. Based on TMAB, TCC, and E. coli counts, the microbiological quality of goat milk was higher than that of ovine milk, while ovine milk had better quality based on LAB, Y/M, and S. aureus values. For Escherichia coli and Staphylococcus aureus, there were no significant variations between the species studied. Results showed that all milk samples studied were completely free of two dangerous pathogens, Salmonella and sulfite-reducing Clostridium. The bacteriological quality of small ruminant’s milk was acceptable and met the regulatory limits set by Tunisian dairy legislation. Regarding camel milk, the microbial analysis revealed poor quality that exceeds standard criteria.
Terrestrial Forcing of Marine Biodiversification
Authors: Martin Ronald , Cardenas Andrés
Published: February 2022

Physical and biological factors have been proposed to account for the long-term development of marine biodiversity through the Phanerozoic Eon. Nutrient availability and primary productivity have, however, received less attention. We demonstrate that the diversification of the major marine faunas during the Phanerozoic was coupled to nutrient runoff from land and the diversification of phosphorus-rich plankton. Nutrient input to the oceans increased dramatically during the Meso-Cenozoic in response to widespread orogeny and peaked repeatedly following the eruption and weathering of phosphorus-rich continental Large Igneous Provinces. Widespread orogeny, forestation, and nutrient runoff during the Permo-Carboniferous was transitional to the Mesozoic and continued during the later Mesozoic and Cenozoic eras with the further tectonism and the spread of angiosperms, modern representatives of which tend to be more nutrient-rich. Early-to-middle Paleozoic diversity was, in contrast, limited by nutrient-poor plankton resulting from less frequent tectonism and poorly-developed terrestrial floras. Our results suggest that biodiversity on geologic time scales is unbounded, provided sufficient nutrients and nutrient-rich plankton are available on optimal timescales.
Spatiotemporal changes of cyanobacterial and bacterial communities during an algal bloom in a subtropical water source reservoir ecosystem of China
Authors: Huang Zhenhua , Jiang Cancan , Xu Shengjun , Zheng Xiaoxu , Lv Ping , Wang Cong , Wang Dongsheng , Zhuang Xuliang
Published: February 2022

Massive nitrogen and phosphorus input into aquatic ecosystems makes algal bloom as one of the most concerning problems in China. Algal blooms not only threaten the health and stability of aquatic ecosystems, but also influence the microbial community within. However, less is known regarding how algal bloom affects the spatiotemporal variation of aquatic microbial community, including cyanobacteria and other bacteria. In this study, we used high-throughput sequencing to investigate how the cyanobacterial and bacterial community diversity and composition spatiotemporally vary along main algal bloom phases in upstream rivers of a eutrophicated water source reservoir. For both cyanobacteria and bacteria, their diversities demonstrated temporal significance amongst different phases in each river, indicating the apparent impact of algal bloom. Dominant cyanobacterial taxa included Chloroplast, Cyanobacteriales, and Synechococcales, and dominant bacterial taxa comprised Acinetobacter, CL500-29, hgcI clade, Limnohabitans, Flavobacterium, Rhodoluna, Porphyrobacter, Rhodobacter, Pseudomonas, and Rhizobiales, whose relative abundance varied along the algal bloom, rendering distinct community composition for each river. Non-metric multidimensional scaling analysis additionally indicated significant differences amongst different phases, and the linear discriminant analysis (LDA) with LDA effect size analysis (LEfSe) helped to identify the significant biomarkers (OTUs) in each river at different phases. Canonical correlation analysis (CCA) or redundancy analysis (RDA) revealed distinct correlation patterns of cyanobacterial and bacterial communities with the environmental parameters, which implies their distinct ecological functions. In general, these results demonstrated the significant influence of algal bloom on microbial communities in a eutrophicated water source reservoir basin. These observations also arouse universal demands for strategies conserving the aquatic microbial equilibrium and alleviating algal blooms in reservoirs.
Environmental drivers dependent habitat expansion of introduced alien trout (Salmo trutta fario and Oncorhynchus mykiss) in the Himalayan ecosystem and management concerns in the time of climate change
Authors: Singh Atul K , Srivast Sharad C
Published: February 2022

Introduced alien brown trout Salmo trutta fario and rainbow trout Oncorhynchus mykiss are although abundantly available in western Himalaya, its distribution is now expanding in different Himalayan states. We present the first assessment of environmental drivers’ responsible for current distribution and potential expansion of S. trutta fario and O. mykiss in the Himalayan ecosystem. MaxEnt model was used in this study, which was overlaid with presence data into environmental layers with a total of 81 occurrence points to estimate contemporary suitable habitat. Results of this study indicated that the precipitation of driest quarter (Bio_17) contributed 71.4% for S. trutta fario and 61.1% for O. mykiss distribution respectively. The other environmental variables responsible were altitudinal variable (GMTED_DEM) 7.9% and precipitation seasonality (Bio_ 15) 10.9% for brown trout distribution. In case of O. mykiss, the contributed three layer of permutation importance were driest quarter (Bio_9) 10.8%; precipitation (Prec_03) 9.6% and length_slope 7%. Our findings facilitate understanding of bioclimatic factors responsible for expanding habitat distribution of trout and forecasting environmental variables and climate change trade-offs towards habitat regime shift in the Himalayan region of Asian continent suggesting need of their sustainable management.
Incidence and Risk Factors Associated with Falls Among Women with Breast Cancer During Taxane-Based Chemotherapy
Authors: Rattanakrong Nida , Siriphorn Akkradate , Boonyong Sujitra
Published: February 2022

Purpose
This study aims to evaluate the falling incidence density and examine the potential risk factors associated with falling among women with breast cancer during taxane-based chemotherapy.
Methods
One hundred and twenty-three women with breast cancers were participated in this study. The fall incidence density, taxane-induced peripheral neuropathy (TIPN) symptoms, and physical performance tests were evaluated at five time points throughout chemotherapy treatment. A fall diary was used to record fall incidence density during treatment. The fall incidence density was calculated by the number of first fall occurrence divide by person-time at risk. The risk factors associated with falls incidence density were analyzed using the Cox proportional hazard model. The Kaplan-Meier curve illustrated the probability to survive from fall during chemotherapy treatment.
RESULTS
Over the course of taxane-based chemotherapy, 29 (23.58%) women with breast cancer reported falls. In addition, the fall incidence density was 3 per 1000 person-day. This study discovered a significant link between age (HR = 1.06; 95% CI: 1.01-1.11), BMI (HR = 1.10; 95% CI: 1.01-1.20), and a 30-s chair stand test (HR = 0.82; 95% CI: 0.79-0.97) and falling.
CONCLUSIONS
As evidenced by the findings, the initial fall occurred after the first cycle of chemotherapy treatment and was found throughout the course of treatment. Furthermore, falls were associated with age, BMI, and a 30-second chair stand test. Early detection of TIPN symptoms and lower limb muscular weakness, particularly among older persons and those with a high BMI, may be essential to prevent falls.
Costs Associated with Adverse Events from Remission Induction for Children with Acute Lymphoblastic Leukemia (ALL)
Authors: Mejía-Aranguré Eréndira , Reyes-López Alfonso , Juárez-Villegas Luis Enrique , Hernández-Olivares Yosef Olaf , Saucedo-Campos Alberto Daniel , Hernández-Pliego Gabriela , Martínez-Valverde Silvia , Barajas-Nava Leticia A. , Garduño-Espinosa Juan
Published: February 2022

BackgroundDuring remission induction (RI) treatment, adverse events (AEs) may require hospital treatment, causing partial or total suspension of the treatment protocol depending on their severity which delays the end of RI. We will follow up patients with AEs initiated in IR assuming that they may require several weeks of treatment before hospital discharge, which may represent a considerable cost for the hospital institution.ObjectiveTo estimate the incremental cost of the RI treatment protocol by the presence of AEs in children with ALL.MethodsChildren with a recent diagnosis of ALL, who are undergoing RI treatment. The AE experienced during remission were classified according to System Organ Class (SOC). With data available from the clinical records, we quantified and compared the direct medical costs generated between a group of patients who presented AE and another group that did not. Generalized linear models were developed to identify cost variations according to the frequency of events, which were associated with characteristics of the patient, such as sex, risk category and alive status.Results297 AEs were identified in 86.8% of the patients, 68.7% of the events were treated in hospital. The total incremental cost to treat a patient who has adverse events during induction exceeds $7,000 and for each additional adverse event the total cost increase $527 dollars.ConclusionThe cost of a pediatric patient undergoing RI without adverse events is $3,078.36. The average incremental cost to treat a patient with AEs exceeds twice the cost of a patient without events and the frequency of inpatient AEs in RI exceeds that of outpatient by three to one. Generalized linear models show that variables such as sex, risk category and alive status are associated with the presence, frequency and cost of AE. This is the first study aiming to analyze the effect of ALL-related AEs on health care costs in pediatric population, so our results may help not only to local decision making but also it may contribute to the research agenda in this field.
Application of trans-sutural distraction osteogenesis based on an optical surgical navigation system to correct midfacial dysplasia
Authors: Zhao ZhenMin , Chen YuJie , Du ShanShan , Lin ZhiYu , Zhang PeiYang , Zhang XinLing , Wang JunCheng
Published: February 2022

Midfacial hypoplasia is a common maxillofacial deformity in patients with cleft lip and palate, which requires surgical treatment. However, achieving noninvasiveness in trans-sutural distraction osteogenesis (TSDO) for midfacial hypoplasia has been difficult. This study aimed to introduce the application of an optical surgical navigation system (OSNS) developed by the authors in TSDO. Six consecutive patients with midfacial hypoplasia (five boys and one girl, with an average age of 10 years; five patients with postoperative cleft lip and palate, and one patient without combined cleft lip and palate) who required TSDO were included in the study. Preoperatively, head computed tomography was performed, and the data were imported into the computer's Mimics software (version 20.0) to design a three-dimensional simulation of the surgical approach. TSDO was performed with the use of the OSNS, and the accuracy and results of the procedure were initially evaluated by comparing the preoperative and postoperative periods. The surgical procedure was successful, with a postoperative follow-up of 4–5 months. All patients demonstrated good treatment results, without complications. Therefore, the OSNS can safely and effectively guide the TSDO technique, essentially correcting midfacial dysplasia, achieving non-invasiveness, improving surgical precision, reducing bleeding, and obtaining better clinical results.
Evaluation the efficacy of optimized two-step-administration therapy with ceftazidime/avibactam for treating Extensively drug-resistance (XDR) Pseudomonas aeruginosa pulmonary infections: a Pharmacokinetic/pharmacodynamic analysis
Authors: Kang Yixin , Cui Junchang
Published: February 2022

Background: The objective of this pharmacokinetic (PK)/pharmacodynamic (PD) analysis was to evaluate the efficacy of different dosing regimens of ceftazidime-avibactam (CZA) for the treatment of extensively drug-resistance (XDR) Pseudomonas aeruginosa pulmonary infections by using optimized two-step-administration therapy (OTAT) and traditional infusion (TI).Methods: We used Monte Carlo simulations (MCS) to integrate PK parameters with PD parameters to assess the adequacy of ceftazidime-avibactam dosing for XDR P. aeruginosa pulmonary infections. We obtained pharmacokinetic parameters from a previously published study and pharmacodynamic parameters from the international network for optimal resistance monitoring (INORM). Dosing models were as follows: 2.5 g q8h, 2.5 g q6h, 4 g q8h, 4g q6h, 1.25 g q8h, 1.25 g q6h, and 0.94 g q12h.Results: MCS showed that the cumulative fraction of response (CFR) of all dosing regimens of OTAT was higher than 90%. Similarly, the probability of target attainments (PTAs) of all dosing regimens of OTAT at MICs of 16-32 mg/L was higher than those of TI. Based on the models, PK/PD goals were met with OTAT regimens even with high MICs (>16 mg/L) compared with traditional infusion intervals. Conclusion: Our work indicated that OTAT with sufficient pharmacokinetic exposures could improve the efficacy of CZA for XDR P. aeruginosa pulmonary infections.
Echinocystic acid induces the apoptosis, and inhibits the migration and invasion of non-small cell lung cancer cells
Authors: zhu duojie , Wang Cheng , Jiang Peng , Tang Futian , Li Yumin , li bin
Published: February 2022

An increasing amount of evidence has demonstrated the anticancer activity of triterpenes extracted from traditional medicines. Echinocystic acid (EA), a natural triterpene isolated from Eclipta prostrata (L.) L., has previously been shown to exhibit anticancer activity in HepG2 and HL-60 cells. The aim of the present study was to investigate the anticancer activity of EA in non-small cell lung cancer (NSCLC) cells. For this purpose, the viability and proliferation of A549 cells were determined using a Cell Counting Kit-8 and 5-ethynyl-2’-deoxyuridine staining. The migratory and invasive ability of the A549 cells were measured using wound healing and Transwell assays. Hoechst staining was also performed to detect the apoptosis of A549 cells. The proliferation of A549 cells and the distributions of different growth phases were determined using a flow cytometer. Western blot analysis was used to detect the expression levels of cyclin D, partitioning defective 3 homolog (Par3), PI3K, Akt, mTOR, Bax, Bcl-2 and caspase-3. EA inhibited the proliferation, and the migratory and invasive abilities of cultured lung carcinoma cells (A549 cells), and induced cell cycle arrest in the G1 phase of the cell cycle. Treatment with EA upregulated Par3 expression and inhibited the PI3K/Akt/mTOR pathway in vitro. In addition, EA treatment inhibited tumor growth, suppressed proliferation and induced the apoptosis of tumor cells in NSCLC tumor xenografts in mice. On the whole, these results suggest that EA may represent a potential therapeutic agent for NSCLC.
Heatstroke-induced late-onset neurological deficits in mice caused by Purkinje cell degeneration, demyelination, and synaptic impairment at cerebellum
Authors: Miyamoto Kazuyuki , Nakamura Motoyasu , Ohtaki Hirokazu , Suzuki Keisuke , Yamaga Hiroki , Yanagisawa Kaoru , Maeda Atsuo , Yagi Masaharu , Hayashi Munetaka , Honda Kazuho , Dohi Kenji
Published: February 2022

Global warming increases the incidence of heatstroke. After heatstroke, patients are bedridden and exhibit neurological symptoms suggesting cerebellar damage. However, the potential long-term adverse outcomes are poorly understood. We studied the cerebellum after heatstroke. In our study, motor coordination disorder significantly appeared 3 weeks post heatstroke and gradually improved to some extent over time. Demyelination was detected at 1 and 3 weeks after heatstroke at the cerebellum. Interestingly, it was not found at the corpus callosum. The Purkinje cell numbers significantly decreased at 1-, 3-, and 9-weeks post heatstroke. The intensity of synaptophysin and postsynaptic density-95 (PSD95) temporarily decreased at 3 weeks post heatstroke; however, both increased at 9 weeks post heatstroke. Motor coordination loss occurred a few weeks after heatstroke and recovered to some extent. Late-onset motor impairment was suggested to be caused by cerebellar dysfunctions that were morphologically assessed by myelin staining and immunostaining of Purkinje cells with pre-and postsynaptic markers. However, the Purkinje cell number did not recover for 9 weeks, the others, including motor coordination were partially recovered probably by synaptic reconstruction, residual Purkinje cells, and other cerebellar neuron remyelination. These phenomena were associated with late-onset neurological deficits and recovery after heatstroke.
Lipstick on a pig: Understanding efforts to redesign audit and feedback reports for primary care.
Authors: Rouleau Geneviève , Reis Catherine , Ivers Noah Michael , Desveaux Laura
Published: February 2022

Background: In Ontario, Canada, a government agency known as Ontario Health is responsible for making audit and feedback reports available to all family physicians. The confidential report provides summary data on three key areas of practice: safe prescribing, cancer screening, and diabetes management. This report was redesigned to improve its usability and the objective of this study was to explore how the redesign was perceived. Methods: We conducted qualitative semi-structured interviews with family physicians who had experience with both versions of the report, recruited through purposeful and snowball sampling. We analysed the transcripts following an emergent and iterative approach. Results: Saturation was reached after 17 family physicians participated. Two key themes emerged as factors that impacted the perceived usability of the report: (1) alignment between report and recipients’ expectations and (2) capacity to engage in quality improvement. Family physicians expected the report and its quality indicators to reflect best practice, to be valid and accurate. They also expected the report to offer feedback on clinical activities they perceived were within their control to change. Further, family physicians expected the goal of the report to be aligned with their perspective on feasible quality improvement activities. Most of these expectations were not met, limiting the perceived usability of the report. The capacity to engage with audit and feedback was hindered by several organizational and physician-level barriers including the lack of fit with existing workflow, competing priorities, time constraints, and insufficient skills for bridging the gaps between their data and the corresponding desired actions.Conclusions: Overall, the redesigned feedback report was not perceived as highly usable, given the misalignement between report and family physicians’ expectations as well as limited capacity to engage with the report. Consequently, the potential impact on clinical practice may be limited. Co-interventions to address the barriers of using audit and feedback report, as well as creating space for bridging together audit and feedback designers and recipients are avenues to consider for improving usability and effectiveness such quality improvement initiatives.
Simulation Based Clinical Skill Training; A Need Of Time
Authors: Nisar Sumera , Rehman Durraiz , Rehman Areeb
Published: February 2022

Objective: To explore the perception and attitude about simulation-based learning (SBL) of clinical skills in undergraduate medical students.Place and Duration of Study: College of Medicine, Princess Noura bint Abdulrehman university; Riyadh, Saudi Arabia, from March to September 2019.Method: A pre-tested structured self-administered questionnaire was used to collect the data about student’s perception about simulation-based learning. Informed written consent was taken from the students. Data analysis was done by SPSS version 21 and Chi square test was used to see the association between the variables of the interest.Result: Mean age of the students was 21.5 (standard deviation ±1.8) years. Majority of the students (81.6%) found SBL as a favorable mode of learning clinical skills. 59% of the students found it useful to manage to see the rarest cases in medicine. Many of them believed it useful to overcome the problems of uncooperative patients (59.1%) and to solve the problem in getting the patients during exam (60.2%). They also strongly believed that simulation should be integrated in medical school curriculum as an efficient tool for learning clinical skillsConclusion: The study strongly suggests student’s positive perspective towards learning through simulation. Medical educators and curriculum designers can use the results of the study to incorporate simulation in undergraduate curriculum to train and enhance student’s clinical skills and maintain patient safety.
On Occurrence of Mixed-torus Bursting Oscillations Induced by Non-Smoothness
Authors: Bi Qinsheng , Chen Shaomin
Published: February 2022

The paper devotes to the slow-fast behaviors of a higher dimensional non-smooth system with the coupling of two scales. Some novel bursting attractors and interesting phenomena are presented, especially the so-called mixed-torus bursting oscillations, in which the trajectory moves along different tori in turn, though the bursting attractor still behaves in quasi-periodic form. Based on a 4-D hyper-chaotic model with two scrolls, a modified non-smooth slow-fast version is established by introducing a non-smooth boundary as well as a periodic external excitation, which can also be easily implemented by circuit. When the exciting frequency is far less than the natural frequency, implying the coupling of two scales in frequency domain exists, the whole exciting term can be regarded as a slow-varying parameter. Upon the bifurcations analysis of the subsystems in the two regions divided by the boundary, together with the non-smooth bifurcations on the boundary, the coexisted attractors with the variation of the slow-varying parameter are derived.
From the dynamical evolution of the full system with the increase of the exciting amplitude, bursting oscillations may change from periodic to quasi-periodic attractor, the mechanism of which is obtained by employing the overlap of the transformed phase portrait and coexisted attractors as well as the bifurcations. Sliding along the boundary on the trajectory can be observed on the bursting attractor, the mechanism of which can be accounted for by employing the non-smooth theory or by the in-turn influence of two pseudo attractors in different regions. Super-cone defined by a unstable focus may leading to the period-adding or period-decreasing phenomena in the spiking oscillations, while fold limit cycle bifurcation may result in the dramatically change of the spiking amplitude. The trajectory may pass across or graze at the boundary, while grazing bifurcation may cause the period-doubling bifurcation of the stable non-smooth limit cycle. Numerical simulation reveals that the grazing point on the trajectory can be removed by increasing the exciting amplitude, which can be used for controlling purpose. Furthermore, it is found that when the amplitude increases to an extent, both the non-smooth limit cycle as well as the cycle bifurcated from it via period-doubling bifurcation may involve the full vector field, resulting in the so-called mixed-torus bursting oscillations, in which the quiescent states seems to be pivots of the oscillations.
A Journey of Digital Co-Production: Introducing the “E-Nabling Digital Co-Production” Framework and Its Performance in Dementia Research
Authors: Molinari-Ulate Mauricio , Woodcock Rebecca , Smith Isabelle , Roest Henriëtte G. van der , Franco-Martín Manuel A. , Craven Michael P.
Published: February 2022

Background
The rapid transition to digital working, accelerated due to the response to the COVID-19 pandemic, has impacted the involvement of patients and public in research. For this reason, this paper presents a narrative of a co-production journey experienced by a Participant and Public Involvement (PPI) group since the lockdowns and recommendations regarding digital working in England, followed by a practical implementation of a framework within the context of dementia research.
Methods
Three online workshops were performed with a group of researchers, facilitators and contributors with experience in PPI in dementia research, and a dementia PPI group that kept working during the pandemic. Thematic analysis was chosen for the data analysis. The project was targeted as a PPI activity and the MindTech Involvement Team (PPI group) was involved in the entire process.
Results
After a refinement of the coding structure, the MindTech Involvement Team and Project Leaders identified the potential of using four coding areas resulting in the ‘E-nabling Digital Co-production' Framework. Through this framework, conflicting positions were identified associated with the transition to digital working. Two main remarks were shared by the participating groups regarding e-PPI; the wider potential in terms of non-geographical constraints, and the perspective of more business-like sessions with reduce social interactions and communication. Specifically for dementia research, e-PPI may allow participants to attend more meetings, although the mutually supportive environment of face-to-face meetings is diminished, and carers can miss out on respite opportunities.
Conclusions
This public engagement activity introduced the ‘E-nabling Digital Co-production' Framework showing an initial potential for the analysis of e-PPI flaws and benefits. It was possible to identify insights of e-PPI regarding general concerns and specific to dementia research. However, the most significant contribution of the framework is the potential to support local journeys of co-production in ongoing public involvement activities.
AR Artificial Antagonist HC-1119 Regulated TNBC BT549 Cells Proliferation and Metastasis via PI3K/Akt/mTOR Signaling Pathway
Authors: Huang Qian , Zhang Qing , Ren Qiuyu , Ma Lu , Li Xinghai , He Tao , Gan Lin
Published: February 2022

Background: Triple negative breast cancer (TNBC) was a specific refractory and aggressive malignancy subtype of breast cancer with high mortality. Our study aimed to explore the underlying molecular mechanism of androgen receptor (AR) antagonist HC-1119 on BT549 cells. Methods: AR, estrogen receptor (ER), progesterone receptor (PR), epidermal growth factor receptor 2 (HER2) were detected by western blotting in common breast cancer cell lines. The cell viability was detected by Cell Counting Kit-8 (CCK8) assay. The apoptotic percentage and cell cycle distribution were assessed by flow cytometry, the cells motility and invasion capability were analyzed by Transwell assay. The potential signaling pathway was explored by RNA-Seq and bioinformatics analysis in BT549 cells treated with HC-1119, and was determined by western blotting. Results: BT549 cells hardly expressed HER2, PR and ER, but highly expressed AR. HC-1119 significantly inhibited the AR expression. HC-1119 and bicalutamide both inhibited the cell proliferation in a concentration-dependent manner and in a time-dependent manner of BT549 cells. HC-1119 and bicalutamide could significantly increase the percentage of apoptosis and S-phase percentage of BT549 cells and reduced BT549 cells motility and invasion capabilities. RNA-Seq and Bioinformatics results showed that HC-1119 regulated BT549 cells proliferation via the PI3K/Akt/mTOR signaling pathway. Western blotting data convinced that HC-1119 could inhibit the expressions of p-mTOR, p-Akt, S6, p-S6 and P21.Conclusions: Our study revealed that the artificial AR antagonist HC-1119 inhibited BT549 cells cell proliferation, motility and invasion capabilities, induced cells apoptosis and arrested the cell cycle progression at the S phase. And HC-1119 may regulate cells proliferation via the PI3K/Akt/mTOR signaling pathway.
A Mobile Web Application Enhancing Knowledge and Providing Health Services Concerning Sexually Transmitted Diseases and Unplanned Pregnancy Prevention Among Akha Adolescents in Chiangrai Province, Northern Thailand
Authors: Chansiri Suphaphan , Wongwatkit Charoenchai
Published: February 2022

Background: Akha adolescents in Chiang Rai lack knowledge about safe sex, the severity of sexually transmitted diseases, and unplanned pregnancy. This research aimed to develop innovative applications to serve as an important tool for enhancing knowledge and understanding of sexual health.Methods: The study consisted of three phases. The first phase was a survey of the needs of Akha adolescents on Doi Mae Salong and Doi Wawee in Chiang Rai Province, using an exploratory qualitative research method. A semi-structured interview was used with a total of 48 subjects in both the formal and non-formal education system. Data were analyzed by content analysis. The second phase was the designing and development of the mobile web application prototype which was given to a group of 37 people, both males and females to try out. The third phase was to test the users’ knowledge improvement and a questionnaire survey of users’ satisfaction and opinions about the mobile web application using a sample of 108 users. Data were analyzed using descriptive statistics: frequency; percentage; mean; and standard deviation including a paired sample t-test.Results: The findings revealed a statistical significance (p ≤ 0.001) in the improvement of users’ knowledge (both males and females) between the pretest (x̅ = 4.15) and the posttest (x̅ = 7.23). Users’ satisfactions were also revealed with their impressions in 3 areas: 1) learning; 2) ease of use; 3) information display. The users found the mobile web application was useful, interesting, and attractive.Conclusions: This innovative application can increase knowledge and practices and prevent pregnancies and sexually transmitted diseases. It can be used in various learning contexts.
CD97 Serves as a Novel Biomarker of Immune Cell Infiltration in Hepatocellular Carcinoma
Authors: Su Qiuming , Li Lu , Li Xiaokai , Li Wang , Zhang Xibing , Dong Yun , Han Lei , Wang Duo , Ran Jianghua
Published: February 2022

Background
CD97 is the most widely expressed G protein-coupled receptor in the epidermal growth factor seven-span transmembrane family. It plays a vital role in cell adhesion, migration, and cell connection regulation. We explored the role of CD97 in hepatocellular carcinoma (HCC).
Methods
We evaluated CD97 mRNA expression in HCC using TNMplot and the Gene Expression Omnibus database. The clinical prognostic significance of CD97 in HCC was evaluated by gene expression profiling interactive analysis, the Kaplan–Meier plotter, and the UALCAN database. The Tumor Immune Estimation Resource (TIMER) and CIBERSORT databases were used to analyze the relationships among CD97, CD97 co-expression genes, and tumor-infiltrating immune cells.
Results
CD97 was highly expressed in HCC and was associated with a poor prognosis. CD97 and its co-expressed genes were positively correlated with tumor-infiltrating immune cells and strongly correlated with tumor-infiltrating macrophages (all r ≥ 0.513, P < 0.0001). CD97 was closely related to M2 macrophage and tumor-associated macrophage markers (both r ≥ 0.464, P < 0.0001). CD97 was found to be an immune-related gene in HCC and positively correlated with the TOX, PD-L1, PD-L2, CTLA4, and PD-1 immune checkpoint genes. CD97 copy number alterations affect the level of immune cell infiltration and mRNA expression.
Conclusions
CD97 can be used as a potential molecular marker of prognosis in HCC, which is associated with immune cell infiltration.
Thermal Decomposition and Kinetic Parameter of Bridgeman- Grown In2Se3-xSbx (x= 0.3) Single Crystals
Authors: Patel P. J. , Vyas S. M. , Patel V. A. , Varasada R.
Published: February 2022

The thermal analysis of the vertical Bridgman-grown In2Se2.7Sb0.3 single crystals was carried out by recording the Thermogravimetric (TG), Differential Thermogravimetric (DTG) and Differential Thermal Analysis (DTA) curves. All the three thermo-curves were recorded simultaneously by thermal analyzer in the temperature range of ambient to 650 0 C in air atmosphere. The thermo-curves were recorded for single heating rates of 10 °C/min. The thermal kinetic parameters of the vertical Bridgman-grown In2Se2.7Sb0.3 single crystals were determined employing the non-mechanistic H-M (Horowitz and Metzger), P-N (Piloyan-Novikova), C-R (Coats-Redfem) and Broido relation from TGA and PRN (Piloyan, Ryabchikov and Novikova) and BD (Borchardt and Daniels) relation from DTA curves. The determined kinetic parameters support the observations of the thermo-curves.
Maternal And Neonatal Exposure To Risk Factors For Neonates With Moderate Or Severe Hypoxic Ischemic Encephalopathy: A Cross-Sectional Study
Authors: wang yiran , luo shuying , wang kaijuan , hou yuwei , yan hui , zhang yaodong
Published: February 2022

Background:To investigate the association between maternal and neonatal exposure to the relevant influencing factors and risk of moderate or severe hypoxic ischemic encephalopathy(HIE),and the possible interactions in the Chinese population. Methods:A cross-sectional study comprising 228 neonates from Henan Children’s Hospital during the five-year period 2015-2020 in China was conducted. All neonatal basic demographic information and clinical records were documented from the neonatal HIE database. Comparisons between mild HIE and moderate or severe HIE were conducted with the t-test or Wilcoxon rank-sum test for continuous variables and the Chi-square test for categorical variables.Unconditional multiple logistic regression models were used to generate the odds ratios(ORs) and 95% confidence intervals(CIs). In addition, we also used an additive model to test for possible biological interactions among the factors. Results: Of the 228 neonates, the males had a statistically significantly higher frequency compared with the females between the two groups (P=0.030). Trend analysis results found that with the decreased of the neonatal birth weight, the detection rates of moderate or severe HIE in males and females were gradually increased (Ptrend＜0.05). The detection of moderate or severe HIE in males and females increased with the decreased of neonatal gestational age at birth(Ptrend＜0.05). However, no interaction was detected between neonatal birth weight and gestational age at birth based on the additive model, the Relative Excess Risk of Interaction and 95% CI was 3.856(-1.753,5.217). The adjusted multiple logistic regression model showed that low birth weight(ORadj:1.965, 95%CI:1.086-4.127),premature infant(ORadj:1.557, 95%CI:1.589-4.862),1-min Apgar’s score＜7(ORadj:5.618, 95%CI:3.724-7.353),intrauterine distress(ORadj:4.916, 95%CI:3.431-7.398),amniotic fluid contamination (ORadj:3.965, 95%CI:2.153-5.782) significantly increased the risk of neonatal moderate or severe HIE. Conclusion:Neonates with low birth weight, premature infant,1-min Apgar’s score＜7, intrauterine distress, amniotic fluid contamination are risk factors for moderate or severe HIE. Notably, we found no biological interaction between risk factors based on the additive model, these findings may help to inform prevention strategies, as this may effectively reduce the incidence of neonatal moderate or severe HIE.
Post-Operative Copeptin Analysis Predicts Which Patients Do Not Develop Diabetes Insipidus After Pituitary Surgery
Authors: Rostom Hussam , Noronha Sean , Jafar-Mohammadi Bahram , May Christine , Borg Anouk , Halliday Jane , Cudlip Simon , James Tim , Guha Nishan , Shine Brian , Pal Aparna
Published: February 2022

Background: Diabetes insipidus (DI) is a recognised complication of pituitary surgery, with diagnosis requiring clinical observation aided by plasma and urine electrolytes and osmolalities. Copeptin is a stable surrogate marker of AVP release and has potential to facilitate prompt diagnosis of post-operative DI. This assay has been shown to accurately predict which patients are likely to develop DI following pituitary surgery. Objective: To determine whether copeptin analysis can be used to predict which patients are at risk of developing DI following transsphenoidal adenomectomy (TSA).Methods: 78 patients undergoing TSA had samples taken for copeptin pre-operatively and at day 1 post-TSA. The majority of patients also had samples from day 2, day 8, and week 6 post-TSA. Results from patients who developed post-operative DI (based on clinical assessment, urine and plasma biochemistry and the need for treatment with DDAVP) were compared to those who did not. Patients with any evidence of pre-operative DI were excluded.Results: Of 78 patients assessed, eleven were clinically determined to have developed DI. Differences were observed between patients with DI and those without in post-operative samples. Of note, there was a significant difference in plasma copeptin at day 1 post-operation (p=0.010 on Kruskal-Wallis test), with copeptin levels greater than 3.4 pmol/L helping to rule out DI (91% sensitivity, 55% specificity at this cut off).Conclusion: In the post-TSA setting, copeptin is a useful rule-out test in patients with values above a defined threshold, which may facilitate earlier decision making and shorter hospital stays.