bluuebunny/crossref_metadata_2025 huggingface dataset:
Knockdown of CD44 inhibits proliferation, migration and invasion of osteosarcoma cells accompanied by downregulation of cathepsin S
Authors: Kong Lingwei , Ji Hairu , Gan Xintian , Cao Sheng , Li Zhehong , Jin Yu
Published: March 2022

Background

Osteosarcoma (OS) is a malignant bone tumour of mesenchymal origin. These tumours are characterised by rich vascularisation, therefore promoting rapid proliferation and facilitating metastasis. CD44 has been reported to be involved in OS, but its role and molecular mechanisms in the pathogenesis of the disease are not fully determined.

Methods

In this study, we investigated the antitumor effect of CD44 on the development of OS and further explored the molecular mechanisms. The expression of CD44, cathepsin S and MMP-9 was detected by Western blot (WB) and reverse transcription-polymerase chain reaction (RT-qPCR) in different cell lines (MG63, U2OS OS and hFOB 1.19). To elucidate the role of CD44 in OS, MG63 and U2OS cells were treated with small interference RNA (siRNA) to knock down CD44, and the knockdown efficiency was validated with GFP and RT-qPCR. Furthermore, cell proliferation was assayed using Cell Counting Kit‑8 (CCK-8) and colony formation assays, and cell migration and invasion were assayed by transwell and wound-healing assays.

Results

We found that CD44 expression in the MG63 and U2OS OS cell lines was markedly increased compared to that of the human osteoblast hFOB 1.19 cell line. Knockdown of CD44 inhibited proliferation, migration and invasion of MG63 and U2OS cells. Cathepsin S expression in the MG63 and U2OS OS cell lines was increased compared to that of the human osteoblast hFOB 1.19 cell line. When CD44 was knocked down, its expression level went down.

Conclusion

Taken together, our data reinforced the evidence that CD44 knockdown inhibited cell proliferation, migration and invasion of OS cells accompanied by altered expression of cathepsin S. These findings offer new clues for OS development and progression, suggesting CD44 as a potential therapeutic target for OS.
HIV infection is not associated with perioperative blood loss in patients undergoing total hip arthroplasty
Authors: Wei Qifeng , Cai Gaorui , Chen Guoneng , Shen Maoye , Gao Ya , Ning Xianjia , Wang Jinghua , Jiang Wenxue
Published: March 2022

Background

Patients with HIV have a higher prevalence of thrombocytopenia than those without HIV infection, increasing their risk of substantial perioperative blood loss (PBL) during total hip arthroplasty (THA). This study aimed to evaluate PBL risk factors in HIV-infected patients undergoing THA.

Methods

Eighteen HIV+ patients (21 hip joints) and 33 HIV− patients (36 joints) undergoing THA were enrolled in this study. PBL was calculated using the Gross equation, which comprises total blood loss (TBL), dominant blood loss (DBL), and hidden blood loss (HBL). Risk factors for post-THA PBL in both patient populations was evaluated using multivariable linear regression.

Results

At baseline, the HIV+ patients were younger, more likely to be male and to have elevated hemoglobin and albumin levels, and lower erythrocyte sedimentation rates than HIV− patients. There were no differences in the T-lymphocyte subsets or coagulation function between the two groups. Age and albumin level were identified as potential HBL risk factors after THA, and albumin level was associated with higher TBL. The unadjusted linear regression analysis showed that the HBL and TBL were significantly higher in HIV+ patients than in HIV− patients. However, after adjusting for other factors, no differences in DBL, HBL, or TBL were observed between HIV− and HIV+ patients.

Conclusion

PBL was similar in both groups undergoing THA, regardless of their HIV-infection status. THA surgery is a safe and effective procedure in HIV+ patients.
Transfemoral aortic valve replacement in a nonagenarian with aortic stenosis and cardiac amyloidosis: case report
Authors: Akras Deena , Bullinger Keith , Kondapaneni Meera , Siraj Aisha , Akhrass Rami , Aneja Ashish
Published: March 2022

Background

Cardiac amyloidosis (CA) is diagnosed with increasing frequency in the elderly population with severe aortic stenosis (AS), especially with the low-flow, low- gradient phenotype. Prognosis is poor with no treatment.

Case presentation

The patient is a 94-year-old active male who presented with a stroke that fully resolved. He was found to have low-flow, low-gradient severe AS, along with concomitant CA. Gradients across the aortic valve worsened with the dobutamine challenge test. He underwent successful transfemoral aortic valve replacement (TAVR) and did well postoperatively, where he remained in the hospital for only one day. Treatment of his CA with Tafamidis was recommended; however, the patient declined due to its cost and personal preference.

Conclusion

To our knowledge, we report on one of the oldest patients to undergo TAVR for low-flow, low-gradient AS with concurrent CA (AS-CA). It might be prudent to screen elderly patients with AS for CA, as prognosis is worse with medical management alone. TAVR has overall improved survival in patients with AS-CA and is considered the procedure of choice, as these patients are typically older and at higher risk for surgical intervention.
Discomfort of postoperative patients with aortic dissection after discharge: telephone follow-up analysis of a cross-sectional study
Authors: Lang Xiaorong , Huang Sufang , Wang Quan , Feng Danni , Xiao Yaru , Li Miqi , Guo Zhiran , Zhou Quan
Published: March 2022

Background

Postoperative discomfort is one of the important manifestations of disease changes, but few studies have reported detailed description of postoperative discomfort in patients with aortic dissection after discharge. The aim of this study is to investigate the discomfort symptoms and to explore the possible influencing factors of discomfort symptoms.

Method

This cross-sectional study based on convenience sampling collected medical records from 999 patients hospitalized in Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of science and technology, Wuhan, Hubei, China from January 1, 2019 to December 31, 2019. Postoperative patients with first onset and confirmed aortic dissection were eligible for follow-up. Telephone follow-up was conducted from July 20, 2020 to August 20, 2020. Symptoms of discomfort were reported by patients or their immediate family members. Univariate and multivariable logistic regression analysis were performed to identify factors associated with symptoms of discomfort.

Results

A total of 675 patients were followed up, 185 patients (27.4%) were lost to follow-up, and the remaining 490 patients were divided into survival group (N = 428) and death group (N = 62) and were included in the study. There was no difference in gender and age among the three groups. 152 of 428 patients reported discomfort. The uncomfortable symptoms of postoperative patients were diverse, and mainly manifested as back and chest pain (32.24%, 49/152), chest tightness (15.79%, 24/152), dizzy (10.53%, 16/152) and weakness (10.53%, 16/152). Multivariable logistic regression analysis of postoperative discomfort showed length of discharge (OR 0.995; P 0.018; 95% CI 0.990–0.999) and positive history of drinking (OR 3.519; P 0.018; 95% CI 1.236–10.022) were significant among patients with Stanford A AD, and diagnosis was made in the first visiting hospital (OR 0.395; P 0.001; 95% CI 0.230–0.677) was a protective factor for patients.

Conclusions

The incidence of postoperative discomfort in patients with aortic dissection was high and the symptoms were diverse and not single. In order to reduce the possibility of postoperative discomfort, it is important to formulate effective public policies to limit the public to drink alcohol and timely diagnose aortic dissection. Long term follow-up is necessary for patients with aortic dissection to observe the recovery process of aortic dissection.
Cinnamomi Ramulus inhibits the growth of colon cancer cells via Akt/ERK signaling pathways
Authors: Pan Boyu , Xia Yafei , Gao Zilu , Zhao Gang , Wang Liangjiao , Fang Senbiao , Liu Liren , Yan Shu
Published: March 2022

Background

Colon cancer (CC) ranks the second highest mortality rate among malignant tumors worldwide, and the current mainstream treatment regimens are not very effective. The unique efficacy of Chinese herb medicine (CHM) for cancer has recently attracted increasing attention. Cinnamomi Ramulus (CR), as a classic CHM, has been widely used in the treatment of a variety of diseases for hundreds of years in China, but its specific pharmacological mechanism against CC needs to be fully evaluated.

Methods

TCMSP and China National Knowledge Infrastructure database were utilized to predict the candidate ingredients of CR, and TCMSP and SwissTargetPrediction database were also employed to predict the drug targets of the candidate ingredients from CR. We subsequently evaluated the therapeutic effect of CR by orally administrating it on CC-bearing mice. Next, we further identified the potential CC-related targets by using Gene Expression Omnibus (GEO) database. Based on these obtained targets, the drug/disease-target PPI networks were constructed using Bisogenet plugin of Cytoscape. The potential core therapeutic targets were then identified through topological analysis using CytoNCA plugin. GO and KEGG enrichment analyses were performed to predict the underlying mechanism of CR against CC. Furthermore, these in silico analysis results were validated by a series of cellular functional and molecular biological assays. UPLC–MS/MS method and molecular docking analysis were employed to identify the potential key components from CR.

Results

In this study, we firstly found that CR has potential therapeutic effect on cancer. Then, oral administration of CR could inhibit the growth of CC cells in C57BL/6 mice, while inhibiting the viability and motility of CC cells in vitro. We obtained 111 putative core therapeutic targets of CR. Subsequent enrichment analysis on these targets showed that CR could induce apoptosis and cell cycle arrest in CC cells by blocking Akt/ERK signaling pathways, which was further experimentally verified. We identified 5 key components from the crude extract of CR, among which taxifolin was found most likely to be the key active component against CC.

Conclusions

Our results show that CR as well as its active component taxifolin holds great potential in treatment of CC.
Laparoscopic versus open resections in the posterosuperior liver segments within an enhanced recovery programme (ORANGE Segments): study protocol for a multicentre randomised controlled trial
Authors: Kuemmerli Christoph , Fichtinger Robert S. , Moekotte Alma , Aldrighetti Luca A. , Aroori Somaiah , Besselink Marc G. H. , D’Hondt Mathieu , Díaz-Nieto Rafael , Edwin Bjørn , Efanov Mikhail , Ettorre Giuseppe M. , Menon Krishna V. , Sheen Aali J. , Soonawalla Zahir , Sutcliffe Robert , Troisi Roberto I. , White Steven A. , Brandts Lloyd , van Breukelen Gerard J. P. , Sijberden Jasper , Pugh Siân A. , Eminton Zina , Primrose John N. , van Dam Ronald , Hilal Mohammed Abu ,   on behalf of the ORANGE trials collaborative
Published: March 2022

Background

A shift towards parenchymal-sparing liver resections in open and laparoscopic surgery emerged in the last few years. Laparoscopic liver resection is technically feasible and safe, and consensus guidelines acknowledge the laparoscopic approach in the posterosuperior segments. Lesions situated in these segments are considered the most challenging for the laparoscopic approach. The aim of this trial is to compare the postoperative time to functional recovery, complications, oncological safety, quality of life, survival and costs after laparoscopic versus open parenchymal-sparing liver resections in the posterosuperior liver segments within an enhanced recovery setting.

Methods

The ORANGE Segments trial is an international multicentre randomised controlled superiority trial conducted in centres experienced in laparoscopic liver resection. Eligible patients for minor resections in the posterosuperior segments will be randomised in a 1:1 ratio to undergo laparoscopic or open resections in an enhanced recovery setting. Patients and ward personnel are blinded to the treatment allocation until postoperative day 4 using a large abdominal dressing.

The primary endpoint is time to functional recovery. Secondary endpoints include intraoperative outcomes, length of stay, resection margin, postoperative complications, 90-day mortality, time to adjuvant chemotherapy initiation, quality of life and overall survival.

Laparoscopic liver surgery of the posterosuperior segments is hypothesised to reduce time to functional recovery by 2 days in comparison with open surgery. With a power of 80% and alpha of 0.04 to adjust for interim analysis halfway the trial, a total of 250 patients are required to be randomised.

Discussion

The ORANGE Segments trial is the first multicentre international randomised controlled study to compare short- and long-term surgical and oncological outcomes of laparoscopic and open resections in the posterosuperior segments within an enhanced recovery programme.

Trial registration

ClinicalTrials.gov NCT03270917. Registered on September 1, 2017. Before start of inclusion. Protocol version: version 12, May 9, 2017
Do biometric payment systems work during the COVID-19 pandemic? Insights from the Spanish users' viewpoint
Authors: Liébana-Cabanillas Francisco , Muñoz-Leiva Francisco , Molinillo Sebastián , Higueras-Castillo Elena
Published: March 2022

Technological developments are changing how users pay for goods and services. In the context of the COVID-19 (coronavirus disease 2019) pandemic, new payment systems have been established to reduce contact between buyer and seller. In addition to the pandemic, the future is payment processing is also uncertain due to the new EU security regulations of the Payment Services Directive (PSD2). Biometric payments one option that would guarantee the security of transactions and reduce the risk of contagion. This research analyses the intention to recommend the use of the mobile phone as a tool for collecting payments in a shop using iris reading as a biometric measure of the buyer. The moderating effect of the fear of contagion in the proposed relationships was also analysed. An online survey was carried out, which yielded a sample of 368 respondents. The results indicate that the main antecedents of intention to use, which precedes intention to recommend, are perceived trust, habit, personal innovativeness and comfort of use. Additionally, the moderating effect of COVID-19 was checked among users with a higher perception of risk. The results obtained have interesting implications for purchase management among manufacturers and retailers.
The governance of imported 2019-nCov infections: What can be learned from China’s experience?
Authors: Li Hao , He Jiaxin , Chen Jiayu , Pan Shuning , Feng Jiehan , Liu Shuang
Published: March 2022

Delta and Omicron variants of 2019-nCoV are still spreading globally, and many imported infections have been identified in China as well. In order to control the spread chain from imported to local, China has implemented the dynamic Covid-zero policy. In this article we summarized China’s governance models and practices of fighting potential imported infections in two directions. One targets at international travelers, which can be outlined as four lines of defense: customs epidemic prevention, quarantine upon arrival, relevant laws and regulations, and community tracking. The other is against other vectors potentially carrying 2019-nCoV, which can be outlined by three lines of defense: customs epidemic prevention, disinfection and personal protection, and information management. However, there are still some challenges that are yet to be addressed, such as illegal immigration, accidental occupational exposure to 2019-nCoV, etc. China’s experience indicates that no country can stay safe during the global pandemic as long as there are local outbreaks in other countries, and active prevention and control measures based on science and a complete set of laws and regulations are still necessary at current stage. What’s more, accountable government commitment and leadership, strengthened health and social governance systems, and whole society participation are required. It is suggested that the global community continue to closely cooperate together and take active rather than passive actions to block the potential imported 2019-nCoV from causing local spreading.
Optimal Location and Sizing of Conglomerate DG- FACTS using an Artificial Neural Network and Heuristic Probability Distribution Methodology for Modern Power System Operations
Authors: Siddiqui Anwar Shahzad , Prashant
Published: March 2022

In existing power system networks, the positioning and sizing of multi-DG is critical at the optimum locations for effective energy management. Initially optimal power flow is assessed using the NR method (without DG) in which performance parameters such as real power loss, accuracy, selectivity and MSE are obtained, but in an undesirable manner. To meet load demand; multi-DGs are placed and their optimal locations are assessed by the proposed heuristic probability distribution methodology and an ANN because existing techniques provides poor performance parameters for selecting the location and sizing of DGs. The optimal positions of multi-DGs are estimated in terms of performance parameters including real power loss of transmission network, accuracy, selectivity and MSE, while the performance parameters obtained with the ANN are better than the heuristic pdf. Then, the sizing of multi-DGs is evaluated in relation to active and reactive power. It is found that that sizes of multi-DGs are smaller with ANN than with heuristic pdf. It is preferable to connect the buses having lowest real power losses with the smallest multi-DGs. The performance analysis is tested in the standard IEEE 9- bus and IEEE 57- bus systems on Simulink. To improve the distortion level in real and reactive power, multi-FACTS namely TCSC, TSC and STATCOM are used. The switching of TCSC and TSC is done by SPWM while STATCOM switching is controlled with ANFIS. The locations of multi-FACTS devices are chosen for buses having larger distortion and the sizing of multi-FACTS devices is also optimally decided. The application of multi-FACTS devices helps to improve power quality and fulfill load demand with minimal size in order to make the system economical.
Local seismic culture in Iranian vernacular architecture: evidence from Yazd earthen architecture
Authors: Azizi-Bondarabadi Hamed , Haji Sadeghi Neda
Published: March 2022

Iran, located in one of the most earthquake-prone regions of the world, has experienced a very large number of destructive earthquakes that brought about considerable loss of human life and economic consequences. The country possesses a vast number of monumental and vernacular built heritages that are constantly threatened by earthquakes. As vernacular techniques for dwellings comply with the needs, comfort, utility, and functionality of people, it is expected that endemic earthquake-resistant techniques make an essential contribution to Iranian vernacular architecture. The city of Yazd presents a unique and rich vernacular for earthen construction within Iranian architectural heritage, which has resulted in the recognition of the historic fabric of the city as a World Heritage Site since 2017. Considering the importance of exploring different local seismic cultures worldwide, this paper introduces an essential part of Iranian local seismic culture by recognising and classifying the vernacular earthquake-resistant techniques used in the earthen architecture of the city of Yazd. The techniques were collected by surveying the historic fabric, using data available in the literature, and interviewing traditional builders and local conservators. Next, the seismic influence of each technique was evaluated using examples from the performance of adobe constructions during the 2003 Bam earthquake.
Generating a labeled data set to train machine learning algorithms for lithologic classification of drill cuttings
Authors: Becerra Daniela , Pires de Lima Rafael , Galvis-Portilla Henry , Clarkson Christopher R.
Published: March 2022

Despite significant developments in the past few years in the application of machine learning algorithms for the lithologic classification of rock samples, publicly available labeled data sets are very scarce. We open source a fully labeled data set containing more than 16,000 scanning electron microscopy (SEM) images of drill cutting samples—mounted on thin sections—from a low-permeability reservoir in western Canada. We develop a simplified image processing workflow to segment and isolate the rock chips into individual SEM images, which in turn are used to identify, classify, and quantify rock types based on textural characteristics. In addition, using this data set, we explore the use of convolutional neural networks (CNNs) as a baseline tool for acceleration and automatization of rock-type classification. Without significant modifications to popular CNN models, we obtain an accuracy of approximately 90% for the test set. Results demonstrate the potential of CNN as a fast approach for lithologic classification in low-permeability siltstone reservoirs. In addition to making the data set publicly available, we believe our workflow to segment and isolate drill cutting samples in individual images of rock chips will facilitate future research of drill cuttings properties (e.g., lithology, porosity, and particle size) using machine learning algorithms.
The Use and Knowledge of Validated Geriatric Assessment Instruments Among US Community Oncologists
Authors: Gajra Ajeet , Jeune-Smith Yolaine , Fortier Stephanie , Feinberg Bruce , Phillips Eli , Balanean Alexandrina , Klepin Heidi D.
Published: March 2022

PURPOSE:

The use of a standardized geriatric assessment (GA) to inform treatment decisions in older adults with cancer improves quality of life, reduces treatment-related toxicity, and is guideline-recommended. This study aimed to assess community oncologists' knowledge and utilization of GAs.

METHODS:

Between September 2019 and February 2020, practicing US-based oncologists were invited to attend live meetings and complete web-based surveys designed to collect information on treatment decision making and various practice-based challenges in oncology care.

RESULTS:

Among the 349 oncologists surveyed, 74% practiced in a community setting. Sixty percent did not use a formal GA to inform treatment decisions for any of their older patients; the most common reasons for not using a GA were “Too cumbersome to incorporate into routine practice” (44%) and “Adds no value beyond the comprehensive history and physical exam” (36%). Validated GA instruments used in routine clinical practice included: Mini-Mental State Exam (54%), Comprehensive Geriatric Assessment (23%), Cancer and Aging Research Group toxicity tool (12%), and Chemotherapy Risk Assessment Scale for High-Age Patients tool (9%). Nineteen percent of oncologists were not aware of any validated GA instruments. Eastern Cooperative Oncology Group performance status and comorbidities were the most frequently used assessment factors to inform treatment decisions (88% and 73%, respectively).

CONCLUSION:

Many oncologists have not incorporated GA tools because of perceptions that GAs are difficult to implement or do not add any value. Increasing education of the benefits of GA-directed therapy could help to increase GA utilization among community oncologists.
11-Oxyandrogens in Adolescents With Polycystic Ovary Syndrome
Authors: Taylor Anya E , Ware Meredith A , Breslow Emily , Pyle Laura , Severn Cameron , Nadeau Kristen J , Chan Christine L , Kelsey Megan M , Cree-Green Melanie
Published: March 2022

Context

Polycystic ovary syndrome (PCOS) is common and diagnosis requires an elevated testosterone. The clinical importance of adrenal 11-oxyandrogens in PCOS is unclear.

Objective

We sought to determine if 11-oxyandrogens 1) better identify PCOS diagnosis compared to testosterone, 2) predict clinical comorbidities of PCOS, and 3) are altered with an combined oral contraceptive pill (COCP) or metformin therapy.

Methods

Data from 200 adolescent female participants aged 12 to 21 years, most with obesity, enrolled across 6 studies in pediatric endocrinology were included: 70 non-PCOS controls, 115 untreated PCOS, 9 PCOS + obesity treated with COCP, and 6 PCOS + obesity treated with metformin. 11-Hydroxyandrostenedione (11-OHA4), 11-hydroxytestosterone (1-OHT), 11-ketotestosterone (11-KT), and testosterone were measured with liquid chromatography–tandem mass spectrometry. Data between 1) untreated PCOS and controls and 2) untreated PCOS and the 2 treatment groups were compared.

Results

Untreated girls with PCOS had higher 11-OHA4 (P = .003) and 11-OHT (P = .005) compared to controls, but not 11-KT (P = .745). Elevated 11-OHA4 remained statistically significant after controlling for obesity. Testosterone better predicted PCOS status compared to 11-oxyandrogens (receiver operating characteristic curve analysis: 11-OHA4 area under the curve [AUC] = 0.620, 11-OHT AUC = 0.638; testosterone AUC = 0.840). Among untreated PCOS patients, all 3 11-oxyandrogens correlated with hirsutism severity. 11-KT (P = .039) and testosterone (P < .006) were lower in those on COCP treatment compared to untreated PCOS. Metformin treatment had no effect on 11-oxyandrogens, although testosterone was lower (P = .01).

Conclusion

Although 11-oxyandrogens do not aid in the diagnosis of PCOS, they relate to excess hair growth. COCP treatment may related to 11-KT; however, further work is needed to determine causality, relationship with metabolic outcomes, and the clinical utility of measuring these androgens in PCOS.
Machine Learning–Driven Clinical Image Analysis to Identify Craniosynostosis: A Pilot Study of Telemedicine and Clinic Patients
Authors: Paro Mitch , Lambert William A. , Leclair Nathan K. , Romano Robert , Stoltz Petronella , Martin Jonathan E. , Hersh David S. , Bookland Markus J.
Published: March 2022

BACKGROUND:

The authors have developed pretrained machine learning (ML) models to evaluate neonatal head shape deformities using top-down and facial orthogonal photographs of the patient’s head. In previous preliminary analysis, this approach was tested with images from an open-source data bank.

OBJECTIVE:

To determine the accuracy of pretrained ML models in identifying craniosynostosis among patients seen in our outpatient neurosurgery clinic.

METHODS:

We retrospectively reviewed top-down and facial orthogonal images of each patient’s head and provider clinical diagnosis from the same encounters. Head shape classifications generated from 3 pretrained ML models (random forest, classification and regression tree, and linear discriminant analysis) were applied to each patient's photograph data set after craniometric extraction using a predefined image processing algorithm. Diagnoses were codified into a binary scheme of craniosynostosis vs noncraniosynostosis. Sensitivity, specificity, and Matthew correlation coefficient were calculated for software vs provider classifications.

RESULTS:

A total of 174 patients seen for abnormal head shape between May 2020 and February 2021 were included in the analysis. One hundred seven patients (61%) were seen in-person and 67 (39%) through telemedicine. Twenty-three patients (13%) were diagnosed with craniosynostosis. The best-performing model identified craniosynostosis with an accuracy of 94.8% (95% CI 90.4-97.6), sensitivity of 87.0% (95% CI 66.4-97.2), specificity of 96.0% (95% CI 91.6-98.5), and Matthew correlation coefficient of 0.788 (95% CI 0.725-0.839).

CONCLUSION:

Machine learning–driven image analysis represents a promising strategy for the identification of craniosynostosis in a real-world practice setting. This approach has potential to reduce the need for imaging and facilitate referral by primary care providers.
SIRT1 regulates cardiomyocyte alignment during maturation
Authors: Fang Yi , Fan Wei , Xu Xiaojiang , Janoshazi Agnes K. , Fargo David C. , Li Xiaoling
Published: March 2022

Cardiomyocyte elongation and alignment, a critical step in cardiomyocyte maturation starting from the perinatal stage, is crucial for formation of the highly organized intra- and inter-cellular structures for spatially and temporally ordered contraction in adult cardiomyocytes. However, the mechanism(s) underlying the control of cardiomyocyte alignment remains elusive. Here, we report that SIRT1, the most conserved NAD+-dependent protein deacetylase highly expressed in perinatal heart, plays an important role in regulating cardiomyocyte remodeling during development. We observed that SIRT1 deficiency impairs the alignment of cardiomyocytes/myofibrils and disrupts normal beating patterns at late developmental stages in an in vitro differentiation system from human embryonic stem cells. Consistently, deletion of SIRT1 at a late developmental stage in mouse embryos induced the irregular distribution of cardiomyocytes and misalignment of myofibrils, and reduced the heart size. Mechanistically, the expression of several genes involved in chemotaxis, including those in the CXCL12/CXCR4 and CCL2/CCR2/CCR4 pathways, was dramatically blunted during maturation of SIRT1-deficient cardiomyocytes. Pharmacological inhibition of CCL2 signaling suppressed cardiomyocyte alignment. Our study identifies a regulatory factor that modulates cardiomyocyte alignment at the inter-cellular level during maturation.
Lipophagy at a glance
Authors: Schott Micah B. , Rozeveld Cody N. , Weller Shaun G. , McNiven Mark A.
Published: March 2022

Lipophagy is a central cellular process for providing the cell with a readily utilized, high energy source of neutral lipids. Since its discovery over a decade ago, we are just starting to understand the molecular components that drive lipophagy, how it is activated in response to nutrient availability, and its potential as a therapeutic target in disease. In this Cell Science at a Glance article and the accompanying poster, we first provide a brief overview of the different structural and enzymatic proteins that comprise the lipid droplet (LD) proteome and reside within the limiting phospholipid monolayer of this complex organelle. We then highlight key players in the catabolic breakdown of LDs during the functionally linked lipolysis and lipophagy processes. Finally, we discuss what is currently known about macro- and micro-lipophagy based on findings in yeast, mammalian and other model systems, and how impairment of these important functions can lead to disease states.
Perilipins at a glance
Authors: Najt Charles P. , Devarajan Mahima , Mashek Douglas G.
Published: March 2022

Lipid droplets (LDs) are ubiquitous organelles that store and supply lipids for energy metabolism, membrane synthesis and production of lipid-derived signaling molecules. While compositional differences in the phospholipid monolayer or neutral lipid core of LDs impact their metabolism and function, the proteome of LDs has emerged as a major influencer in all aspects of LD biology. The perilipins (PLINs) are the most studied and abundant proteins residing on the LD surface. This Cell Science at a Glance and the accompanying poster summarize our current knowledge of the common and unique features of the mammalian PLIN family of proteins, the mechanisms through which they affect cell metabolism and signaling, and their links to disease.
Echolocating Daubenton's bats call louder, but show no spectral jamming avoidance in response to bands of masking noise during a landing task
Authors: Pedersen Michael Bjerre , Uebel Astrid Særmark , Beedholm Kristian , Foskolos Ilias , Stidsholt Laura , Madsen Peter Teglberg
Published: March 2022

Echolocating bats listen for weak echoes to navigate and hunt, which makes them prone to masking from background noise and jamming from other bats and prey. As for electrical fish that display clear spectral jamming avoidance responses (JAR), bats have been reported to mitigate the effects of jamming by shifting the spectral contents of their calls, thereby reducing acoustic interference to improve echo-to-noise ratio (ENR). Here, we tested the hypothesis that frequency-modulating bats (FM bats) employ a spectral JAR in response to six masking noise bands ranging from 15 to 90 kHz, by measuring the −3 dB endpoints and peak frequency of echolocation calls from five male Daubenton's bats (Myotis daubentonii) during a landing task. The bats were trained to land on a noise-generating spherical transducer surrounded by a star-shaped microphone array, allowing for acoustic localization and source parameter quantification of on-axis calls. We show that the bats did not employ spectral JAR as the peak frequency during jamming remained unaltered compared with that of silent controls (all P>0.05, 60.73±0.96 kHz, mean±s.e.m.), and −3 dB endpoints decreased in noise irrespective of treatment type. Instead, Daubenton's bats responded to acoustic jamming by increasing call amplitude via a Lombard response that was bandwidth dependent, ranging from a mean of 0.05 dB/dB (95% confidence interval 0.04–0.06 dB/dB) noise for the most narrowband noise (15–30 kHz) to 0.17 dB/dB (0.16–0.18 dB/dB) noise for the most broadband noise (30–90 kHz). We conclude that Daubenton's bats, despite having the vocal flexibility to do so, do not employ a spectral JAR, but defend ENRs via a bandwidth-dependent Lombard response.
Accreditation of medical education in Vietnam: From local to global excellence
Authors: Ha Thuy Minh , Siddiqui Zarrin Seema
Published: March 2022

Medical education in Vietnam is going through a period of transformation. The number of medical schools is growing with increased enrollment of the students to meet the workforce needs of the country. Simultaneously, there is a need to ensure the quality of medical graduates and that there are mechanisms in place through relevant regulatory bodies.As part of general framework, accreditation of higher education institutions is already a requirement in Vietnam with individual programs and disciplines to be accredited by the professional organizations within Vietnam or externally where appropriate. However, accreditation of medical education programs is not established as a separate entity. No medical education program in Vietnam has undergone an external evaluation but there are ongoing discussions at various forums to initiate an independent process for medical education programs. There is a consensus among stakeholders that the accreditation of medical education programs will have a potential to drive quality improvement. In this paper, we present a brief overview of the trajectory of accreditation process in Vietnam with recommendations to move forward. The journey ahead will require a coordinated approach from all stakeholders to build an accreditation system, which ensures that quality healthcare, is offered by the workforce in Vietnam.

doi: https://doi.org/10.12669/pjms.38.4.5077

How to cite this:Ha TM, Siddiqui ZS. Accreditation of medical education in Vietnam: From local to global excellence. Pak J Med Sci. 2022;38(4):---------. doi: https://doi.org/10.12669/pjms.38.4.5077

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.
Framing and understanding the whole aspect of oral sex from social and health perspective: a narrative review
Authors: Pakpahan Cennikon , Darmadi Darmadi , Agustinus Agustinus , Rezano Andri
Published: March 2022

Since thousands of years ago, oral sex has become part of sexual behavior among humans. Oral sex is considered taboo. Its taboo does not lie in the behavior, but its expression is deemed inappropriate. As technology becomes more sophisticated, human rights also stand out, leading to the disclosure of the practice in the 21st century. The oral sex that is discussed on a large scale in media encourages people to express it as feedback whether within right or not. It all depends on the value of each people. We found that this sexual behavior is found everywhere regardless of religion, culture, and race.

Pop culture influences this behavior so much, it can be seen from music, movies, and television programs that provoke oral sex. Many motivations underlying this behavior include getting sexual pleasure for the sake of psychological well-being. But it is undeniable that this behavior is still controversial. It could be at risk of causing disease and, on the other hand, is reported to provide many benefits.

According to our theory, oral sex is not a new behavior crossing boundaries. It is just an old behavior that surfaces because of the factors that support it. This behavior, which is still considered taboo, has its disadvantages such as sexually transmitted disease and oral cancer but has also benefits such as preventing preeclampsia.
Molecular mechanisms of flavonoids and their modulatory effects against breast cancer: A scoping review
Authors: Murithi Mary , Wambugu Esbon , Nyanjom Steven , Mobegi Victor , Shahin Sayed , Makokha Francis
Published: March 2022

Background: Breast cancer is the most prevalent malignancy among women. It is a disease whose incidence and mortality rates are on the upsurge globally. Debilitating effects, cost and resistance to available chemotherapeutic interventions render them unideal. Dietary phytochemicals have been shown to have preventive and therapeutic effects. Research continues to affirm the role of flavonoids as potential chemotherapeutic agents in combating the disease. Understanding modulation of key cellular signalling pathways by flavonoids presents promising molecular targets that may be leveraged to develop better chemotherapeutic agents for breast cancer.

Methods:  To describe the in vitro and in vivo modulatory effects of flavonoids on molecular anti-cancer mechanisms we searched three databases. We included original articles describing modulation of cell signalling processes such as; cell cycle, apoptosis, autophagy, angiogenesis, invasion and migration which are involved in tumorigenesis. The search guidelines such as; year of publication, search strategy, study design and language informed article selection.

Results: Thirty-six articles were reviewed. Modulatory effects of six subclasses of flavonoids on breast cancer tumorigenic pathways were reported. The effects included enhanced apoptosis, attenuation of; angiogenesis, cell cycle, invasion, migration and metastasis. For instance, pectolinarigenin inhibited signal transducer and activator of transcription 3 (stat3) signalling pathway in triple negative breast cancer. Whereas, sideritoflavone caused cell cycle arrest and inhibited migration in trastuzumab resistant breast cancer cells. Additionally, quercetin and ampelopsin inhibited stemness features in triple negative breast cancer cells.

Conclusion: Evidently flavonoids showed significant modulatory effects on cellular signalling pathways crucial for breast cancer progression. The ability of flavonoids to act on a wide range of mechanisms as well as on aggressive breast cancer types presents an array of hope. We recommend that further studies be done to ascertain the applicability of these compounds in treatment of breast cancers.
A multi-spectral myelin annotation tool for machine learning based myelin quantification
Authors: Çapar Abdulkerim , Çimen Sibel , Aladağ Zeynep , Ekinci Dursun Ali , Ayten Umut Engin , Kerman Bilal Ersen , Töreyin Behçet Uğur
Published: March 2022

Myelin is an essential component of the nervous system and myelin damage causes demyelination diseases. Myelin is a sheet of oligodendrocyte membrane wrapped around the neuronal axon. In the fluorescent images, experts manually identify myelin by co-localization of oligodendrocyte and axonal membranes that fit certain shape and size criteria. Because myelin wriggles along x-y-z axes, machine learning is ideal for its segmentation. However, machine-learning methods, especially convolutional neural networks (CNNs), require a high number of annotated images, which necessitate expert labor. To facilitate myelin annotation, we developed a workflow and software for myelin ground truth extraction from multi-spectral fluorescent images. Additionally,  to the best of our knowledge, for the first time, a set of annotated myelin ground truths for machine learning applications were shared with the community.
The parallels between particle induced lung overload and particle induced periprosthetic osteolysis (PPOL)
Authors: Borm Paul J.A.
Published: March 2022

Background: When particles deposit for instance in the lung after inhalation or in the hip joint after local release from a hip implant material they can initiate a defense response. Even though these particles originate from inert materials such as polyethylene (PE) or titanium, they may cause harm when reaching high local doses and overwhelming local defense mechanisms.

Main body: This paper describes the parallels between adverse outcome pathways (AOP) and particle properties in lung overload and periprosthetic osteolysis (PPOL). It is noted that in both outcomes in different organs , the macrophage and cytokine orchestrated persistent inflammation is the common driver of events, in the bone leading to loss of bone density and structure, and in the lung leading to fibrosis and cancer. Most evidence on lung overload and its AOP is derived from chronic inhalation studies in rats, and the relevance to man is questioned. In PPOL, the paradigms and metrics are based on human clinical data, with additional insights generated from in vitro and animal studies. In both organ pathologies the total volume of particle deposition has been used to set threshold values for the onset of pathological alterations. The estimated clinical threshold for PPOL of 130 mg/ml is much higher than the amount to cause lung overload in the rat (10 mg/ml),although the threshold in PPOL is not necessarily synonymous to particle overload.

Conclusions: The paradigms developed in two very different areas of particle response in the human body have major similarities in their AOP. Connecting the clinical evidence in PPOL to lung overload challenges relevance of rat inhalation studies to the human lung cancer hazard.

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FAIR4Health: Findable, Accessible, Interoperable and Reusable data to foster Health Research
Authors: Alvarez-Romero Celia , Martínez-García Alicia , Sinaci A. Anil , Gencturk Mert , Méndez Eva , Hernández-Pérez Tony , Liperoti Rosa , Angioletti Carmen , Löbe Matthias , Ganapathy Nagarajan , Deserno Thomas M. , Almada Marta , Costa Elisio , Chronaki Catherine , Cangioli Giorgio , Cornet Ronald , Poblador-Plou Beatriz , Carmona-Pírez Jonás , Gimeno-Miguel Antonio , Poncel-Falcó Antonio , Prados-Torres Alexandra , Kovacevic Tomi , Zaric Bojan , Bokan Darijo , Hromis Sanja , Djekic Malbasa Jelena , Rapallo Fernández Carlos , Velázquez Fernández Teresa , Rochat Jessica , Gaudet-Blavignac Christophe , Lovis Christian , Weber Patrick , Quintero Miriam , Perez-Perez Manuel M. , Ashley Kevin , Horton Laurence , Parra Calderón Carlos Luis
Published: March 2022

Due to the nature of health data, its sharing and reuse for research are limited by ethical, legal and technical barriers. The FAIR4Health project facilitated and promoted the application of FAIR principles in health research data, derived from the publicly funded health research initiatives to make them Findable, Accessible, Interoperable, and Reusable (FAIR). To confirm the feasibility of the FAIR4Health solution, we performed two pathfinder case studies to carry out federated machine learning algorithms on FAIRified datasets from five health research organizations. The case studies demonstrated the potential impact of the developed FAIR4Health solution on health outcomes and social care research. Finally, we promoted the FAIRified data to share and reuse in the European Union Health Research community, defining an effective EU-wide strategy for the use of FAIR principles in health research and preparing the ground for a roadmap for health research institutions to offer access to certified FAIR datasets.

This scientific report presents a general overview of the FAIR4Health solution: from the FAIRification workflow design to translate raw data/metadata to FAIR data/metadata in the health research domain to the FAIR4Health demonstrators’ performance.
On the Test Accuracy and Effective Control of the COVID-19 Pandemic: A Case Study in Singapore
Authors: Cheng Guang , Gao Sarah Yini , Yuan Yancheng , Zhang Chenxiao , Zheng Zhichao
Published: March 2022

This study examines the impact of coronavirus disease 2019 (COVID-19) test accuracy (i.e., sensitivity and specificity) on the progression of the pandemic under two scenarios of limited and unlimited test capacity. We extend the classic susceptible– exposed–infectious–recovered model to incorporate test accuracy and compare the progression of the pandemic under various sensitivities and specificities. We find that high-sensitivity tests effectively reduce the total number of infections only with sufficient testing capacity. Nevertheless, with limited test capacity and a relatively high cross-infection rate, the total number of infected cases may increase when sensitivity is above a certain threshold. Despite the potential for higher sensitivity tests to identify more infected individuals, more false positive cases occur, which wastes limited testing capacity, slowing down the detection of infected cases. Our findings reveal that improving test sensitivity alone does not always lead to effective pandemic control, indicating that policymakers should balance the trade-off between high sensitivity and high false positive rates when designing containment measures for infectious diseases, such as COVID-19, particularly when navigating limited test capacity.

History: This paper was refereed. This article has been selected for inclusion in the Special Issue on Analytics Remedies to COVID-19.