bluuebunny/crossref_metadata_2025 huggingface dataset:
The Role of Mitochondria in Optic Atrophy With Autosomal Inheritance
Authors: Strachan Elin L. , Mac White-Begg Delphi , Crean John , Reynolds Alison L. , Kennedy Breandán N. , O’Sullivan Niamh C.
Published: November 2021

Optic atrophy (OA) with autosomal inheritance is a form of optic neuropathy characterized by the progressive and irreversible loss of vision. In some cases, this is accompanied by additional, typically neurological, extra-ocular symptoms. Underlying the loss of vision is the specific degeneration of the retinal ganglion cells (RGCs) which form the optic nerve. Whilst autosomal OA is genetically heterogenous, all currently identified causative genes appear to be associated with mitochondrial organization and function. However, it is unclear why RGCs are particularly vulnerable to mitochondrial aberration. Despite the relatively high prevalence of this disorder, there are currently no approved treatments. Combined with the lack of knowledge concerning the mechanisms through which aberrant mitochondrial function leads to RGC death, there remains a clear need for further research to identify the underlying mechanisms and develop treatments for this condition. This review summarizes the genes known to be causative of autosomal OA and the mitochondrial dysfunction caused by pathogenic mutations. Furthermore, we discuss the suitability of available in vivo models for autosomal OA with regards to both treatment development and furthering the understanding of autosomal OA pathology.
Effect of Noradrenaline on the Facial Stimulation-Evoked Mossy Fiber-Granule Cell Synaptic Transmission in Mouse Cerebellar Cortex
Authors: Li Bing-Xue , Jin Hua , Zhang Guang-Jian , Cui Li-Na , Chu Chun-Ping , Qiu De-Lai
Published: November 2021

Noradrenaline is an important neuromodulator in the cerebellum. We previously found that noradrenaline depressed cerebellar Purkinje cell activity and climbing fiber–Purkinje cell synaptic transmission in vivo in mice. In this study, we investigated the effect of noradrenaline on the facial stimulation-evoked cerebellar cortical mossy fiber–granule cell synaptic transmission in urethane-anesthetized mice. In the presence of a γ-aminobutyrateA (GABAA) receptor antagonist, air-puff stimulation of the ipsilateral whisker pad evoked mossy fiber–granule cell synaptic transmission in the cerebellar granular layer, which expressed stimulus onset response, N1 and stimulus offset response, N2. Cerebellar surface perfusion of 25 μM noradrenaline induced decreases in the amplitude and area under the curve of N1 and N2, accompanied by an increase in the N2/N1 ratio. In the presence of a GABAA receptor blocker, noradrenaline induced a concentration-dependent decrease in the amplitude of N1, with a half-maximal inhibitory concentration of 25.45 μM. The noradrenaline-induced depression of the facial stimulation-evoked mossy fiber–granule cell synaptic transmission was reversed by additional application of an alpha-adrenergic receptor antagonist or an alpha-2 adrenergic receptor antagonist, but not by a beta-adrenergic receptor antagonist or an alpha-1 adrenergic receptor antagonist. Moreover, application of an alpha-2 adrenergic receptor agonist, UK14304, significantly decreased the synaptic response and prevented the noradrenaline-induced depression. Our results indicate that noradrenaline depresses facial stimulation-evoked mossy fiber–granule cell synaptic transmission via the alpha-2 adrenergic receptor in vivo in mice, suggesting that noradrenaline regulates sensory information integration and synaptic transmission in the cerebellar cortical granular layer.
Cortical Hub for Flavor Sensation in Rodents
Authors: Samuelsen Chad L. , Vincis Roberto
Published: November 2021

The experience of eating is inherently multimodal, combining intraoral gustatory, olfactory, and somatosensory signals into a single percept called flavor. As foods and beverages enter the mouth, movements associated with chewing and swallowing activate somatosensory receptors in the oral cavity, dissolve tastants in the saliva to activate taste receptors, and release volatile odorant molecules to retronasally activate olfactory receptors in the nasal epithelium. Human studies indicate that sensory cortical areas are important for intraoral multimodal processing, yet their circuit-level mechanisms remain unclear. Animal models allow for detailed analyses of neural circuits due to the large number of molecular tools available for tracing and neuronal manipulations. In this review, we concentrate on the anatomical and neurophysiological evidence from rodent models toward a better understanding of the circuit-level mechanisms underlying the cortical processing of flavor. While more work is needed, the emerging view pertaining to the multimodal processing of food and beverages is that the piriform, gustatory, and somatosensory cortical regions do not function solely as independent areas. Rather they act as an intraoral cortical hub, simultaneously receiving and processing multimodal sensory information from the mouth to produce the rich and complex flavor experience that guides consummatory behavior.
Effects of Early vs. Late Time-Restricted Eating on Cardiometabolic Health, Inflammation, and Sleep in Overweight and Obese Women: A Study Protocol for the ChronoFast Trial
Authors: Peters Beeke , Koppold-Liebscher Daniela A. , Schuppelius Bettina , Steckhan Nico , Pfeiffer Andreas F. H. , Kramer Achim , Michalsen Andreas , Pivovarova-Ramich Olga
Published: November 2021

Background: Time-restricted eating is a promising dietary strategy for weight loss, glucose and lipid metabolism improvements, and overall well-being. However, human studies demonstrated contradictory results for the restriction of food intake to the beginning (early TRE, eTRE) or to the end of the day (late TRE, lTRE) suggesting that more carefully controlled studies are needed.

Objective: The aim of the ChronoFast trial study is to determine whether eTRE or lTRE is a better dietary approach to improve cardiometabolic health upon minimized calorie deficits and nearly stable body weight.

Methods: Here, we present the study protocol of the randomized cross-over ChronoFast clinical trial comparing effects of 2 week eTRE (8:00 to 16:00 h) and lTRE (13:00 to 21:00 h) on insulin sensitivity and other glycemic traits, blood lipids, inflammation, and sleep quality in 30 women with overweight or obesity and increased risk of type 2 diabetes. To ensure timely compliance and unchanged dietary composition, and to minimize possible calorie deficits, real-time monitoring of dietary intake and body weight using a smartphone application, and extensive nutritional counseling are performed. Continuous glucose monitoring, oral glucose tolerance test, 24 h activity tracking, questionnaires, and gene expression analysis in adipose tissue and blood monocytes will be used for assessment of study outcomes.

Discussion: The trial will determine whether eTRE or lTRE is more effective to improve cardiometabolic health, elucidate underlying mechanisms, and contribute to the development of recommendations for medical practice and the wider population.

Clinical Trial Registration:www.ClinicalTrials.gov, Identifier [NCT04351672]
Consumption of Free Sugar Predicts Nutrient Intake of Saudi Children
Authors: Mumena Walaa Abdullah
Published: November 2021

Data concerning the association between free sugar intake and nutrient intake in children in the Middle East are not available. This study aimed to explore the association between the consumption of free sugar and nutrient intake among Saudi children. A cross-sectional study included 424 Saudi children ages between 6 and 12 years old and their mothers. An online survey collected sociodemographic data from mothers. Trained data collector personal contacted mothers to arrange for a phone interview in order to collect 24-h dietary recall to assess the dietary intake of children. Only 0.90% of children consumed free sugar within the recent recommendation of the World Health Organization (WHO) of <5% of total energy intake, whereas 10.6% of children consumed free sugar <10% of total energy intake. The percentage of free sugar intake was negatively associated with total energy intake. Multiple linear regression analysis of free sugar consumption and nutrient intake adjusted for children's age and sex indicated that a higher percentage of free sugar intake significantly predicted lower intake of saturated fat, fiber, sodium, potassium, calcium, iron, zinc, and vitamin B12. Excessive intake of free sugar predicted a lower intake of many essential nutrients. Interventions that aim to reduce the intake of free sugar are urgently needed in order to improve diet of growing children. Future research to explore top food sources of free sugar is needed to establish effective interventions that aim to limit free sugar intake among children.
Case Report: Dermoscopic, High-Frequency Ultrasound, Contrast-Enhanced Ultrasound Appearances and Special Treatment of a Patient With Syringoid Eccrine Carcinoma on the Chest
Authors: Zhang Jing , Liu Xun , Zheng Mo , Yin Jing , Xing Weibin
Published: November 2021

This article aims to explain the use of a variety of noninvasive of minimally invasive examinations to obtain reliable diagnostic clues. The choice of treatment methods and repair techniques for wound defects are also critical in terms of the prognosis. Here, we describe the case of a 53-year-old male patient who visited our dermatology clinic due to a red plaque on the inner side of his left nipple without any symptoms for more than 30 years. He was given dermoscopy, high-frequency ultrasound (HFUS), Color Doppler flow imaging (CDFI), and contrast-enhanced ultrasound (CEUS) examinations. Currently, there are no literatures on these auxiliary examinations for this disease. Dermoscopy revealed that there were abundant blood vessels on the periphery of the skin lesion with obvious dilation. HFUS revealed an inhomegeneous hypoechoic solid mass in the dermis with clear borders and irregular shape. CDFI indicated that there are abundant blood flow signals in the periphery and central of the tumor. CEUS showed a mixed inhomogeneous, grid-like high-enhancement pattern. Based on the above auxiliary findings, the possibility of malignant lesion was suspected. Therefore, the patient was given a pathological examination, which showed that many luminal structures of the dermis layer were embedded in the hyperplastic fibrous tissue. The atypical cells were not obvious but showed an infiltrating growth pattern. Immunohistochemistry showed positive reaction for cytokeratin 7 (CK7), epithelial membrane antigen (EMA), and carcinoembryonic antigen (CEA) and a weak positive results was obtained for S-100. There was also a negative result for CK20, gross cystic disease fluid protein 15 (GCDFP-15), and P63. As a result, the patient was diagnosed with “syringoid eccrine carcinoma.” The treatment was surgical excision. Mohs microsurgery was combined with the looped, broad, and deep-buried suturing technique (LBD tension-reduced suturing technique). This technique directly sutures the wound instead of carrying out traditional skin grafting or flap transfer. The postoperative follow-up results were satisfactory as no obvious keloid formed on the wound during the follow-ups. In conclusion, ultrasound is greatly advantageous in tumor morphology and hemodynamics. It orients the therapeutic management and assesses the therapeutic efficacy and the tumoral prognosis. In surgical treatments, a less-traumatic operation should be selected to reduce the patient’s pain.
Near-Infrared Imaging With Indocyanine Green for the Treatment of Endometriosis: Results From the Gre-Endo Trial
Authors: Turco Luigi Carlo , Vizzielli Giuseppe , Vargiu Virginia , Gueli Alletti Salvatore , De Ninno Maria , Ferrandina Gabriella , Pedone Anchora Luigi , Scambia Giovanni , Cosentino Francesco
Published: November 2021

Introduction

A current challenge for endometriosis surgery is to correctly identify the localizations of disease, especially when small or hidden (occult endometriosis), and to exactly define their real extension. The use of near-infrared radiation imaging (NIR) after injection of indocyanine green (ICG) represents one of the most encouraging method. The aim of this study is to assess the diagnostic value of NIR-ICG imaging in the surgical treatment of endometriosis compared with the standard of treatment.

Material and Methods

The Gre-Endo trial is a prospective, single-arm study (NCT03332004). After exploring the operatory field using the white light (WL) mode, patients were injected with ICG and then observed in NIR mode. All suspected areas were classified and chronicled according to lesions visualized only in WL, NIR-ICG, or in the combination of both. Lesion not visualized in WL was considered as suspect occult lesion (s-OcL). In addition, a random control biopsy from an apparent negative peritoneum visualized in WL and NIR-ICG imaging was taken for all patients (control cases). All lesions removed were considered “suspect endometriosis” until pathology.

Results

Fifty-one patients were enrolled between January 2016 and October 2019. A total of 240 suspected lesions have been identified with both methods (WL + NIR-ICG). Two hundred and seven (86.2%) lesions out of the overall 240 were visualized with WL imaging, and 200 were confirmed to be pathologic (true positive for WL). The remaining 33/240 (13.75%) (false negative for WL) lesions were identified only with NIR-ICG imaging and collected as s-OcL. All 33 s-OcLs removed were confirmed to be pathologic (c-OcL = 100%). NIR-ICG vision showed PPV of 98.5%, NPV of 87.1%, Se of 87%, and Sp of 98.5%, confirming that this kind of imaging is an excellent diagnostic and screening test (p = 0.001 and p = 0.835, according to McNemar’s and Cohen’s kappa tests, respectively).

Conclusions

The use of NIR-ICG vision alone and combined with WL showed good results in intraoperative detection rate and fluorescence-guided surgery of endometriosis. Furthermore, NIR-ICG allowed surgeons to remove occult lesions that otherwise would remain, leading to possible greater postoperative pain and a higher risk of persistence and relapse.
Research Progress on the Role of Regulatory T Cell in Tumor Microenvironment in the Treatment of Breast Cancer
Authors: Liu Jianyu , Wang Xueying , Deng Yuhan , Yu Xin , Wang Hongbin , Li Zhigao
Published: November 2021

The tumor microenvironment (TME) is a complex ecosystem comprised of cancer cells, stromal cells, and immune cells. Analysis of the composition of TME is essential to assess the prognosis of patients with breast cancer (BC) and the efficacy of different regimes. Treg plays a crucial role in the microenvironment of breast cancer subtypes, and its function contributes to the development and progression of BC by suppressing anti-tumor immunity directly or indirectly through multiple mechanisms. In addition, conventional treatments, such as anthracycline-based neoadjuvant chemotherapy, and neo-therapies, such as immune-checkpoint blockades, have a significant impact on the absence of Tregs in BC TME, thus gaining additional anti-tumor effect to some extent. Strikingly, Treg in BC TME revealed the predicted efficacy of some therapeutic strategies. All these results suggest that we can manipulate the abundance of Treg to achieve the ultimate effect of both conventional and novel treatments. In this review, we discuss new insights into the characteristics of Treg in BC TME, the impact of different regiments on Treg, and the possibilities of Treg as a predictive marker of efficacy for certain treatments.
Long-Term Outcomes in Real Life of Lumacaftor–Ivacaftor Treatment in Adolescents With Cystic Fibrosis
Authors: Bui Stéphanie , Masson Alexandra , Enaud Raphaël , Roditis Léa , Dournes Gaël , Galode François , Collet Cyrielle , Mas Emmanuel , Languepin Jeanne , Fayon Michael , Beaufils Fabien , Mittaine Marie
Published: November 2021

Background: The combination of the CFTR corrector lumacaftor (LUM) and potentiator ivacaftor (IVA) has been labeled in France since 2015 for F508del homozygote cystic fibrosis (CF) patients over 12 years. In this real-life study, we aimed (i) to compare the changes in lung function, clinical (e.g., body mass index and pulmonary exacerbations) and radiological parameters, and in sweat chloride concentration before and after initiation of LUM/IVA treatment; (ii) to identify factors associated with response to treatment; and (iii) to assess the tolerance to treatment.

Materials and Methods: In this tri-center, non-interventional, and observational cohort study, children (12–18 years old) were assessed prospectively during the 2 years of therapy, and retrospectively during the 2 years preceding treatment. Data collected and analyzed for the study were exclusively extracted from the medical electronic system records of the patients.

Results: Forty adolescents aged 12.0–17.4 years at LUM/IVA initiation were included. The lung function decreased significantly during and prior to treatment and increased after LUM/IVA initiation, becoming significant after 2 years of treatment. LUM/IVA significantly improved the BMI Z-score and sweat chloride concentration. By contrast, there was no significant change in exacerbation rates, antibiotic use, or CT scan scores. Age at LUM/IVA initiation was lower in good responders and associated with greater ppFEV1 change during the 2 years of treatment. LUM/IVA was well-tolerated.

Conclusion: In F508del homozygote adolescents, real-life long-term LUM/IVA improved the ppFEV1 trajectory, particularly in the youngest patients, nutritional status, and sweat chloride concentration but not exacerbation rates or radiological scores. LUM/IVA was generally well-tolerated and safe.
Blood Pressure Tracking From Childhood to Adulthood
Authors: Azegami Tatsuhiko , Uchida Keiko , Tokumura Mitsuaki , Mori Masaaki
Published: November 2021

Hypertension is the most common non-communicable disease among adults and is the most important modifiable risk factor for premature cardiovascular disease. The increasing worldwide burden of hypertension is a major global health issue. Early prevention with lifestyle modification or pharmaceutical treatment reduces the incidence of hypertension and the risk of subsequent cardiovascular disease. Therefore, identification of young persons at risk for hypertension has the obvious benefit of providing a chance for early intervention. Previous studies have demonstrated the positive association of elevated childhood blood pressure with hypertension in adulthood. Accumulated evidence also indicates the possibility that elevated pediatric blood pressure is associated with increased risk of future cardiovascular disease. In this article, we review the tracking of blood pressure from childhood to adulthood and emphasize the importance of pediatric blood pressure monitoring and control for predicting and preventing adult hypertension and cardiovascular disease.
Polygoni Multiflori Radix Praeparata Ethanol Extract Exerts a Protective Effect Against High-Fat Diet Induced Non-Alcoholic Fatty Liver Disease in Mice by Remodeling Intestinal Microbial Structure and Maintaining Metabolic Homeostasis of Bile Acids
Authors: Dai Xuyang , He Linfeng , Hu Naihua , Guo Chaocheng , Zhou Mengting , Zhao Xingtao , Wang Cheng , Gong Lihong , Ma Cheng , Xue Xinyan , Li Yunxia
Published: November 2021

In the prescription of Traditional Chinese Medicine for lipid metabolism, Polygoni Multiflori Radix Preparata (ZhiHeShouWu, RPMP) was widely used. In recent years, RPMP ethanol extract has been reported for the treatment of non-alcoholic fatty liver disease (NAFLD). However, the role of RPMP ethanol extract in the treatment of NAFLD has not been fully elucidated. Therefore, we examined the optimal therapeutic dose of RPMP ethanol extracts. Afterward, a mouse model of non-alcoholic fatty liver induced by a high-fat diet (HFD) was treated with RPMP ethanol extract to further evaluate the mechanism of action of RPMP ethanol extract treatment. And the serum lipid metabolism indexes and liver function indexes showed that the RPMP ethanol extract in the 1.35 g/kg dose group exhibited better therapeutic effects than the 2.70 g/kg dose group. Meanwhile, RPMP ethanol extract can regulate the biochemical indicators of serum and liver to normal levels, and effectively reduce liver steatosis and lipid deposition. RPMP ethanol extract treatment restored HFD-induced disruption of the compositional structure of the intestinal microbial (IM) and bile acids (BAs) pools. And restore the reduced expression of intestinal barrier-related genes caused by HFD administration, which also effectively regulates the expression of genes related to the metabolism of BAs in mice. Thus, RPMP ethanol extract can effectively improve the abnormal lipid metabolism and hepatic lipid accumulation caused by HFD, which may be related to the regulation of IM composition, maintenance of intestinal barrier function, and normal cholesterol metabolism in the body.
Research Progress on Terahertz Quantum-Well Photodetector and Its Application
Authors: Shao Dixiang , Fu Zhanglong , Tan Zhiyong , Wang Chang , Qiu Fucheng , Gu Liangliang , Wan Wenjian , Cao Juncheng
Published: November 2021

Compared with other typical terahertz (THz) detectors, the quantum-well photodetector (QWP) has the advantages of high detection sensitivity, fast response, mature fabrication, small size, and easy integration. Therefore, it is suitable for high-speed detection and imaging applications at the THz band. Researchers, both domestic and overseas, have systematically studied material design and device performance of the THz QWP. The design of the device is such that the peak frequency error is within 8%, the maximum peak responsibility is 5.5 A/W, the fastest response speed is 6.2 GHz, the best noise equivalent power is ∼10−13 W/Hz0.5, and the spectrum range is 2.5–6.5 THz. In this article, firstly the basic principles and theoretical calculations of the THz QWP are described, and then the research progress of the THz QWP in our research group at imaging and communication is reviewed, which looks forward to its future development.
Feasibility of Data-Driven, Model-Free Quantitative MRI Protocol Design: Application to Brain and Prostate Diffusion-Relaxation Imaging
Authors: Grussu Francesco , Blumberg Stefano B. , Battiston Marco , Kakkar Lebina S. , Lin Hongxiang , Ianuş Andrada , Schneider Torben , Singh Saurabh , Bourne Roger , Punwani Shonit , Atkinson David , Gandini Wheeler-Kingshott Claudia A. M. , Panagiotaki Eleftheria , Mertzanidou Thomy , Alexander Daniel C.
Published: November 2021

Purpose: We investigate the feasibility of data-driven, model-free quantitative MRI (qMRI) protocol design on in vivo brain and prostate diffusion-relaxation imaging (DRI).

Methods: We select subsets of measurements within lengthy pilot scans, without identifying tissue parameters for which to optimise for. We use the “select and retrieve via direct upsampling” (SARDU-Net) algorithm, made of a selector, identifying measurement subsets, and a predictor, estimating fully-sampled signals from the subsets. We implement both using artificial neural networks, which are trained jointly end-to-end. We deploy the algorithm on brain (32 diffusion-/T1-weightings) and prostate (16 diffusion-/T2-weightings) DRI scans acquired on three healthy volunteers on two separate 3T Philips systems each. We used SARDU-Net to identify sub-protocols of fixed size, assessing reproducibility and testing sub-protocols for their potential to inform multi-contrast analyses via the T1-weighted spherical mean diffusion tensor (T1-SMDT, brain) and hybrid multi-dimensional MRI (HM-MRI, prostate) models, for which sub-protocol selection was not optimised explicitly.

Results: In both brain and prostate, SARDU-Net identifies sub-protocols that maximise information content in a reproducible manner across training instantiations using a small number of pilot scans. The sub-protocols support T1-SMDT and HM-MRI multi-contrast modelling for which they were not optimised explicitly, providing signal quality-of-fit in the top 5% against extensive sub-protocol comparisons.

Conclusions: Identifying economical but informative qMRI protocols from subsets of rich pilot scans is feasible and potentially useful in acquisition-time-sensitive applications in which there is not a qMRI model of choice. SARDU-Net is demonstrated to be a robust algorithm for data-driven, model-free protocol design.
Controlling Citrus Huanglongbing: Green Sustainable Development Route Is the Future
Authors: Li Xue , Ruan Huaqin , Zhou Chengqian , Meng Xiangchun , Chen Wenli
Published: November 2021

Huanglongbing (HLB) is the most severe bacterial disease of citrus crops caused by Candidatus Liberibacter spp. It causes a reduction in fruit yield, poor fruit quality, and even plants death. Due to the lack of effective medicine, HLB is also called citrus “AIDS.” Currently, it is essential for the prevention and control of HLB to use antibiotics and pesticides while reducing the spread of HLB by cultivating pathogen-free seedlings, removing disease trees, and killing Asian citrus psyllid (ACP). New compounds [e.g., antimicrobial peptides (AMPs) and nanoemulsions] with higher effectiveness and less toxicity were also found and they have made significant achievements. However, further evaluation is required before these new antimicrobial agents can be used commercially. In this review, we mainly introduced the current strategies from the aspects of physical, chemical, and biological and discussed their environmental impacts. We also proposed a green and ecological strategy for controlling HLB basing on the existing methods and previous research results.
Online User Information Sharing and Government Pandemic Prevention and Control Strategies-Based on Evolutionary Game Model
Authors: Xiao Yao , Xu Wanting , Zeng Shouzhen , Peng Qiao
Published: November 2021

Background: The sharing and utilization of online users' information has become an important resource for governments to manage COVID-19; however, it also involves the risk of leakage of users' personal information. Online users' sharing decisions regarding personal information and the government's COVID-19 prevention and control decisions influence each other and jointly determine the efficiency of COVID-19 control and prevention.

Method: Using the evolutionary game models, this paper examines the behavioral patterns of online users and governments with regard to the sharing and disclosure of COVID-19 information for its prevention and control.

Results: This paper deduce the reasons and solutions underlying the contradiction between the privacy risks faced by online users in sharing information and COVID-19 prevention and control efforts. The inconsistency between individual and collective rationality is the root cause of the inefficiency of COVID-19 prevention and control.

Conclusions: The reconciliation of privacy protection with COVID-19 prevention and control efficiency can be achieved by providing guidance and incentives to modulate internet users' behavioral expectations.
Gene Therapy Knowledge and Attitude Among Healthcare Professionals: A Cross-Sectional Study
Authors: AlRasheed Maha M. , AlAli Hatoon , Alsuwaid Abdulrahman F. , Khalaf Suhail , Ata Sondus I. , BinDhim Nasser F. , Bakheet Dana , Khurshid Fowad , Alhawassi Tariq M.
Published: November 2021

This study aimed to assess healthcare professionals' knowledge, attitudes, and concerns toward gene therapy in Saudi Arabia. We conducted an online cross-sectional survey via convenience sampling during the period from December 2018 to March 2019. A total of 419 (358 pharmacists and 61 physicians) responded to our questionnaire. Three hundred and nine (73.7%) were male, and the mean (±SD) age of 32.0 ± 7.7 years. The mean knowledge scores of all participants, pharmacists, and physicians were 3.8 ± 1.9, 3.8 ± 1.9, and 3.7 ± 1.9, respectively (P = 0.73). Higher knowledge score was associated with younger age (Coefficient: −0.03; P = 0.02), male (Coefficient: 0.57; P = 0.01), master's degree (Coefficient: 0.93; P = 0.003) and Ph.D. holders (Coefficient: 1.10; P = 0.01), and participants graduated from Canada (Coefficient: 2.10; P = 0.01).Moreover, about half of the respondents (55%) were concerned about gene therapy, and genetics training at college was considered the best gene therapy education method by 69.4%. Attitude score was not significantly associated with the profession (P = 0.88) but positively correlated with the knowledge score (rho= 0.4; P < 0.001). In conclusion, pharmacists and physicians showed limited knowledge with a positive attitude toward gene therapy. Therefore, educational programs on gene therapy need to be considered, focusing primarily on the safety, and social acceptance of such new therapeutic management.
Real Time Estimator to Perform Targeted Biopsies With a Free-Wrist Robot Despite Large Deformations of the Insertion Orifice
Authors: Chalard Rémi , Fazel Afshin , Vitrani Marie-Aude
Published: November 2021

In the context of keyhole surgery, and more particularly of uterine biopsy, the fine automatic movements of a surgical instrument held by a robot with 3 active DOF’s require an exact knowledge of the point of rotation of the instrument. However, this center of rotation is not fixed and moves during an examination. This paper deals with a new method of detecting and updating the interaction matrix linking the movements of the robot with the surgical instrument. This is based on the method of updating the Jacobian matrix which is named the “Broyden method”. It is able to take into account body tissue deformations in real time in order to improve the pointing task for automatic movements of a surgical instrument in an unknown environment.
Genetic Profile of Adenomatoid Odontogenic Tumor and Ameloblastoma. A Systematic Review
Authors: Marín Constanza , Niklander Sven E. , Martínez-Flores René
Published: November 2021

Purpose: To perform a comprehensive and systematic critical appraisal of the genetic alterations reported to be present in adenomatoid odontogenic tumor (AOT) compared to ameloblastoma (AM), to aid in the understanding in their development and different behavior.

Methods: An electronic search was conducted in PubMed, Scopus, and Web of Science during March 2021. Eligibility criteria included publications on humans which included genetic analysis of AOT or AM.

Results: A total of 43 articles reporting 59 AOTs and 680 AMs were included. Different genomic techniques were used, including whole-exome sequencing, direct sequencing, targeted next-generation sequencing panels and TaqMan allele-specific qPCR. Somatic mutations affecting KRAS were identified in 75.9% of all AOTs, mainly G12V; whereas a 71% of the AMs harbored BRAF mutations, mainly V600E.

Conclusions: The available genetic data reports that AOTs and AM harbor somatic mutations in well-known oncogenes, being KRAS G12V/R and BRAFV600E mutations the most common, respectively. The relatively high frequency of ameloblastoma compared to other odontogenic tumors, such as AOT, has facilitated the performance of different sequencing techniques, allowing the discovery of different mutational signatures. On the contrary, the low frequency of AOTs is an important limitation for this. The number of studies that have a assessed the genetic landscape of AOT is still very limited, not providing enough evidence to draw a conclusion regarding the relationship between the genomic alterations and its clinical behavior. Thus, the presence of other mutational signatures with clinical impact, co-occurring with background KRAS mutations or in wild-type KRAS cases, cannot be ruled out. Since BRAF and RAS are in the same MAPK pathway, it is interesting that ameloblastomas, frequently associated with BRAFV600E mutation have aggressive clinical behavior, but in contrast, AOTs, frequently associated with RAS mutations have indolent behavior. Functional studies might be required to solve this question.
Gradient Cleaning Method of Potato Based on Multi-Step Operation of Dry-Cleaning and Wet Cleaning
Authors: Yang Hongguang , Yan Jianchun , Wei Hai , Wu Huichang , Wang Shenying , Ji Longlong , Xu Xiaowei , Xie Huanxiong
Published: November 2021

In view of the poor effectiveness of existing potato cleaning methods in China and reflecting the findings of a research analysis of basic sizes and types of impurities on potato tubers, a gradient cleaning method for potato based on a multi-step dry-cleaning and wet cleaning operation was proposed. The method mainly consists of dry-cleaning and wet cleaning. The dry-cleaning stage, which combines vibration and brushing, could effectively remove impurities such as residual rhizomes, peeled potato skin, and large pieces of soil and crushed stone from the surface of potato tubers. The wet cleaning stage adopts the gradient cleaning method of pre-cleaning, rough cleaning and fine cleaning, which could further remove soil and crushed stone attached to the surface and hidden in the sprout eyes of potato tubers. The optimal parameter combination for the gradient cleaning method was determined as follows. The potato feeding amount was 3 t/h, the speed of the rubber chain rod mechanism was 25 r/min, the speed of the first and third brush roller was 40 r/min, the speed of the second and fourth brush roller was 56 r/min, the moving speed of the immersion mechanism conveying net chain was 0.04 m/s, the speed of the brush roller in the high pressure spray and brush roller combination mechanism was 40 r/min, the ultrasonic power was 1200 W, the ultrasonic frequency was 33 kHz, the bubble intensity was 300 L/min, and the moving speed of the conveying net chain in the ultrasonic and bubble combination mechanism was 0.05 m/s. Taking the impurity removal rate and damage rate of potato tuber as the test indexes, a potato cleaning performance test was carried out under the optimal parameters combination. The results showed that the average impurity removal rate and damage rate of potato tubers were 99.05% and 2.48%, respectively. Additionally, the operational performance fully met the requirements for potato cleaning. This study provides a new method for potato cleaning in China and can also provide a reference for cleaning other root and tuber crops.
Ammonium Fertilizer Reduces Nitrous Oxide Emission Compared to Nitrate Fertilizer While Yielding Equally in a Temperate Grassland
Authors: Rahman Niharika , Forrestal Patrick J.
Published: November 2021

Emissions of nitrous oxide (N2O), a potent greenhouse gas, are a challenge associated with application of nitrogen (N) fertilizers to soil. However, N source selection can play a role in reducing these emissions. Nitrous oxide emissions were measured from ammonium (ammonium sulfate) and nitrate (calcium nitrate) fertilizers over one year in temperate grassland using the closed static chamber method. Nitrogen was applied at a system representative rate of 220 kg ha−1 y−1 in six split applications. Cumulative annual N2O-N emissions were 0.29 kg ha−1 for the control, 1.07 kg ha−1 for the ammonium fertilizer and significantly higher at 2.54 kg ha−1 for the nitrate fertilizer. The annual emission factor (EF) for the ammonium fertilizer was 0.35% vs 1.02% for the nitrate fertilizer, a 66% reduction in the EF for ammonium vs nitrate and a 2.9 times higher EF for nitrate compared with ammonium. No difference in grass yield or N uptake was detected between fertilizers. This study shows that an ammonium fertilizer produces the same yield and N efficiency as a nitrate fertilizer with lower N2O emissions. The results also demonstrate that the nitrate portion of fertilizers is a key factor in N2O emissions in temperate grassland. This work is the first of its kind detailing the annual EF of both a solely ammonium-N and a solely nitrate-N fertilizer we could find.
Calibration of the Discrete Element Method Parameters in Living Juvenile Manila Clam (Ruditapes philippinarum) and Seeding Verification
Authors: Li Hangqi , Zhang Guochen , Li Xiuchen , Zhang Hanbing , Zhang Qian , Liu Wenbo , Mu Gang
Published: November 2021

The Manila Clam is an important economic shellfish in China’s seafood industry. In order to improve the design of juvenile Manila Clam seeding equipment, a juvenile clam discrete element method (DEM) particle shape was established, which is based on 3D scanning and EDEM software. The DEM contact parameters of clam-stainless steel, and clam-acrylic were calibrated by combining direct measurements and test simulations (slope sliding and dropping). Then, clam DEM simulation and realistic seeding tests were carried out on a seeding wheel at different rotational speeds. The accuracy of the calibrated clam DEM model was evaluated in a clam seeding verification test by comparing the average error of the variation coefficient between the realistic and simulated seeding tests. The results showed that: (a) the static friction coefficients of clam-acrylic and clam-stainless steel were 0.31 and 0.23, respectively; (b) the restitution coefficients of clam-clam, clam-acrylic, and clam-stainless steel were 0.32, 0.48, and 0.32, respectively. Furthermore, the results of the static repose angle from response surface tests showed that when the contact wall was acrylic, the coefficient rolling friction and static friction of clam-clam were 0.17 and 1.12, respectively, and the coefficient rolling friction of clam-acrylic was 0.20. When the contact wall was formed of stainless steel, the coefficient rolling friction and static friction of clam-clam were 0.33 and 1.25, respectively, and the coefficient rolling friction of clam-stainless steel was 0.20. The results of the verification test showed that the average error between the realistic and simulated value was <5.00%. Following up from these results, the clam DEM model was applied in a clam seeding simulation.
An Overview of Antibiotics as Emerging Contaminants: Occurrence in Bivalves as Biomonitoring Organisms
Authors: Baralla Elena , Demontis Maria P. , Dessì Filomena , Varoni Maria V.
Published: November 2021

Antibiotics are used for therapeutic and prophylactic purposes in both human and veterinary medicine and as growth promoting agents in farms and aquaculture. They can accumulate in environmental matrices and in the food chain, causing adverse effects in humans and animals including the development of antibiotic resistance. This review aims to update and discuss the available data on antibiotic residues, using bivalves as biomonitoring organisms. The current research indicates that antibiotics’ presence in bivalves has been investigated along European, American and Asian coasts, with the majority of studies reported for the last. Several classes of antibiotics have been detected, with a higher frequency of detection reported for macrolides, sulfonamides and quinolones. The highest concentration was instead reported for tetracyclines in bivalves collected in the North Adriatic Sea. Only oxytetracycline levels detected in this latter site exceeded the maximum residual limit established by the competent authorities. Moreover, the risk that can be derived from bivalve consumption, calculated considering the highest concentrations of antibiotics residues reported in the analyzed studies, is actually negligible. Nevertheless, further supervisions are needed in order to preserve the environment from antibiotic pollution, prevent the development of antimicrobial resistance and reduce the health risk derived from seafood consumption.
Nanoparticles-Facilitated Intracellular Transport of siRNAs against Individual Integrin Subunits Inhibits Growth of Breast Cancer Cells
Authors: Ashaie Maeirah , Chowdhury Ezharul Hoque
Published: November 2021

For cells and tissues, cell–cell and cell–extracellular matrix adhesion is important for proliferation, differentiation, and response to mechanical stimuli. This adhesion is provided by various cell adhesion molecules (CAMs). However, in breast cancer, depending upon the type and stage, this adherence is dysregulated where the expression of these cell adhesion molecules is either overregulated or unregulated, triggering essential oncogenic pathways. Thus, to control the invasiveness of tumor cells, and reduce metastasis, regulating the homophilic and heterophilic interaction of these molecules and controlling the essential cell pathways is important. In this study, we targeted critical CAMs- integrins to regulate their aberrated behavior via siRNAs delivery. However, as due to charge repulsion and propensity to be degraded by nucleases prior to reaching the target site, naked siRNAs are unable to cross plasma membrane, use of a suitable carrier vehicle is essential. Thus, we employed carbonate apatite (CA), to deliver the selected siRNAs targeting integrin αv, α6, β1, β3, β4, β5, and β6 subunits to various breast cancer cell lines and 4T1-breast cancer induced murine model. Delivery of individual integrin siRNAs complexed with CA nanoparticles (NPs) reduced cell viability and caused decrease in tumor burden. To check the gene knockdown effects on phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) and extracellular signal–regulated kinases/mitogen-activated protein kinase (ERK/MAPK) pathways, Western blot analysis was performed, revealing downregulation of the signaling molecules. Thus, CA-facilitated gene therapy targeting various integrins could poise potential therapeutic modality against breast cancer.
On Constrained Set-Valued Semi-Infinite Programming Problems with ρ-Cone Arcwise Connectedness
Authors: Das Koushik , Treanţă Savin
Published: November 2021

In this paper, we establish sufficient Karush–Kuhn–Tucker (for short, KKT) conditions of a set-valued semi-infinite programming problem (SP) via the notion of contingent epiderivative of set-valued maps. We also derive duality results of Mond–Weir (MWD), Wolfe (WD), and mixed (MD) types of the problem (SP) under ρ-cone arcwise connectedness assumptions.
On Turing Machines Deciding According to the Shortest Computations
Authors: Manea Florin
Published: November 2021

In this paper we propose and analyse from the computational complexity point of view several new variants of nondeterministic Turing machines. In the first such variant, a machine accepts a given input word if and only if one of its shortest possible computations on that word is accepting; on the other hand, the machine rejects the input word when all the shortest computations performed by the machine on that word are rejecting. We are able to show that the class of languages decided in polynomial time by such machines is PNP[log]. When we consider machines that decide a word according to the decision taken by the lexicographically first shortest computation, we obtain a new characterization of PNP. A series of other ways of deciding a language with respect to the shortest computations of a Turing machine are also discussed.
“Multiomics” Approaches to Understand and Treat COVID-19: Mass Spectrometry and Next-Generation Sequencing
Authors: Appiasie Diane , Guerra Daniel J. , Tanguay Kyle , Jelinek Steven , Guerra Damian D. , Sen Rwik
Published: November 2021

In the race against COVID-19 for timely therapeutic developments, mass spectrometry-based high-throughput methods have been valuable. COVID-19 manifests an extremely diverse spectrum of phenotypes from asymptomatic to life-threatening, drastic elevations in immune response or cytokine storm, multiple organ failure and death. These observations warrant a detailed understanding of associated molecular mechanisms to develop therapies. In this direction, high-throughput methods that generate large datasets focusing on changes in protein interactions, lipid metabolism, transcription, and epigenetic regulation of gene expression are extremely beneficial sources of information. Hence, mass spectrometry-based methods have been employed in several studies to detect changes in interactions among host proteins, and between host and viral proteins in COVID-19 patients. The methods have also been used to characterize host and viral proteins, and analyze lipid metabolism in COVID-19 patients. Information obtained using the above methods are complemented by high-throughput analysis of transcriptomic and epigenomic changes associated with COVID-19, coupled with next-generation sequencing. Hence, this review discusses the most recent studies focusing on the methods described above. The results establish the importance of mass spectrometry-based studies towards understanding the infection process, immune imbalance, disease mechanism, and indicate the potential of the methods’ therapeutic developments and biomarker screening against COVID-19 and future outbreaks.
Heat-Inactivation of Fetal and Newborn Sera Did Not Impair the Expansion and Scaffold Engineering Potentials of Fibroblasts
Authors: Pellerin Félix-Antoine , Caneparo Christophe , Pellerin Ève , Chabaud Stéphane , Pelletier Martin , Bolduc Stéphane
Published: November 2021

Heat inactivation of bovine sera is routinely performed in cell culture laboratories. Nevertheless, it remains debatable whether it is still necessary due to the improvement of the production process of bovine sera. Do the benefits balance the loss of many proteins, such as hormones and growth factors, that are very useful for cell culture? This is even truer in the case of tissue engineering, the processes of which is often very demanding. This balance is examined here, from nine populations of fibroblasts originating from three different organs, by comparing the capacity of adhesion and proliferation of cells, their metabolism, and the capacity to produce the stroma; their histological appearance, thickness, and mechanical properties were also evaluated. Overall, serum inactivation does not appear to provide a significant benefit.
3D Hepatic Organoid-Based Advancements in LIVER Tissue Engineering
Authors: Panwar Amit , Das Prativa , Tan Lay Poh
Published: November 2021

Liver-associated diseases and tissue engineering approaches based on in vitro culture of functional Primary human hepatocytes (PHH) had been restricted by the rapid de-differentiation in 2D culture conditions which restricted their usability. It was proven that cells growing in 3D format can better mimic the in vivo microenvironment, and thus help in maintaining metabolic activity, phenotypic properties, and longevity of the in vitro cultures. Again, the culture method and type of cell population are also recognized as important parameters for functional maintenance of primary hepatocytes. Hepatic organoids formed by self-assembly of hepatic cells are microtissues, and were able to show long-term in vitro maintenance of hepato-specific characteristics. Thus, hepatic organoids were recognized as an effective tool for screening potential cures and modeling liver diseases effectively. The current review summarizes the importance of 3D hepatic organoid culture over other conventional 2D and 3D culture models and its applicability in Liver tissue engineering.