bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prevalence and Determinants of Hand and Face Dermatitis during COVID-19 Pandemic: A Population-Based Survey
Authors: Alsaidan Mohammed Saud , Abuyassin Aisha H. , Alsaeed Zahra H. , Alshmmari Saqer H. , Bindaaj Tariq F. , Alhababi Alwa’ad A.
Published: December 2020

Background. During the current COVID-19 pandemic, prevention is the key to limiting the spread of this disease. The frequent handwashing and use of sanitizers resulted in notable skin changes among some individuals. The aim of the study was to determine the prevalence and determinants of the new onset of dermatitis during the COVID-19 pandemic in a university population from Saudi Arabia. Methods. A cross-sectional study was conducted using a self-administered online questionnaire by sending an invitation link to students and employees of Prince Sattam Bin Abdulaziz University in June 2020. A chi-squared test was used to note differences regarding hand and face dermatitis. Results. Of the total 2356 participants, 34.8% reported skin changes or symptoms over hands, and 15.3% reported skin changes on their face during this pandemic. 88.7% of the participants reported a change in handwashing habits during the COVID-19 pandemic, and 62.2% of participants were not using any hand sanitizers before COVID-19 but began using them during the pandemic. There were significantly higher percentage of skin conditions in females (on hands (ScH): 42.6% and face (ScF):19.2%), individuals working in environments requiring frequent handwashing (ScH: 40.3% vs. ScF: 17.2%), those working in facilities where they have to interact with people during the pandemic (ScH: 41.1% vs. ScF: 18.7%), those encountering COVID-19 patients (ScH: 48.6% vs. ScF: 24.8%), those exposed to chemicals (ScH: 48.6% vs. ScF: 24.8%), and healthcare workers (ScH: 51.3% vs. ScF: 24.3%). Conclusion. It was found that during the pandemic, skin changes were common among the general population as well as among healthcare workers. The frequency of handwashing and the use of alcohol-based sanitizers were contributing factors for dermatitis. Although hygiene is an extremely important preventive measure in this pandemic, maintaining skin integrity is also vital. Appropriate knowledge and good practice can prevent dermatitis in this pandemic, with regular hydration of the skin being a key factor.
A Privacy-Protection Model for Patients
Authors: Cheng Wenzhi , Ou Wei , Yin Xiangdong , Yan Wanqin , Liu Dingwan , Liu Chunyan
Published: December 2020

The collection and analysis of patient cases can effectively help researchers to extract case feature and to achieve the objectives of precision medicine, but it may cause privacy issues for patients. Although encryption is a good way to protect privacy, it is not conducive to the sharing and analysis of medical cases. In order to address this problem, this paper proposes a federated learning verification model, which combines blockchain technology, homomorphic encryption, and federated learning technology to effectively solve privacy issues. Moreover, we present a FL-EM-GMM Algorithm (Federated Learning Expectation Maximization Gaussian Mixture Model Algorithm), which can make model training without data exchange for protecting patient’s privacy. Finally, we conducted experiments on the federated task of datasets from two organizations in our model system, where the data has the same sample ID with different subset features, and this system is capable of handling privacy and security issues. The results show that the model was trained by our system with better usability, security, and higher efficiency, which is compared with the model trained by traditional machine learning methods.
VSNL1 Promotes Gastric Cancer Cell Proliferation and Migration by Regulating P2X3/P2Y2 Receptors and Is a Clinical Indicator of Poor Prognosis in Gastric Cancer Patients
Authors: Dai Qiao-Qiong , Wang Yuan-Yu , Jiang Yu-peng , Li Li , Wang Hui-Ju
Published: December 2020

Purpose. The aim of this study was to investigate the role of Visinin Like 1 (VSNL1) in the proliferation and migration of gastric cancer (GC) cells as well as its clinical prognostic significance. Methods. To this end, we evaluated VSNL1 expression in GC tissues and cell lines by real-time PCR and immunohistochemistry. To further explore the effects of VSNL1, a lentiviral vector expressing a short hairpin RNA (shRNA) against VSNL1 was constructed and transduced into the GC cell lines BGC-823 and SGC-7901. The interference efficiency of VSNL1-shRNA was determined by western blot. The effects of VSNL1 on the migration and invasion of GC cells as well as the expression of P2X3/P2Y2 were explored using MTS, colony formation, migration, and western blot assays. Results. VSNL1 mRNA and protein levels were increased in GC tissues and cell lines. Furthermore, VSNL1 expression was positively correlated with Lauren’s classification, lymph node metastasis, distant metastasis, TNM stage, and prognosis. VSNL1 expression was inversely correlated with the 5-year survival rate of GC patients. VSNL1 expression was markedly reduced in cells transduced with lentivirus expressing shRNA against VSNL1, and inhibiting VSNL1 expression significantly suppressed cell growth, migration, and colony formation and reduced the expression of P2X3/P2Y2. Conclusion. VSNL1 may promote the proliferation and migration of GC cells by regulating P2X3 and P2Y2 expression. VSNL1 plays important roles in GC development and metastasis and may be correlated with patient prognosis.
Hypolipidemic and Hepatoprotective Effects of Polysaccharides Extracted from Liriope spicata Var. Prolifera in C57BL/6J Mice with High‐Fat Diet‐Induced Hyperlipidemia
Authors: Liu Yi-Hui , Xiang Zhi-Nan , Chen Chen , Wan Luo-Sheng , Chen Jia-Chun
Published: December 2020

In this study, C57BL/6J mice with high‐fat diet‐ (HFD‐) induced hyperlipidemia were treated with total Liriope spicata var. prolifera polysaccharides (TLSP: 200, 400, and 800 mg/kg body weight), simvastatin (3 mg/kg body weight), or saline for 8 weeks, respectively. The results showed that TLSP had strong lipid‐lowering and hepatoprotective effects on C57BL/6J mice with HFD‐induced hyperlipidemia. TLSP administration significantly reduced serum total cholesterol (TC), triglyceride (TG), and low‐density lipoprotein cholesterol (LDL‐C) levels and downregulated the expressions of peroxisome proliferator‐activated receptor (PPAR)γ and fatty acid synthase (FAS) in the adipose and liver tissues of the mice. TLSP exerted hypolipidemic and hepatoprotective effects by activating lipid/bile acid metabolism via the FXH‐SHP/CYP7A1 and SEBP‐1c/FAC/ACC signaling pathways. Thus, TLPS is a promising natural polymer with hepatoprotective and hypolipidemic properties.
Inverse Modeling of Nonlinear Artificial Muscle Using Polynomial Parameterization and Particle Swarm Optimization
Authors: Mat Dzahir Mohd Azuwan , Yamamoto Shin-ichiroh
Published: December 2020

The properties of pneumatic artificial muscle (PAM) with excellent power‐to‐weight ratio and natural compliance made it useful for healthcare engineering applications. However, it has undesirable hysteresis effect in controlling a robotic manipulator. This behavior is quasistatic and quasirate dependent which changed with excitation frequency and external force. Apart from this, it also inherits frictional presliding behavior with nonlocal memory effect. These nonlinearities need to be compensated to achieve optimal performance of the control system. Even though an inverse modeling of PAM has limited application, it is important on certain control system implementation that requires the solution to the inverse problem. In this paper, the inverse modeling of PAM in the form of activation pressure was proposed. This activation pressure model was derived according to static pressure and extracted hysteresis components from pressure/length hysteresis. The derivation of the static pressure model follows the phenomenological‐based model of third‐order polynomial. It is capable of characterizing the nonlinear region of PAM at low and high pressure. The derivation of extracted hysteresis model follows the mechanism of dynamic friction. In this principle, the activation pressure model was dependent on regression coefficient of the static pressure model and dynamic friction coefficients of the extracted hysteresis model. The regression constants of these coefficients were characterized from the hysteresis dataset by using model parameter identification and the particle swarm optimization (PSO) method. The result from model simulation shows the root mean square error (RMSE) value of less than 10% error was evaluated at various excitation frequencies and external forces. This inverse modeling of PAM implemented a simple approach, but it should be useful in control design applications such as rehabilitation robotics, biomedical system, and humanoid robots.
Assessment of Systemic and Cerebral Oxygen Saturation during Diagnostic Bronchoscopy: A Prospective, Randomized Study
Authors: Vaskó Attila , Kovács Sándor , Fülesdi Béla , Molnár Csilla
Published: December 2020

Background. Arterial hypoxemia occurs in about 2.5–69% of cases during fiberoptic bronchoscopy and may necessitate administration of supplemental oxygen. Whether routine supplementary administration is indicated for all patients is a debated issue. In this prospective randomized study, we assessed the incidence of systemic desaturation (SpO2 <90% or a >4% decrease lasting for more than 60 s) and wanted to find out whether cerebral desaturation occurs in parallel with systemic changes. Patients and Methods. 92 consecutive patients scheduled for diagnostic bronchoscopy were randomly assigned to the no oxygen (O2- group), 2 l/min supplemental O2, or 4 l/min supplemental O2 groups. Primary end points were systemic and cerebral desaturation rate during the procedure. Secondary end points were to delineate the main risk factors of systemic and cerebral desaturation. Results. In the entire cohort, systemic desaturation occurred in 18.5% of patients (n = 17), corresponding to 5 patients (16%) in the O2 (−)group, 6 patients (19%) in the 2 l/min group, and 6 patients (20%) in 4 l/min group, respectively. In the O2 (−) group, the probability of desaturation was 41.7 times higher than that in the 2 l/min group (

p
=
0.014

s), while there was no difference in the probabilities of desaturation between the 2 l/min and 4 l/min groups (

p
=
0.22

). Cerebral desaturation (more than 20% rSO2 decrease compared to baseline) did not occur in any patients in the three groups. Systemic desaturation developed earlier, and recovery after desaturation was longer in the O2 (−) group. Male gender, smoking, and systemic oxygen saturation at baseline and FEV1% were the most significant factors contributing to systemic desaturation during bronchoscopy. Conclusions. Administration of supplemental oxygen does not prevent systemic desaturation during flexible bronchoscopy, but may contribute to the shortening of desaturation episodes and faster normalization of oxygen saturation. According to our results, 2 l/min supplemental oxygen should routinely be administered to patients throughout the procedure. This trial is registered with NCT04002609
The Metabolomic Rationale for Treating Perimenopausal Syndrome as Kidney Deficiency
Authors: Chen Xueqin , Wu Caiming , Liang Wen’na , Shen Jianying , Zhuo Zewei , Hu Liu , Ruan Luwei , Zhang Pengheng , Xu Leqin , Li Chengfu , Lin Shengyuan , Lan Junjie , Ren Haixia , Yao Hongwei , Zhao Tongjin , Gao Bizhen , Lin Tianwei , Huang Huiying , Li Candong
Published: December 2020

Background. Traditional Chinese medicine (TCM) typically attributes the etiopathogenesis of perimenopausal syndrome (PMS) to kidney deficiency in the TCM stratification system for diagnosis. However, the molecular basis of this classical attribution remains to be investigated. Aim of the Study. By unraveling the responses to TCM treatment for kidney deficiency, the metabolomic link between PMS and kidney deficiency can be evaluated for in‐depth understanding of the mechanism of TCM treatment and development of better treatment protocols. Materials and Methods. With naturally aged rats as a model for PMS, the metabolomic response to TCM treatment for kidney deficiency was investigated by 1H NMR. Results. 1H NMR metabolomic evidence of plasma samples demonstrates that treatments with two classical TCM prescriptions for kidney deficiency, decoctions of Yougui and Zuogui, result in modulating the metabolic state of the disease model towards that of rats of younger age. Conclusion. The data support the notion that kidney deficiency is responsible, in part at least, for PMS, and the relevant prescriptions are helpful in dampening the changes in the body’s metabolic states to alleviate symptoms of the disorder.
Reliability Assessment of Steel‐Concrete Composite Beams considering Metal Corrosion Effects
Authors: Nguyen Trong-Ha , Nguyen Duy-Duan
Published: December 2020

Steel‐concrete composite (SCC) beams have been widely used in civil engineering and industrial structures. This kind of structure has some advantages such as fast fabrication time and optimized weight. However, designers are often concerned about the initial reliability, while over time the structural reliability will be reduced, especially due to metal corrosion. The objective of the paper is to assess the structural reliability of corroded SCC beams, in which the input parameters are considered as random variables. The SCC beam has been designed according to Eurocode‐4 (EC‐4), in which input parameters consist of cross‐sectional dimensions of the beam, material properties, and applied loads. The effects of the random input variables on the reliability of structures are evaluated by sensitivity analyses, which are calculated by the global sensitivity analysis using Sobol’s method and Monte Carlo simulation. The developed reliability analysis algorithm in this study is verified with previous studies, highlighting the capability of the used method. Four different corrosion levels, which are pristine, 10‐year, 20‐year, and 50‐year, are considered in the sensitivity analyses of the SCC beam. Finally, a series of first‐order and total‐order Sobol’s indices are obtained for measuring the sensitivity of input parameters with four corrosion levels.
Zinner’s Syndrome: A Rare Diagnosis of Dysuria Based on Imaging
Authors: Ibrahimi Ahmed , Hosni Abdelmoughit , Ziani Idriss , Laamrani Fatima Zahra , El Sayegh Hachem , Jroundi Laila , Benslimane Lounis , Nouini Yassine
Published: December 2020

Zinner’s syndrome is a rare congenital malformation of the seminal vesicle and ipsilateral upper urinary tract, due to developmental arrest in early embryogenesis of the Müllerian duct. Clinical presentation is nonspecific and includes voiding symptoms such as dysuria, ejaculatory disorders, and hypogastric or perineal pain. The diagnosis is made with imaging techniques, notably Magnetic Resonance Imaging (MRI) which remains the gold standard exam for diagnosis confirmation and therapeutic management. Treatment options depend on the severity of symptoms, the size of the cyst, and the complications. Herein, we report a rare case of a 33-year-old young patient who presented recurrent dysuria and ejaculatory disorders for the last 5 years. Imaging studies revealed an empty left renal fossa, with cystic pelvic mass related to the seminal vesicle and which was compatible with the diagnosis of Zinner’s syndrome. The patient underwent successful laparoscopic removal of the cyst and seminal vesicle, with total disappearance of urinary and sexual complaints with a 3-year follow-up.
Lipidomics and Anti-Inflammation Activity of Brown Algae, Lobophora sp., in Vietnam
Authors: Pham Thu Hue , Nguyen Van Tuyen Anh , Do Thi Thanh Trung , Do Anh Duy , Dam Duc Tien , Tran Thi Thanh Van , Pham Quoc Long , Le Tat Thanh
Published: December 2020

Lobophora sp., belonging to brown macro algae phylum, is found in coral reefs. In this study, the fatty acid composition, lipid classes, polar lipid molecular forms, and bioactivities of this algae have been determined. It follows that five classes including polar lipid (Pol), sterol (ST), free fatty acids (FFA), triacylglycerol (TAG), and hydrocarbon and wax (HW), 23 fatty acids containing 5 PUFAs (ALA, GLA, AA, EPA, and DHA) and 157 molecular types of polar lipid group containing 48 phospholipid molecular forms belonging to 4 subclasses (PI (11), PC (14), PG (22), PA (1)), 45 glycolipid molecular forms classified into 3 subclasses of MGDG (8), DGDG (1), SQDG (36), and 64 betaine lipid molecular forms belonging to 2 subclasses (DGTA (37), DGTS (27)) have been identified for the first time from this algae. Furthermore, both polar lipid (PL) and unpolar lipid (UPL) show the NO inhibition activities with values of IC50 ranging from 52.10 to 66.21 µg/mL. Thus, lipid of this brown algae could promise to be a potential source for application in food, cosmetic, and pharmaceutic industry.
Determinants of Home Delivery among Mothers in Abobo District, Gambella Region, Ethiopia: A Case Control Study
Authors: Mitiku Asmelash Abera , Dimore Abraham Lomboro , Mogas Solomon Berhanu
Published: December 2020

Introduction. Home delivery is one of the major reasons for high maternal mortality ratio in sub-Saharan Africa. Sub-Saharan Africa and South Asia together contribute over 85% of maternal deaths, of which, only half of deliveries are institutional. However, data are scarce on the availability of information with regard to the determinant factors for this high prevalence of home delivery in the study area. Objective. This study is aimed at determining factors associated with home delivery, among mothers in Abobo Woreda, Gambella region, Southwest Ethiopia, 2019. Methods. A case control study conducted from 12 March 2019 up to 2 April 2019 on 88 cases and 176 controls. Cases include mothers who gave birth at home and those mothers who gave birth at health facility in the last one year preceding the study included as controls. Data entry was made using Epi-Data version 3.1, and analysis was made using SPSS version 20. A binary logistic regression analysis was conducted to assess candidate variables and subsequently a multivariable regression to determine the statistical associations. Adjusted odds ratio (AOR) with 95% confidence interval (CI) was calculated to determine strength of association, and

p

value <0.05 was used to establish significant associations. Results. No formal education (AOR: 5.07; 95% CI: 2.18-11.50), poor knowledge on obstetric complications (AOR: 3.83; 95% CI: 1.98-7.40), negative attitude towards delivery service (AOR: 3.25; 95% CI: 1.70-6.19), poor household wealth index (AOR: 4.55; 95% CI: 2.01-10.31), and no antenatal care visit (AOR: 3.29; 95% CI: 1.63-6.63) were found to be significantly associated with home delivery. Conclusions. The findings do support that no formal education, poor knowledge on obstetric complications, negative attitude towards delivery service, poor household wealth index, and no antenatal care visit showed a significant association with home delivery.
Heterogeneous Acupuncture Effects of Taixi (KI3) on Functional Connectivity in Healthy Youth and Elder: A Functional MRI Study Using Regional Homogeneity and Large-Scale Functional Connectivity Analysis
Authors: He Linlu , Chen Guangxiang , Zheng Ruwen , Hu Yan , Chen Xiu , Ruan Jianghai
Published: December 2020

Heterogeneous neurological responses of acupuncture between different groups have been proposed by previous studies but rarely studied. The study described here was designed to explore the divergence of acupuncture at Taixi (KI3) on spontaneous activity of brain regions and functional connectivity (FC) between healthy youth and elder with functional magnetic resonance imaging (fMRI). 20 healthy young volunteers and 20 healthy elders underwent 10-minute-resting-state fMRI before acupuncture, and then acupuncture at Taixi (KI3) for 3 minutes; after withdrawing the needles, volunteers underwent a second fMRI scan for 10 minutes. Regional homogeneity (ReHo) and large-scale FC analysis using Power 264 atlas were utilized to analyze the changes of brain spontaneous activity. Compared with the resting state, the decreased ReHo after acupuncture at KI3 in both groups were concentrated in the left postcentral, right paracentral lobule, and right SMA. Moreover, the subjects in the HY group showed declined ReHo in brain regions involving the right lingual and precentral. However, those subjects in the HE group presented decreased ReHo in the right postcentral and precentral, left supramarginal gyrus and SMA, and both cingulum middle after needling in KI3. Compared with the resting state, the HY group in the postneedling state showed lower mean intranetwork FC in sensory/somatomotor and subcortical network. And the internetwork FC between sensory/somatomotor and dorsal attention had significantly decreased after acupuncture. Furthermore, the internetwork FC between subcortical and dorsal attention and between subcortical and cerebellar showed the most obvious elevations after needling in the HY group. In the elder group, both FCs of internetwork and intranetwork primarily involving sensory/somatomotor, cingulo-opercular, and dorsal attention were declined after acupuncture. These results indicated that acupuncture at KI3 had heterogeneous acupuncture effects in different age groups. Our study led to converging evidence supporting the acupuncture effect segregation of different condition subjects and supporting evidence for prevention and treatment with acupuncture in the future.
Antioxidant Activities of Methanol Extracts of Thirteen Cameroonian Antibacterial Dietary Plants
Authors: Djeussi Doriane E. , Noumedem Jaurès A. K. , Mihasan Marius , Kuiate Jules-Roger , Kuete Victor
Published: December 2020

This study falls within the search for alternative solutions to problems related to diseases associated with oxidative stress. It involved the evaluation of antioxidant activities extracts from thirteen antibacterial Cameroonian food plants, namely, P. nigrum, A. cruentus, L. sativa, S. edule, S. nigrum, V. amygdalina, A. hybridus, V. hymenolepis, L. capensis, M. esculenta, C. melo, T. occidentalis, and T. triangulare. The thirteen plant extracts with a broad spectrum of antibacterial activity all showed total reducing powers ranging between 2.41 and 27.81 AAE (mg ascorbic acid equivalents per gram of dried extract) and total phenol contents between 2.65 and 35.03 GAE (mg of gallic acid equivalents per gram of dried extract) of dry extract. Except for extracts of L. capensis, the other 12 extracts showed flavonoid contents ranging between 0.29 and 5.99 RE (rutin equivalents per gram of dried extract). All 13 plant extracts also showed free radical scavenging activity against DPPH· with IC50 ranging between 1.65 and 310.52 μg/ml, while 12 of these extracts exhibited inhibitory activity against NO· radical (IC50 ranging from 19.77 to 157.72 μg/ml). Statistically insignificant positive correlations (p>0.5) were found between antibacterial activities of these plants and their antioxidant activities. The different results of this study provide scientific evidence for the use of these antibacterial food plants in the control of different conditions associated with oxidative stress.
Inter-rater Variability in Malaria Microscopy at the LEKMA Hospital, Ghana
Authors: Bekoe Andrew Nii Adzei , Allotey Emmanuel Alote , Akorsu Elliot Elikplim , Abaka-Yawson Albert , Adusei Samuel , Kpene Godsway Edem , Kwadzokpui Precious Kwablah
Published: December 2020

Background. Malaria remains a major cause of morbidity and mortality worldwide and particularly in sub-Saharan Africa where it is endemic. As such, it is important that a proper diagnosis is made before treatment is initiated. Malaria parasite count plays a key role in the diagnosis and management of malaria. Variations in ratings by laboratory personnel can impact negatively on the treatment regimen for malaria-infected patients. The study is thus aimed at evaluating and comparing the proficiency and parasitaemia counts by two different categories of laboratory staff at the LEKMA Hospital, Ghana. Materials and Methods. A total of 200 confirmed malaria-positive samples were used in the study. Six thick and thin films were prepared from each sample and uniquely labelled. Two of the six slides were given to two WHO-accredited malaria microscopists to examine and report their respective parasite count/μl (

parasite
 
count
/
WBC
×
8000

). These were used as the reference for the two categories of laboratory staffs: rater A being diploma holders (Technical Officers referred to as untrained rater) and rater B being degree holders (Medical Laboratory Scientist referred to as trained rater) at the LEKMA Hospital. Results. In comparison to the expected outcome, the parasite count by the rater group A (190 (151-239)]) and the rater group B (177 (140-224)) demonstrated significant positive correlation (

r
=
0.995

,

p
<
0.0001

vs.

r
=
0.995

,

p
<
0.0001

, respectively) with the expected outcome in the cases of heavy parasitaemia. A statistically significant difference (

p
<
0.05

) between counts by the different raters in low parasitemia was observed in this study. A persistent nosedive inter-rater agreement from

k
=
0.82

to

k
=
0.40

with increasing density cutoff was observed in this study. Conclusion. The study observed that the degree of inter-rater agreement of parasite density count by various categories of laboratory personnel is almost perfect. However, the parasite count between raters varied significantly with very low levels of parasitemia but better correlated with heavy parasitemia.
Excitation‐Independent Emission of Carbon Quantum Dot Solids
Authors: Mai Xuan-Dung , Phan Yen Thi Hai , Nguyen Van-Quang
Published: December 2020

Solid assemblies of carbon quantum dots (CQDs) are important for diverse applications including LEDs, solar cells, and photosensors; their optical and electrical properties have not been explored yet. Herein, we used amphiphilic CQDs synthesized from citric acid and thiourea by a solvothermal method to fabricate CQD solid films. Optical properties of CQDs studied by UV‐Vis and photoluminescence spectroscopies indicate that CQDs possess three different emission centers at 425 nm, 525 nm, and 625 nm originating from C sp2 states, N‐states, and S‐states, respectively. In a solid state, π‐π stacking quenched the blue emission, while the red emission increased. Importantly, CQD films exhibited excitation independence, which is important to design solid‐state lighting applications.
Prolonged Survival of a Patient with Advanced-Stage Combined Hepatocellular-Cholangiocarcinoma
Authors: Loosen Sven H. , Gaisa Nadine T. , Schmeding Maximilian , Heining Christoph , Uhrig Sebastian , Wirtz Theresa H. , Kalverkamp Sebastian , Spillner Jan , Tacke Frank , Stenzinger Albrecht , Glimm Hanno , Fröhling Stefan , Trautwein Christian , Roderburg Christoph , Longerich Thomas , Neumann Ulf Peter , Luedde Tom
Published: December 2020

Combined hepatocellular-cholangiocarcinoma (cHCC/CCA) represents a rare type of primary liver cancer with a very limited prognosis. Although just recently genomic studies have contributed to a better understanding of the disease’s genetic landscape, therapeutic options, especially for advanced-stage patients, are limited and often experimental, as no standardized treatment protocols have been established to date. Here, we report the case of a 38-year-old male patient who was diagnosed with extensive intrahepatic cHCC/CCA in an otherwise healthy liver without signs of chronic liver disease. An interdisciplinary stepwise therapeutic approach including locoregional liver-targeted therapy, systemic chemotherapy, liver transplantation, surgical pulmonary metastasis resection, and next-generation sequencing-based targeted therapy led to a prolonged overall survival beyond 5 years with an excellent quality of life. This case report comprises several provocative treatment decisions that are extensively discussed in light of the existing literature on this rare but highly aggressive malignancy.
Sulforaphane Protects Piglet Brains from Neonatal Hypoxic-Ischemic Injury
Authors: Wang Bing , Kulikowicz Ewa , Lee Jennifer K. , Koehler Raymond C. , Yang Zeng-Jin
Published: December 2020

The striatal, primary sensorimotor cortical, and thalamic neurons are highly vulnerable to hypoxia-ischemia (HI) in term newborns. In a piglet model of HI that exhibits similar selective regional vulnerability, we tested the hypothesis that early treatment with sulforaphane, an activator of the Nrf2 transcription factor, protects vulnerable neurons from HI injury. Anesthetized piglets (aged 3–7 days) were subjected to 45 min of hypoxia and 7 min of airway occlusion. At 15 min after resuscitation, the piglets received intravenous vehicle or sulforaphane. At 4 days of recovery, the density of viable neurons in the putamen of vehicle-treated piglets was 31 ± 34% (±SD) that of sham-operated controls. Treatment with sulforaphane significantly increased viability to 77 ± 31%. In the sensorimotor cortex, neuronal viability was also increased; it was 59 ± 35% in the vehicle-treated and 89 ± 15% in the sulforaphane-treated animals. Treatment with sulforaphane increased the nuclear Nrf2 and γ-glu­tamylcysteine synthetase expression at 6 h of recovery in these regions. We conclude that systemic administration of sulforaphane 15 min after HI can induce the translocation of Nrf2 to the nucleus, increase expression of an enzyme involved in glutathione synthesis, and salvage neurons in the highly vulnerable putamen and sensorimotor cortex in a large-animal model of HI. Therefore, targeting Nrf2 activation soon after recovery from HI is a feasible approach for neuroprotection in the newborn brain.
Die Rolle von Verhaltensexperimenten in der Behandlung von Zwangsstörungen: Ein Update zur effektiven Gestaltung und Durchführung in der Praxis
Authors: Herzog Philipp , Jelinek Lena
Published: December 2020

Das Ziel des Artikels ist es, den neuesten Stand zum effektiven Einsatz von Verhaltensexperimenten im Rahmen der Psychotherapie für Zwangsstörungen darzulegen. Dazu werden im ersten Teil die evidenzbasierten Psychotherapien zur Behandlung von Zwangsstörungen vorgestellt sowie die Probleme bei der Implementierung dieser Verfahren aufgezeigt. Dabei zeigt sich, dass trotz der guten Evidenzlage die Verfahren zu selten eingesetzt werden und so die Forschungs-Praxis-Lücke fördern. Im Anschluss werden die zugrundeliegenden Rationale zur Durchführung von Verhaltensexperimenten erläutert, in Bezug zu aktuellen Forschungsarbeiten gestellt und damit die Bedeutung von Verhaltensexperimenten in der Therapie von Zwangsstörungen unterstrichen. Daraus werden Empfehlungen für die effektive Umsetzung von Verhaltensexperimenten in der Praxis abgeleitet. Die Funktionsanalyse der zwangsspezifischen Symptomatik stellt das zentrale Element im Rahmen der Behandlung von Zwangsstörungen dar. Dabei müssen die Verhaltensexperimente an die individuell befürchtete Konsequenz bei Unterlassen von Ritualen und Sicherheitsverhalten (d.h. die furchtbasierte Überzeugung) ausgerichtet sein, um eine maximale Erwartungsverletzung zu ermöglichen. Klinische Fallbeispiele werden skizziert, anhand deren effektive Verhaltensexperimente anschaulich und praxisnah dargestellt werden. Abschließend werden noch Hinweise, Tipps und Fallstricke für Praktiker zur Durchführung von effektiven Verhaltensexperimenten beleuchtet und die Grenzen von Verhaltensexperimenten benannt.
Incidence of Stroke and Ischemic Stroke Subtypes: A Community-Based Study in Brno, Czech Republic
Authors: Sedova Petra , Brown Robert D. , Zvolsky Miroslav , Belaskova Silvia , Volna Michaela , Baluchova Jana , Bednarik Josef , Mikulik Robert
Published: December 2020

Background: There are few contemporary epidemiological data on stroke for Central Europe. We performed a population-based study evaluating the incidence of stroke, stroke types, and ischemic stroke (IS) subtypes in Brno, the second biggest city in the Czech Republic (CR). Methods: Using the National Registry of Hospitalized Patients, and hospital databases, we identified all patients hospitalized with a stroke diagnosis in Brno hospitals in 2011. For Brno residents with validated stroke diagnosis, we calculated (a) the overall incidence of hospitalized stroke, (b) incidence rates for IS, subarachnoid hemorrhage (SAH) and intracerebral hemorrhage (ICH), and (c) incidence rates for IS subtypes. We calculated the average annual age- and sex-standardized incidence (European Standard Population and World Health Organization), to compare our results with other studies. Results: The overall crude incidence of stroke in Brno was 213/100,000 population. The incidence of stroke for stroke types were as follows: SAH, 6.9; ICH, 26.4; and IS, 180 cases per 100,000 population, respectively. The WHO-standardized annual stroke incidence was 107 for all strokes and 88 for IS, 14.4 for ICH, and 5 for SAH. For IS subtypes, the WHO-standardized incidence was large artery atherosclerosis 25.8, cardioembolism 27.8, lacunar 21.6, other determined etiology 6.2, and undetermined etiology 6.5 cases per 100,000 population. Conclusions: The stroke incidence is lower than that previously reported for the CR and Eastern Europe probably reflecting socioeconomic changes in post-communistic countries in the region. These findings could contribute to stroke prevention strategies and influence health policies.
Effects of COVID-19 Home Confinement on Eating Behaviour and Physical Activity: Results of the ECLB-COVID19 International Online Survey
Authors: Papaspanos Nikolaos
Published: December 2020

Background: Public health recommendations and governmental measures during the COVID-19 pandemic have resulted in numerous restrictions on daily living including social distancing, isolation and home confinement. While these measures are imperative to abate the spreading of COVID-19, the impact of these restrictions on health behaviours and lifestyles at home is undefined. Therefore, an international online survey was launched in April 2020, in seven languages, to elucidate the behavioural and lifestyle consequences of COVID-19 restrictions. This report presents the results from the first thousand responders on physical activity (PA) and nutrition behaviours. Subjects and methods: Following a structured review of the literature, the «Effects of home Confinement on multiple Lifestyle Behaviours during the COVID-19 outbreak (ECLB-COVID19)» Electronic survey was designed by a steering group of multidisciplinary scientists and academics. The survey was uploaded and shared on the Google online survey platform. Thirty-five research organisations from Europe, North Africa, Western Asia and the Americas promoted the survey in English, German, French, Arabic, Spanish, Portuguese and Slovenian languages. Questions were presented in a differential format, with questions related to responses «before» and «during» confinement conditions. Results: 1047 replies (54% women) from Asia (36%), Africa (40%), Europe (21%) and other (3%) were included in the analysis. The COVID-19 home confinement had a negative effect on all PA intensity levels (vigorous, moderate, walking and overall). Additionally, daily sitting time increased from 5 to 8 h per day. Food consumption and meal patterns (the type of food, eating out of control, snacks between meals, number of main meals) were more unhealthy during confinement, with only alcohol binge drinking decreasing significantly. Summary: While isolation is a necessary measure to protect public health, results indicate that it alters physical activity and eating behaviours in a health compromising direction. A more detailed analysis of survey data will allow for a segregation of these responses in different age groups, countries and other subgroups, which will help develop interventions to mitigate the negative lifestyle behaviours that have manifested during the COVID-19 confinement.
Targeting Thymidine Phosphorylase With Tipiracil Hydrochloride Attenuates Thrombosis Without Increasing Risk of Bleeding in Mice
Authors: Belcher Adam , Zulfiker Abu Hasanat Md , Li Oliver Qiyue , Yue Hong , Gupta Anirban Sen , Li Wei
Published: December 2020

Objective:

Current antiplatelet medications increase the risk of bleeding, which leads to a clear clinical need in developing novel mechanism-based antiplatelet drugs. TYMP (Thymidine phosphorylase), a cytoplasm protein that is highly expressed in platelets, facilitates multiple agonist-induced platelet activation, and enhances thrombosis. Tipiracil hydrochloride (TPI), a selective TYMP inhibitor, has been approved by the Food and Drug Administration for clinical use. We tested the hypothesis that TPI is a safe antithrombotic medication.

Approach and Results:

By coexpression of TYMP and Lyn, GST (glutathione S-transferase) tagged Lyn-SH3 domain or Lyn-SH2 domain, we showed the direct evidence that TYMP binds to Lyn through both SH3 and SH2 domains, and TPI diminished the binding. TYMP deficiency significantly inhibits thrombosis in vivo in both sexes. Pretreatment of platelets with TPI rapidly inhibited collagen- and ADP-induced platelet aggregation. Under either normal or hyperlipidemic conditions, treating wild-type mice with TPI via intraperitoneal injection, intravenous injection, or gavage feeding dramatically inhibited thrombosis without inducing significant bleeding. Even at high doses, TPI has a lower bleeding side effect compared with aspirin and clopidogrel. Intravenous delivery of TPI alone or combined with tissue plasminogen activator dramatically inhibited thrombosis. Dual administration of a very low dose of aspirin and TPI, which had no antithrombotic effects when used alone, significantly inhibited thrombosis without disturbing hemostasis.

Conclusions:

This study demonstrated that inhibition of TYMP, a cytoplasmic protein, attenuated multiple signaling pathways that mediate platelet activation, aggregation, and thrombosis. TPI can be used as a novel antithrombotic medication without the increase in risk of bleeding.
Endothelial TFEB (Transcription Factor EB) Improves Glucose Tolerance via Upregulation of IRS (Insulin Receptor Substrate) 1 and IRS2
Authors: Sun Jinjian , Lu Haocheng , Liang Wenying , Zhao Guizhen , Ren Lu , Hu Die , Chang Ziyi , Liu Yuhao , Garcia-Barrio Minerva T. , Zhang Jifeng , Chen Y. Eugene , Fan Yanbo
Published: December 2020

Objective:

Vascular endothelial cells (ECs) play a critical role in maintaining vascular homeostasis. Aberrant EC metabolism leads to vascular dysfunction and metabolic diseases. TFEB (transcription factor EB), a master regulator of lysosome biogenesis and autophagy, has protective effects on vascular inflammation and atherosclerosis. However, the role of endothelial TFEB in metabolism remains to be explored. In this study, we sought to investigate the role of endothelial TFEB in glucose metabolism and underlying molecular mechanisms.

Approach and Results:

To determine whether endothelial TFEB is critical for glucose metabolism in vivo, we utilized EC-selective TFEB knockout and EC-selective TFEB transgenic mice fed a high-fat diet. EC-selective TFEB knockout mice exhibited significantly impaired glucose tolerance compared with control mice. Consistently, EC-selective TFEB transgenic mice showed improved glucose tolerance. In primary human ECs, small interfering RNA-mediated TFEB knockdown blunts Akt (AKT serine/threonine kinase) signaling. Adenovirus-mediated overexpression of TFEB consistently activates Akt and significantly increases glucose uptake in ECs. Mechanistically, TFEB upregulates IRS1 and IRS2 (insulin receptor substrate 1 and 2). TFEB increases IRS2 transcription measured by reporter gene and chromatin immunoprecipitation assays. Furthermore, we found that TFEB increases IRS1 protein via downregulation of microRNAs (miR-335, miR-495, and miR-548o). In vivo, Akt signaling in the skeletal muscle and adipose tissue was significantly impaired in EC-selective TFEB knockout mice and consistently improved in EC-selective TFEB transgenic mice on high-fat diet.

Conclusions:

Our data revealed a critical role of TFEB in endothelial metabolism and suggest that TFEB constitutes a potential molecular target for the treatment of vascular and metabolic diseases.
Endoplasmic Reticulum Stress Mediates Vascular Smooth Muscle Cell Calcification via Increased Release of Grp78 (Glucose-Regulated Protein, 78 kDa)-Loaded Extracellular Vesicles
Authors: Furmanik Malgorzata , van Gorp Rick , Whitehead Meredith , Ahmad Sadia , Bordoloi Jayanta , Kapustin Alexander , Schurgers Leon J. , Shanahan Catherine M.
Published: December 2020

Objective:

Vascular calcification is common among aging populations and mediated by vascular smooth muscle cells (VSMCs). The endoplasmic reticulum (ER) is involved in protein folding and ER stress has been implicated in bone mineralization. The role of ER stress in VSMC-mediated calcification is less clear.

Approach and Results:

mRNA expression of the ER stress markers PERK (PKR (protein kinase RNA)-like ER kinase), ATF (activating transcription factor) 4, ATF6, and Grp78 (glucose-regulated protein, 78 kDa) was detectable in human vessels with levels of PERK decreased in calcified plaques compared to healthy vessels. Protein deposition of Grp78/Grp94 was increased in the matrix of calcified arteries. Induction of ER stress accelerated human primary VSMC-mediated calcification, elevated expression of some osteogenic markers (Runx2 [RUNX family transcription factor 2], OSX [Osterix], ALP [alkaline phosphatse], BSP [bone sialoprotein], and OPG [osteoprotegerin]), and decreased expression of SMC markers. ER stress potentiated extracellular vesicle (EV) release via SMPD3 (sphingomyelin phosphodiesterase 3). EVs from ER stress-treated VSMCs showed increased Grp78 levels and calcification. Electron microscopy confirmed the presence of Grp78/Grp94 in EVs. siRNA (short interfering RNA) knock-down of Grp78 decreased calcification. Warfarin-induced Grp78 and ATF4 expression in rat aortas and VSMCs and increased calcification in an ER stress-dependent manner via increased EV release.

Conclusions:

ER stress induces vascular calcification by increasing release of Grp78-loaded EVs. Our results reveal a novel mechanism of action of warfarin, involving increased EV release via the PERK-ATF4 pathway, contributing to calcification. This study is the first to show that warfarin induces ER stress and to link ER stress to cargo loading of EVs.
Best Practices in the Measurement and Evaluation of Track Two Dialogues: Towards a “Reflective Practice Model”
Authors: Shillings Elizabeth , Jones Peter
Published: December 2020

Measuring the impact of Track Two dialogues has proven a difficult challenge for the field over many years. Each dialogue is different, which makes a standardized test difficult to achieve. Moreover, different actors wish to measure different things: “value” for money; impact on the conflict; how certain facilitation techniques work; and others. In this article, we present a model that can be used to measure the impact of a dialogue over time, while also encouraging reflective practice in the field. This “Reflective Practice Model” can be used to provide a snapshot of a particular moment – or as a vehicle for the accumulation of a series of such moments – thereby providing a means to observe and measure changes as the dialogue goes on.
Introduction
Authors: Brooks Lisa Allette , Cerulli Anthony , Sheldon Victoria
Published: December 2020

This opening piece introduces the eight articles in this special issue of Asian Medicine, all of which emerged out of the daylong Science, Technology, and Medicine in South Asia Symposium: Medicine and Memory, at the 2018 Annual Conference on South Asia in Madison, Wisconsin. These articles are concerned with the ways in which time and healing entangle across regions and healing traditions in South Asia, including Unani, Ayurveda, Naturopathy, and biomedicine. Linking the findings from these articles with recent scholarship, our conversation in the symposium moved beyond the notion of medical pluralisms to a notion of dynamic plurals, through historicizing regional and local diversities in practices and philosophies, often grouped under a single name by communities and practitioners. In an increasingly communalist and politically fractured modern South Asia, we suggest that the discussions in this special issue make a critical contribution to understanding how cultural institutions of knowledge function in society.
A Surgeon’s Hand
Authors: Brooks Lisa Allette
Published: December 2020

The Suśrutasaṃhitā, an early first-millennium Ayurvedic treatise with an emphasis on surgery, recommends a procedure for examining a corpse after first submerging it in a river. Prompted by the sensory insights of a contemporary Ayurvedic physician who simulated “hydro-dissection” on a human hand, I offer a sensory reading of representations of surgeons and surgical tactility in early South Asia. This study demonstrates that surgeons are represented in early first-millennium treatises as possessing specialized medical knowledge, performing dangerous procedures, and having greater sensory and bodily intimacy in their engagement with patients than general physicians. First, I compare passages describing physicians’ sensory engagements in diagnostic examination in the Carakasaṃhitā and Suśrutasaṃhitā. Then I examine representations of surgeons and surgical practice in the Carakasaṃhitā, a general medical compendium. Finally, I demonstrate that surgical tactility is represented in the Suśrutasaṃhitā as an interplay of sensory knowledge, technical skill, experience, and judgment, constituting the surgeon’s hand.
Imagining Indian Medicine
Authors: Datoo Sabrina
Published: December 2020

In 1923, the Presidency of Madras published The Report of the Committee on the Indigenous Systems of Medicine, the first of many Indian policy documents to regulate indigenous medicine. At first glance, the report seems to offer more evidence of the increasing entrenchment of religious nationalist positions within medical networks in the colonial period. Scholars have analyzed its main text, and a significant “Memorandum” associated with it, and found them emblematic of the formation of Hindu science in the early twentieth century. In this article, drawing on the methods of intellectual and cultural history, I conduct a close analysis of the unstudied Urdu-language sections of the report, which suggest a different interpretation. I argue that within the Urdu-language testimonies written by Hindu men, one finds a continuity with early modern medical courtly culture, whose resonances in the colonial period have largely been elided by modern historiography.
To Do Nothing
Authors: Sheldon Victoria
Published: December 2020

In Kerala, South India, individual pursuits of nature cure (prakr̥ti cikitsa) invoke ethical narratives about an idealized purer past, contrasting a dangerous present saturated with social and environmental toxins. While first popularized in India by M. K. Gandhi, nature cure has gained contemporary fame as a low-cost intervention for Kerala’s purported health crisis: chronic lifestyle diseases. Nonprofessionalized natural healers identify as public health activists, teaching predominantly urban, middle-class patients how to revive local lifeways of self-doctorhood. This article narrates how two aging patients internalize their naturopathic doctors’ advice to detoxify and “do nothing” rather than strive for biomedical cure. By naturally revitalizing their bodies, they cultivate feelings of intense independence and ecological attachment that reconfigure experiences of migrated-kin isolation. In counterpoint to literature that frames biopolitical and medical discourses as causally producing moral subjectivities, this article demonstrates how persons agentively craft counternormative, vitalistic models of aging and health, contributing to broader localist imaginaries of reviving pre-toxic lifeways.