bluuebunny/crossref_metadata_2025 huggingface dataset:
Blinding in electric current stimulation in subacute neglect patients with current densities of 0.8 A/m2: a cross-over pilot study
Authors: Gorsler Anna , Grittner Ulrike , Külzow Nadine , Rackoll Torsten
Published: January 2021

Objective

Neglect after stroke is a disabling disorder and its rehabilitation is a major challenge. Transcranial direct current stimulation (tDCS) seems to be a promising adjuvant technique to improve standard care neglect therapy. Since electric fields are influenced by age-related factors, higher current densities are probably needed for effective treatment in aged stroke patients. Validation of treatment efficacy requires sham-controlled experiments, but increased current densities might comprise blinding. Therefore, a pilot study was conducted to test sham adequacy when using current density of 0.8 A/m2. Whether especially neglect patients who mainly suffer from perceptual and attentional deficits are able to differentiate beyond chance active from sham tDCS was investigated in a randomized cross-over design (active/sham stimulation) in 12 early subacute patients with left-sided hemineglect. Stimulation (0.8 A/m2) was performed simultaneous to standard care neglect therapy.

Results

Odds ratio of correct guessing an atDCS condition compared to wrongly judge an atDCS condition as sham was 10.00 (95%CI 0.65–154.40, p = 0.099). However, given the small sample size and high OR, although likely somewhat overestimated, results require careful interpretation and blinding success in neglect studies with current densities of 0.8 A/m2should be further confirmed.
Genetic developmental disability diagnosed in adulthood: a case report
Authors: Langenfeld Adam , Schema Lynn , Eckerle Judith K.
Published: January 2021

Background

Developmental disabilities (DD) are an umbrella term for conditions associated with functional impairments in physical, learning, language, or behavior areas. Intellectual disability (ID) is a type of developmental disability that results in delays in cognitive or intellectual functioning, such as reasoning, learning, and problem-solving, and adaptive behaviors including social and practical life skills. DD can be due to a variety of factors, ranging from environmental exposures to genetic mutations, and studies suggest that up to 40% of DDs may be caused by genetic issues.

Case presentation

In this case study, we present an 18-year-old internationally adopted female Chinese American patient with a known history of developmental delay, intellectual disability, strabismus, and a congenital heart defect who had not been tested for genetic causes of her delay prior to presentation. When evaluated with chromosomal microarray, the patient demonstrated a deletion on the short arm of chromosome 5, an area associated with Cri-du-chat syndrome. This chromosomal deletion was a likely explanation for her history of developmental delays, intellectual disability, and congenital heart defect, in addition to her history of institutionalization and the trauma of multiple caregiver transitions in early childhood. The patient was referred for further evaluation by a geneticist and genetic counselor.

Conclusions

This case highlights that the underlying cause of developmental delay is often multifactorial, and underscores the importance of a full medical evaluation, including genetic testing, for children with intellectual disability. Using this approach, healthcare professionals can identify potential diagnoses and provide more targeted resources to families.
Free air after laparoscopic hysterectomy; from sigmoid perforation to upper airway compromise: a case report
Authors: Melemeni Aikaterini , Tympa Grigoriadou Aliki , Tsaroucha Athanasia
Published: January 2021

Background

Free air after laparoscopic hysterectomy is a common finding; in rare cases, free air represents gastrointestinal perforation, requiring emergency laparotomy. Ectopic air localizations after pneumoperitoneum have been reported in various laparoscopic surgical techniques. Delayed diagnosis of visceral perforation is associated with high mortality rates.

Case presentation

We present a white Caucasian female in which dysphonia due to air entrapment in the cervical area, pneumomediastinum and pneumothorax, occured afterlaparoscopic hysterectomy.

Conclusions

Upon mobilization of the patient, air from sigmoid perforation moved cephalad. Through the same path, pneumoperitoneum, causes subcutaneous emphysema in the neck and face, pneumomediastinum and pneumothorax.
Dental pulp stem cells can improve muscle dysfunction in animal models of Duchenne muscular dystrophy
Authors: Nitahara-Kasahara Yuko , Kuraoka Mutsuki , Guillermo Posadas Herrera , Hayashita-Kinoh Hiromi , Maruoka Yasunobu , Nakamura-Takahasi Aki , Kimura Koichi , Takeda Shin’ichi , Okada Takashi
Published: January 2021

Background

Duchenne muscular dystrophy (DMD) is an inherited progressive disorder that causes skeletal and cardiac muscle deterioration with chronic inflammation. Dental pulp stem cells (DPSCs) are attractive candidates for cell-based strategies for DMD because of their immunosuppressive properties. Therefore, we hypothesized that systemic treatment with DPSCs might show therapeutic benefits as an anti-inflammatory therapy.

Methods

To investigate the potential benefits of DPSC transplantation for DMD, we examined disease progression in a DMD animal model, mdx mice, by comparing them with different systemic treatment conditions. The DPSC-treated model, a canine X-linked muscular dystrophy model in Japan (CXMDJ), which has a severe phenotype similar to that of DMD patients, also underwent comprehensive analysis, including histopathological findings, muscle function, and locomotor activity.

Results

We demonstrated a therapeutic strategy for long-term functional recovery in DMD using repeated DPSC administration. DPSC-treated mdx mice and CXMDJ showed no serious adverse events. MRI findings and muscle histology suggested that DPSC treatment downregulated severe inflammation in DMD muscles and demonstrated a milder phenotype after DPSC treatment. DPSC-treated models showed increased recovery in grip-hand strength and improved tetanic force and home cage activity. Interestingly, maintenance of long-term running capability and stabilized cardiac function was also observed in 1-year-old DPSC-treated CXMDJ.

Conclusions

We developed a novel strategy for the safe and effective transplantation of DPSCs for DMD recovery, which included repeated systemic injection to regulate inflammation at a young age. This is the first report on the efficacy of a systemic DPSC treatment, from which we can propose that DPSCs may play an important role in delaying the DMD disease phenotype.
RETRACTED ARTICLE: Effects of miR-672 on the angiogenesis of adipose-derived mesenchymal stem cells during bone regeneration
Authors: Chen Mingjiao , Zhou Meng , Fu Yao , Li Jin , Wang Zi
Published: January 2021

Background

Sufficient vascular network plays an important role in the repair of bone defects. Bone morphogenetic protein 2 (BMP2) being a key regulator of angiogenesis has attracted the attention of researchers. In addition, evidence has suggested that BMP2 coordinates with microRNAs (miRNAs) to form intracellular networks regulating mesenchymal stem cells (MSCs) angiogenesis. Elucidating the underlying mechanisms that are regulating adipose-derived mesenchymal stem cells (ADSCs) angiogenesis might provide more effective method to enhance bone regeneration.

Methods

We identified the specific miRNA in rat ADSCs during BMP2-induced angiogenesis and chose the most significant differentially expressed miRNA, miR-672. Three lentiviral system named Lenti-miR-672, Lenti-as-miR-672, and Lenti-miR-NC were transduced into the ADSCs individually. Then, the quantitative real-time polymerase chain reaction (qPCR), western blotting, and blood vessel formation analysis were performed to investigate the effects of miR-672 on ADSCs angiogenesis. Bioinformation platforms were used to screen the potential target of miR-672. Small interfering RNA (siRNA) against TIMP2 (si-TIMP2) mRNA were obtained from GenePharma, and then si-TIMP2 miRNA and miR-672 were co-transfected into ADSCs to detect the effects of TIMP2 on angiogenesis. Calcium phosphate cement (CPC) scaffolds that seeded the lentiviral-modified ADSCs were constructed to test the vascularized bone regeneration in vivo.

Results

Our data showed that after the angiogenesis of ADSCs induced by BMP2, miR-672 was the most significantly upregulated miRNA. Overexpression of miR-672 promoted the angiogenesis of ADSCs, while knockdown of miR-672 repressed the angiogenesis of ADSCs. The bioinformation prediction showed that TIMP2 might be the one of miR-672′ potential targets. TIMP2 protein expression was gradually decreased in ADSCs with overexpressed miR-672. And the angiogenic factors were upregulated in the ADSCs which were transduced with si-TIMP2. Then, the CPC scaffolds coupled the miR-672-modified ADSCs and showed the good potential in vascularized bone regeneration. The overexpressed miR-672 could greatly enhance the blood vessel volume and Microfil-labeled blood vessel numbers in newly formed bone.

Conclusion

BMP2 could promote the angiogenesis of ADSCs through stimulating the expression of miR-672 in ADSCs. miR-672 acted as a positive regulator on the angiogenesis of ADSCs, and incorporating the miR-672-modified ADSCs in the CPC could significantly promote the vascularization and the bone regeneration.
Exosomes derived from miR-301a-3p-overexpressing adipose-derived mesenchymal stem cells reverse hypoxia-induced erectile dysfunction in rat models
Authors: Liang Li , Zheng Dachao , Lu Chao , Xi Qinghong , Bao Hua , Li Wengfeng , Gu Yufei , Mao Yuanshen , Xu Bin , Gu Xin
Published: January 2021

Background

Erectile dysfunction (ED) has often been observed in patients with obstructive sleep apnea (OSA). Research on adipose-derived mesenchymal stem cell (ADSC)-derived exosomes has shown that they have significant therapeutic effects in many diseases including ED.

Methods

In this study, ED was induced in Sprague Dawley (SD) rats using chronic intermittent hypoxia (CIH) exposure. CIH-mediated influences were then measured in the corpus cavernous smooth muscle cells (CCSMCs).

Results

Our data showed that miR-301a-3p-enriched exosome treatment significantly recovered erectile function in rats and CCSMCs by promoting autophagy and inhibiting apoptosis. The treatment also significantly recovered the level of alpha smooth muscle actin (α-SMA) in rats and CCSMCs. Bioinformatics predicted that phosphatase and tensin homolog (PTEN) and Toll-like receptor 4 (TLR4) might be targets of miR-301a-3p.

Conclusions

Our results indicate that PTEN-overexpression vectors or TLR4-overexpression vectors reverse the therapeutic effects achieved by miR-301a-3p in CCSMCs indicating that PTEN/hypoxia-inducible factor-1 alpha (HIF-1α) and TLR4 signaling pathways play key roles in the progression of ED. The findings in this study suggest that miR-301a-3p should be considered a new therapeutic target for treating ED associated with OSA.
Preliminary study of AI-assisted diagnosis using FDG-PET/CT for axillary lymph node metastasis in patients with breast cancer
Authors: Li Zongyao , Kitajima Kazuhiro , Hirata Kenji , Togo Ren , Takenaka Junki , Miyoshi Yasuo , Kudo Kohsuke , Ogawa Takahiro , Haseyama Miki
Published: January 2021

Background

To improve the diagnostic accuracy of axillary lymph node (LN) metastasis in breast cancer patients using 2-[18F]FDG-PET/CT, we constructed an artificial intelligence (AI)-assisted diagnosis system that uses deep-learning technologies.

Materials and methods

Two clinicians and the new AI system retrospectively analyzed and diagnosed 414 axillae of 407 patients with biopsy-proven breast cancer who had undergone 2-[18F]FDG-PET/CT before a mastectomy or breast-conserving surgery with a sentinel lymph node (LN) biopsy and/or axillary LN dissection. We designed and trained a deep 3D convolutional neural network (CNN) as the AI model. The diagnoses from the clinicians were blended with the diagnoses from the AI model to improve the diagnostic accuracy.

Results

Although the AI model did not outperform the clinicians, the diagnostic accuracies of the clinicians were considerably improved by collaborating with the AI model: the two clinicians' sensitivities of 59.8% and 57.4% increased to 68.6% and 64.2%, respectively, whereas the clinicians' specificities of 99.0% and 99.5% remained unchanged.

Conclusions

It is expected that AI using deep-learning technologies will be useful in diagnosing axillary LN metastasis using 2-[18F]FDG-PET/CT. Even if the diagnostic performance of AI is not better than that of clinicians, taking AI diagnoses into consideration may positively impact the overall diagnostic accuracy.
Relationship between body image, anxiety, food-specific inhibitory control, and emotional eating in young women with abdominal obesity: a comparative cross-sectional study
Authors: He Zhong-Hua , Li Ming-De , Liu Chan-Jun , Ma Xiao-Yue
Published: January 2021

Background

Abdominal fat deposition is a key component of obesity, which is associated with an increased risk for a number of mental disorders. The current study aims to explore the relationship between body image, anxiety, food-specific inhibitory control, and emotional eating in young women with abdominal obesity.

Method

A total of 224 participants were recruited: 168 were non-abdominal obesity and 56 were abdominal obesity. Participants completed the following questionnaires and behavioral tests: the Body Mass Index (BMI) -based Silhouette-Matching Test (SMT), the State-Trait Anxiety Inventory (STAI), Food Stop Signal Task (SST), the Emotional Eating Scale (EES).

Results

Abdominal obesity women had significantly higher levels of trait anxiety, cognitive difference, expectational difference in body image but lower self-reported emotional eating level compared to the control group. Anxiety mediated the relationship between cognitive difference of body image and depression eating in young females with abdominal obesity. In addition, only among abdominal obesity individuals, expectational difference of body image were significantly and positively correlated with food-specific inhibitory control and trait/state anxiety.

Conclusion

The findings suggest it is of critical importance to promote a healthy body image recognition and expectation and improve mood regulation for young females with abdominal obesity high in trait anxiety.
Indicators of guideline-concordant care in lung cancer defined with a modified Delphi method and piloted in a cohort of over 5,800 cases
Authors:   on behalf of the Lombardy Lung Cancer Working Group, Andreano Anita , Valsecchi Maria Grazia , Russo Antonio Giampiero , Siena Salvatore
Published: January 2021

Background

To identify indicators of guideline-concordant care in lung cancer, to implement such indicators with cancer registry data linked to health databases, and to pilot them in a cohort of patients from the cancer registry of the Milan Province.

Methods

Thirty-four indicators were selected by revision of main guidelines by cancer epidemiologists, and then evaluated by a multidisciplinary panel of clinicians involved in lung cancer care and working on the pathway of lung cancer diagnosis and treatment in the Lombardy region, Italy. With a modified Delphi method, they assessed for each indicator the content validity as a quality measure of the care pathway, the degree of modifiability from the health professional, and the relevance to the health professional. Feasibility was assessed using the cancer registry and the routine health records of the Lombardy region. Feasible indicators were then calculated in the cohort of lung cancer patients diagnosed in 2007–2012 derived from the cancer registry of the Milan Province. Criterion validity was assessed reviewing clinical records of a random sample of 114 patients (threshold for acceptable discordance ≤20%). Finally, reliability was evaluated at the provider level.

Results

Initially, 34 indicators were proposed for evaluation in the first Delphi round. Of the finally 22 selected indicators, 3 were not feasible because the required information was actually not available. The remaining 19 were calculated on the pilot cohort. After assessment of criterion validity (3 eliminated), 16 indicators were retained in the final set and evaluated for reliability.

Conclusion

The developed and piloted set of indicators is now available to implement and monitor, over time, quality initiatives for lung cancer care in the studied health system.
Optimal bioconversion for compound K production from red ginseng root (C.A. Mayer) by sequential enzymatic hydrolysis and its characteristics
Authors: Park Yeong-Ju , Hwang Unsik , Park Suyeon , Sim Sol , Jeong Soyeon , Park Misun , Kang Minji , Lee Youngsoo , Song Youngju , Park Hoon , Suh Hee-Jae
Published: January 2021

Compound K (CK; 20-O-β-(d-glucopyranosyl)-20(S)-protopanaxadiol) is one of the metabolites of ginsenosides contained in red ginseng (RG) and is known to have high bioavailability. This study aimed to establish the optimal conditions for enzyme treatment to convert ginsenosides from RG extract to CK, and to prove the characteristics of bioconverted red ginseng (BRG) extract. CK was not detected in unenzyme-treated RG extract, and in the single-step enzyme treatment, it was produced at less than 4.58 mg/g only in treatment group with Pyr-flo or Sumizyme AC (at 50 °C for 48 h). The highest yield of CK (14.32 mg/g) was obtained by Ultimase MFC treatment at 50 °C for 48 h after treatment with a mixture of Pyr-flo and Rapidase at 50 °C for 24 h. Total polyphenol, 2,2-diphenyl-1-picrylhydrazyl (DPPH), and 2,2-azinobis-(3-ethylbenzothiazoline-6-sulfonic acid)) (ABTS) radical scavenging activity were higher in BRG than in RG (p < 0.5). High-fat diet (HD) rat fed 1% BRG had significantly lower body weight, heart weight, fat pads (periosteal fat, epididymal fat), serum glucose levels, and hepatic triglyceride levels than those HD rat fed 1% RG (p < 0.05). In conclusion, the sequential enzymatic bioconversion was produces higher CK in RG root extract than single-step enzyme treatment.
Preparation of Self-healing Additives for Concrete via Miniemulsion Polymerization: Formulation and Production Challenges
Authors: Taheri Shima , Clark Simon Martin
Published: January 2021

Concrete structures undergo internal damage; this usually starts at the atomic level with defects that then grow and form cracks, which can propagate through the material. Here, a method of preparation of poly(methyl methacrylate) (PMMA) nanocapsules adhesive system via miniemulsion polymerization technique is reported, where MMA + DMA (resin + accelerator) and BPO (hardener) components are separately encapsulated by PMMA shells. The crack-healing potential of these nanocapsules was then investigated by embedding them into the mortar matrix. The prepared PMMA core–shell self-healing nanostructures survived the mixing and hardening processes, and the hardened mortar alkaline environment. The stress fields associated with propagating cracks (load‐induced cracking) broke the brittle/weak inert shell of these core–shell structures, resulted in releasing the healing agents to bridge the nascent and early-stage fractures (< 10 µm) in a short time. Long-term healing was achieved through the formation of polymorph calcite crystals in the presence of moisture and CO2, which improved the durability of mortar by filling the gaps. Formulation design (addition of chemical admixtures) and process parameters (blade design and mixing speed) were found to directly impact the uniform distribution of nanocapsules, the survival rate of nanocapsules, and the overall strength of the hardened concrete. The stepwise approach to formulate and fabricate a novel high-strength self-healing concrete system unlocks unique opportunities to design nanomaterials that safeguard the integrity of concrete structures.
The risk-value trade-off: price and brand information impact consumers’ intentions to purchase OTC drugs
Authors: Aufegger Lisa , Yanar Celine , Darzi Ara , Bicknell Colin
Published: January 2021

Background

European countries face fiscal pressure regarding the long-term sustainability of their healthcare system due to increasing levels of public health expenditures and mounting demographic pressures. The promotion of generic drugs is considered to be an efficient means to tackle these challenges; however, market diffusion remains slow. The aim of this study was to investigate the impact of price and brand cues on purchase intentions by means of Direct-to-Consumer (DTC) advertising, and to build on the market cue evaluation model by Dodd et al.

Methods

Participants rated purchase intentions on six DTC adverts varying in price and brand information, followed by self-reports on purchase intentions, attitudes towards generics, brand loyalty, price consciousness, as well as perceptions of quality, risk and value. Open-ended questions explored attitudes toward generic drugs.

Results

Brand information and purchase intentions were mediated by perceived risk and perceived quality, while price information influenced purchase intention through perceptions of quality, risk and value. Consumers’ purchase behaviour was furthermore  influenced by unawareness and misconceptions, past experiences, and advertising as a decision-making tool.

Conclusions

Advertisements, including price and brand information, are an important tool to improve consumers’ awareness of the availability of different OTC drugs. Practical and theoretical implications are discussed.
Development of space environment customized risk estimation for satellites (SECURES)
Authors: Nagatsuma Tsutomu , Nakamizo Aoi , Kubota Yasubumi , Nakamura Masao , Koga Kiyokazu , Miyoshi Yoshizumi , Matsumoto Haruhisa
Published: January 2021

Plasma variations in the geospace environment driven by solar wind–magnetosphere interactions are one of the major causes of satellite anomaly. To mitigate the effect of satellite anomaly, the risk of space weather disturbances predicted by space weather forecasting needs to be known in advance. However, the risk of satellite anomaly owing to space weather disturbances is not the same for all satellites, because the risk depends not only on the space environment itself but also on the design and materials of individual satellites. From the viewpoint of satellite operators, it is difficult to apply a general alert level of the space environment to the risk of individual satellites. To provide tailored space weather information, we have developed SECURES (Space Environment Customized Risk Estimation for Satellites) by combining models of the space environment and those of spacecraft charging. In SECURES, we focus on the risk of spacecraft charging (surface/internal) for geosynchronous satellites. For the risk estimation of surface charging, we have combined the global magnetosphere magnetohydrodynamics (MHD) model with the satellite surface charging models. For the risk estimation of internal charging, we have combined the radiation belt models with the satellite internal charging models. We have developed prototype products for both types of charging/electrostatic discharge (ESD). The development of SECURES and our achievements are introduced in this paper.
Lung ultrasound and computed tomography to monitor COVID-19 pneumonia in critically ill patients: a two-center prospective cohort study
Authors: Heldeweg Micah L. A. , Lopez Matta Jorge E. , Haaksma Mark E. , Smit Jasper M. , Elzo Kraemer Carlos V. , de Grooth Harm-Jan , de Jonge Evert , Meijboom Lilian J. , Heunks Leo M. A. , van Westerloo David J. , Tuinman Pieter R.
Published: January 2021

Background

Lung ultrasound can adequately monitor disease severity in pneumonia and acute respiratory distress syndrome. We hypothesize lung ultrasound can adequately monitor COVID-19 pneumonia in critically ill patients.

Methods

Adult patients with COVID-19 pneumonia admitted to the intensive care unit of two academic hospitals who underwent a 12-zone lung ultrasound and a chest CT examination were included. Baseline characteristics, and outcomes including composite endpoint death or ICU stay > 30 days were recorded. Lung ultrasound and CT images were quantified as a lung ultrasound score involvement index (LUSI) and CT severity involvement index (CTSI). Primary outcome was the correlation, agreement, and concordance between LUSI and CTSI. Secondary outcome was the association of LUSI and CTSI with the composite endpoints.

Results

We included 55 ultrasound examinations in 34 patients, which were 88% were male, with a mean age of 63 years and mean P/F ratio of 151. The correlation between LUSI and CTSI was strong (r = 0.795), with an overall 15% bias, and limits of agreement ranging − 40 to 9.7. Concordance between changes in sequentially measured LUSI and CTSI was 81%. In the univariate model, high involvement on LUSI and CTSI were associated with a composite endpoint. In the multivariate model, LUSI was the only remaining independent predictor.

Conclusions

Lung ultrasound can be used as an alternative for chest CT in monitoring COVID-19 pneumonia in critically ill patients as it can quantify pulmonary involvement, register changes over the course of the disease, and predict death or ICU stay > 30 days.

Trial registration: NTR, NL8584. Registered 01 May 2020—retrospectively registered,https://www.trialregister.nl/trial/8584
Combating an invisible enemy: the American military response to global pandemics
Authors: Dutton Lauren K. , Rhee Peter C. , Shin Alexander Y. , Ehrlichman Richard J. , Shemin Richard J.
Published: January 2021

The present moment is not the first time that America has found itself at war with a pathogen during a time of international conflict. Between crowded barracks at home and trenches abroad, wartime conditions helped enable the spread of influenza in the fall of 1918 during World War I such that an estimated 20–40% of U.S. military members were infected. While the coronavirus disease 2019 (COVID-19) pandemic is unparalleled for most of today’s population, it is essential to not view it as unprecedented lest the lessons of past pandemics and their effect on the American military be forgotten. This article provides a historical perspective on the effect of the most notable antecedent pandemic, the Spanish Influenza epidemic, on American forces with the goal of understanding the interrelationship of global pandemics and the military, highlighting the unique challenges of the current pandemic, and examining how the American military has fought back against pandemics both at home and abroad, both 100 years ago and today.
Investigating metalinguistic written corrective feedback focused on EFL learners’ discourse markers accuracy in mobile-mediated context
Authors: Pourdana Natasha , Nour Payam , Yousefi Fariba
Published: January 2021

Among a growing body of research that examined the contradictory role of written corrective feedback (WCF) in development of L2 writing accuracy, this study investigated the possible impact of focused metalinguistic WCF on discourse markers (DMs) in writing performance of an intact group of 42 Iranian English as a Foreign Language (EFL) learners over an eight-week period. In an authentic, situated, and personalized learning platform, giving and receiving WCF were made possible only through the mobile-mediated application of WhatsApp. Before participants wrote on selected elicitation topics, they had taken part in a 2004 version of Oxford Preliminary Test in order to be screened for their initial differences in writing performance. After receiving metalinguistic WCF on their scripts, participants were required to work on the coded feedback and try to eliminate the DM errors in their revised writing assignment. After collecting the scripts over an eight-week period, the content of written assignment was thematically analyzed using NVivo 21 Software for the additive, adversative, causal and temporal DMs, following Halliday and Hasan’s (Cohesion in English., 1976) typology. In a convergent mixed-methods design, the content analysis of the qualitative data showed a larger distribution of additive DM than adversative, causal, and temporal DMs in all participants’ written scripts. Exploring the possible impact of metalinguistic WCF on improving the DMs accuracy, analysis of the frequency count data with Statistical Package for the Social Sciences (SPSS) multivariate Chi-square test reported the fluctuation and unsystematic patterns of distribution for four types of DMs with no sign of significant long-term improvement in DMs accuracy after receiving metalinguistic WCF. These findings implied further research on practicing alternative WCF strategies focused on variety of error types in actual and virtual L2 writing environments.
Toxicity of tobacco Nicotiana tabacum Linnaeus (Solanaceae) leaf extracts to the rice weevil Sitophilus oryzae Linnaeus 1763 (Coleoptera: Curculionidae)
Authors: Kanmani Sekar , Kumar Lokesh , Raveen Rajasingh , Tennyson Samuel , Arivoli Subramanian , Jayakumar Manickkam
Published: January 2021

Background

Rice is the agricultural commodity with the third highest worldwide production and losses in rice storage due to insect pests may drastically affect the food availability for a large number of people. One of its serious pests in tropics is the “rice weevil”,Sitophilus oryzae. Although few effective fumigants are available, there is a global concern about environmental pollution, toxicity to non-target organisms, and pesticide residues. Botanicals are a promising source of pest control compounds as the pool of plants possessing insecticidal substances are enormous and have generated extraordinary interest in recent years as potential sources of natural insect control agents. The present study was conducted to determine the toxicity of tobacco (Nicotiana tabacum) leaf extracts as an alternative to synthetic insecticides in the management of rice weevils. The crude solvent leaf extracts ofN. tabacumwere analyzed for its phytochemical compounds via GC-MS and tested for its toxicity to the adults ofS. oryzaeat concentrations of 0.625, 1.25, 2.50, 5.00, 10.00, and 20.00 mg/L by Petri dish bioassay method. Adult mortality was calculated 24, 48, and 72 h after exposure.

Results

The constituent compounds in the chloroform and acetone revealed 13 compounds represented by benzene carboxylic acid ester, alkaloids, and steroids. The major compounds found in GC-MS analysis are nicotine, nicotinonitrile, nornicotine, nicotinic acid, neonicotine, cotinine, indole, farnesol, sclareol, 9,12-octadecadienoic acid, squalene, palmitic acid, and 15-tetracosenoic acid methyl ester. Overall assessment indicates that the chloroform and acetone extracts ofN. tabacumleaves exhibited the highest adulticidal activity againstS. oryzae. Their LD50values were 1.62, 0.64, and 0.48; 1.54, 0.83, and 0.48 mg/L after 24, 48, and 72 h of exposure respectively. In addition, the petroleum ether extract also indicated high adult mortality with LD50value of 0.53 mg/L only at 72 h.

Conclusions

The present research has documented its first report for the management of rice weevil using tobacco leaf extracts, and therefore on the basis of the results of the present study, it is highly encouraging to note that the use of tobacco leaf extracts with its excellent insecticidal activity owing to the action of nicotine would be economically feasible to alleviate the rice weevil problem.
Multi-detector computed tomography (MDCT) as a diagnostic tool in assessment of thoracic aortic anomalies in pediatric patients
Authors: Eltatawy Dawlat Nader , Elsharawy Fatma Anas , Elbarbary Aly Aly , Elsheikh Raghda Ghonimy , Badawy Manal Ezzat
Published: January 2021

Background

A wide variety of congenital thoracic aortic variants and pathological anomalies could be assessed recently in diagnostic and interventional radiology. Multi-detector computed tomography (MDCT) is one of the most important non-invasive diagnostic tools for their detection. The aim of the study was to evaluate role of MDCT scanning for diagnosis of thoracic aortic anatomic variants and diseases in pediatric patients.

Results

Thirty patients (15 male and 15 female), mean age (8.49 ± 20.29 months) were diagnosed with different thoracic aortic anomalies by MDCT then confirmed by surgical results. MDCT was more sensitive than echocardiography in detection of hypo plastic arch, vascular rings, interrupted aortic arch anomalies, and aortic coarctation. Both MDCT and echocardiography showed 100% sensitivity in their detection of TGA, TOF, and PDA. MDCT detected 6 cases of right-sided aortic arch while echo missed 2 cases. Different aortic arch branching patterns and coronary origin were better demonstrated by MDCT.

Conclusion

320-Multi-detector computed tomography is a reliable tool for optimal detection of thoracic aortic anomalies and preoperative planning.
Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02)
Authors: Wang Feng-Hua , Wei Xiao-Li , Feng Jifeng , Li Qi , Xu Nong , Hu Xi-Chun , Liao Wangjun , Jiang Yi , Lin Xiao-Yan , Zhang Qing-yuan , Yuan Xiang-Lin , Huang Hai-Xin , Chen Ye , Dai Guang-Hai , Shi Jian-Hua , Shen Lin , Yang Shu-Jun , Shu Yong-Qian , Liu Yun-Peng , Wang Weifeng , Wu Hai , Feng Hui , Yao Sheng , Xu Rui-Hua
Published: January 2021

PURPOSE

As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed to evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) inhibitor for recurrent or metastatic NPC (RM-NPC) refractory to standard chemotherapy.

PATIENTS AND METHODS

In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression or unacceptable toxicity. The primary end point was objective response rate (ORR). The secondary end points included safety, duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

RESULTS

Among all 190 patients, the ORR was 20.5% with median DOR 12.8 months, median PFS 1.9 months, and median OS 17.4 months. Among 92 patients who failed at least two lines of systemic chemotherapy, the ORR was 23.9%. The ORRs were 27.1% and 19.4% in PD-L1+ and PD-L1− patients, respectively ( P = .31). Patients with ≥ 50% decrease of plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better ORR than those with < 50% decrease, 48.3% versus 5.7% ( P = .0001). Tumor mutational burden had a median value of 0.95 muts/mega-base in the cohort and had no predictive value for response. Whole-exome sequencing results from 174 patients revealed that the patients with genomic amplification in 11q13 region or ETV6 genomic alterations had poor responses to toripalimab.

CONCLUSION

The POLARIS-02 study demonstrated a manageable safety profile and durable clinical response of toripalimab in patients with chemorefractory metastatic NPC. An early decrease in plasma EBV DNA copy number correlated with favorable response.
Dissecting dynamics and differences of selective pressures in the evolution of human pigmentation
Authors: Huang Xin , Wang Sijia , Jin Li , He Yungang
Published: January 2021

Human pigmentation is a highly diverse and complex trait among populations and has drawn particular attention from both academic and non-academic investigators for thousands of years. Previous studies detected selection signals in several human pigmentation genes, but few studies have integrated contribution from multiple genes to the evolution of human pigmentation. Moreover, none has quantified selective pressures on human pigmentation over epochs and between populations. Here, we dissect dynamics and differences of selective pressures during different periods and between distinct populations with new approaches. We use genotype data of 19 genes associated with human pigmentation from 17 publicly available datasets and obtain data for 2346 individuals of six representative population groups from across the world. Our results quantify the strength of natural selection on light pigmentation not only in modern Europeans (0.0259/generation) but also in proto-Eurasians (0.00650/generation). Our results also suggest that several derived alleles associated with human dark pigmentation may be under positive directional selection in some African populations. Our study provides the first attempt to quantitatively investigate the dynamics of selective pressures during different time periods in the evolution of human pigmentation.

This article has an associated First Person interview with the first author of the article.
Molecular mechanisms of neurodegeneration in the entorhinal cortex that underlie its selective vulnerability during the pathogenesis of Alzheimer's disease
Authors: Olajide Olayemi Joseph , Suvanto Marcus E. , Chapman Clifton Andrew
Published: January 2021

The entorhinal cortex (EC) is a vital component of the medial temporal lobe, and its contributions to cognitive processes and memory formation are supported through its extensive interconnections with the hippocampal formation. During the pathogenesis of Alzheimer's disease (AD), many of the earliest degenerative changes are seen within the EC. Neurodegeneration in the EC and hippocampus during AD has been clearly linked to impairments in memory and cognitive function, and a growing body of evidence indicates that molecular and functional neurodegeneration within the EC may play a primary role in cognitive decline in the early phases of AD. Defining the mechanisms underlying molecular neurodegeneration in the EC is crucial to determining its contributions to the pathogenesis of AD. Surprisingly few studies have focused on understanding the mechanisms of molecular neurodegeneration and selective vulnerability within the EC. However, there have been advancements indicating that early dysregulation of cellular and molecular signaling pathways in the EC involve neurodegenerative cascades including oxidative stress, neuroinflammation, glia activation, stress kinases activation, and neuronal loss. Dysfunction within the EC can impact the function of the hippocampus, which relies on entorhinal inputs, and further degeneration within the hippocampus can compound this effect, leading to severe cognitive disruption. This review assesses the molecular and cellular mechanisms underlying early degeneration in the EC during AD. These mechanisms may underlie the selective vulnerability of neuronal subpopulations in this brain region to the disease development and contribute both directly and indirectly to cognitive loss.

This paper has an associated Future Leader to Watch interview with the first author of the article.
Quantified growth of the human embryonic heart
Authors: Faber Jaeike W. , Hagoort Jaco , Moorman Antoon F. M. , Christoffels Vincent M. , Jensen Bjarke
Published: January 2021

The size and growth patterns of the components of the human embryonic heart have remained largely undefined. To provide these data, three-dimensional heart models were generated from immunohistochemically stained sections of ten human embryonic hearts ranging from Carnegie stage 10 to 23. Fifty-eight key structures were annotated and volumetrically assessed. Sizes of the septal foramina and atrioventricular canal opening were also measured. The heart grows exponentially throughout embryonic development. There was consistently less left than right atrial myocardium, and less right than left ventricular myocardium. We observed a later onset of trabeculation in the left atrium compared to the right. Morphometry showed that the rightward expansion of the atrioventricular canal starts in week 5. The septal foramina are less than 0.1 mm2 and are, therefore, much smaller than postnatal septal defects. This chronological, graphical atlas of the growth patterns of cardiac components in the human embryo provides quantified references for normal heart development. Thereby, this atlas may support early detection of cardiac malformations in the foetus.

This article has an associated First Person interview with the first author of the paper.
Auxin confers protection against ER stress in Caenorhabditis elegans
Authors: Bhoi Anupam , Palladino Francesca , Fabrizio Paola
Published: January 2021

Auxins are plant growth regulators that influence most aspects of plant development through complex mechanisms. The development of an auxin-inducible degradation (AID) system has enabled rapid, conditional protein depletion in yeast and cultured cells. More recently, the system was successfully adapted to Caenorhabditiselegans to achieve auxin-dependent degradation of targets in all tissues and developmental stages. Whether auxin treatment alone has an impact on nematode physiology is an open question. Here we show that indole-3-acetic acid (IAA), the auxin most commonly used to trigger AID in worms, functions through the conserved IRE-1/XBP-1 branch of the Unfolded Protein Response (UPR) to promote resistance to endoplasmic reticulum (ER) stress. Because the UPR not only plays a central role in restoring ER homeostasis, but also promotes lipid biosynthesis and regulates lifespan, we suggest that extreme caution should be exercised when using the AID system to study these and related processes.
SFPQ regulates the accumulation of RNA foci and dipeptide repeat proteins from the expanded repeat mutation in C9orf72
Authors: Malnar Mirjana , Rogelj Boris
Published: January 2021

The expanded GGGGCC repeat mutation in the C9orf72 gene is the most common genetic cause of the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). The expansion is transcribed to sense and antisense RNA, which form RNA foci and bind cellular proteins. This mechanism of action is considered cytotoxic. Translation of the expanded RNA transcripts also leads to the accumulation of toxic dipeptide repeat proteins (DPRs). The RNA-binding protein splicing factor proline and glutamine rich (SFPQ), which is being increasingly associated with ALS and FTD pathology, binds to sense RNA foci. Here, we show that SFPQ plays an important role in the C9orf72 mutation. Overexpression of SFPQ resulted in higher numbers of both sense and antisense RNA foci and DPRs in transfected human embryonic kidney (HEK) cells. Conversely, reduced SPFQ levels resulted in lower numbers of RNA foci and DPRs in both transfected HEK cells and C9orf72 mutation-positive patient-derived fibroblasts and lymphoblasts. Therefore, we have revealed a role of SFPQ in regulating the C9orf72 mutation that has implications for understanding and developing novel therapeutic targets for ALS and FTD.

This article has an associated First Person interview with the first author of the paper.
Automata: Professional Lives and the Time of the Contingent
Authors: Marinou Chryssa
Published: January 2021

Kostas Peroulis’s collection of short stories Automata (2015) consists of ten short stories that narrate the experience of ten different characters involved in differentkinds of labor. The stories’ characters constitute the book’s labor force and have afoothold in all sectors of economy: the primary sector (agriculture), the secondary sector (industrial production) and the tertiary sector (services, including sex work). The automatisation and repetition that define the work experience of Peroulis's unnamed characters also define their present while the context of the Greek crisis and its social and political effects lurk in the background. This essay reads the characters’relation to labour at a time of historical contingency that is well beyond the austerity measures and what is generally called the financial crisis. I argue that the stories map the experience of the contingent in contemporary Greece as Peroulis’s text focuses onthe minutiae of the characters’ professional lives. The details of their labour reveal the condition of contingency which becomes dominant in a literary text that, as this essay argues, returns to the subject, and thus, to the modern.
Contributors
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Published: January 2021

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Erica Jong’s Sappho’s Leap:(Re-)constructing Gender and Authorship through Sappho
Authors: Hauser Emily
Published: January 2021

For contemporary female authors, Sappho is a literary forebear who is both a model for women’s writing and a reminder of the ways in which women have been excluded from the literary canon. Poet and novelist Erica Jong takes up the challenge to gender and authorship posed by Sappho in her 2003 novel, Sappho’s Leap. Jong weaves Sappho’s poetry into her fiction to both complement the Sapphic tradition and to supplant it, proving that female poetry —and authorship— is alive and well, with Sappho continually mediated by and validating each subsequent writer in the female tradition. In addition, Jong’s emphasis on the authentic expression of sexual desire as a bridge to authorship transcends gender binaries, turning Sappho’s Leap into a study of authorship that is not confined to gender. This enables Jong to shift the debate away from the sense of burden placed on female authors post- Sappho and to transform her Sappho into a positive role model for all authors, turning the focus towards a poetics of passion and away from prescriptive assumptions of the relationship between gender and authorship.
A protocol to assess the risk of dementia among patients with coronary artery diseases using CAIDE score
Authors: Omi Fardina Rahman , Barua Lingkan , Banik Palash Chandra , Faruque Mithila
Published: January 2021

Introduction: The impact of coronary artery disease (CAD) on the later development of dementia is not well studied globally. Therefore, this study aims to determine the long-term risk of dementia using a mobile application-based tool in addition to elucidating the contributing factors among CAD patients. 

Protocol: This cross-sectional study collected data from 285 stable CAD patients admitted to the “Ibrahim Cardiac Hospital and Research Institute” for coronary revascularization from August 2019 to July 2020. The patients were recruited using a convenient sampling technique due to economic and logistical issues. Data were collected through a face-to-face interview using a pretested semi-structured questionnaire. Physical parameters (blood pressure and anthropometry) were measured while maintaining the adequate privacy of the patients. The biochemical parameters analyzed by the hospital lab were also collected. The next phase of this study involves the use of a mobile application-based tool, “The Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE)” risk score, to determine the risk factors associated with dementia. In addition, a descriptive statistical and inferential analysis will also be performed to determine the key contributing risk factors linked to the development of dementia.

Ethics and dissemination: The study has been reviewed and approved by the Ethical Review Committee of Bangladesh University of Health Sciences. The results will be actively disseminated through peer-reviewed journals, conference presentations, social media, online news portal, the internet, and various community/stakeholder engagement activities.

Conclusion: As a baseline study of the country, this study will fill a key knowledge gap in the pathway to the development of better interventions for dementia in Bangladesh. Outcomes from this study will also help with raising awareness on the association of mental health-related issues with cardiovascular diseases so that an improved cardiac rehabilitation program can be implemented in Bangladesh.