bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of Conventional Imaging and 18F-Fluorodeoxyglucose Positron Emission Tomography/Computed Tomography in the Diagnostic Accuracy of Staging in Patients With Intrahepatic Cholangiocarcinoma
Authors: Nishioka Eiko , Tsurusaki Masakatsu , Kozuki Ryohei , Im Sung-Woon , Kono Atsushi , Murakami Takamichi , Ishii Kazunari
Published: October 2022

18F-fluorodeoxyglucose positron emission tomography and computed tomography (18F-FDG PET-CT) is increasingly used in the diagnosis, prognosis, staging, and treatment monitoring of many tumor types. However, only a small number of studies have reported the use of 18F-FDG PET-CT in intrahepatic cholangiocarcinoma (ICC). This study aimed to examine the accuracy of tumor staging in ICC by using 18F-FDG PET-CT. Between January 2009 and December 2020, patients with suspected ICC were retrospectively enrolled in the study and underwent imaging. The sensitivity and specificity of 18F-FDG PET-CT, CT, and magnetic resonance imaging (MRI) in detecting tumors, satellite focus, vascular invasion, and lymph node metastases were analyzed. The efficacy of 18F-FDG PET-CT for tumor staging was evaluated. Of the 110 patients who were enrolled in the study, 52 underwent surgical treatment and 45 were histologically diagnosed with ICC. When compared with CT or MRI, 18F-FDG PET-CT had similar sensitivity and specificity values for diagnosing satellite focus and vascular and bile duct invasion; however, PET-CT showed higher accuracy in diagnosing regional lymph node metastases. The accuracy of tumor staging by 18F-FDG PET-CT was higher than that by CT/MRI. Thus, 18FDG PET-CT may support tumor staging in ICC.
Survival in Patients With Relapsed-Refractory Multiple Myeloma: Indirect Comparison of Six New Treatments
Authors: Cancanelli Luca , Rivano Melania , Di Spazio Lorenzo , Chiumente Marco , Mengato Daniele , Messori Andrea
Published: October 2022

In recent years, new treatments have been studied for relapsed-refractory multiple myeloma (RRMM), including two CAR-T products and a variety of non CAR-T agents. Since direct comparisons between these innovative treatments are not available, indirect comparisons can be of interest. Reconstruction of individual patient data from Kaplan-Meier graphs (Shiny method) has been employed in numerous reports that have validated its performance. In the present review, we evaluated six treatments proposed for RRMM including two CAR-T products (ciltacabtagene autoleucel and idecabtagene vicleucel) and four treatments not based on a CAR-T (melflufen plus dexamethasone, isatuximab plus dexamethasone, selinexor, and belantamab). The end-point was overall survival (OS); the Shiny method was used to generate reconstructed survival curves. Our results showed statistically significant differences in OS across these treatments. Compared with pharmacological treatments, CAR-T products significantly prolonged OS with an improvement of remarkable clinical relevance. In particular, ciltacabtagene autoleucel showed better OS than idecabtagene vicleucel. As regards non CAR-T treatments, the ranking in OS was headed by isatuximab plus dexamethasone, followed by belantamab, selinexor, and melflufen plus dexamethasone. In conclusion, while the Shiny method has confirmed its validity in reconstructing individual patient data, our indirect comparisons have offered some original clues to better interpret the information on OS published in these studies.
Design Process of Whippletree-Like Mechanism for Versatile Gripping in Arm Prosthesis
Authors: Trusaji Wildan , Irianto Dradjad , Satriawan Ardianto , Setianingsih Casi , Nurtriandari Erza , Geosasi Rachmat Zulkarnain
Published: October 2022

One of the biggest challenges in arm prosthesis design is to resemble normal hand functionality. Some of arm prosthesis try to mimic all hand movement, while other try to produce several main hand grip patterns. We design a Versatile Gripping Technology (VGT) from a basic whippletree mechanism to produce main hand grip patterns in arm prosthesis. VGT development is the result of abstraction, negation, and systemic variation process of existing solution. To validate VGT, we test it to produce six pattern of hand grip from Southampton Hand Assessment Procedure. VGT capable to produce lateral, power, tip, extension, and spherical grip. In other hand, VGT including the thumb movement and it only use one simple shape moving part. Thus, VGT is effective and efficient. With this result, we argue that abstraction, negation, and systemic variation process of existing solution can create a novel solution and it is applicable in another problem or domain.
Effects of 5-aza-2'-deoxycytidine on DNA Methylation within Female Mouse Reproductive Tissues
Authors: Colwell Mathia , Flack Nicole , Medida Ramya Lekha , Drown Chelsea , Faulk Christopher , Mauro Laura
Published: October 2022

5-aza-2'-deoxycytidine (decitabine), is a chemotherapeutic DNA methyltransferase (DNMT) inhibitor widely used to treat myelodysplastic syndrome and acute myeloid leukemias. Decitabine’s anti-neoplastic activity is thought to result from inhibition of DNMTs leading to passive demethylation of 5’methylcytosines (5mC) in rapidly dividing tissues, resulting in cell death. However, we previously reported paradoxical effects on DNA methylation by decitabine in somatic tissues. Given the potential for lasting damage to DNA methylation in reproductive tissues from even short courses of decitabine in reproductive age humans, we chose to characterize its long-term effects here. Mice were treated with two clinically relevant doses of decitabine (0.15 mg/kg, 0.35 mg/kg) for 7 weeks and DNA methylation was assessed within female reproductive tract tissues. We found methylated cytosines within the ovary to be the least sensitive to decitabine exposure at both doses, whereas the uterus and the oviduct exhibited higher 5mC dysregulation, surprisingly biased towards hypermethylation at the 0.35 mg/kg dose. We identified the sites of differential methylation; revealing specific genes and pathways involved in cell differentiation, development, communication, and cell signaling that were universally altered in all tissues. In addition to our differential methylation data, we identified dysregulated transcription and pathways using RNAseq analyses. Overall, our findings show decitabine exposure causes an epigenetic insult to DNA methylation within female reproductive tissues. Our data provides evidence that further evaluation is needed to fully establish the long-term phenotypic effects post-decitabine exposure.
Interaction of L-Tryptophan with Selected Important Ions in Aqueous Solution
Authors: Begum Ulfat , Muhammad Riaz , Saadiq Muhammad , Idrees Muhammad
Published: October 2022

Effect of selected ions (Fe3+, Au3+, Al3+, Zn2+, Ni2+, Mg2+, Hg2+, Ca2+ and CN-) on fluorescence behavior of L-tryptophan was studied in aqueous solution. All the cations suppressed the fluorescence of L-tryptophan except CN- which caused an increase in the fluorescence of L-tryptophan. Fluorescence suppression were explained by the equation of Stern-Volmer which produced constants of Stern-Volmer (). and sensitivity was observed in the order Hg2+ > Au3+ > Fe3+ > Zn2+ > Ni2+ > Ca2+ > Al3+ > Mg2+. Detection and quantification threshold were calculated as 3 (S.D3) and 10 times of the standard deviation (10S.D) of the blank for twelve number of readings. was found between 6.8631104 and 0.1883104 M. Detection threshold (DT) was observed between 2.8710-7 – 6.38 10-6 while quantification threshold (QT) was observed between 9.58 10-7 and 2.13 10-5 mol L-1. In case of CN- a linear association between the enhancement in fluorescence intensity of L-tryptophan and CN- concentration was found between 0.00 -1.0x10-3 M. DT and QT were found in the order 2.710-5 and 9.0210-5 M respectively. The method is reproducible both for cations and anion and useful for their determination in the samples of the environment.
Lifesaving Skills Training in Schools – A Qualitative study to explore students, teachers, and parent's perceived opportunities and challenges
Authors: Shaukat Natasha , Ali Daniyal Mansoor , Jaffer Mehtab , Jarrar Zeerak , Ashraf Naela , Hassan Sheza , Daudpota Ali Azim , Qadir Muskaan Abdul , Khowaja Aly Hamza , Razzak Junaid
Published: October 2022

Objective
The objective of this study is to explore the perception of teachers, parents and students’ regarding implementation of a school-based lifesaving skills program and help predict potential barriers and solutions.
Methods
This qualitative exploratory study was conducted in Karachi, Pakistan, from December 2020- to October 2021. We included students, teachers, and parents of secondary (grades VIII, IX, and X) and higher secondary level students (grades XI and XII) in Karachi, Pakistan's public and private schools and colleges. We selected one public, two semi-private, and two private schools. We recruited students, teachers, and parents through convenience sampling. We conducted fifteen focus group discussions (FGDs) with the students, six FGDs with the teachers, and eighteen in-depth interviews (IDIs) with parents. We transcribed the data from audio recordings and translated it into the English language. Finally, we manually analyzed the data using thematic analyses.
Results
This study found that bystanders' main barriers to performing lifesaving skills are lack of knowledge, fear of legal involvement, fear of hurting the patient by incorrect technique, lack of empathy among community stakeholders, and gender bias. The participants had a positive and supportive attitude toward implementing lifesaving skills training in schools. They suggested starting student training in the early teenage years, preferred medical staff as trainers, and suggested frequent small sessions in English/Urdu both or Urdu language and training via theory and practical hands-on drills. Furthermore, it was proposed that the training be integrated into the school curriculum to make it sustainable. Finally, the government needs to support the program and make the legal environment more conducive for the bystanders.
Conclusion
This study identified the significant barriers to performing lifesaving skills in an emergency in a low- and middle-income country (lmic). The participants showed support for implementing a national lifesaving skills program in schools and colleges. However, the participants expressed that support is needed by the government for sustainability, integrating the lifesaving skills into the school curriculum, providing legal support to the bystanders, and creating awareness among the general public.
Single Cell Genetic Analysis of COVID-19: A Deep Learning Approach
Authors: Schonfeld Elan
Published: October 2022

COVID-19 was declared by the World Health Organization in 2020 to be a pandemic. Analysis of COVID-19 related genetic pathways allows for a better understanding of the possible effects and sequelae of the disease. Using 6178 scRNA sequenced human cells, having a status of control/mild/severe COVID-19 disease status, differential expression of genes and pathways was analyzed. Using Gene Set Enrichment Analysis (GSEA), mild COVID-19 was found to over-express the Influenza Pathway. In order to identify genes important in COVID-19 severity, a deep learning classifier was trained. Classifiers were repeatedly trained for this task using 10 randomly selected genes from the total number of 18,958 genes. The highest performing classifier (AUC = 0.748) was trained using: AC008626.1, SGO1, RHOBTB2, RBM41, NDUFAF4P1, COX5A, ZDHHC17, STX11, IPP, NUDT5 genes. These results further illustrate the other factors contributing to mild versus severe COVID-19, as well as evidence of potential misdiagnosis or overlapping pathway effects of Influenza and COVID-19.
Additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores
Authors: Bouzan Jobar , Willschrei Peter , Horstmann Marcus
Published: October 2022

Background: Cognitive impairment is poorly addressed in G8 screening. Aim of the presents study was to evaluate the additional value of Mini-Cog© in urogeriatric patients concurrently screened by G8 scores.
Methods: 74 consecutive urogeriatric patients at the age of 75 and above were evaluated. All underwent G8 and Mini-Cog© screening. Patients with a G8 score above 14 were considered geriatric “healthy or fit”. A Mini-Cog© of four to five points was considered inconspicuous in screening for cognitive impairment. The additional information of a Mini-Cog© screening during G8 screening was evaluated by looking at G8 “fit and healthy” patients who had conspicuous Mini-Cog© tests and vice versa. Additionally, the results of the neuropsychological subitem “E” of the G8 score were compared with the results of Mini-Cog© screening.
Results: Mean age of the patients was 83 y (min. 75 – max. 102). 61 of the patients were males and 13 females. 29 of the patients had a normal G8 score and were considered “healthy or fit” and 45 not. 43 of the patients had an inconspicuous and 31 a conspicuous Mini-Cog© of less than four points. The majority of G8 “healthy or fit” patients (n=24/29) had an inconspicuous Mini-Cog© test. However, of them 5 patients had a Mini-Cog© of less than four points suspicious for cognitive disorders. Furthermore, of the 43 patients with a normal G8 sub score in item “E” of two points, 6 patients had a conspicuous Mini-Cog© of less than four points.
Conclusion:
As shown by the present study, the Mini-Cog© helpfully extends the G8 screening with regard to the detection of cognitive functional impairments that are not detected by the G8 screening alone. It can be easily added to G8 screening.
Value of Information analysis for pandemic response: intensive care unit preparedness at the onset of COVID-19
Authors: Eze Peter , Geard Nicholas , Baker Christopher M. , Campbell Patricia T. , Chades Iadine
Published: October 2022

Background: During the early stages of the COVID-19 pandemic, there was considerable uncertainty surrounding epidemiological and clinical aspects of SARS-CoV-2. Governments around the world, starting from varying levels of pandemic preparedness, needed to make decisions about how to respond to SARS-CoV-2 with only limited information about transmission rates, disease severity and the likely effectiveness of public health interventions. In the face of such uncertainties, formal approaches to quantifying the value of information can help decision makers to prioritise research efforts.
Methods: In this study we use Value of Information (VoI) analysis to quantify the likely benefit associated with reducing three key uncertainties present in the early stages of the COVID-19 pandemic: the basic reproduction number (R0), case severity (CS ), and the relative infectiousness of children (CI) compared to adults. The specific decision problem we consider is the optimal level of investment in intensive care unit (ICU) beds. Our analysis incorporates mathematical models of disease transmission and clinical pathways in order to estimate ICU demand and disease outcomes across a range of scenarios.
Results: We found that VoI analysis enabled us to estimate the relative benefit of resolving different uncertainties about epidemiological and clinical aspects of SARS-CoV-2. Given the initial beliefs of an expert, obtaining more information about case severity had the highest parameter value of information, followed by the basic reproduction number R0. Resolving uncertainty about the relative infectiousness of children did not affect the decision about the number of ICU beds to be purchased for any COVID-19 outbreak scenarios defined by these three parameters.
Conclusion: For the scenarios where the value of information was high enough to justify monitoring, if CS and R0 are known, management actions will not change when we learn about child infectiousness. VoI is an important tool for understanding the importance of each disease factor during outbreak preparedness and can help to prioritise the allocation of resources for relevant information.
Apprehension of Spurious Information - A Hybrid Architecture to Detect COVID Fake News
Authors: Mahalakshmi G S , Srih S , Shakthiprarthana V , Sendhilkumar S
Published: October 2022

Propagation of false information has an enduring effect on the economy and can lead to political tensions. In order to counterattack this unexpected repercussion, a system has to be modelled to distinguish the hoax from the real. This paper proposes a deep learning based hybrid model that can determine if the news is veracious. The performance of the model is tested on four datasets including COVID fake news to ensure that it is able to generalise across different domains and achieve best results. Bidirectional Gated Recurrent Units emerges to be the ideal decoder to work along with the Convolutional Neural Network in this hybrid architecture while the words being represented using the glove.6B.50D embeddings provided to be the best representation when juxtaposed with Word2Vec, BERT Embeddings, glove.6B.100D and keras embedding layer. Experiments on the datasets show promising results with an overall accuracy of 80.17% on Disaster Tweets, 99% on ISOT dataset, 59.86% on LIAR and 90.05% on COVID Fake News dataset.
Frozen sections in decision-making regarding the axillary procedures in breast conserving surgery for intraductal carcinoma at preoperative diagnosis
Authors: Kim Sanghwa , Lee Kwanbum , Alshahrani Mushabab Ali , Ahn Jee Hyun , Lee Jeea , Park Hyung Seok
Published: October 2022

Background
Axillary evaluation is unnecessary for pure ductal carcinoma in situ (DCIS); however, it is performed because of upstaging risks. Purpose of this study is to decrease the upstaging rate to invasive cancer and unnecessary axillary evaluation in patients with preoperative DCIS.
Methods
We reviewed patients with preoperative DCIS who underwent breast-conserving surgery (BCS) with IOF biopsy. Positive Intra-operative frozen section (IOF) biopsy findings were defined as the presence of invasive or micro-invasive cancer. The IOF biopsy and permanent pathology findings were compared.
Result
Seventy-eight patients underwent BCS with IOF biopsy. Six patients showed positive IOF biopsy findings; five of these patients showed concordant permanent pathology findings. Sentinel lymph node biopsy (SLNB) was positive in one patient. Thirteen patients with invasive breast cancer were not diagnosed with IOF biopsy; they underwent SLNB during the second surgery. None of them had metastatic lymph nodes. The sensitivity and specificity of IOF biopsy were 27.7% and 98.3%, respectively, with 82.1% accuracy. None of the other factors showed statistically significant relationships with the permanent pathology findings, except for the IOF biopsy findings.
Conclusion
IOF evaluation can aid in detecting the invasiveness of tumors in patients with preoperative DCIS.
Supported online self-management versus care as usual for symptoms of fatigue, pain and urgency/incontinence in adults with inflammatory bowel disease (IBD-BOOST): study protocol for a randomised controlled trial – an update to the published protocol
Authors: Norton Christine
Published: October 2022

Not applicable - this is a brief update to the published protocol
Association between neonatal uterine bleeding and endometriosis-related symptoms later in life
Authors: Ogawa Kanae , Khan Khaleque N , Kuroboshi Haruo , Koshiba Akemi , Horiguchi Go , Teramukai Satoshi , Fujishita Akira , Itoh Kyoko , Guo Sun-Wei , Kitawaki Jo , Mori Taisuke
Published: October 2022

Neonatal uterine bleeding (NUB) has been postulated to cause early-onset endometriosis, but so far there has been no information on whether young women with a history of NUB may manifest various symptoms related to endometriosis. In this retrospective case-controlled cohort study, we investigated the prevalence and risk factors of NUB and prospectively evaluated endometriosis-related symptoms by web-based questionnaire survey. Among 807 female babies born at our hospital between 2013 and 2017, NUB occurred in 25 cases with a prevalence of 3.1%. Multiple Logistic regression analysis indicated that younger age of the mother [odds ratio (OR) 0.92, 95% confidence interval (CI) 0.85-1.00, P = 0.048] and longer gestational age of 39 weeks (OR 3.04, 95% CI 1.43–6.45, P = 0.004) and ≥ 40 weeks (OR 4.54, 95% CI 2.20–9.39, P < 0.0001) of gestation were significantly associated with the occurrence of NUB. We confirmed the validity of the reported prevalence and risk factors of NUB. Young mothers and longer gestational age are the risk factors for NUB and newborn females with or without NUB similarly suffer from various endometriosis-related symptoms later in life during adulthood. Future prospective cross-sectional study is warranted to confirm the endometriosis-related symptoms in NUB + and NUB- cases by physical examination, ultrasound and/or MRI.
Investigating Long-term Prognostication of CT-based Radiomics for Subgroup of High-risk Localized Prostate Cancer Patients Treated by Whole-pelvic Radiotherapy
Authors: Leung Wan Shun , Lam Sai Kit , Wong Po Tsz , Ng Ka Yan , Tam Cheuk Hong , Lee Tsz Ching , Chow Kin Chun , Chow Yan Kate , Tam Victor CW , Lee Shara WY , Lim Mei Ying , Wu Q Jackie , Cai Jing
Published: October 2022

Background
To investigate capability of planning computed tomography (CT)-based radiomics for prediction of long-term prognostication, for the first time, in subgroup of high-risk localized prostate cancer (PCa) patients treated by whole-pelvic radiotherapy (WPRT).
Methods
A total of 64 high-risk localized PCa patients [training cohort (n=45) and validation cohort (n=19)] were enrolled. The planning CT and clinical data were collected. The least absolute shrinkage selection operator (LASSO) was used for model training in conjunction with 3-fold cross validation. The predictive performance of the model was assessed using the Area-under-the-curve (AUC) values generated from receiver operating characteristic analysis. The resultant radiomics signature was used for calculation of radiomics score (Rad-score) for every patients. A cut-off of the Rad-score was suggested for classification of the risk of having progression within 6 years, based on the evaluation of model accuracy, sensitivity, and specificity.
Results
The model incorporated 2 features: the run entropy of gray level run length matrix after Laplacian of Gaussian (LoG) filtering with a sigma value of 2 mm (RE-GLRLMσ2mm); and the small area emphasis of gray level size zone matrix after LoG filtering with a sigma value of 4.5 mm (SAE-GLSZMσ4.5mm). AUC values of the training and testing cohorts were 0.76 and 0.71, respectively. With the cut-off as the third-quartile value for stratification into high-risk and low-risk group, the respective accuracy, sensitivity, and specificity of the radiomics signature were 77.8%, 83.3% and 55.6% in the training cohort and 84.2%, 86.7% and 75% in the testing cohort.
Conclusions
Radiomics signature based on pre-treatment planning CT images can be used as a potential biomarker for differentiating the risk of 6-year disease progression in high-risk localized PCa patients treated with WPRT. Further development is warranted that may help to support clinical decisions about follow-up and treatment options in this subgroup of patients.
Identification of novel immune related transcriptional regulatory network in sarcopenia
Authors: Zhang Xianzhong , Zhu Guanglou , Zhang Fengmin , Yu Dingye , Jia Xuyang , Ma Bingwei , Chen Weizhe , Cai Xinyu , Mao Lingzhou , Zhuang Chengle , Yu Zhen
Published: October 2022

Background: Sarcopenia is highly prevalent in elderly and has a significant adverse effect on their physical health and quality of life, but the mechanisms remain unclear. Studies have indicated that transcription factors (TFs) and immune microenvironment played a vital role in skeletal muscle atrophy.
Methods: RNA-seq data of 40 muscle samples were downloaded from GEO database. Then differential expressed genes (DEGs), TFs, pathways, and immune gene sets were identified with edgeR package, Cistrome Database, GO, KEGG, ORA, GSVA, and ssGAES, respectively. In silico regulatory network was built by Cytoscape and the potential medicine was screened by Connectivity Map. Finally, regulatory mechanisms and RNA expression of DEGs and TFs were identified by multiple online databases and RT-qPCR.
Results: We primary screened 808 DEGs (log2 fold change (FC) > 1or < −1, p < 0.05), 4 differential expressed transcription factors (DETFs) (log2FC > 0.7 or < −0.7, p < 0.05), 304 differential expressed pathways (DEPs) (enrichment scores (ES) > 1or < −1, p < 0.05 or), and 1208 differential expressed immune genes sets (p < 0.01). Based on the results of Pearson correlation analysis (Correlation coefficient (CC) > 0.4 or < -0.4, p < 0.01), we then structured immune related network with 4 DETFs, 9 key DEGs, 11 DEPs, 5 immune cells and 1 immune reaction. Combining the results of online databases and vitro experiments, we found that PAX5-SERPINA5-PI3K/Akt (CC≤0.444, p≤ 0.004) was a potential transcriptional regulation axis, and the B cells (R = 0.437, p = 0.005) may play a vital role in this signal transduction. Finally, the compound of Tanespimycin (enrichment = -0.403, p < 0.0001) might be a potential medicine for sarcopenia based on mechanism of actions database and the result of literature review.
Conclusions: We firstly identified immune related transcriptional regulatory network with High-throughput RNA-seq data in sarcopenia. We supposed that PAX5-SERPIAN5-PI3K/Akt axis was a potential mechanism in sarcopenia, and the B cells may play a vital role in this signal transduction. Besides, Tanespimycin is a potential medicine for sarcopenia by targeting Akt degradation.
Aqueous habitats and carbon inputs shape the microscale geography and interaction ranges of soil bacteria
Authors: Bickel Samuel , Or Dani
Published: October 2022

Earth’s diverse soil microbiomes host bacteria within dynamic and highly fragmented aqueous habitats that occupy complex pore spaces and often restrict the spatial range of ecological interactions. Notwithstanding recent advances in resolving global drivers of soil bacterial biogeography, the spatial distribution of bacterial communities within soil volumes remains largely unknown. Here, we propose a framework for representing submillimeter-scale distributions of soil bacteria based on physical constraints supported by individual-based model results and direct observations. The spatial distribution of bacterial cell clusters modulates various metabolic interactions and soil microbiome functioning. For dry soils with prohibitively long diffusion times, interactions are highly localized among sparse communities. Frequently wet soils promote long-range trophic interactions between dense cell clusters through aqueous pathways. Biomes with high carbon inputs support large and dense cell clusters where anoxic microsites form even in aerated soils. Micro-geographic considerations of yet unobservable processes can improve interpretation of data from bulk soil samples.
The health and economic burden of musculoskeletal disorders in Belgium from 2013 to 2018
Authors: Gorasso Vanessa , Heyden Johan Van der , De Pauw Robby , Pelgrims Ingrid , De Clercq Eva , De Ridder Karin , Vandevijvere Stefanie , Vansteelandt Stijn , Vaes Bert , De Smedt Delphine , Devleesschauwer Brecht
Published: October 2022

Introduction

Low back pain (LBP), neck pain (NKP), osteoarthritis (OST) and rheumatoid arthritis (RHE) are among the most disabling musculoskeletal (MSK) disorders. The current study aims to analyse the health and economic impact of these MSK disorders in Belgium, providing a summary of morbidity and mortality outcomes from 2013 to 2018, as well as direct and indirect costs from 2013 to 2017.

Methods

The health burden of LBP, NKP, OST and RHE in Belgium from 2013 to 2018 was summarized in terms of prevalence and disability-adjusted life years (DALY) using data from the Belgian health interview surveys (BHIS), the INTEGO database (Belgian registration network for general practitioners) and the Global Burden of Diseases (GBD) study 2019. The economic burden included estimation of direct medical costs and indirect costs, measured by cost of work absenteeism. For this purpose, data of the respondents to the BHIS-2013 was linked with the national health insurance data (intermutualistic agency [IMA] database) 2013–2017.

Results

In 2018, 2.5 million Belgians were affected by at least one MSK disorder. OST represented the disorder with the highest number of cases for both men and women, followed by LBP. In the same year, MSK disorders contributed to a total of 180,746 DALY for female and 116,063 DALY for men. LBP appeared to be the largest contributor to the health burden of MSK. Having at least one MSK disorder costed on average 3 billion € in medical expenses and 2 billion € in indirect costs per year, with LBP being the most costly.

Conclusion

MSK disorders represent a major health and economic burden in Belgium. As their burden will probably continue to increase in the future, acting on the risk factors associated to these disorders is crucial to mitigate both the health and economic burden.
Trends in the Utilization of Medicines Sold in the Private Sector Post- Registration in South Africa and the Implications for Similar Countries
Authors: Mpanza Ntobeko , Godman Brian , Keele Godfrey , Matlala Moliehi
Published: October 2022

Background: Regulatory authorities register medicines for patients to access within a reasonable time. There is a paucity of available data regarding the extent to which registered medicines reach the public after market authorisation by the South African Health Products Regulatory Authority (SAHPRA). This is important since time spent by SAHPRA assessing medicines that are subsequently not launched onto the South African market means time wasted, which could be spent on assessing new medicines that address an unmet need in the country. Consequently, we initially analysed the time taken for registered medicines to reach patients and the relationship between medicines registered at SAHPRA and those subsequently dispensed in private pharmacies. The extent of registration of multiple sourced versus new patented medicines was also explored.
Methods: A retrospective, descriptive and quantitative investigation was conducted for medicines registered between 2014 -2019. Registered and dispensed medicines were compared to establish accessibility post registration. Data sources included SAHPRA and IQVIA datasets. Microsoft Excel and SAS (SAS Institute Inc, Carey, NC, USA), Release 9.4.was used for data storage, analysis, and computation of descriptive statistical analysis.
Results: Of (N=2175) registered medicines, only 358 (16.5%; 95% CI 15.0% - 18.1%)were dispensed to patients, andout of 1735 medicines registered during 2015 – 2019 only 57 (3.3%; 95% CI 2.5% - 4.2%) were dispensed during the study period. Medicines acting on the central nervous system were registered and dispensed the most at 21.0% and 18.0%, respectively, whereas antineoplastic, and immunomodulation agents were registered and dispensed at only 11% and 5%, respectively. A concern was that only 13.0% of registered medicines were originators, with most either as generics, including branded generics, or pseudo-generics.
Conclusion: Regulatory measures should be implemented to ensure increased medicine access post-registration for new originators, especially for priority disease areas that benefit patients. Mental health diseases and improved access to oncology medicines require special attention and further investigation in South Africa.
Risk map of human intake of methylmercury through fish consumption in Latin America and the Caribbeans
Authors: Vergara Elvira , Pancetti Floria , Zuñiga Liliana , Bahamonde Paulina
Published: October 2022

Methylmercury is a high bioaccumulated pollutant persistent in the aquatic environment, that biomagnifies in the food web reaching concerning levels in predator fish. Mining is one of the most important economic activities of Latin America and the Caribbean, and a relevant global anthropogenic mercury emission. Studies have correlated high fish consumption with higher levels of MeHg in humans along with neurotoxic effects. Latin America occupies one of the top 3 regions with the highest fishery exploitation and aquaculture production, and simultaneously, it has been reported in several Latin American and the Caribbean country’s high levels of mercury in marine and freshwater fishes, and in human hair associated with fish consumption. Therefore, this review seeks to assess the risk of mercury exposure and consequently health hazard due to fish consumption in Latin America and the Caribbean. The data of mercury levels in fish and fish consumption rates was searched from all countries in Latin America and the Caribbean. A large data set was created evidencing a concerning presence of methylmercury in fish that are widely consumed. The 6.1% of the total fish species studied were found to have concentrations of MeHg ≥ 1.5 µg g− 1 dw, independently of the water habitat these were mainly carnivore species, which is recommended to not consume. Furthermore, high risk values (HQ ≥ 1) were estimated in Peru and Venezuela, and even higher-risk values (HQ ≥ 10) were estimated in some fish species inhabiting watersheds in Trinidad. The recommendation is to lower the consumption of this kind of fish species or to avoid mercury pollution.
Moral distress in psychiatric nurses in Covid-19 crisis
Authors: tavakol nahid , molazem zahra , rakhshan mahnaz , asemani omid , bagheri shahpar
Published: October 2022

Background:
The COVID-19 epidemic has put heavy pressure on nurses. Psychiatric nurses are also exposed to moral distress due to the special conditions of psychiatric patients and patient’s lack of cooperation in observing health protocols.
This study has been conducted to explore and describe factors that caused moral distress in psychiatric nurses during the COVID-19 epidemic.
Method:
This qualitative study with a conventional content analysis approach involved 12 nurses at Shiraz University of Medical Sciences in Iran. This study was conducted in the winter of 2021. Data collection was performed by unstructured interviews, data analysis was performed based on the five steps of Graneheim and Lundman.
Results:
From the data analysis, 252 initial codes were extracted, which were obtained by continuous comparison and integration of subcategories of 4 main categories including emotional responses, relational factors, Institutional factors, and management factors caused by Moral Distress in psychiatric nurses.
Conclusion: new dimensions of the causes of moral distress associated with the COVID-19 pandemic are discovered. Managers and planners should equip psychiatric hospitals with isolation facilities and Personal Protection Equipment for patients and nurses. Strengthening the ethical climate by improving communication skills and individual nursing empowerment to prevent moral distress is recommended.
Development and Evaluation of an Acceptance and Commitment Therapy based on Religious Content to Control Obsessive-Compulsive Disorder, Dysfunctional Beliefs, Feeling Guilty, Scrupulosity, and Thought Control among Muslims in Iran
Authors: Dehaghi Ashraf Akbari , Dolatshahi Behrooz , Taremian Farhad , Pourshahbaz Abbas , Ansari Hasan
Published: October 2022

Background
Religious or moral obsessions, also known as scrupulosity has not been adequately investigated in studies of acceptance and commitment therapy (ACT). The present study aimed to develop an integrated protocol by combining religious content and ACT and evaluate its effectiveness in controlling obsessive-compulsive disorder (OCD), dysfunctional beliefs, feeling guilty, scrupulosity, and thought control among Muslims in Iran.
Methods
An exploratory mixed-method research design was applied in this study. In the qualitative stage, the document analysis method was used to extract components related to ACT with religious content. Also, the content and face validity of the intervention were confirmed by experts. Subsequently, a semi-experimental, pretest-posttest, control-group design was performed to evaluate the effectiveness of the adapted protocol with a three-month follow-up. In the quantitative stage, a total of 35 participants were randomly assigned into two groups using the convenience sampling method based on the inclusion criteria. The experimental and control groups participated in 25 individual treatment sessions based on the adapted protocol and eight conventional ACT sessions, respectively. The research instrument included the Yale-Brown Obsessive-Compulsive Scale, the Guilt Inventory, the Penn Inventory of Scrupulosity, the Questionnaire of Religious Beliefs about Purification Rituals, and the Thought Control Questionnaire.
Results
The present findings indicated the interactive effects of time and group on the severity of purity/impurity obsessions (F = 9.455, P < .001) and dysfunctional religious beliefs (F = 7.963, P = .001) in patients with OCD. The Bonferroni correction results showed no significant difference between the intervention and control groups in the severity of obsession (P = .448), dysfunctional religious beliefs (P = .176), feeling guilty (P = .787), scrupulosity (P = .891), and thought control (P = .554) in the follow-up. According to the results, the effectiveness of the religion-adapted ACT intervention on the severity of obsession and dysfunctional religious beliefs was higher in patients with OCD compared to the control group in the posttest. Although the intervention influenced scrupulosity, the difference was not significant with the control group. Besides, the findings showed that group and time failed to significantly affect feeling guilty and thought control.
Conclusion
The present study showed that adding religious components to the ACT protocol can increase its effectiveness in reducing the severity of purity/impurity obsessions compared to the conventional ACT in the Muslim Iranian population.
Discovery of Small Molecule PARKIN Activator as Therapeutics for PD: An in-silico Repurposing Approach
Authors: Ibrahim Abdulwasiu , Ipinloju Nureni , Muhammad Sulieman Alhaji , Oyeneyin Oluwatoba Emmanuel , Atasie Nkechi Hope
Published: October 2022

Background
Although there is presently no cure for Parkinson's disease (PD), the available therapies are only able to lessen symptoms and preserve the quality of life. Around 10 million people globally had PD as of 2020. The widely used standard drug has recently been revealed to have several negative effects. Additionally, there is a dearth of innovative compounds entering the market as a result of subpar ADMET characteristics. Drug repurposing provides a chance to reenergize the sluggish drug discovery process by identifying new applications for already-approved medications. As this strategy offers a practical way to speed up the process of developing alternative medications for PD. This study used a computer-aided technique to select therapeutic agent(s) from FDA-approved neuropsychiatric/psychotic drugs that can be adopted in the treatment of Parkinson's disease.
Method
In the current work, a computational approach via molecular docking, density functional theory (DFT), and pharmacokinetics were used to identify possible (anti)neuropsychiatric/psychotic medications for the treatment of PD. By using molecular docking, about eight (anti)neuropsychiatric/psychotic medications were tested against PARKIN, a key protein in PD
Result
Based on the docking score, the best ligand in the trial was determined. The top hits were compared to the reference ligand levodopa (L-DOPA). A large proportion of the drugs displayed binding affinity that was relatively higher than L-DOPA. Also, DFT analysis confirms the ligand-receptor interactions and the molecular charges transfer. All the compounds were found to obey Lipinski's rule with acceptable pharmacokinetic properties.
Conclusion
The current study has revealed the effectiveness of antineuropsychiatric/antipsychotic drugs against PARKIN in the treatment of PD and lumateperone was revealed to be the most promising candidate interacting with PARKIN.
Clinical features and markers to identify pulmonary lesions caused by infection or vasculitis in AAV patients
Authors: Wang Yujuan , Qu Zhuan , Liang Wei , Chen Xinghua , Chen Cheng , Cheng Hui , Hu Haiyun , Wei Zhongpin , Su Ke , Yang Lianhua , Wang Huiming
Published: October 2022

Objectives Pulmonary lesion is frequently seen in ANCA-associated vasculitis (AAV) patients primarily due to AAV lung involvement or infection, which are hard to differentiate due to their high similarity in clinical manifestations. We aimed to analyze the clinical features of pulmonary lesions consequent to AAV involvement or infection in AAV patients and further identify the markers for differential diagnosis.
Methods 140 AAV patients who admitted to the Renmin Hospital of Wuhan University from January 2016 to July 2021 were included in this study. According to the nature of lung conditions, these patients were divided into the non-pulmonary lesion group, the lung infection group and the non-pulmonary infection group, and their demographics, clinical symptoms, imaging features, as well as laboratory findings were compared. A receiver operating characteristic (ROC) curve was drawn, and the diagnostic efficacy of single biomarker and composite biomarkers on pulmonary infection was then evaluated.
Results The patients in the lung infection group were significantly older than those in the no lesion group (63.19±14.55 vs 54.82±15.08, p=0.022). Patients in the lung infection group presented more frequent symptoms and more obvious pulmonary image findings. Compared with patients in the non-pulmonary infection group, patients in the lung infection group showed a higher symptom incidence of fever, chest tightness, cough and expectoration, and hemoptysis (52.94% vs 16.00%, 61.76% vs 40.00%, 72.06% vs 46.00%, 27.94% vs 8.00%, p<0.05, respectively), and more changes in pulmonary CT scanning images in terms of patched/striped compact opacity, alveolar hemorrhage, bronchiectasis, pleural effusion, as well as mediastinal lymphadenopathy (89.71% vs 52.00%, 11.76% vs 2.00%, 22.06% vs 8.00%, 50.00% vs 20.00%, 48.53% vs 24.00%, p<0.05, respectively). In addition, patients in the lung infection group had significantly higher levels of serum pro-calcitonin (PCT), C-reaction protein (CRP), amyloid A (SAA), blood neutrophil-to-lymphocyte ratio (NLCR), erythrocyte sedimentation rate (ESR), as well as Birmingham vasculitis activity score (BVAS) than patients in the other two groups (p<0.05). Among all biomarkers, PCT exhibited the highest diagnostic efficacy (0.928; 95%CI 0.89-0.97) for pulmonary infected AAV patients at a cut-off score of 0.235 ng/ml with 85.3% sensitivity and 84% specificity. Moreover, the composite biomarker of PCT-CRP-NLCR showed more diagnostic efficacy (0.979; 95% CI 0.95-1.00) in distinguishing the infectious and non-infectious lung injuries in AAV patients.
Conclusions AAV patients with lung infection manifested more clinical symptoms and prominent lung image changes. The PCT and composite biomarker PCT-CRP-NLCR showed high diagnostic efficacy for a lung infection in AAV patients.
Bones of contention: a double blind study of experts’ ability to classify sheep and goat astragali from images
Authors: Sipilä Ilkka M. V. , Steele James , Dickens Luke , Martin Louise
Published: October 2022

In zooarchaeology, animal bones are normally identified using comparative macro-morphological methods, which involve visual comparison of the bone with reference materials. However, recent work has oppugned the reliability of these methods. Although previous studies applying macro-morphological methods to identify sheep and goat bones have found low error rates, these results are based on small numbers of analysts, large numbers of different bone types and do not properly account for ambiguous "sheep/goat" classifications. We present an extensive blind study of performance and reliability for binary macro-morphological species identification using just the astragalus. Each participant made independent comparative identifications on a random subset, including repeat presentations for consistency analysis. No sheep/goat category was offered. Instead, participants reported confidence scores on each sample. The participants also reported the reference materials used and indicated their regions of attention in each image. Findings indicate that neither the use of reference materials nor experience are good predictors of accuracy, although more experienced analysts are found to be more consistent. Forcing binary classifications leads to a more transparent analysis but indicates lower performance scores than reported elsewhere, while corresponding confidence scores positively correlate with accuracy. Qualitative analysis of reported attention regions indicate that mistakes can occur when there is an overlap in the morphologies of the two species. We conclude that overreliance on reference materials impacts performance when the morphology of reference materials is not representative of the population variance, which is especially evident when the wider bone morphology is not adequately integrated into the classification decision.
Therapeutic potential of FLT4-targeting peptide in acute myeloid leukemia
Authors: Lee Ji Yoon , Park Soojin , Han A-Reum , Hwang Hee-Sun , Kim Hee-Je
Published: October 2022

Fms-related tyrosine kinase-4 (FLT4) is involved in tumor progression. Previously, we found that dysfunctional natural killer (NK) cells with low interferon-gamma (IFN-γ) were restored in acute myeloid leukemia (AML) by the FLT4 antagonist MAZ51. In this work, we developed 12 peptides targeting FLT4 for clinical application and ultimately selected 4 of them to examine whether they restored the frequency of lymphocytes, especially T cells and NK cells, and high IFN-γ expression, as MAZ51 treatment did in our previous study. Although clinical data from using intracellular kinase domain–targeting peptides are currently available, peptides targeting FLT4 to modulate immune cells have not been fully elucidated. In this study, we focus on novel peptide 4 (P4) from the intracellular domain of FLT4 because it had dominant negative activity. Similar to MAZ51, high IFN-γ levels were expressed in AML-mononuclear cells (MNCs) exposed to P4. In addition, T and NK cell levels were restored, as were high IFN-γ levels, in a leukemic environment when P4 was co-cultured with cytosine β-D-arabinofuranoside. Interestingly, the frequency of regulatory T cells was significantly decreased by P4, implying that the peptide plays a role in modulating the tumor niche. Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and propose the development of advanced therapeutic approaches against AML by using immune cells.
Variational Iteration Method for 2d Hyperbolic Quasi-linear Pde
Authors: Sahu Subrata Kumar , Derke Simon
Published: October 2022

In this paper, we have constructed two dimensional (2D ) hyperbolic quasi-linear partial differential equations (HQLPDE) by considering two cases. The Cauchy data is given in the form of exponential curve in the 1st case. The initial value problems (IVP) are mentioned as sin x in the 2nd case where as all the cases are associated with time. We have obtained the solutions by using variational iteration method (VIM). In the both cases, we found that solution represents flat surface during the initial stage. We have observed the exponential surface in the 1st case and the curved surface in the 2nd case subject to the increasing values of x and y.
Mathematics subject classification: 35Lxx, 35L04