bluuebunny/crossref_metadata_2025 huggingface dataset:
Sickle cell disease in Sri Lanka: clinical and molecular basis and the unanswered questions about disease severity
Authors: Darshana Thamal , Bandara Dayananda , Nawarathne Upul , de Silva Udaya , Costa Yasinta , Pushpakumara Kalavitigoda , Pathirage Sumithra , Basnayake Seuwandi , Epa Chamila , Dilrukshi Pradeepa , Wijayawardena Maheshaka , Anthony Angela A. , Rodrigo Rexan , Manamperi Aresha , Smith Frances , Allen Angela , Menzel Stephan , Rees David , Premawardhena Anuja
Published: July 2020

Background

Though case reports and limited case series of Sickle cell disease in Sri Lanka have been reported previously, no attempt has been made hitherto to undertake a comprehensive genotypic-phenotypic analysis of this “rare” group of patients.

Results

All accessible Sickle cell disease patients, totaling 60, including, 51 Sickle β-thalassaemia and 9 homozygous sickle patients were enrolled from seven thalassaemia treatment centres between December 2016–March 2019. The majority of patients were of Sinhalese ethnicity (n = 52, 86.67%). Geographically, two prominent clusters were identified and the distribution of Sickle haemoglobin in the island contrasted markedly with the other haemoglobinopathies. 3/ 9 homozygous sickle patients and 3/ 51 Sickle β-thalassaemia patients were receiving regular transfusion. Joint pain was the commonest clinical symptom among all sickle cell disease patients (n = 39, 65.0%). Dactylitis was significantly more common in homozygous sickle patients compared with the Sickle β-thalassaemia groups (p 0.027). Two genetic backgrounds sickle mutation were identified namely, Arab Indian and Benin. Among the regulators of Foetal hemoglobin in Sickle patients of the present study rs1427407 G > T seemed to be the most prominent modifier, with a significant association with Foetal haemoglobin levels (p 0.04).

Conclusions

Overall, the clinical course of the Asian version of Sickle cell disease in Sri Lanka appears to be milder than that described in India.
Constructing an automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning
Authors: Kong Yanguo , Kong Xiangyi , He Cheng , Liu Changsong , Wang Liting , Su Lijuan , Gao Jun , Guo Qi , Cheng Ran
Published: July 2020

Due to acromegaly’s insidious onset and slow progression, its diagnosis is usually delayed, thus causing severe complications and treatment difficulty. A convenient screening method is imperative. Based on our previous work, we herein developed a new automatic diagnosis and severity-classification model for acromegaly using facial photographs by deep learning on the data of 2148 photographs at different severity levels. Each photograph was given a score reflecting its severity (range 1~3). Our developed model achieved a prediction accuracy of 90.7% on the internal test dataset and outperformed the performance of ten junior internal medicine physicians (89.0%). The prospect of applying this model to real clinical practices is promising due to its potential health economic benefits.
Metformin inhibits cervical cancer cell proliferation by modulating PI3K/Akt-induced major histocompatibility complex class I-related chain A gene expression
Authors: Xia Chenglai , Liu Chang , He Zhihong , Cai Yantao , Chen Jinman
Published: July 2020

Background

Recent studies have shown that the classic hypoglycemic drug metformin inhibits tumor growth; however, the underlying mechanism remains unclear. We previously showed that metformin disrupts the sponge effect of long non-coding RNA MALAT1/miR-142-3p to inhibit cervical cancer cell proliferation. In this study, we interrogated the ability of metformin to modulate the anti-tumor immune response in cervical cancer.

Methods

The cell counting kit-8 assay was used to detect the viability of cervical cancer cells. Flow cytometry assays were performed to measure cell apoptosis and cell cycle. Lactate dehydrogenase (LDH) cytotoxicity assay was used to detect NK Cell Cytotoxicity. Relative protein levels were determined by immunoblotting and relative gene levels were determined by quantitative real-time PCR. Tumor Xenograft Modeling was used to evaluate the effect of metformin in vivo.

Results

Metformin inhibited cervical cancer cell proliferation, cervical cancer xenograft growth, expression of PCNA, p-PI3K and p-Akt. Moreover metformin induced cervical cancer cell apoptosis and caused cancer cell cycle arrest. In addition, metformin upregulated the expression of DDR-1 and p53 in human cervical cancer cells. Furthermore, metformin also regulated the mRNA and protein expression of MICA and HSP70 on the surface of human cervical cancer cells via the PI3K/Akt pathway, enhancing NK cell cytotoxicity.

Conclusions

In conclusion, our results suggest that metformin may be used as immunopotentiator to inhibit cervical cancer progression and may be considered a viable candidate for combination therapy with immunotherapy.
Emerging roles and the regulation of aerobic glycolysis in hepatocellular carcinoma
Authors: Feng Jiao , Li Jingjing , Wu Liwei , Yu Qiang , Ji Jie , Wu Jianye , Dai Weiqi , Guo Chuanyong
Published: July 2020

Liver cancer has become the sixth most diagnosed cancer and the fourth leading cause of cancer death worldwide. Hepatocellular carcinoma (HCC) is responsible for up to 75–85% of primary liver cancers, and sorafenib is the first targeted drug for advanced HCC treatment. However, sorafenib resistance is common because of the resultant enhancement of aerobic glycolysis and other molecular mechanisms. Aerobic glycolysis was firstly found in HCC, acts as a hallmark of liver cancer and is responsible for the regulation of proliferation, immune evasion, invasion, metastasis, angiogenesis, and drug resistance in HCC. The three rate-limiting enzymes in the glycolytic pathway, including hexokinase 2 (HK2), phosphofructokinase 1 (PFK1), and pyruvate kinases type M2 (PKM2) play an important role in the regulation of aerobic glycolysis in HCC and can be regulated by many mechanisms, such as the AMPK, PI3K/Akt pathway, HIF-1α, c-Myc and noncoding RNAs. Because of the importance of aerobic glycolysis in the progression of HCC, targeting key factors in its pathway such as the inhibition of HK2, PFK or PKM2, represent potential new therapeutic approaches for the treatment of HCC.
Targeted re-sequencing for early diagnosis of genetic causes of childhood epilepsy: the Italian experience from the ‘beyond epilepsy’ project
Authors: Amadori Elisabetta , Scala Marcello , Cereda Giulia Sofia , Vari Maria Stella , Marchese Francesca , Di Pisa Veronica , Mancardi Maria Margherita , Giacomini Thea , Siri Laura , Vercellino Fabiana , Serino Domenico , Orsini Alessandro , Bonuccelli Alice , Bagnasco Irene , Papa Amanda , Minetti Carlo , Cordelli Duccio Maria , Striano Pasquale
Published: July 2020

Background

Childhood epilepsies are a heterogeneous group of conditions differing in diagnostic criteria, management, and outcome. Late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) is a neurodegenerative condition caused by biallelic TPP1 variants. This disorder presents with subtle and relatively non-specific symptoms, mimicking those observed in more common paediatric epilepsies and followed by rapid psychomotor deterioration and drug-resistant epilepsy. A prompt diagnosis is essential to adopt appropriate treatment and disease management strategies.

Methods

This is a prospective, multicentre study on the efficiency of targeted re-sequencing in the early identification of the genetic causes of childhood epilepsy, with particular regard to CLN2. After phenotypic characterization, a 283-gene Next Generation Sequencing panel was performed in 21 Italian children with neurodevelopmental abnormalities, aged between 24 and 60 months, experiencing first unprovoked seizure after 2 years of age.

Results

The average age at enrolment was 39.9 months, with a mean age at seizure onset of 30.9 months and a mean time interval between seizure onset and targeted resequencing of 9 months. Genetic confirmation was achieved in 4 out of 21 patients, with a diagnostic yield of 19%. In one case, the homozygous splice acceptor variant c.509-1G > C in TPP1 was identified, leading to a CLN2 diagnosis. Three pathogenic variants in MECP2 were also detected in three patients, including the frameshift variant c.1157_1186delinsA (p.Leu386Hisfs*9) in a girl with negative single gene sequencing. Variants of unknown significance (VUS) were found in 11 out of 21 (52.4%) individuals, whereas no clinically significant variants were observed in the remaining 6 subjects.

Conclusions

Our findings support the efficacy of target re-sequencing in the identification of the genetic causes of childhood epilepsy and suggest that this technique might prove successful in the early detection of CLN2 as well as other neurodevelopmental conditions.
Risk and predictors of in-hospital mortality from COVID-19 in patients with diabetes and cardiovascular disease
Authors: Rastad Hadith , Karim Hossein , Ejtahed Hanieh-Sadat , Tajbakhsh Ramin , Noorisepehr Mohammad , Babaei Mehrdad , Azimzadeh Mehdi , Soleimani Alireza , Inanloo Seyed Hasan , Shafiabadi Hassani Neda , Rasanezhad Fariba , Shahrestanaki Ehsan , Khodaparast Zeinab , Golami Hossein , Qorbani Mostafa
Published: July 2020

Background

Diabetes mellitus (DM) and cardiovascular disease (CVD) are present in a large number of patients with novel Coronavirus disease 2019 (COVID-19). We aimed to determine the risk and predictors of in-hospital mortality from COVID-19 in patients with DM and CVD.

Methods

This retrospective cohort study included hospitalized patients aged ≥ 18 years with confirmed COVID-19 in Alborz province, Iran, from 20 February 2020 to 25 March 2020. Data on demographic, clinical and outcome (in-hospital mortality) data were obtained from electronic medical records. Self-reported comorbidities were classified into the following groups: “DM” (having DM with or without other comorbidities), “only DM” (having DM without other comorbidities), “CVD” (having CVD with or without other comorbidities), “only CVD” (having CVD without other comorbidities), and “having any comorbidity”. Multivariate logistic regression models were fitted to quantify the risk and predictors of in-hospital mortality from COVID-19 in patients with these comorbidities.

Results

Among 2957 patients with COVID-19, 2656 were discharged as cured, and 301 died. In multivariate model, DM (OR: 1.62 (95% CI 1.14–2.30)) and only DM (1.69 (1.05–2.74)) increased the risk of death from COVID-19; but, both CVD and only CVD showed non-significant associations (p > 0.05). Moreover, “having any comorbidities” increased the risk of in-hospital mortality from COVID-19(OR: 2.66 (95% CI 2.09–3.40)). Significant predictors of mortality from COVID-19 in patients with DM were lymphocyte count, creatinine and C-reactive protein (CRP) level (all P-values < 0.05).

Conclusions

Our findings suggest that diabetic patients have an increased risk of in-hospital mortality following COVID-19; also, lymphocyte count, creatinine and CRP concentrations could be considered as significant predictors for the death of COVID-19 in these patients.
Transposable elements in Drosophila
Authors: Mérel Vincent , Boulesteix Matthieu , Fablet Marie , Vieira Cristina
Published: July 2020

Drosophila has been studied as a biological model for many years and many discoveries in biology rely on this species. Research on transposable elements (TEs) is not an exception. Drosophila has contributed significantly to our knowledge on the mechanisms of transposition and their regulation, but above all, it was one of the first organisms on which genetic and genomic studies of populations were done. In this review article, in a very broad way, we will approach the TEs of Drosophila with a historical hindsight as well as recent discoveries in the field.
Prevalence of Helicobacter pylori among Sudanese patients diagnosed with colon polyps and colon cancer using immunohistochemistry technique
Authors: Mohamed Aziza K. , Elhassan Nazik M. , Awhag Zahra A. , Ali Fadwa S. , Ali Eman T. , Mhmoud Najwa A. , Siddig Emmanuel E. , Hassan Rowa , Ahmed Eiman S. , Fattahi Azam , Ahmed Ayman , Muneer Mohamed S. , Osman Hussam A. , Mohamed Nouh S. , Edris Ali M. M.
Published: July 2020

Objectives

Infection with the bacteria Helicobacter pylori has been classified as class one carcinogen associated with increasing susceptibility of gastritis and gastric carcinoma. This study is aiming at investigating the prevalence of H. pylori among colon polyps and colon cancer patients. A descriptive cross-sectional hospital-based study was conducted between February and June 2017. Sixty-nine formalin-fixed paraffin blocks collected from colon polyps and colon cancer patients to detect H. pylori using immunohistochemistry technique.

Results

Of the 69 patients included in the study, 39 (56.5%) males and 30 (43.5%) were females, their age ranged from 21 to 80 years with a mean age of 47.1 ± 19.7. Of the 69 colon polyps and colon cancer patients, 44 (63.8%) were diagnosed as adenocarcinoma, 10 (14.5%) colitis, 15 (21.7%) juvenile polyposis syndrome. The results of immunohistochemistry technique showed the presence of 16 (23.2%) positive patients for H. pylori infection. Of these 16, 13 (81.3%) patients were diagnosed with adenocarcinoma and 3 (18.7%) patients were diagnosed with juvenile polyps. The results of H. pylori detection among the different colon polyps and colon cancer patients were showing a statistically significant association for H. pylori infection and adenocarcinoma, P value 0.028.
Scintigraphy evaluation of hyperthyroidism and its correlation with clinical and biochemical profiles
Authors: Alswat Khaled , Assiri Sara Ahmad , Althaqafi Raad M. M. , Alsufyani Atheer , Althagafi Abaad , Alrebaiee Sara , Alsukhayri Najd
Published: July 2020

Objective

Hyperthyroidism is the excessive synthesis of thyroid hormones. Thyroid uptake scans and ultrasonography provide an accurate diagnosis of hyperthyroidism, especially when thyroid receptor antibody (TRAb) measurement is not readily available. This study explored the prevalence of various hyperthyroidism causes using retrospective scintigraphy results and evaluated their relationship with clinical, biochemical, and sonographic imaging parameters from patients who underwent 99mTc-pertechnetate thyroid scans between 2016 and 2019 in Taif, Saudi Arabia, where literature is insufficient. Furthermore, the inappropriate use of thyroid scanning in different thyroid diseases was evaluated.

Results

The study enrolled 207 patients (mean age: 42.5 ± 14.7 years). The mean free T4, T3, antithyroid peroxidase antibody, antithyroglobulin antibody, C-reactive protein, and erythrocyte sedimentation rate levels were high. Graves’ disease was the most common diagnosis. Compared to toxic solitary/multinodular goiter, patients with Graves’ disease were usually younger, used carbimazole during both the uptake and the scan, had an enlarged thyroid gland, and had higher FT4 and FT3 levels. Inappropriate thyroid uptake and scan use was reported in approximately 10% of patients, and 25% of the patients used carbimazole during the uptake and scan. Thus, better patient education is needed to avoid misinterpreting the scan results.
Enzymatic activity and brine shrimp lethality of venom from the large brown spitting cobra (Naja ashei) and its neutralization by antivenom
Authors: Okumu Mitchel Otieno , Mbaria James Mucunu , Gikunju Joseph Kangangi , Mbuthia Paul Gichohi , Madadi Vincent Odongo , Ochola Francis Okumu
Published: July 2020

Objective

Naja asheiis a snake of medical importance in Kenya, Ethiopia, Somalia, Uganda, and Tanzania. Little is known about the enzymatic (snake venom phospholipases A2; svPLA2’s) and toxic (lethal) activities ofN. asheivenom and crucially, the safety and capacity of available antivenom to neutralize these effects. This study aimed to determine the enzymatic and toxic activities ofN. asheivenom and the capacity of Indian and Mexican manufactured antivenoms to neutralize these effects. The protein content of the venom and the test antivenoms were also evaluated. A 12-point log concentration–response curve (0.5–22.5 µg/mL) was generated on an agarose-egg yolk model to predict the svPLA2activity of the venom. The toxicity profiles of the venom and antivenoms were evaluated in the brine shrimp lethality assay. Lowry’s method was used for protein estimation.

Results

Low and intermediate concentrations of the venom exhibited similar svPLA2activities. The same was true for concentrations > 15 µg/mL. Intermediate and high doses of the venom exhibited similar mortalities in brine shrimp and test antivenoms were generally non-toxic but poorly neutralized svPLA2activity. Mexican manufactured antivenom had lower protein content but neutralized venom-induced brine shrimp lethality much more effectively than Indian manufactured antivenom.
Current status of development of methylation biomarkers for in vitro diagnostic IVD applications
Authors: Taryma-Leśniak Olga , Sokolowska Katarzyna Ewa , Wojdacz Tomasz Kazimierz
Published: July 2020

A significant volume of research clearly shows that disease-related methylation changes can be used as biomarkers at all stages of clinical disease management, including risk assessment and predisposition screening through early diagnostics to personalization of patient care and monitoring of the relapse and chronic disease. Thus disease-related methylation changes are an attractive source of the biomarkers that can have significant impact on precision medicine. However, the translation of the research findings in methylation biomarkers field to clinical practice is at the very least not satisfactory. That is mainly because the evidence generated in research studies indicating the utility of the disease-related methylation change to predict clinical outcome is in majority of the cases not sufficient to postulate the diagnostic use of the biomarker. The research studies need to be followed by well-designed and systematic investigations of clinical utility of the biomarker that produce data of sufficient quality to meet regulatory approval for the test to be used to make clinically valid decision. In this review, we describe methylation-based IVD tests currently approved for IVD use or at the advanced stages of the development for the diagnostic use. For each of those tests, we analyze the technologies that the test utilizes for methylation detection as well as describe the types of the clinical studies that were performed to show clinical validity of the test and warrant regulatory approval. The examples reviewed here should help with planning of clinical investigations and delivery of the clinical evidence required for the regulatory approval of potential methylation biomarker based IVD tests.
Four-class emotion classification in virtual reality using pupillometry
Authors: Zheng Lim Jia , Mountstephens James , Teo Jason
Published: July 2020

Background

Emotion classification remains a challenging problem in affective computing. The large majority of emotion classification studies rely on electroencephalography (EEG) and/or electrocardiography (ECG) signals and only classifies the emotions into two or three classes. Moreover, the stimuli used in most emotion classification studies utilize either music or visual stimuli that are presented through conventional displays such as computer display screens or television screens. This study reports on a novel approach to recognizing emotions using pupillometry alone in the form of pupil diameter data to classify emotions into four distinct classes according to Russell’s Circumplex Model of Emotions, utilizing emotional stimuli that are presented in a virtual reality (VR) environment. The stimuli used in this experiment are 360° videos presented using a VR headset. Using an eye-tracker, pupil diameter is acquired as the sole classification feature. Three classifiers were used for the emotion classification which are Support Vector Machine (SVM), k-Nearest Neighbor (KNN), and Random Forest (RF).

Findings

SVM achieved the best performance for the four-class intra-subject classification task at an average of 57.05% accuracy, which is more than twice the accuracy of a random classifier. Although the accuracy can still be significantly improved, this study reports on the first systematic study on the use of eye-tracking data alone without any other supplementary sensor modalities to perform human emotion classification and demonstrates that even with a single feature of pupil diameter alone, emotions could be classified into four distinct classes to a certain level of accuracy. Moreover, the best performance for recognizing a particular class was 70.83%, which was achieved by the KNN classifier for Quadrant 3 emotions.

Conclusion

This study presents the first systematic investigation on the use of pupillometry as the sole feature to classify emotions into four distinct classes using VR stimuli. The ability to conduct emotion classification using pupil data alone represents a promising new approach to affective computing as new applications could be developed using readily-available webcams on laptops and other mobile devices that are equipped with cameras without the need for specialized and costly equipment such as EEG and/or ECG as the sensor modality.
Laser digital patterning of conductive electrodes using metal oxide nanomaterials
Authors: Nam Vu Binh , Giang Trinh Thi , Koo Sangmo , Rho Junsuk , Lee Daeho
Published: July 2020

As an alternative approach to the conventional deposition and photolithographic processes, the laser digital patterning (LDP) process, which is also known as the laser direct writing process, has attracted considerable attention because it is a non-photolithographic, non-vacuum, on-demand, and cost-effective electrode fabrication route that can be applied to various substrates, including heat-sensitive flexible substrates. The LDP process was initially developed using noble metal nanoparticles (NPs) such as Au and Ag because such materials are free from oxidation even in a nanosize configuration. Thus, the NPs must be fused together to form continuous conductive structures upon laser irradiation. However, common metals are easily oxidized at the nanoscale and exist in oxidized forms owing to the extremely large surface-to-volume ratio of NPs. Therefore, to fabricate conductive electrodes using common metal NPs via the LDP process, laser irradiation should be used to sinter the NPs and simultaneously induce additional photochemical reactions, such as reduction, and defect structure modification to increase the conductivity of the electrodes. This review summarizes recent studies on the LDP process in which metal oxide NPs, such as ITO, ZnO, CuO, and NiO, were exclusively utilized for fabricating conductive electrodes. The outlook of the LDP process for these materials is also discussed as a method that can be used together with or as a replacement for conventional ones to produce next-generation transparent conductors, sensors, and electronics.
Classification of long-term very long period (VLP) volcanic earthquakes at Whakaari/White Island volcano, New Zealand
Authors: Park Iseul , Jolly Arthur , Lokmer Ivan , Kennedy Ben
Published: July 2020

We have observed very long period earthquakes (VLPs) over the period 2007 to the end of 2019 at Whakaari/White Island volcano, New Zealand. The earthquakes exhibit similitude between waveforms which suggests repeating source locations and processes. VLPs recorded at two permanent stations were detected using waveform semblance and were then classified into two main families (F1 and F2) using a clustering analysis. The two families are characterized by ‘mirror image’ reverse waveform polarity suggesting that they are genetically related, but occur during different evolutionary phases of volcanic activity. F1 events occurred throughout the observation period, while F2 events mainly occurred as swarms that mark the onset of volcanic unrest. A detailed cluster analysis reveals possible sub-families implying slight temporal evolutions within a family. Our results add to our understanding of the volcanic magma–hydrothermal system at Whakaari/White Island indicating that relatively stable VLP sources may be exploited to improve monitoring for future unrest.
Day-to-day variation of pre-reversal enhancement in the equatorial ionosphere based on GAIA model simulations
Authors: Ghosh Priyanka , Otsuka Yuichi , Mani Sivakandan , Shinagawa Hiroyuki
Published: July 2020

Using a whole atmosphere–ionosphere coupled model GAIA (ground-to-topside model of atmosphere and ionosphere), we have investigated which parameters mainly control day-to-day variation of vertical plasma drift at the evening terminator over magnetic equator, so-called pre-reversal enhancement (PRE). Day-to-day variations of the peak PRE are compared with those of electron density, eastward current density and eastward neutral wind in the E- and F-region over Chumphon (10.7° N, 99.4° E; 0.86° N magnetic latitude), Thailand during equinoctial months in 2011–2013. Eastward neutral wind in the F-region shows positive correlation with peak PRE, indicating that the F-region winds control the peak PRE through the mechanisms of the F-region dynamo (including E- and F-region coupling processes). Daytime eastward electric current at an altitude of 110 km, corresponding to equatorial electro jet (EEJ), is also positively correlated with the peak PRE. Correlation between the EEJ and PRE is the largest at 1700 LT, approximately 1.5 h prior to the peak PRE.
Microbial communities from arid environments on a global scale. A systematic review
Authors: Vásquez-Dean Javiera , Maza Felipe , Morel Isidora , Pulgar Rodrigo , González Mauricio
Published: July 2020

Arid environments are defined by the lack of water availability, which is directly related to the mean annual precipitation (MAP), and high values of solar irradiation, which impacts the community composition of animals, plants, and the microbial structure of the soil. Recent advances in NGS technologies have expanded our ability to characterize microbiomes, allowing environmental microbiologists to explore the complete microbial structure. Intending to identify and describe the state-of-the-art of bacterial communities in arid soils at a global scale, and to address the effect that some environmental features may have on them, we performed a systematic review based on the PRISMA guideline. Using a combination of keywords, we identified a collection of 66 studies, including 327 sampled sites, reporting the arid soil bacterial community composition by 16S rDNA gene high-throughput sequencing. To identify factors that can modulate bacterial communities, we extracted the geographical, environmental, and physicochemical data. The results indicate that even though each sampled site was catalogued as arid, they show wide variability in altitude, mean annual temperature (MAT), soil pH and electric conductivity, within and between arid environments. We show that arid soils display a higher abundance of Actinobacteria and lower abundance of Proteobacteria, Cyanobacteria, and Planctomycetes, compared with non-arid soil microbiomes, revealing that microbial structure seems to be strongly modulated by MAP and MAT and not by pH in arid soils. We observed that environmental and physicochemical features were scarcely described among studies, hence, we propose a reporting guideline for further analysis, which will allow deepening the knowledge of the relationship between the microbiome and abiotic factors in arid soil. Finally, to understand the academic collaborations landscape, we developed an analysis of the author’s network, corroborating a low degree of connectivity and collaborations in this research topic. Considering that it is crucial to understand how microbial processes develop and change in arid soils, our analysis emphasizes the need to increase collaborations between research groups worldwide.
Edaravone alleviates cell apoptosis and mitochondrial injury in ischemia–reperfusion-induced kidney injury via the JAK/STAT pathway
Authors: Zhao Xiaoying , Zhang Erfei , Ren Xiaofen , Bai Xiaoli , Wang Dongming , Bai Ling , Luo Danlei , Guo Zheng , Wang Qiang , Yang Jianxin
Published: July 2020

Background

Kidney ischemia–reperfusion injury is a common pathophysiological phenomenon in the clinic. A large number of studies have found that the tyrosine protein kinase/signal transducer and activator of transcription (JAK/STAT) pathway is involved in the development of a variety of kidney diseases and renal protection associated with multiple drugs. Edaravone (EDA) is an effective free radical scavenger that has been used clinically for the treatment of postischemic neuronal injury. This study aimed to identify whether EDA improved kidney function in rats with ischemia–reperfusion injury by regulating the JAK/STAT pathway and clarify the underlying mechanism.

Methods

Histomorphological analysis was used to assess pathological kidney injury, and mitochondrial damage was observed by transmission electron microscopy. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) staining was performed to detect tubular epithelial cell apoptosis. The expression of JAK2, P-JAK2, STAT3, P-STAT3, STAT1, P-STAT1, BAX and Bcl-2 was assessed by western blotting. Mitochondrial function in the kidney was assessed by mitochondrial membrane potential (ΔΨm) measurement.

Results

The results showed that EDA inhibited the expression of p-JAK2, p-STAT3 and p-STAT1, accompanied by downregulation of the expression of Bax and caspase-3, and significantly ameliorated kidney damage caused by ischemia–reperfusion injury (IRI). Furthermore, the JC-1 dye assay showed that edaravone attenuated ischemia–reperfusion-induced loss of kidney ΔΨm.

Conclusion

Our findings indicate that EDA protects against kidney damage caused by ischemia–reperfusion through JAK/STAT signaling, inhibiting apoptosis and improving mitochondrial injury.
Early life adversity and health inequality: a dual interaction model
Authors: Shi Zhilei , Wu Cary
Published: July 2020

This article examines the impact of early life adversity on health inequality from a life course perspective. We develop a dual interaction model that considers how both the frequency as well as the duration of early life adversity might shape an individual's health. Analyzing data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2014), we show that not only does early life adversity have a direct effect on an individual's health, but throughout the life course it also produces cumulative disadvantages through worsening the individual's life conditions such as less education, lower social-economic status, and less job security. The combination of the frequency of adversity experience and the length of exposure creates an exponential effect on poor health, contributing to the persistence of health inequality in contemporary Chinese society.
A case of perforation of Meckel’s diverticulum with enterolith
Authors: Shimagaki Tomonari , Konishi Kozo , Kawata Koto , Edahiro Keitaro , Edagawa Makoto , Takenaka Tomoyoshi , Ohmine Takahiro , Kinjo Nao , Yamaguchi Shohei , Maeda Takashi , Tsutsui Shinichi , Matsuda Hiroyuki
Published: July 2020

Background

Perforation of Meckel’s diverticulum with enteroliths is a rare complication. Here, we report a case of perforation of Meckel’s diverticulum with one enterolith, which could not be accurately diagnosed by preoperative computed tomography.

Case presentation

A 16-year-old male patient with acute onset of severe abdominal pain and a localized muscle guarding in the right hypochondrium had a solitary stone detected in the right abdomen by radiography. Abdominal computed tomography revealed a saclike outpouching of the small intestine, which contained fluid levels and an enterolith, with a mesenteric inflammatory change in the right paraumbilical area. He was diagnosed with peritonitis due to appendicitis or Meckel’s diverticulitis with enterolith, and emergency operation was indicated. The perforated Meckel’s diverticulum was identified approximately 30 cm proximal to the ileocecal valve. The diverticulum was transected at the base and removed. The patient’s postoperative course was uneventful.

Conclusions

It is crucial for clinicians to thoroughly examine patients and appropriately request investigations that consider perforation of Meckel’s diverticulum as a possible diagnosis to facilitate prompt treatment.
Diagnostic dilemma of amyotrophic lateral sclerosis (ALS): insights from the first ALS specialized clinic in Egypt
Authors: Rashed Hebatallah R. , Tork Mohamed A.
Published: July 2020

Introduction

Amyotrophic lateral sclerosis (ALS) diagnosis could be challenging in some cases and a thorough workup should be done to rule out ALS mimics. Thus, diagnosis should be made by an experienced neurologist and should be regularly reviewed.

Objectives

Review challenging cases from the ALS clinic that were misdiagnosed as ALS.

Method/patients

This is a descriptive study. We registered data of all patients coming for evaluation in the period between December 2018 and January 2020 at the international medical center (IMC) where the ALS specialized clinic is located. All patients underwent thorough clinical assessment according to the EFNS guidelines on the Clinical Management of Amyotrophic Lateral Sclerosis (MALS), and the diagnosis of ALS was made based on El Escorial revised criteria.

Results

The records of 30 patients were available for review. Twenty-four patients out of 30 patients (80%) were diagnosed with ALS, and 6 patients (20%) were diagnosed with other disorders (ALS mimics). In the ALS group (24 patients), there are 18 males and 6 females (male to female ratio is 3:1); mean age of onset of ALS patients is 49.2 years ± SD 15.1 years; 18 patients (75%) had limb onset ALS and 6 patients (25%) had bulbar onset ALS. In the ALS mimics group (6 patients), there were 3 patients with multifocal motor neuropathy (MMN); 1 patient with celiac disease, 1 patient with mesothelioma, and 1 patient with cervical myelopathy.

Discussion

The percentage of ALS mimics in our study is higher than that reported in previous studies. This could be due to the small sample size and the deficiency of specialized ALS centers across the country. MMN was the most common ALS mimic syndrome. Factors leading to change the diagnosis from ALS to another ALS mimic disorder were the adherence to El Escorial revised criteria for the diagnosis of ALS, following EFNS guidelines for management, and looking for demyelinating features in electrophysiological studies according to the EFNS criteria.
A method of improving ambiguity fixing rate for post-processing kinematic GNSS data
Authors: Zhang Xiaohong , Zhang Yuxi , Zhu Feng
Published: July 2020

Global Navigation Satellite System precise positioning using carrier phase measurements requires reliable ambiguity resolution. It is challenging to obtain continuous precise positions with a high ambiguity fixing rate under a wide range of dynamic scenes with a single base station, thus the positioning accuracy will be degraded seriously. The Forward–Backward Combination (FBC), a common post-processing smoothing method, is simply the weighted average of the positions of forward and backward filtering. When the ambiguity fixing rate of the one-way (forward or backward) filter is low, the FBC method usually cannot provide accurate and reliable positioning results. Consequently, this paper proposed a method to improve the accuracy of positions by integrating forward and backward AR, which combines the forward and backward ambiguities instead of positions—referred to as ambiguity domain-based integration (ADBI). The purpose of ADBI is to find a reliable correct integer ambiguities by making full use of the integer nature of ambiguities and integrating the ambiguities from the forward and backward filters. Once the integer ambiguities are determined correctly and reliably with ADBI, then the positions are updated with the fixing ambiguities constrained, in which more accurate positions with high confidence can be achieved. The effectiveness of the proposed approach is validated with airborne and car-borne dynamic experiments. The experimental results demonstrated that much better accuracy of position and higher ambiguity-fixed success rate can be achieved than the traditional post-processing method.
Organizational characteristics conducive to the implementation of health programs among Latino churches
Authors: Allen Jennifer D. , Shelton Rachel C. , Kephart Lindsay , Jandorf Lina , Folta Sara C. , Knott Cheryl L.
Published: July 2020

Background

Faith-based organizations (FBOs) can be effective partners in the implementation of health interventions to reach underserved audiences. However, little is known about the capacity they have or need to engage in these efforts. We examined inner-setting organizational characteristics hypothesized to be important for program implementation by the Consolidated Framework for Implementation Research (CFIR).

Methods

This cross-sectional study involved 34 churches with predominantly Latino congregations in Massachusetts. FBO leaders completed a survey assessing inner-setting CFIR organizational characteristics, including organizational readiness, implementation climate, organizational culture, and innovation “fit” with organizational mission.

Results

There was limited variability in CFIR organizational characteristics, with scores on a scale from 1 to 5 skewed toward higher values, ranging from 3.27 (SD 0.94) for implementation climate to 4.58 (SD 0.54). Twenty-one percent of the FBOs had offered health programs in the prior year.

Conclusions

FBOs had high scores on most of the organizational factors hypothesized to be important for the implementation of health programs, although relatively few FBOs offered them. While this suggests that FBOs have favorable characteristics for health programming, prospective studies are needed to understand relative salience of inner-setting organizational characteristics versus factors external to the organization (e.g., policies, incentives), as well as the potential direction of relationships between internal organizational characteristics and health program offerings.

Trial registration

Clinical trials identifier number NCT01740219 (clinicaltrials.gov)
Stress-free-state based structural analysis and construction control theory for staged construction bridges
Authors: Qin Shunquan , Wei Kai , Qin Jingxi , Yuan Renan , Xu Leiping , Dan Qilian
Published: July 2020

Structural analysis and construction control of staged construction process is a major subject for modern long-span bridges. This paper introduces the concept of stress-free-state variable of structural elements and deduces the mechanical equilibrium equations and geometric shape governing equations for staged construction structures utilizing the minimum potential energy theorem. As the core of stress-free-state theory, the two aforementioned equations demonstrate following principles, 1) when the stress-free-state variable of a structural element is set, the internal force and deformation of the element are unique at the completion state of the structure regardless of its construction process; 2) the stress-free length of a cable is independent of its external loads, change in stress-free length of the cable corresponds to a unique variation of the cable force when load is constant; and 3) the internal force of a structural element can be independent from its geometric shape within the completion state of a staged construction structure through an active manipulation of stress-free-state variables of the element. Stress-free-state theory establishes the stage-to-stage and stage-to-completion relationships for staged construction bridges, provides a direct and efficient method for theoretical calculations and a flexible and convenient approach for the control of staged construction, and makes parallel construction and auto-filtering of thermal and temporary loading effect possible.
ARETTA: Assessing Response to Neoadjuvant Taxotere and Subcutaneous Trastuzumab in Nigerian Women With HER2-Positive Breast Cancer: A Study Protocol
Authors: Ntekim Atara I. , Ibraheem Abiola , Sofoluwe Adenike A. , Kotila Olayinka , Babalola Chinedum , Karrison Theodore , Olopade Christopher O.
Published: July 2020

Human epidermal growth factor receptor 2 (HER2) subtype of breast cancer is aggressive, leading to a poor outcome. Targeted therapy with trastuzumab has been shown to be effective in the treatment of HER2-positive breast cancer. Cardiotoxicity is a specific adverse effect associated with trastuzumab. The initial formulation of trastuzumab was intravenous, but presently, a subcutaneous formulation (Herceptin SC) is available. Insufficient data on the response rate and cardiotoxic effects of trastuzumab among indigenous Black populations exist. In all studies evaluating the efficacy and toxicity of trastuzumab alone or in combination with chemotherapy, indigenous Black populations in Africa were not included, yet they are the ones most likely to benefit from highly effective cancer medicines. This is partly due to poor oncology clinical trial infrastructure in sub-Saharan Africa. The ARETTA study protocol (ClinicalTrials.gov identifier: NCT03879577 ) is a phase II multicenter feasibility study to evaluate the efficacy and toxicity of docetaxel given every 3 weeks for 4 cycles plus trastuzumab in 60 previously untreated women with nonmetastatic breast cancer. The primary endpoint is to assess the proportion of patients with complete pathologic response. Secondary endpoints include the number of patients who require dose delays in docetaxel and trastuzumab attributed to hematologic, GI, and cardiac toxicity. Pharmacokinetic profiles of subcutaneous trastuzumab will also be determined. The ARETTA study will provide important information on the clinical response and cardiac safety of subcutaneous trastuzumab in combination with docetaxel among indigenous African women with nonmetastatic breast cancer. It can also be used as a blueprint for conducting biomarker-driven oncology clinical trials in low-resource settings such as sub-Saharan Africa.
Patient Flow Analysis Using Real-Time Locating System Data: A Case Study in an Outpatient Oncology Center
Authors: Kang Hyojung , Haswell Ethan
Published: July 2020

PURPOSE:

Electronic health records (EHRs) have been mainly used to analyze bottlenecks in care processes of outpatient oncology clinics. However, EHR data lead to some limitations in understanding patient flow because they are manually entered and not updated in real time. Data generated from a real-time location system (RTLS) can supplement EHR data. This study aims to demonstrate how RTLS data combined with EHR data can be used to evaluate potential interventions to improve patient flow in an outpatient cancer center.

METHODS:

EHR and RTLS data obtained from a large cancer center in central Virginia were analyzed to estimate process times and determine the various patient paths patients follow during their visit for infusion. Using the input data, we developed a discrete-event simulation (DES) model and assessed 5 what-if scenarios involving changes in staff scheduling and care processes.

RESULTS:

Raw RTLS data including > 3.5 million observations were preprocessed to remove noise and extract meaningful information. The DES results showed that new nursing schedules for the infusion center and improved pharmacy processes have positive impacts on reducing patient waiting times by approximately 20% and overall length of stay by approximately 3.4% to 4.6%, compared with the current system.

CONCLUSION:

Combining EHR and RTLS data, we were able to capture dynamic aspects of patient flow more realistically. DES models that represent a complex system based on accurate input data can help decision making on determining operational changes to improve patient flow.
New Horizons: Novel Adrenal Regenerative Therapies
Authors: Bornstein Stefan R , Malyukov Maria , Heller Carolin , Ziegler Christian G , Ruiz-Babot Gerard , Schedl Andreas , Ludwig Barbara , Steenblock Charlotte
Published: July 2020

Adrenal insufficiency requires lifelong corticoid replacement therapies. However, current therapies are not able to replace the physiological circadian pattern of the adrenal cortex and are associated with many metabolic, vascular, neuroendocrine, and mental perturbations. Therefore, regenerative and more curative strategies would be desirable. In the current perspective, we describe emerging new regenerative therapies for the treatment of adrenal insufficiency. In particular, we discuss gene therapy and cell replacement strategies. Furthermore, we discuss how adrenal cells might be used as a source for regenerative therapies of nonadrenal neurodegenerative diseases such as Parkinson disease.
The spectrin-based membrane skeleton is asymmetric and remodels during neural development in C. elegans
Authors: Jia Ru , Chai Yongping , Xie Chao , Liu Gai , Zhu Zhiwen , Huang Kaiyao , Li Wei , Ou Guangshuo
Published: July 2020

Perturbation of spectrin-based membrane mechanics causes hereditary elliptocytosis and spinocerebellar ataxia, but the underlying cellular basis of pathogenesis remains unclear. Here, we introduced conserved disease-associated spectrin mutations into the Caenorhabditis elegans genome and studied the contribution of spectrin to neuronal migration and dendrite formation in developing larvae. The loss of spectrin resulted in ectopic actin polymerization outside of the existing front and secondary membrane protrusions, leading to defective neuronal positioning and dendrite morphology in adult animals. Spectrin accumulated in the lateral region and rear of migrating neuroblasts and redistributes from the soma into the newly formed dendrites, indicating that the spectrin-based membrane skeleton is asymmetric and remodels to regulate actin assembly and cell shape during development. We affinity-purified spectrin from C. elegans and showed that its binding partner ankyrin functions with spectrin. Asymmetry and remodeling of the membrane skeleton might enable spatiotemporal modulation of membrane mechanics for distinct developmental events.
Conflito de Jurisdição e crime de lesa-majestade: O caso da capitania da Bahia entre 1783-1787
Authors: Prisco Teixeira Milena Pinillos
Published: July 2020

Este artigo apresenta informações sobre um conflito de jurisdição ocorrido no ano de 1783 na capitania da Bahia, envolvendo o Tribunal da Relação da Bahia e o Conselho de Guerra. A questão central que permeou este caso foi a dúvida sobre qual jurisdição, civil ou militar, ficaria responsável pelo julgamento de um militar condenado ao crime de resistência à justiça. Em meio a um período de acomodação das reformas empreendidas pelo Marquês de Pombal no campo jurídico, e de transição nos campos da justiça e do direito, este caso despertou a atenção das instâncias superiores de justiça no reino. Não obstante o parecer de especialistas nos dois lados do atlântico, a culpa permaneceu pendente em segredo de justiça por mais de quatro anos, sem indícios documentais do desfecho do caso.
Reforma trabalhista, privacidade e responsabilização na era digital
Authors: Sampaio Giovanna
Published: July 2020

O presente artigo objetivou a análise da regulamentação do teletrabalho pela “Reforma trabalhista”, observando as ocorrências e impactos nas condições ambientais laborais. O trabalho avaliou brevemente os pontos positivos e negativos do teletrabalho, bem como abordou o contexto da regulação do teletrabalho, perpassando pela seara dos direitos fundamentais e concluindo pela responsabilidade do patrão. Quanto à metodologia desenvolvida, consistiu primordialmente na revisão bibliográfica dos principais autores nacionais e estrangeiros da seara dos Direitos Fundamentais, e da doutrina consagrada do Direito do Trabalho. Outros artigos acadêmicos físicos e digitais também foram consultados, dado à novidade deste tema relativo ao Teletrabalho.