bluuebunny/crossref_metadata_2025_split huggingface dataset:
GPR4 signaling is essential for the promotion of acid-mediated angiogenic capacity of endothelial progenitor cells by activating STAT3/VEGFA pathway in patients with coronary artery disease
Authors: Ouyang Shun , Li Yan , Wu Xing , Wang Yan , Liu Fanmao , Zhang Jianning , Qiu Yumin , Zhou Zhe , Wang Zhichao , Xia Wenhao , Lin Xiufang 
Published: February 2021

AbstractBackgroundPatients with coronary artery disease (CAD) are characterized by a decline in vascular regeneration, which is related to the dysfunction of endothelial progenitor cells (EPCs). G-protein-coupled receptor 4 (GPR4) is a proton-sensing G-protein-coupled receptor (GPCR) that contributes to neovascularization in acidic microenvironments. However, the role of GPR4 in regulating the angiogenic capacity of EPCs from CAD patients in response to acidity generated in ischemic tissue remains completely unclear.MethodsThe angiogenic capacity of EPCs collected from CAD patients and healthy subjects was evaluated in different pH environments. The GPR4 function of regulating EPC-mediated angiogenesis was analyzed both in vitro and in vivo. The downstream mechanisms were further investigated by genetic overexpression and inhibition.ResultsAcidic environment prestimulation significantly enhanced the angiogenic capacity of EPCs from the non-CAD group both in vivo and in vitro, while the same treatment yielded the opposite result in the CAD group. Among the four canonical proton-sensing GPCRs, GPR4 displays the highest expression in EPCs. The expression of GRP4 was markedly lower in EPCs from CAD patients than in EPCs from non-CAD individuals independent of acid stimulation. The siRNA-mediated knockdown of GPR4 with subsequent decreased phosphorylation of STAT3 mimicked the impaired function of EPCs from CAD patients at pH 6.4 but not at pH 7.4. Elevating GPR4 expression restored the neovessel formation mediated by EPCs from CAD patients in an acidic environment by activating STAT3/VEGFA signaling. Moreover, the beneficial impact of GPR4 upregulation on EPC-mediated angiogenic capacity was abrogated by blockade of the STAT3/VEGFA signaling pathway.ConclusionsOur present study demonstrated for the first time that loss of GPR4 is responsible for the decline in proton sensing and angiogenic capacity of EPCs from CAD patients. Augmentation of GPR4 expression promotes the neovessel formation of EPCs by activating STAT3/VEGF signaling. This finding implicates GPR4 as a potential therapeutic target for CAD characterized by impaired neovascularization in ischemic tissues.
The impact of physical activity and exercise interventions for physical health in people with cystic fibrosis: protocol for a systematic review
Authors: Tomlinson Owen W. , Denford Sarah , Barker Alan R. , Schneiderman Jane E. , Campisi Emma S. , Douglas Helen , Rand Sarah , McNarry Melitta A. , Mackintosh Kelly A. , Williams Craig A. 
Published: February 2021

Abstract
Background
Cystic fibrosis (CF) is a genetically inherited, life-limiting condition, affecting ~90,000 people globally. Physical activity (PA) and exercise form an integral component of CF management, and have been highlighted by the CF community as an area of interest for future research. Previous reviews have solely focused on PA or structured exercise regimens independent of one another, and thus a comprehensive assessment of the physical health benefits of all PA, including exercise, interventions, is subsequently warranted. Therefore, the purpose of this review is to evaluate the effects of both PA and exercise upon outcomes of physical health and healthcare utilisation in people with CF.

Methods
A systematic review has been registered and reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis-P guidelines. This will include randomised control trials on the effects of PA and exercise, relative to usual treatment, upon people with CF. Primary outcomes will include variables associated with fitness, PA, lung health, inflammation, body composition, glycaemic control and patient-reported outcomes. Secondary outcomes will include adverse events and healthcare utilisation. Searches will be undertaken in Ovid MEDLINE, OVID EMBASE, PsychINFO, ERIC, SPORTDiscus, ASSIA, CCTR, CINHAL and Web of Science databases, and will be searched from date of inception onwards. Two reviewers will independently screen citations and abstracts, and full-texts, for inclusion and data extraction, respectively. Methodological quality will be assessed using the Cochrane Risk of Bias-2 tool. If feasible, random-effects meta-analyses will be conducted where appropriate. Additional analyses will explore potential sources of heterogeneity, such as age, sex, and disease severity.

Discussion
This systematic review will build on previous research, by comprehensively assessing the impact of both PA and exercise upon physical health and healthcare utilisation in people with CF. Results of this review will be utilised to inform discussions that will ultimately result in a consensus document on the impact of physical activity and exercise for people with CF.

Systematic review registration
PROSPERO CRD42020184411
Finite time stability and sliding mode control for uncertain variable fractional order nonlinear systems
Authors: Jiang Jingfei , Li Hongkui , Zhao Kun , Cao Dengqing , Guirao Juan L. G. 
Published: February 2021

AbstractThis paper deals with the finite time stability and control for a class of uncertain variable fractional order nonlinear systems. The variable fractional Lyapunov direct method is developed to provide the basis for the stability proof of the system considered. The sliding mode control method is applied for robust control of uncertain variable fractional order systems; furthermore, the chattering phenomenon is avoided. And the finite time stability of the systems under control law is proved based on the proposed stability criterion. Finally, numerical simulations are proposed and the efficiency of the controller is verified.
Emden–Fowler-type neutral differential equations: oscillatory properties of solutions
Authors: Bazighifan Omar , Almutairi Alanoud 
Published: February 2021

AbstractIn this paper, we study the oscillation of a class of fourth-order Emden–Fowler delay differential equations with neutral term. Using the Riccati transformation and comparison method, we establish several new oscillation conditions. These new conditions complement a number of results in the literature. We give examples to illustrate our main results.
Higher order solitary solutions to the meta-model of diffusively coupled Lotka–Volterra systems
Authors: Timofejeva Inga , Telksnys Tadas , Navickas Zenonas , Marcinkevicius Romas , Ragulskis Minvydas 
Published: February 2021

AbstractA meta-model of diffusively coupled Lotka–Volterra systems used to model various biomedical phenomena is considered in this paper. Necessary and sufficient conditions for the existence ofnth order solitary solutions are derived via a modified inverse balancing technique. It is shown that as the highest possible solitary solution ordernis increased, the number of nonzero solution parameter values remains constant for solitary solutions of order$n>3$n>3. Analytical and computational experiments are used to illustrate the obtained results.
Novel existence techniques on the generalized φ-Caputo fractional inclusion boundary problem
Authors: Alzabut Jehad , Ahmad Bashir , Etemad Sina , Rezapour Shahram , Zada Akbar 
Published: February 2021

AbstractOur basic purpose is to derive several existence aspects of solutions for a novel class of the fractional inclusion problem in terms of the well-defined generalized φ-Caputo and φ-Riemann–Liouville operators. The existing boundary conditions in such an inclusion problem are endowed with mixed generalized φ-Riemann–Liouville conditions. To reach this goal, we utilize the analytical methods on α-ψ-contractive maps and multifunctions involving approximate endpoint specification to derive the required results. In the final part, we formulate an illustrative simulation example to examine obtained theoretical outcomes by computationally and numerically.
Close up to the surface: reflections on a preliminary forensic study of four Chinese bronze mirrors
Authors: Liang Jiafang , Parker Quentin 
Published: February 2021

Abstract
This article presents a generic, objective and evidence based forensic study of 4 very different Chinese bronze mirrors. The work was done within the Architectural Conservation Laboratory (ACLab), the Department of Physics, the Faculty of Medicine and also the Planetary Spectroscopy and Mineralogy Laboratory (PSML) all at the University of Hong Kong. The mirrors nominally cover the period of the Warring States (475–221 BC), Han (206 BC to 220 AD) and later Song (960–1279AD) dynasties. Comprehensive, mostly non-invasive, analytical methods and techniques were used. These included surface microscopy of tool marks, patina, corrosion and any residual archaeological evidence. Ultraviolet radiation examination, chemical spot testing and polarised light microscopy of ground-up patina samples was also done. More sophisticated “pXRF” X-ray fluorescence, “MARS” tomographic X-ray scanning and infrared spectroscopic analysis of the bronze alloys, corrosions and any earthen encrustations were also performed. This was to uncover as much forensic evidence as possible for these unprovenanced bronze mirrors. The results have revealed key metallurgical information of those four mirrors along with surface patina morphology and details of the corrosion and residual surface archaeology. A database on the physical condition of these mirrors has been established and burial/treatment history revealed. Mirrors 1 and 2 appear to have been heavily cleaned, polished and treated with abrasives in modern times. Mirror 2 in particular, has some problematic corrosion and inconclusive alloy composition. Mirror 3 and 4 both have archaeological evidence and no contrary forensic data that questions authenticity. Forensic study and verification of objects and artworks for academic purposes remains a legitimate and vital undertaking for universities, museums and national collections across the globe. Hence, the issue of authenticity when archaeological context is lacking is discussed. However, our key aim is to establish what can be learnt from technological, forensic investigation when studying bronze mirrors without further context and records, and what firm, generic evidence can be extracted from such close forensic examination to shed light on their true nature. We hope this will be useful for other researchers.
Artemisinin attenuated oxidative stress and apoptosis by inhibiting autophagy in MPP+-treated SH-SY5Y cells
Authors: Yan Junqiang , Ma Hongxia , Lai Xiaoyi , Wu Jiannan , Liu Anran , Huang Jiarui , Sun Wenjie , Shen Mengmeng , Zhang Yude 
Published: February 2021

Abstract
Background
Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer's disease. The oxidative stress is an important component of the pathogenesis of PD. Artemisinin (ART) has antioxidant and neuroprotective effects. The purpose of this study is to explore the neuroprotective effect of ART on 1-methyl-4-phenyliodine iodide (MPP +)-treated SH-SY5Y cells and underlying mechanism.

Methods
We used MPP+-treated SH-SY5Y cells to study the neuroprotective effect of ART. Cell viability was measured by MTT assay after incubating the cells with MPP+ and/or ART for 24 h. DCFH-DA was used to detect the level of intracellular reactive oxygen species (ROS), and WST-8 was used to detect the level of superoxide dismutase (SOD). The level of intracellular reduced glutathione (GSH) was detected with 5,5΄-dithiobis-(2-nitrobenzoic acid), and the level of malondialdehyde (MDA) was assessed based on the reaction of MDA and thiobarbituric acid. A mitochondrial membrane potential detection kit (JC-1) was used to detect changes in the mitochondrial membrane potential (MMP), and an Annexin V-FITC cell apoptosis kit was used to detect cell apoptosis. The expression levels of caspase-3, cleaved caspase-3 and the autophagy-related proteins LC3, beclin-1, and p62 were detected by Western blotting. In addition, to verify the change in autophagy, we used immunofluorescence to detect the expression of LC3 and p62.

Results
No significant cytotoxicity was observed at ART concentrations up to 40 μM. ART could significantly increase the viability of SH-SY5Y cells treated with MPP+ and reduce oxidative stress damage and apoptosis. In addition, the Western blotting and immunofluorescence results showed that MPP+ treatment could increase the protein expression of beclin1 and LC3II/LC3I and decrease the protein expression of p62, indicating that MPP+ treatment could induce autophagy. Simultaneous treatment with ART and MPP+ could decrease the protein expression of beclin1 and LC3II/LC3I and increase the protein expression of p62, indicating that ART could decrease the level of autophagy induced by MPP+.

Conclusion
Our results indicate that ART has a protective effect on MPP+-treated SH-SY5Y cells by the antioxidant, antiapoptotic activities and inhibition of autophagy. Our findings may provide new hope for the prevention and treatment of PD.
Epidermoid cyst of the cecum resected by single-incision laparoscopic colectomy: a case report
Authors: Tominaga Tetsuro , Nonaka Takashi , Fukuda Akiko , Moriyama Masaaki , Oyama Shosaburo , Ishii Mitsuhisa , Sawai Terumitsu , Ueki Nozomi , Nagayasu Takeshi 
Published: February 2021

Abstract
Background
Epidermoid cyst arising from the cecum is extremely rare. Single-incision laparoscopic surgery is the latest innovation in minimally invasive surgery, and shortens incisions, improves cosmesis, and reduces postoperative pain. We report here the first description of a patient with epidermoid cyst of the cecum treated by ileocecal resection by single-incision laparoscopic surgery.

Case presentation
A 20-year-old woman presented to our hospital with abdominal pain in the right lower quadrant. Abdominal contrast-enhanced computed tomography showed a 56 × 35-mm cystic mass in the ileocecal area. Magnetic resonance imaging revealed a 56 × 43-mm, T1-hypointense, T2-hyperintense mass attached to the cecum. Gastrointestinal tumor or duplication cyst was suspected, and ileocecal resection was performed using single-incision laparoscopic surgery. Intraoperative examination showed the tumor as a round, whitish mass arising from the cecum. Operation time was 162 min, and intraoperative blood loss was 10 ml. Macroscopic examination showed a 56 × 45-mm elastic-hard, whitish, round mass arising from the cecal wall. Microscopic examination revealed the cyst wall lined by keratinized stratified squamous epithelium. No malignant findings were identified. The final diagnosis was epidermoid cyst of the cecum. The postoperative course was uneventful and she was discharged on postoperative day 5.

Conclusions
A rare case of cecal epidermoid cyst is reported. Single-incision laparoscopic colectomy using an organ retractor represents a promising option for treating cecal epidermoid cyst.
A case of a common bile duct stone that formed around a fish bone as a nidus after distal gastrectomy with Roux-en-Y reconstruction
Authors: Hirata Ken , Kawamura Daichi , Orita Masahiko 
Published: February 2021

Abstract
Background
The presence of a foreign body in the common bile duct (CBD) is a rare phenomenon. Thus, the route and mechanism of its migration remain difficult to fully clarify, especially for cases that occur after gastrectomy with Roux-en-Y reconstruction. Herein, we present a case of a CBD stone that formed around a fish bone as a nidus subsequent to distal gastrectomy with Roux-en-Y reconstruction.

Case presentation
A 70-year-old man was admitted to our hospital due to repeated episodes of epigastralgia. He had undergone distal gastrectomy with Roux-en-Y reconstruction for gastric cancer approximately 10 years prior. Blood tests revealed obstructive jaundice, hepatobiliary dysfunction, and inflammation. Multi-plane reconstructed computed tomography (CT) revealed a CBD stone with a needle-shaped calcification density at the center, oriented along the length of the CBD. Surgery was performed using an upper median laparotomy approach. Lithotomy with choledochotomy was performed to remove one fragile bilirubin stone that had formed around a 3-cm, needle-shaped fish bone. A choledochoduodenal fistula was not detected intraoperatively. A review of the imaging of a prior examination revealed that the formation of the CBD stone around the fish bone was observable on a follow-up CT performed approximately 2 years prior. However, no clinical symptoms associated with the migration of the fish bone to the CBD were reported and the fish bone was not detected at that time.

Conclusion
In this case, transpapillary migration of the fish bone could only be speculated in the absence of an observable fistula, choledochostomy, or any clinical symptoms. Our case is clinically relevant as cholangitis developed after CBD stone formation around the fish bone that acted as a nidus.
Bounded Integer Modeling of Symptom Scales Specific to Lower Urinary Tract Symptoms Secondary to Benign Prostatic Hyperplasia
Authors: Lyauk Yassine Kamal , Jonker Daniël M. , Hooker Andrew C. , Lund Trine Meldgaard , Karlsson Mats O. 
Published: February 2021

AbstractThe International Prostate Symptom Score (IPSS), the quality of life (QoL) score, and the benign prostatic hyperplasia impact index (BII) are three different scales commonly used to assess the severity of lower urinary tract symptoms associated with benign prostatic hyperplasia (BPH-LUTS). Based on a phase II clinical trial including 403 patients with moderate to severe BPH-LUTS, the objectives of this study were to (i) develop traditional pharmacometric and bounded integer (BI) models for the IPSS, QoL score, and BII endpoints, respectively; (ii) compare the power and type I error in detecting drug effects of BI modeling with traditional methods through simulation; and (iii) obtain quantitative translation between scores on the three abovementioned scales using a BI modeling framework. All developed models described the data adequately. Pharmacometric modeling using a continuous variable (CV) approach was overall found to be the most robust in terms of type I error and power to detect a drug effect. In most cases, BI modeling showed similar performance to the CV approach, yet severely inflated type I error was generally observed when inter-individual variability (IIV) was incorporated in the BI variance function (g()). BI modeling without IIV in g() showed greater type I error control compared to the ordered categorical approach. Lastly, a multiple-scale BI model was developed and estimated the relationship between scores on the three BPH-LUTS scales with overall low uncertainty. The current study yields greater understanding of the operating characteristics of the novel BI modeling approach and highlights areas potentially requiring further improvement.
Quaternionic elastic scattering
Authors: Giardino Sergio 
Published: February 2021

Abstract
We study the elastic scattering of quantum particles based on a real Hilbert space approach to quaternionic quantum mechanics (

QM) and derive expression for the wave function, the phase shifts, as well as the optical theorem for the case of a hard sphere scattering potential. The strong agreement between these new quaternionic results and the corresponding results in complex quantum mechanics reinforce the validity of the

QM generalization of ordinary complex quantum mechanics (

QM).
Differential Immune Landscape of Hepatocellular Carcinoma Suggests Potential role of Macrophages in Hepatocarcinogenesis
Authors: Shafique Yusra , Qureshi Muhammad Asif , Khan Saeed , Mirza Talat 
Published: February 2021

Objectives: To investigate immune cell densities in tumor microenvironment of hepatocellular carcinoma.
Methods: This cross-sectional study was conducted during 2017-2019 at the Dow University of Health Sciences Karachi. A total of 42 subsequent patients undergoing liver biopsy/resection and diagnosed with hepatocellular carcinoma were included in the study. Moreover, a total of 10 control tissues were also included. In order to investigate immune cells densities in hepatocellular carcinoma, immunohistochemistry was performed using antibodies including α-MPO(neutrophils), α-CD-68(macrophages), α-CD-3(T-cells), α-CD-20(B-cells), α-CD-4(CD4+ T-cells) and α-CD-8(CD8+ T-cells). Quantification of immune cells/mm2 was performed as per the College of American Pathologists’ guidelines. Data were analyzed using SPSS version 21. A p-value of 0.05 was considered significant at all times.
Results: We report significantly increased infiltration of macrophages (mean macrophages= 306.57/mm2, p-value<0.05), moderately significant infiltration of neutrophils (p-value=0.06) and B-cells (p-value=0.07) while no significant infiltration of CD4+T-cells (p- value=0.31), and CD8+T-cells (p-value=0.39) in tumour microenvironment of patients with hepatocellular carcinoma.
Conclusion: We provide evidence for increased macrophage infiltration in liver cancer microenvironment suggesting a potential role of these cells in hepatocarcinogenesis.
doi: https://doi.org/10.12669/pjms.37.3.2973
How to cite this:Shafique Y, Qureshi MA, Khan S, Mirza T. Differential Immune Landscape of Hepatocellular Carcinoma Suggests Potential role of Macrophages in Hepatocarcinogenesis. Pak J Med Sci. 2021;37(3):858-862. doi: https://doi.org/10.12669/pjms.37.3.2973
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Intraoperative flexible nephroscopy during percutaneous nephrolithotomy: An 8 years’ experience
Authors: Masood Yasir , Iqbal Nadeem , Farooq Raja Mohsin , Iqbal Sajid , Khan Faheemullah 
Published: February 2021

Objectives: To see the effect of intra operative antegrade flexible nephroscopy during Percutaneous nephrolithotomy on stone free rate.
Methods: We retrospectively reviewed electronic medical records of patients who underwent percutaneous nephrolithotomy from 2010 to 2017 for renal stones >2cm. Patients found eligible were divided in, Group-I who did not have intraoperative Flexible nephroscopy and Group-II who had flexible nephroscopy during percutaneous nephrolithotomy. All procedures were done by senior consultants. Variables like Mean age, side, stone size, skin to stone distance and Hounsfield unit were compared. Outcomes like Stone free rate, hospital stay and operative time were compared between the groups.
Results: The study included 248 patients, consisting 85 (34.3%) females and 163 (65.7%) males. Mean age ± SD was 45.8±13.8 years. Both group were similar in characteristics like mean age, stone size, skin to stone distance and Hounsfield units. The overall stone free rate was 71%. It was not significantly different between the groups, 76% in Group-II vs. 67% in Group-I. However stone free rate markedly improved with flexible nephroscopy in patients with staghorn calculi. Mean operative time and hospital stay were similar between the groups.
Conclusions: Intraoperative flexible nephroscopy during percutaneous nephrolithotomy significantly increases stone free rate in patients with staghorn stones.
doi: https://doi.org/10.12669/pjms.37.3.3565
How to cite this:Masood Y, Iqbal N, Farooq RM, Iqbal S, Khan F. Intraoperative flexible nephroscopy during percutaneous nephrolithotomy: An 8 years’ experience. Pak J Med Sci. 2021;37(3):716-720. doi: https://doi.org/10.12669/pjms.37.3.3565
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.