bluuebunny/crossref_metadata_2025 huggingface dataset:
Heavy metal contamination assessment of soils in Shendong coal base of the Kuye River basin, China: Spatial distribution, source identification and ecological risk
Authors: fu changchang , Li Xiangquan , Ma Jianfei , Gao Ming , Bai Zhanxue , Liu Cong
Published: August 2022

We collect a total of 129 top mine soil samples from Shendong coal base, the largest underground coal mine area in China, and analyze their concentrations of eight heavy metals: arsenic (As), cadmium (Cd), chromium (Cr), cuprum (Cu), mercury (Hg), nickel (Ni), lead (Pb), and zinc (Zn). To estimate contamination and the potential ecological risk from heavy metals, we employ the pollution load index (PLI) and potential ecological risk index (RI), while we use the geostatistical analysis to analyze spatial distribution patterns of heavy metals. Multivariate statistical analysis helps us to identify the main sources of heavy metal contamination, and the results we obtained indicate that the average concentrations of eight metals in mine soils in Shendong coal base are lower than the Chinese national standard (GB15618—2018), nor did they exceed the background values of soils in Shaanxi. We find the mine soils to be heavily contaminated by Hg and Zn, moderately contaminated by Cd, low contaminated by Cd and Cu, and slightly contaminated by all the eight heavy metal elements. Furthermore, we find the spatial distribution patterns of the concentrations and contamination levels of the eight heavy metals in mine soils to be substantially heterogeneous. Heavy metals in mine soils show a low ecological risk level, and Cd poses the most widely distributed and Hg presents the most significant ecological risk among the investigated heavy metals, indicating these two elements should be the priority contaminants for soil heavy metal pollution prevention and control. As, Cr, Cu and Ni in mine soils stem mainly from natural sources, whereas Hg and Zn mainly originate from anthropogenic sources. However, Cd and Pb come from both natural and anthropogenic sources.
Universal scaling of extinction time in stochastic evolutionary dynamics
Authors: Huang Ching-I , Chen Chun-Chung , Lin Hsiu-Hau
Published: August 2022

Evolutionary dynamics is well captured by the replicator equations when the population is infinite and well-mixed. However, there is controversy how the extinction dynamics is modified with finite and structured populations. Experiments on the non-transitive ecosystem containing three populations of bacteria found that the ecological stability sensitively depends on the spatial structure of the populations. We use agent-based Monte Carlo simulations to investigate the extinction dynamics in the rock-paper-scissors ecosystem with finite and structured populations. Going beyond the usual Moran process, we devise a more realistic Reference-Gamble-Birth (RGB) algorithm, requiring only local fitness information. On the fully-connected network, the extinction time in stable and unstable regimes falls into two universal functions when plotted with the rescaled variables. On the two dimensional grid, the spatial structure changes the transition boundary between stable and unstable regimes but doesn’t change its extinction trend. The finding of universal scaling in extinction dynamics is unexpected, and may provide a powerful method to classify different evolutionary dynamics into universal classes.
Factors related to the mortality risk of severe hand, foot, and mouth diseases (HFMD)：a 5-year hospital-based survey in Guangxi, Southern China
Authors: Peng Yuanjun , He Weitao , Zheng Zhigang , Pan Peijiang , Ju Yu , Lu Zhenwei , Liao Yanyan , Wang Hailong , Zhang Chao , Wang Jing , Jiang Lina , Liang Hao , Chen Minmei , Ye Li
Published: August 2022

Background: To understand the factors influencing clinical outcomes of severe hand, foot, and mouth diseases (HFMD), and to provide scientific evidence for reducing the mortality risk of severe HFMD.Methods: From 2014 to 2018, children diagnosed with severe HFMD cases in Guangxi, China, were enrolled in this hospital-based study. The epidemiological data obtained through face-to-face interviews with the parents and guardians. Univariate and multivariate logistics regression models were used to analyze the factors influencing the clinical outcomes of severe HFMD. Survival analysis was performed by the Kaplan-Meier method. The impact of the EV-A71 vaccination on inpatient mortality was analyzed by a comparison approach. Stratified analysis and propensity score matching (PSM) analysis were performed to eliminate the influence of potential confounding factors.Results: A total of 1,565 severe HFMD cases were enrolled in this survey, including 1474 (94.19%) survival cases and 91 (5.81%) death cases. The multivariate logistic analysis demonstrated that males, HFMD history of playmates in the last three months, first visit to the village hospital, time from the first visit to admission less than two days, critical illness, and having no rash symptoms were the independent risk factors for severe HFMD cases (all P<0.05). While EV-A71 vaccination was a protective factor (P<0.05). Stratified analysis and Kaplan-Meier survival analysis further confirmed the result of the multivariate regression. The 1:1 PSM of the EV-A71 vaccination group versus the non-vaccination group showed 2.34% of death in the vaccination group and 7.01% of death in the non- vaccination group. The EV-A71 vaccination protected 66.62% of the death of severe HFMD cases, with an effective index of 3.00.Conclusions: The mortality risk of severe HFMD in Guangxi was related to gender, hospital grade, clinical severity at admission, EV-A71 vaccination, and rash symptom. EV-A71 vaccination can significantly reduce mortality among severe HFMD. The findings are of great significance for the effective prevention and control of HFMD in Guangxi, southern China.
Linear stability of homogeneous and quasi-homogeneous N-body problem by symmetry groups
Authors: Li Yingli
Published: August 2022

Motivated by Xia-Zhou's recent work on applying symmetry groups to the N-body problem, we will study relative equilibria of the equilateral triangle and the square configurations under α-homogeneous and quasi-homogeneous potentials with this method. After linearizing the corresponding second order equations, with appropriate coordinate transformations, we study the linear stability of the relative equilibria by decomposing each 2n x 2n matrix into a series of 2 x 2 matrices.
Healthcare provider perceptions on the implementation of the Universal Test-and-Treat policy in South Africa: A qualitative inquiry
Authors: Nicol Edward , Mehlomakulu Vuyelwa , Jama Ngcwalisa Amanda , Hlongwa Mbuzeleni , Basera Wisdom , Pass Desiree , Bradshaw Debbie
Published: August 2022

BackgroundThe number of people living with HIV (PLHIV) in South Africa was estimated at 7.1 million, accounting for approximately 20% of the 36.9 million PLHIV globally in 2017. In 2015, the World Health Organization (WHO) recommended the universal test and treat (UTT) intervention with UNAIDS 90-90-90 targets. South Africa began implementing the UTT strategy in September 2016. We conducted a qualitative study to understand the impact of implementing the UTT strategy on the patients, healthcare providers, and the health system in uThukela District Municipality (DM) in KwaZulu-Natal province, South Africa. MethodsA qualitative study design approach was conducted with one hundred and sixty-one (161) healthcare providers (HCPs) within 18 healthcare facilities in three subdistricts, comprising of Managers (facility managers and PHC manager/supervisors); Nurses (enrolled, auxiliary, and professional nurses) and Lay workers (lay counsellors, community health workers, linkage officers) were included. HCPs were interviewed using open ended-survey questions to gather their experiences with providing HIV care under the UTT strategy. Participants were consented and interviewed in English or Zulu. The HCPs’ responses were recorded on Redcap and exported to Excel for quality checks. All interviews were analysed using ATLAS.ti v.8 software. ResultsDespite a general acceptance of the UTT policy implementation and delivery, healthcare providers expressed challenges such as work overload, caused by the increased number of service users and the need to meet the 90-90-90 targets. The surge in the workload under conditions of inadequate systems’ capacity and human resources, gave rise to a greater burden on healthcare providers in this study. ConclusionsHealth system strengthening such as providing more systems’ capacity, and human resources might decrease the already over-burdened system, and thus improve the delivery of the comprehensive UTT services to people living with HIV.
An Artificial Intelligence Model for the Pathological Diagnosis of Invasion Depth and Histologic Grade in Bladder Cancer
Authors: Lin Tianxin , Pan Jiexin , Hong Guibin , Zeng Hong , Liao Chengxiao , Li Huarun , Yao Yuhui , Gan Qinghua , Wang Yun , Wu Shaoxu
Published: August 2022

Background: Accurate pathological diagnosis of invasion depth and histologic grade is key for clinical management in patients with bladder cancer (BCa), but it is labour-intensive, experience-dependent and subject to interobserver variability. Here, we aimed to develop a pathological artificial intelligence diagnostic model (PAIDM) for BCa diagnosis. Methods: A total of 854 whole slide images (WSIs) from 692 patients were included and divided into training and validation sets. The PAIDM was developed using the training set based on the deep learning algorithm ScanNet, and the performance was verified at the patch level in validation set 1 and at the WSI level in validation set 2. An independent validation cohort (validation set 3) was employed to compare the PAIDM and pathologists. Model performance was evaluated using the area under the curve (AUC), accuracy, sensitivity, specificity, positive predictive value and negative predictive value.Results: The AUCs of the PAIDM were 0.878 (95% CI 0.875-0.881) at the patch level in validation set 1 and 0.870 (95% CI 0.805-0.923) at the WSI level in validation set 2. In comparing the PAIDM and pathologists, the PAIDM achieved an AUC of 0.847 (95% CI 0.779-0.905), which was non-inferior to the average diagnostic level of pathologists. There was high consistency between the model-predicted and manually annotated areas, improving the PAIDM’s interpretability.Conclusions: We reported an artificial intelligence-based diagnostic model for BCa that performed well in identifying invasion depth and histologic grade. Importantly, the PAIDM performed admirably in patch-level recognition, with a promising application for transurethral resection specimens.
There is a trade-off between forest productivity and animal biodiversity in Europe
Authors: Khamila C. N. , Groen T. A. , Toxopeus A. G. , Santini L. , Neumann M. , Swaay C. Van , Sierdsema H.
Published: August 2022

While forest productivity and biodiversity are expected to be correlated, prioritizing either forest productivity or biodiversity can result in different management. Spatial quantification of the congruence between areas suitable for either one can inform planning. Here we quantify the relationship between net primary productivity of European forests and biodiversity of mammals, birds, reptiles, amphibians, and butterflies both separately and in combination, and map their spatial congruence. We used richness maps obtained by stacking species distribution models for these animal species, and average net primary production from 2000 to 2012 using Moderate Resolution Imaging Spectroradiometer (MODIS) data. We tested how biodiversity and primary productivity are correlated and quantified the spatial congruence of these two sources. We show the areas where high or low productivity co-occur with high or low biodiversity using a quantile-based overlay analysis. Productivity was positively correlated to overall biodiversity and mammal, herptile and butterfly biodiversity, but biodiversity of birds showed a weak negative correlation. There were no significant differences in the strength of relationship across species groups, while herptiles had stronger relationships with productivity compared to other groups. Overlap analysis revealed significant spatial overlap between productivity and biodiversity in all species groups, except for birds. High value areas for both productivity and biodiversity in all species groups, except birds, co-occurred in the Mediterranean and temperate regions. The areas with high biodiversity of birds are mainly found in the boreal areas of Europe, while for all other species groups these areas are mostly located on the Iberian Peninsula and the Balkan ranges. Based on the presented maps, areas where regulating wood production activities to conserve species can be identified. But the maps also help to identify areas where either biodiversity or productivity is high and focusing on just one aspect is more straightforward.
Ocean Alkalinity Enhancement Through Blue Carbon Ecosystem Restoration
Authors: Fakhraee Mojtaba , Planavsky Noah , Reinhard Christopher
Published: August 2022

Blue carbon ecosystems provide a wide range of ecosystem services, are critical in maintaining marine biodiversity, and may potentially serve as sites of economically viable carbon dioxide removal through enhanced organic carbon storage. Here we show that restoring two key blue carbon ecosystems — mangroves and seagrasses — will also foster high rates of permanent atmospheric carbon dioxide removal (potentially up to ~10 tCO2 ha-1 year-1) by driving ocean alkalinity enhancement.
Metabolic and Cardiovascular Responses to Continuous and Intermittent Plank Exercises
Authors: Huang Zihao , Wang Biru , Song Kangping , Wu Shaoping , Kong Huimin , Guo Lan , Liang Qi
Published: August 2022

Background: Plank exercise (PE) is a whole-body isometric muscle training which is beneficial for physical health. However, none of the previous studies investigated the responses within a typical isometric muscle training or PE protocol consisting of multiple sets. The application of PE was restricted for the understudied metabolic and cardiovascular responses, especially for the patients with cardiovascular diseases. This study is to compare the metabolic (ratio of maximal oxygen uptake per kilogram of body mass [%VO2max/kg] and respiratory exchange ratio [RER]) and cardiovascular (ratio of maximal heart rate [%HRmax] and blood pressure [BP]) responses between continuous (CPE) and intermittent plank exercises (IPEs).Methods: Eleven male recreational-level college students completed a baseline cardiopulmonary exercise test and two PEs; %VO2max/kg, %HRmax, and RER were continuously measured and divided into seven equal timepoints. BP was measured every minute during, before, and after PEs. A mixed-model repeated measures ANOVA was used to examine the interaction effect of exercise × phase.Results: The %VO2max/kg (F6,69=11.25, P<0.001), %HRmax (F6,65=7.74, P<0.001), RER (F6,69=11.56, P<0.001), and BP (systolic BP, F2,26=8.42, P=0.002; diastolic BP, F2,24=22.63, P<0.001) increased by safe magnitudes. Compared with the corresponding period in the IPE group, the %VO2max/kg (33.5 [2.2] vs. 27.7 [1.9], P=0.043) and %HRmax (63.2 [3.9] vs. 53.3 [2.1], P=0.019) increased more significantly from the 40% duration of CPE. Systolic BP increased by larger magnitudes during CPE than IPE (154.2 [3.8] vs. 142.3 [4.8] mmHg, P=0.002). RERs were >1 during PEs without cardiovascular and metabolic variables over the anaerobic threshold.Conclusions: Energy was mainly supplied by anaerobic metabolism during PEs. CPE may be preferable for trainees aiming at anaerobic capacity enhancement. IPEs may be preferable to CPEs for patients with cardiovascular diseases due to their lower metabolic and cardiovascular responses.
Electrochemical assessment of highly reversible SnO2 coated Zn metal anodes prepared via atomic layer deposition for aqueous Zn-ion batteries
Authors: Gong Sang Hyuk , Lim Hyo Jin , Lee Ji Hyeon , Yoo Yiseul , Yu Seungho , Lim Hee-Dae , Jung Hyun Wook , Ko Jesse S. , Kim In Soo , Kim Hyung-Seok
Published: August 2022

Aqueous electrochemical energy storage systems that rely on earth-abundant elements are considered as cost-effective alternatives to current lithium-ion batteries which have dominated the technological landscape. For zinc-based energy storage, dendrite growth is an underlying challenge that needs to be addressed to enact high performance and long-term stability. In the present study, we employ atomic layer deposition to produce a thin tin oxide layer that allows dendrite-free cycling for aqueous zinc-ion batteries. Tin oxide is particularly interesting as it provides two distinct advantages—dendrite-free cycling and mitigation of parasitic hydrogen gas evolution. The presence of the tin oxide layer leads to hydrogen gas suppression and homogeneous zinc plating/stripping, both of which are essential to improve the performance of zinc-ion batteries. When paired in a full-cell configuration with manganese oxide, this anode delivers a high specific capacity of 250 mAh g–1 at an imposed current rate of 30 mA g–1. Through density functional theory calculations, we elucidate further that the adsorption energy of Zn for bare Zn is higher than that in the presence of a tin oxide layer.
Temporary tracheotomy for post-intubation laryngeal edema after lung cancer surgery: A case report
Authors: Iijima Yoshihito , Takaoka Yuki , Motono Nozomu , Uramoto Hidetaka
Published: August 2022

Background: In the post-intubation period, laryngeal edema is one of the most severe complications, which can cause significant morbidity and even death. Herein, we report a case in which we performed a temporary tracheostomy during surgery because of the risk of postoperative laryngeal edema, successfully avoiding post-intubation laryngeal edema complications.Case presentation: A 78-year-old man underwent surgery for left upper lobe lung cancer. He had a history of chemoradiotherapy for laryngeal cancer, bronchial asthma, and chronic obstructive pulmonary disease. He was diagnosed with grade 1 laryngeal edema using computed tomography, and there was a risk of the post-intubation laryngeal edema. Additionally, there was a decrease in laryngeal and pulmonary functions; therefore, postoperative aspiration pneumonia was judged to be a fatal risk. A temporary tracheostomy was performed during surgery to avoid postoperative intubation laryngeal edema. He was found to have exacerbated laryngeal edema; a serious complication of airway stenosis.Conclusion: Temporary tracheostomy should be considered to avoid airway stenosis due to post-intubation laryngeal edema in patients with laryngeal edema after radiotherapy.
Experimental and computational investigation on the charge storage performance of a novel Al2O3 -grpahene hybrid electrode
Authors: Ratha Satyajit , Sahoo Surjit , Mane Pratap , Polai Balaram , Sathpathy Bijoy , Chakraborty Brahmananda , Nayak Saroj Kumar
Published: August 2022

The advancements in electrochemical capacitors have noticed a remarkable enhancement in the electrochemical performance for smart electronic device applications, which has led to the invention of novel and low-cost electroactive material. Herein, we synthesized nanostructured Al2O3 and Al2O3-grpahene hybrid, through hydrothermal and post-hydrothermal calcination process. The synthesized materials have been subject to both morphological (FE-SEM, HR-TEM) and structural (XRD and XPS) characterisations. The electrochemical performances of nanostructured Al2O3 and Al2O3-grpahene hybrid were evaluated through computational and experimental analyses. Al2O3-grpahene hybrid shows much improved electrochemical performance, as compared to bare Al2O3. Further, a symmetric supercapacitor device (SSD) was designed using the Al2O3-grpahene hybrid electrodes, which showed 98.56% capacity retention, even after ~ 10,000 charge-discharge cycles. Both, Al2O3 and its graphene hybrid, have been analysed extensively with the help of Density Functional Theory, to provide detailed structural and electronic properties. With the introduction of graphene, the available electronic states, near the Fermi level, are greatly enhanced, imparting a significant increment in the conductivity of the hybrid system. Lower diffusion energy barrier for electrolyte ions and higher quantum capacitance for the hybrid structure compared to pristine Al2O3 justify improvement in charge storage performance for the hybrid structure supporting our experimental findings.
Research on quality assessment method of blockchain multi-source heterogeneous business data
Authors: Wang Junlu , Zhang Ran , Ji Wanting , Zhang Haolin , Song Baoyan
Published: August 2022

The application of blockchain technology in business is more and more widespread. Business data mostly come from different data sources, the information representation is inconsistent, the information ambiguity between blocks in the same blockchain is too large, resulting in information consistency, credibility and value is difficult to evaluate, and other problems, this paper proposes a multi-source heterogeneous blockchain data quality assessment method for business activities. Firstly, the entity information representation method based on CEKGRL model is proposed, and the triplet structure of related entities is introduced into the blockchain, which is associated with the business activity category. The similarity is calculated through the context information to realize the consistency evaluation of blockchain information. Secondly, a credibility representation method based on information source, information comment and information content is proposed, and the credibility assessment of business activity information is obtained by fusing the representation results. Finally, on the basis of information credibility representation, the value evaluation method is introduced to evaluate the total value of business information in the blockchain, and the blockchain quality evaluation model is constructed. Experimental results show that the proposed method is superior to the existing methods in evaluating inter-block consistency, intra-block information credibility and value.
Clinical outcomes of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for metastasised rectal or anal canal adenocarcinoma
Authors: Hasegawa Hiroshi , Matsuda Takeru , Yamashita Kimihiro , Sawada Ryuichiro , Harada Hitoshi , Urakawa Naoki , Goto Hironobu , Kanaji Shingo , Oshikiri Taro , Kakeji Yoshihiro
Published: August 2022

Purpose
Rectal or anal canal adenocarcinoma with inguinal lymph node metastasis (ILNM) is rare and is associated with poor prognostic outcomes. This study aimed to elucidate the clinical significance of neoadjuvant therapy followed by selective inguinal lymph node dissection and total mesorectal excision for rectal or anal canal adenocarcinoma with clinically suspected ILNM.
Methods
This study enrolled 15 consecutive patients who underwent neoadjuvant therapy and curative resection for rectal or anal canal adenocarcinoma with clinically suspected ILNM between 2005 and 2019 at a single institution. Inguinal lymph node dissection was selectively performed on the side of suspected metastasis before neoadjuvant therapy. Short- and long-term outcomes were retrospectively reviewed.
Results
Out of the15 patients, 11 were treated with neoadjuvant chemoradiation, three with chemotherapy, and one with chemoradiation followed by chemotherapy. Six patients had negative fluorodeoxyglucose (FDG) accumulation in inguinal lymph nodes on preoperative FDG-positron emission tomography (FDG-PET) scan, and their inguinal lymph nodes were also pathologically negative for metastasis. Of the nine patients who had positive FDG accumulation, four had pathologically positive inguinal lymph nodes. Seven patients (46.7%) had inguinal seroma postoperatively. Five-year-overall survival was 77.5%, and 5-year-relapse-free survival was 64.2%. No patient had a recurrence in the inguinal region.
Conclusion
In patients with rectal or anal canal adenocarcinoma associated with clinical ILNM, radical resection with neoadjuvant therapy provides a good long-term survival.
Investigating the Perceptions and Practices of EFL Teachers in Teaching English Vocabulary to Young Learners: The Case of Some Selected Primary Schools in Dawro Zone, Tercha Town, and its Surroundings, SWRS, Ethiopia
Authors: Bedilu Woldemariam Bezabih , Wubshet Hailu
Published: August 2022

The authors have requested that this preprint be removed from Research Square.
Reasons for Disagreement Between Screening and Standard Echocardiography in Primary Care: Data from the PROVAR+ Study
Authors: Galdino Bruno Fernandes , Amaral Arthur Maia , Santos Luiza Pereira Afonso , Nogueira Marcelo Augusto Almeida , Rocha Rodrigo Tavares Lanna , Nunes Maria Carmo Pereira , Beaton Andrea Zawacki , Oliveira Kaciane Krauss Bruno , Franco Juliane , Barbosa Márcia Melo , Silva Victor Raggazzi Hohne , Reese Alison Tompsett , Ribeiro Antonio Luiz P. , Sable Craig , Nascimento Bruno Ramos
Published: August 2022

Purpose: To evaluate the reasons for disagreement between screening echocardiography (echo), acquired by non-experts, and standard echo in the Brazilian primary care (PC). Methods: Over 20 months, 22 PC workers were trained on simplified handheld (GE VSCAN) echo protocols. Screening groups, consisting of patients aged 17-20, 35-40 and 60-65 years, and patients referred for clinical indications underwent focused echo. Studies were remotely interpreted in US and Brazil, and those diagnosed with major or severe HD were referred for standard echo performed by an expert. Major HD was defined as moderate to severe valve disease, ventricular dysfunction/hypertrophy, pericardial effusion or wall-motion abnormalities. A random sample of exams was selected for evaluation of variables accounting for disagreement.Results: A sample of 768 patients was analyzed, 651 (85%) in the referred group. Quality issues were reported in 5.8%, and the random Kappa for major HD between screening and standard echo was 0.51. The most frequent reasons for disagreement were: overestimation of mitral regurgitation (MR) (17.9%, N=138), left ventricular (LV) dysfunction (15.7%, N=121), aortic regurgitation (AR) (15.2%, N=117), LV hypertrophy (13.5%, N=104) and tricuspid regurgitation (12.7%, N=98). Misdiagnosis of mitral and aortic morphological abnormalities was observed in 12.4% and 3.0%, and underestimation of AR and MR occurred in 4.6% and 11.1%. Among 257 patients with suspected mild/moderate MR, 129 were reclassified to normal. Conclusion: Although screening echo with task-shifting in PC is a promising tool in low-income areas, estimation of valve regurgitation and LV function and size account for considerable disagreement with standard exams.
CALCULATION AND ANALYSIS OF THE COSTS OF BIOCHEMISTRY EXAMINATIONS BY THE ACTIVITY-BASED COSTING METHOD -ABC-CASE OF THE LABORATORY AT THE PREFECTURAL HOSPITAL OF SALE- MOROCCO
Authors:   Ministry of Health and Social Protection of Morocco, Regional Direction of Health and Social Protection, Delegation of Health and Social Protection to the Prefecture of Sale, Prefectural Hospital Center of Sale., Shaimi Sanae ,   Ministry of Health and Social Protection of Morocco, National School of Public Health of Morocco., Boukhalfa Chakib ,   Ministry of Health and Social Protection of Morocco, National School of Public Health of Morocco.
Published: August 2022

Objectives: The implementation of Universal Health Coverage, as a necessary step towards achieving the Sustainable Development Target, in particular MDT3, brings into play the question of good management, the efficiency of hospitals with a view to reduce costs, which seems to be an international issue. It is in this context that the present study fits. It aims to analyze and calculate the cost of biochemistry examinations. Methods: This is a retrospective accounting study in the year 2019 which focuses on the calculation of the average cost by the accounting method based on the activity of 32 biochemical examinations at the Prefectural Hospital of SALE. Data analysis was performed by SPSS 20.0. ï»¿Results: The costs of biochemistry examinations are around 15,335,689.58MAD, which is three times higher than the income envisaged by the application of the national pricing system, which is of the order of 5,081,280.00 MAD. The most significant expenses are attributed to laboratory consumables and personnel they represent respectively 45.20% and 40.05% of the overall expenses. The activities that consume the largest share of resources with 74.03% and 9.12% are respectively the processing of examinations and the management of the laboratory. Among the costs examinations, we quote Uric acid (114.78MAD)-Albuminemia117.12MAD)- Ferritin (250.96MAD)-PSA (253.22MAD). Conclusions: The results could be essential for both efficient resource allocation, hospital reimbursement and health policy decision-making. Also, the introduction of ABC in our Moroccan hospitals could help the transition from a flat-rate pricing system to fee-for-service (T2A).
The Interaction Between Two Metabolites of Polygala tenuifolia and
Cholinesterases
Authors: Gao Chengxia , Du Huizhi
Published: August 2022

Objective:

The work aimed to compare the binding between the two main components of
Polygala tenuifolia Willd. and two cholinesterases (ChEs) by using a variety of spectral techniques.

Methods:

Two main components of Polygala tenuifolia Willd. included Tenuifolin (Ten) and
Onjisaponin B (Onj B), and two ChEs included acetylcholinesterase (AChE) and butyrylcholinesterase
(BChE).

Results:

The UV-visible absorption spectra results showed that Ten had no effect on the structure of
ChEs, and the combination of Onj B with ChEs changed its structure. Onj B statically quenched the
endogenous fluorescence of both of ChEs, Ten dynamically quenched the endogenous fluorescence of
AChE with no effect on BChE. The fluorescence quenching rate of ChEs by Onj B was much higher
than that of AChE by Ten, and only one binding site of each protein spontaneously interacted with the
compound to bind to or collide. Synchronous fluorescence results showed that Ten and Onj B
quenched the fluorescence intensity by affecting tryptophan and tyrosine residues in cholinesterases,
respectively. Hydrophobic force played an important role in the interaction between Ten and AChE,
and van der Waals force and hydrogen bond were the main driving forces for the binding of Onj B to
ChEs. The Enzyme activity test showed that Onj B inhibited ChE activity, and Ten never inhibited
ChE activity.

Conclusion:

Onj B has the potential to inhibit ChE activity and increase the neurotransmitter
acetylcholine content in the nerve system, improving the Alzheimer's disease (AD).
Modified Levels of Renin Angiotensin Related Components in the Frontal
Cortex and Hippocampus were Associated with Neuroinflammation and
Lower Neuroprotective Effects of NGF During Acute Hepatic
Encephalopathy in Mice
Authors: Oliveira Natália Katley , de Brito Toscano Eliana Cristina , Silva Oliveira Bruna da , Dias Lima Luiza Cioglia , Simões e Silva Ana Cristina , de Miranda Aline Silva , Teixeira Antônio Lúcio , Rachid Milene Alvarenga
Published: August 2022

Background:

Hepatic encephalopathy (HE) is a neuropsychiatric syndrome that involves
cognitive and motor dysfunctions due to hepatic failure. The clinical and experimental studies suggest
that the angiotensin (Ang) converting enzyme (ACE), Ang II, and angiotensin type 1 receptor (AT1R),
which compose the classical pathway of the renin–angiotensin system (RAS), exacerbate
neuroinflammation in different neurologic diseases. Conversely, Ang-(1-7), ACE2, and Mas receptor,
which integrate the alternative RAS axis, have been shown as promising therapeutic targets in
neuropsychiatric disorders, leading to neuroprotection.

Objective:

This study aimed to investigate the potential participation of the RAS components in
thioacetamide (TAA)-induced HE in mice.

Methods:

We also evaluated the levels of neurotrophic factors, pro-inflammatory cytokines, and
chemokine in the central nervous system of TAA-induced HE in mice. Mice were submitted to acute
liver failure induced by TAA administration by intraperitoneal route. Measurements of RAS
components (ACE, Ang II, ACE2 and Ang1-7) and neurotrophic factors (BDNF, GDNF and NGF)
were obtained by ELISA assay. Pro-inflammatory cytokines (TNF, IFN-γ, IL-6, IL-12p70) and the
chemokine (CCL2) were quantified by cytometric bead array. The student’s t-test was applied for
statistical analysis.

Results:

Mice presented increased cortical levels of ACE, while Ang-(1-7) levels were decreased in
cortical and hippocampal samples compared to controls. Moreover, HE mice had an increase in the
Ang II/Ang-(1-7) ratio along with reduced levels of neural growth factor (NGF) in the prefrontal
cortex. They also showed elevated levels of IFN-γ and CCL2 in the prefrontal cortex and of TNF, IL-6,
IL-12, and CCL2 in the hippocampus compared with controls.

Conclusion:

This study suggested that the reduction of components of the alternative RAS axis was
associated with the deleterious effects of neuroinflammation and lower neuroprotective effects of NGF
during TAA-induced HE.
Elabela Peptide: An Emerging Target in Therapeutics
Authors: Bhatt Lokesh Kumar , Sharma Maneesha , Prabhavalkar Kedar S.
Published: August 2022

Elabela, a bioactive micropeptide, is recognized as the second endogenous ligand for Apelin receptor and is widely distributed in different tissues and organs. Elabela plays important role in various physiological processes such blood pressure control, heart morphogenesis, apoptosis, angiogenesis, cell proliferation, migration, etc. Elabela is also implicated in pathological conditions like cardiac dysfunctions, heart failure, hypertension, kidney diseases, cancer and CNS disorders. The association of Elabela with these disease conditions makes it a potential target for their therapy. This review summarizes physiological role of Elabela peptide as well as its implication in various disease conditions.
Fibrinogen, Fibrin, and Fibrin Degradation Products in COVID-19
Authors: Flick Matthew J. , Kangro Kadri , Wolberg Alisa S.
Published: August 2022

Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is the highly patho-genic and highly transmissible human coronavirus that is the causative agent for the worldwide COVID-19 pandemic. COVID-19 manifests predominantly as a respiratory illness with symptoms consistent with viral pneumonia, but other organ systems (e.g., kidney, heart, brain) can also be-come perturbed in COVID-19 patients. Accumulating data suggest that significant activation of the hemostatic system is a common pathological manifestation of SARS-CoV-2 infection. The clotting protein fibrinogen is one of the most abundant plasma proteins. Following activation of coagulation, the central coagulation protease thrombin converts fibrinogen to fibrin monomers, which self-assemble to form a matrix, the primary structural component of the blood clot. Severe COVID-19 is associated with a profound perturbation of circulating fibrinogen, intra- and extravascular fibrin deposition and persistence, and fibrin degradation. Current findings suggest high levels of fibrino-gen and the fibrin degradation product D-dimer are biomarkers of poor prognosis in COVID-19. Moreover, emerging studies with in vitro and animal models indicate fibrin(ogen) as an active play-er in COVID-19 pathogenesis. Here, we review the current literature regarding fibrin(ogen) and COVID-19, including possible pathogenic mechanisms and treatment strategies centered on clotting and fibrin(ogen) function.
The Dual Functions of Non-Coding RNA CRNDE in Different Tumors
Authors: Wang Zhuowei , Wu Yinxin , Du Zhuoyin , Tan Fangshun , Zhou Yunxi , Zhang Zhicheng , Yuan Chengfu
Published: August 2022

Long non-coding RNA has attracted the interest of researchers as a relevant factor that can
influence human cancers. As an oncogene and suppressor gene, it has numerous pathways and is
closely related to the pathophysiology of human diseases. Meanwhile, it may become a novel treatment
option and target for tumor treatment. CRNDE is the gene symbol for Colorectal Neoplasia Differentially
Expressed (non-protein-coding) since it was found to be considerably higher in colorectal
cancer when it was first discovered. It's transcribed from human chromosome 16. Many studies have
shown that it is intimately linked to the etiology of many tumors and malignancies. According to the
paper, the biological function and pathophysiological mechanism of CRNDE in tumors have been
studied extensively in recent years. PubMed served as an essential platform for conducting literature
searches and related analyses. CRNDE, a long non-coding RNA closely related to tumors, was highly
expressed in many tumor cells. There were various underlying mechanisms affecting the progression
of CRNDE-regulated tumorigenesis, including hepatocellular carcinoma, gastric cancer, prostate carcinoma,
oral squamous cell carcinoma, breast cancer, thyroid cancer, myeloma, leukemia, melanoma,
colorectal cancer, glioblastoma, osteosarcoma, cervical cancer, intrahepatic cholangiocarcinoma, nonsmall
cell lung cancer, hepatoblastoma cell tumor, abdominal aortic aneurysm, nasopharyngeal carcinoma,
bladder cancer, Wilms tumor, medulloblastoma, pancreatic cancer, gallbladder cancer, ovarian
cancer, and renal cell carcinoma. CRNDE is involved in the processes of proliferation, migration, invasion,
and inhibition of apoptosis of various cancer cells.
RON Receptor Tyrosine Kinase in Tumorigenic Stemness as a Therapeutic
Target of Antibody-drug Conjugates for Eradication of Triple-negative
Breast Cancer Stem Cells
Authors: Wang Ming-Hai , Suthe Sreedhar Reddy , Yao Hang-Ping , Weng Tian-Hao
Published: August 2022

Background:

Cancer stem-like cells in triple-negative breast cancer (TNBC-SLCs) are the
tumorigenic core for malignancy. Aberrant expression of the RON receptor tyrosine kinase has implications
in TNBC tumorigenesis and malignancy.

Objective:

In this study, we identified the RON receptor as a pathogenic factor contributing to TNBC
cell stemness and validated anti-RON antibody-drug conjugate Zt/g4-MMAE for eradication of RONexpressing
TNBC-SLCs.

Methods:

Immunofluorescence and Western blotting were used for analyzing cellular marker expression.
TNBC-SLCs were isolated by magnetic-immunofluorescence cell-sorting techniques. Spheroids
were generated using the ultralow adhesion culture methods. Levels of TNBC-SLC chemosensitivity
were determined by MTS assays. TNBC-SLC mediated tumor growth was determined in athymic nude
mice. The effectiveness of Zt/g4-induced RON internalization was measured by immunofluorescence
analysis. Efficacies of Zt/g4-MMAE in killing TNBC-SLCs in vitro and in eradicating TNBC-SLCmediated
tumors were determined in mouse models. All data were statistically analyzed using the
GraphPad Prism 7 software.

Results:

Increased RON expression existed in TNBC-SLCs with CD44+/CD24- phenotypes and ALDH
activities and facilitated epithelial to mesenchymal transition. RON-positive TNBC-SLCs enhanced
spheroid-formatting capability compared to RON-negative TNBC-SLCs, which were sensitive to small
molecule kinase inhibitor BMS-777607. Increased RON expression also promoted TNBC-SLC chemoresistance
and facilitated tumor growth at an accelerated rate. In vitro, Zt/g4-MMAE caused massive
TNBC-SLC death with an average IC50 value of ~1.56 μg per/ml and impaired TNBC cell spheroid
formation. In mice, Zt/g4-MMAE effectively inhibited and/or eradicated TNBC-SLC mediated tumors
in a single agent regimen.

Conclusions:

Sustained RON expression contributes to TNBC-SLC tumorigenesis. Zt/g4-MMAE is
found to be effective in vivo in killing TNBC-SLC-mediated xenograft tumors. Our findings highlight
the feasibility of Zt/g4-MMAE for the eradication of TNBC-SLCs in the future.
An Immune-suppressive Triterpenoid from the Stem of Kadsura coccinea
Authors: Gao Feng , Tian Jiaxin , Li Kunyu , Ma Guanghai , Cui Yong
Published: August 2022

Kadsura coccinea has been used as a folk medicine in China, treating various diseases, including
chronic gastritis and rheumatoid arthritis (RA). Chemical studies have revealed that lignans
and triterpenes are the main constituents of its roots and stems. In this paper, a chemical investigation
on the stem of K. coccinea was performed and a previously undescribed 3,4-secolanostane (1) was afforded.
The structure of 1 was determined through comprehensive NMR and HRESI-MS data analysis.
The stereo-configuration of 1 was established based on a comparison of experimental and calculated
ECD spectra. Bioactivity assay carried out in immune cells indicated that 1 could show moderate
effects on ConA (5 μg/mL)-induced T-cell proliferation with an IC50 value of 13.28 μM (cyclosporine
A as the positive drug, IC50 = 0.13 μM) while the IC50 value was 23.12 μM in LPS (10 μg/mL)-induced
B cells (mycophenolate mofetil as the positive drug, IC50 = 16.71 μM).
Investigation of Therapeutic Drug Monitoring of Tacrolimus in Different
Age Groups: Results from a Turkish Nationwide Study
Authors: Caglayan Murat , Gonel Ataman , Celik Osman , Sozuer Abdulvahit , Ulgu Mustafa Mahir , Ata Naim , Birinci Suayip
Published: August 2022

Background:

The blood level of tacrolimus (TAC) used for post-transplant immunosuppression
should be within the therapeutic index. Geriatric individuals may be at risk of organ rejection because,
in this age group, routine drug use is usually disrupted, and the bioavailability of aging-related
drugs is decreased.

Objective:

The aim of this study was to analyze the age-related variability of blood TAC levels in patients
in Turkey.

Methods:

In this study, 697,616 patients who underwent TAC measurement in the laboratories of public,
private, and university hospitals between 2018 and 2020 were identified from the Health-net database of
the Ministry of Health. The results of patients aged ≥65 years were compared with those of patients aged
<65 years. The differences between the sexes in the same age group were also examined. Data from the
Turkish Ministry of Health National Electronic Database were used to design a multicenter retrospective
cohort study.

Results:

The study included 697,616 patients. The mean TAC concentration was 7.2 ± 6.25 ng/mL for all
the patients, 7.13 ± 6.7 ng/mL for the female patients, and 7.24 ± 5.96 ng/mL for the male patients. A
statistically significant difference in TAC concentration was found between men and women in the general
population. Groups aged ≥65 years were compared among themselves. A statistically significant decrease
in TAC concentration was found only in the age group of 75–79 years (5.63 ± 4.09 ng/mL) of
women compared with the men. In all other age groups, the TAC levels of the men were lower.

Conclusions:

The proportion of patients with TAC concentrations lower than the therapeutic index was
higher in the groups aged ≥65 years. Thus, patients aged ≥65 years may be at risk of organ rejection, as
optimum immunosuppression cannot be achieved. In these patients, more frequent drug monitoring and
providing training to ensure the compliance of the patient and the patient's relatives in the use of TAC
may be recommended.
Implementation of the QbD Approach to the Development and Validation
of an Analytical Method for Alpha-beta Arteether
Authors: Baldi Ashish , Bajwa Neha , Mahal Shipra , Madan Jitender
Published: August 2022

Background:

The development of effective, cost-effective, robust, sensitive, and specific analytical techniques for the analysis of drug(s), degradation product(s), and contaminants in dosage forms and biological samples is constantly required as part of the pharmaceutical product life-cycle. The adoption of systematic analytical development methodologies such as quality by design (QbD) is particularly advantageous for enhancing method performance since analytical method development encompasses a number of variables that are significant in explaining variability in method performance. Analytical Quality by Design (AQbD) is a standardised method to process validation that covers all aspects of an analytical procedure. It comprises determining the analytical target profile (ATP), identifying critical method parameters or variables, and selecting critical method attributes (CMAs) or qualities.

Objective:

Spectroscopic and chromatographic methods were developed, conferring the Quality by Design (QbD) tactic as per ICH Q8(R2) guidelines for analytical method development of α-β-arteether.

Methods:

Understanding dependent variables, various factors, and their interaction effects through a desired series of experiments on the answers to be examined is referred to as QbD. Various variable factors were detected using the Ishikawa diagram. As a result, many essential factors for chromatography methods were investigated. A desired set of experiments on the answers to be evaluated was used to comprehend dependent variables, various factors, and their interaction effects using Design-Expert software version 13. Statistical research such fractional factorial designs and Plackett-Burman were employed for this. The QbD methodology was used to establish a durable, precise, and accurate HPLC analytical method for arteether.

Result:

Using Design Expert 13's statistical software, the findings of the Plackette Burman research were studied, and the influence of each parameter on the answers was analysed using an overlay plot. Mobile phase (Acetonitrile: water), column C18250nmX4.6mm, column temperature 300 οC, wavelength: 254 nm, injection volume 20l/min, run time 10 mins, detector waters 2489 UV/Visible detector, retention time 4.149 are among the critical parameters estimated for the development of an analytical method for α,β- arteether.

Conclusion:

The analytical method developed by the QbD approach was validated according to ICH Q2(R1) guidelines, and it was found that the developed analytical method is robust and specific.
Meta-analysis of Lung Cancer Patients in COVID-19
Authors: Pandey Ramendra Pati , Ghouse Peer Gajala Deethamvali
Published: August 2022

Background:

Lung cancer patients have a higher chance of getting infected and showing severe outcomes from coronavirus disease 2019 (COVID-19). This infection influences the respiratory system, albeit other organs are also involved with high risk related to health. The blend of COVID-19 disease and lung cancer predicts a higher mortality rate and more serious clinical results.

Objective:

This research reports the Systemic Review and Meta-analysis correlation between COVID-19 patients with lung cancer and comprehensive proof with regards to the mortality of these patients.

Methods:

A systematic review and meta-analysis are planned to evaluate the data from a PubMed systematic search on Lung Cancer Patients reported by COVID-19, as well as an efficient literature review and information research from 2019 to 2021.

Results:

22 out of 3639 review and research literature assessments were gathered, and 10951 patients were COVID +ve and suffering from cancer, with 21% of the patients suffering from SCLC and NSCLC, and lung cancer accounting for 6% of the mortality.

Conclusion:

Lung cancer Patients who are suffering from COVID-19 additionally reflected the seriousness of the illness and higher rates of intensive care unit confirmations and mechanical ventilation. COVID-19 in patients with lung cancer is related to extreme disease and expanded mortality compared with patients with different tumours and everyone. There is conflicting proof of explicit lung cancer therapies' results. Until more conclusive data is available, lung cancer-coordinated therapy should be restarted as soon as possible in mild to moderate cases to avoid decline and cancer-related mortality.