bluuebunny/crossref_metadata_2025 huggingface dataset:
A Routine Sanger Sequencing Target Specific Mutation Assay For SARS-CoV-2 Variants Of Concern And Interest
Authors: Lee Sin Hang
Published: November 2021

As SARS-CoV-2 continues to spread among human populations, genetic changes occur and accumulate in the circulating virus. Some of these genetic changes have caused amino acid mutations, including deletions, which may have potential impact on critical SARS-CoV-2 countermeasures, including vaccines, therapeutics, and diagnostics. Considerable efforts have been made to categorize the amino acid mutations of the angiotensin-converting enzyme 2 (ACE2) receptor binding domain (RBD) of the spike (S) protein along with certain mutations in other regions within the S protein as specific variants in an attempt to study the relationship between these mutations and the biological behavior of the virus. However, the currently used whole genome sequencing surveillance technologies can test only a small fraction of the positive specimens with high viral loads and often generate uncertainties in nucleic acid sequencing that needs additional verification for precision determination of mutations. This article introduces a generic protocol to routinely sequence a 437-bp nested RT-PCR cDNA amplicon of the ACE2 RBD and a 490-bp nested RT-PCR cDNA amplicon of the N-terminal domain (NTD) of the S gene for detection of the amino acid mutations needed for accurate determination of all variants of concern and variants of interest according to the definitions published by the U.S. Centers for Disease Control and Prevention. This protocol was able to amplify both nucleic acid targets into cDNA amplicons to be used as templates for Sanger sequencing on all 16 clinical specimens that were positive for SARS-CoV-2.
A Blockchain-Based Intelligent Machine Learning System for Smart Health Care
Authors: Hassan Mir , Paulavicius Remigijus , Filatovas Ernestas , Iftekhar Adnan
Published: November 2021

Blockchain and Machine Learning gives the best solutions together in performing various tasks in the Smart Health care system. With these two new emerging technologies, that have materialized in the last decade. In this paper, we proposed secure, transparent and intelligent methods in the Internate of medical things industry using Machine learning models and blockchain technology to enhance security level and train our models to improve diagnostic, prevention, treatment of the patient, patient rights, patient autonomy and equality in the health care system.
Thermal Quantum Coherence properties in Two-Qubit Heisenberg XXX Model in Nonhomogeneous Magnetic Field
Authors: Ali Asad , Khan Muhammad Anees
Published: November 2021

We investigate the behavior of thermal quantum coherence in the Heisenberg XXX model for a two-qubit system placed in independently controllable Inhomogeneous magnetic fields applied to two qubits respectively. We discuss the behavior of quantum coherence by systematically varying the coupling parameter, magnetic field, and temperature for both ferromagnetic and antiferromagnetic cases. The results show the interesting behavior of quantum coherence in a certain range of parameters. Generally, it is observed that quantum correlations decay with temperature, but in the ferromagnetic case with uniform magnetic interaction, it rises with temperature up to a certain threshold value and ultimately it decreases its value to zero. Moreover, it is observed that preserving the quantum coherence for small temperatures is very hard with the increasing magnetic field because, at small temperatures, quantum coherence decays sharply with the increase in magnetic field whereas at larger temperatures it decays completely at fairly large values of the magnetic field. The variation of quantum coherence with uniform magnetic field in the antiferromagnetic case is observed to be Gaussian for larger temperature but at zero or nearly zero temperature, it behaves as a constant function for uniform magnetic field up to a threshold value and then decays to zero with an infinite slope. This shows the signature of quantum phase transition from quantum nature to classicality.
Class 2 Heating Cycles: A New Class of Thermodynamic Cycles
Authors: Li Hua-Yu , Li Hong-Rui
Published: November 2021

Considering the significance of thermodynamic cycles in the global energy system, it is necessary to develop new general classes of thermodynamic cycles to relieve current energy and environmental problems. Inspired by the relationship between power cycles and refrigeration cycles, we realize that general classes of thermodynamic cycles should occur in pairs with opposite functions. Here we reverse class 1 heating cycles to obtain another new general class of thermodynamic cycles named class 2 heating cycles (HC-2s). HC-2s have two basic forms, and each contains six thermodynamic processes. HC-2s present the simplest and most general approach to utilizing the temperature difference between a medium-temperature heat source and a low-temperature heat sink to achieve efficient high-temperature heating. HC-2s fill the gaps that have existed since the origin of thermal science, and they will play significant roles in the global sustainable energy system.
Managing Skin Ageing as a Modifiable Disorder – The Clinical Application of Nourella® Dual Approach Comprising a Nano-encapsulated Retinoid, Retilex-A® and a Skin Proteoglycan Replacement Therapy, Vercilex®
Authors: Wadstein Jan , Alvarez Israel Sánchez , Thom Erling , López Lidia Bernal
Published: November 2021

Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.
The Effect of Natural Falling and Dipping of House Fly (Musca domestica) on the Microbial Contamination of Water and Milk: A Short Communication Report
Authors: Baeshen Nabih Abdulrahman , Elsharawy Nagwa Thabet , Baeshen Naseebh Nabih , Baeshen Mohammed Nabih
Published: November 2021

Background: The study describes the comparison of different microbial load results of natural falling and dipping of the house fly (Musca domestica) in water and milk to investigate the possibilities of preventing the effect of the transferred pathogens from the house fly to our sources by pointing out the existence of antimicrobial factors within the house fly.
Methods: Samples of house fly were collected from Jeddah and Makkah (Makkah region) and were directly transferred to the laboratory. Each house fly was packed in sterile test tubes. Each tube was opened oppositely to a larger test tube containing 10 ml of sterile tap water, and sterile water at pH 4.0 in other similar series of treatments to represent the reactions of stomach fluids. Later, the house flies were left for 20 seconds after reaching the water surface, and then cultured on different microbial media to evaluate the microbial load of the natural falling of the house fly. To evaluate the complete dipping of house flies in the water, two methods were tested by one complete dip for the flies for 20 seconds, and three times complete dipping for 20 seconds in water before evaluating the microbial load. The same methods were achieved on milk in a series of experiments and the microbial load was evaluated after the incubation at room temperature for three hours.
Results: It was found that dipping treatments of house flies gave lower microbial contamination in water at pH 4.0 than neutral pH. The lower microbial load was also observed when dipping the house flies three times in water as compared to once dipping and natural falling treatments. It was also found that the complete dipping of house flies’ treatments in milk will reduce the microbial contamination as compared to natural falling treatments.
Conclusion: The observed results support the presence of antimicrobial factors on the house fly.
Green Reduction of Graphene Oxide Involving Extracts of Plants from Different Taxonomy Groups and Its Applications
Authors: Perumal Dharshini , Albert Emmellie Laura , Abdullah Che Azurahanim Che
Published: November 2021

Graphene is a remarkable material with numerous applications. Due to its thin and lightweight design, it is ideal for a variety of applications. The synthesis of high-quality graphene in a cost-effective and environmentally friendly manner continues to be a significant challenge. Chemical reduction is considered to be the most advantageous method for preparing reduced graphene oxide (rGO). However, this process necessitates the use of toxic and harmful substances, which can have a detrimental effect on the environment and human health. Thus, to accomplish the objective, the green synthesis principle has prompted researchers worldwide to develop a simple method for green reduction of graphene oxide (GO), which is readily accessible, sustainable, economical, renewable, and environmentally friendly in nature. For example, the use of natural materials such as plants is generally considered safe. Furthermore, plants contain reducing and capping agents. The current review will focus on the discovery and application of rGO synthesis using extracts from a variety of different parts of the plant. The review aims to aid current and future researchers in their search for a novel plant extract that acts as a reductant in the green synthesis of rGO. The review aims to assist current and future researchers in their research for a novel plant extract that acts as a reductant in the green synthesis of rGO as well as their potential applications in a variety of industries.
Recent Applications of Pd-Catalyzed Suzuki-Miyaura and Buchwald-Hartwig Couplings in Pharmaceutical Process Chemistry.
Authors: Takale Balaram S. , Kong Fan Yi , Thakore Ruchita R.
Published: November 2021

Cross coupling reactions have changed the way complex molecules are synthesized. In particular, Suzuki-Miyaura and Buchwald-Hartwig amination reactions have given opportunities to elegantly make pharmaceutical ingredients. Indeed, these reactions are forefront at both the stages of drug development, medicinal chemistry, and process chemistry. On one hand, these reactions have given medicinal chemists a tool to derivatize the core molecule to arrive at scaffold rapidly. On the other hand, these cross couplings have offered the process chemists a smart tool to synthesize the development candidates safely, quickly, and efficiently. Generally, the application of cross coupling reactions is broad, and this review will specifically focus on their real (pharma) world applications in large scale synthesis those appeared in last two years.
Analysis Implementation of COVID-19 Prevention Policy for Disability in Social Institution (Case Study: Jakarta Capital City)
Authors: Margaretha Cindy , Ayuningtyas Dumilah
Published: November 2021

One of the most vulnerable groups in the current COVID-19 pandemic situation is people with disabilities. People with disabilities generally have more health care needs, both standard needs and needs related to the disorders/limitations they have. As part of human beings and citizens of Indonesia, constitutionally persons with disabilities have the same rights and position before the law and government. This study aims to analyze the implementation of COVID-19 prevention policies at the social institutions for disability in Jakarta Capital City, provide information about the implementation, find out the obstacles, and recommend policymakers in the prevention of COVID-19 in social institutions with disabilities. This study used an exploratory study design with a rapid assessment survey approach, uses a secondary data analysis method which is supported by interviewing stakeholders at the Social Institutions in Jakarta Capital City that handle disabilities. The results of this study conclude that the overall implementation has been going well. The socialization and coordination process related to the COVID-19 prevention policy at the Social Institution for Disabilities in Jakarta Capital City has gone well among fellow officers but has communication barriers with residents.
The Effectiveness and Safety of Favipiravir in COVID-19 Hospitalized Patients at Tertiary Referral Hospital, Bali, Indonesia
Authors: Damayanti Herni , Sajinadiyasa I Gede K , Risni Hindun Wilda , Sauriasari Rani
Published: November 2021

COVID-19 is a major public health problem, with still questionable specific cure. Favipiravir is a COVID-19 antiviral that is potentially a therapy for COVID-19. This study aimed to analyze its effectivity and safety in moderate to critical hospitalized patients. This study was a retrospective cohort in a tertiary referral hospital in Denpasar City, Bali Province, Indonesia, from August 2020 to January 2021. There was a total of 192 patients; 96 in the favipiravir group and 96in the non-favipiravir group (remdesivir/oseltamivir). Effectivity was measured by assessing the clinical condition at the end of the isolation period of 14 days. The favipiravir group showed better clinical conditions than the non-favipiravir group (79.2% vs. 56.3%; adjusted RR = 2.196; 95% CI = 1.084 – 4.451; p-value= 0.029), seen from being free of fever and respiratory problems. Stratification analysis demonstrated that the clinical improvement was significantly differentin the severe/critical group in favor of favipiravir (RR = 1.573; 95% CI = 1.139-2.172). The most common non-serious adverse events (AE) found in the use offavipiravir were gastrointestinal disturbances (12.5%). In brief, favipiravir is effective in severe/critical cases, and less serious AE were found in its use. Appropriate treatment is expected to help in reducing the public health burden.
Recapitulating neural tube morphogenesis with human pluripotent stem cells
Authors: Karzbrun Eyal , Khankhel Aimal H. , Streichan Sebastian J.
Published: November 2021

Neural tube morphogenesis is the first step in the formation of the nervous system, and tube defects are among the highest rate birth defects. However, it is not possible to study the dynamics of organ formation in humans. Animals differ from humans in key aspects, and in particular in the development of the nervous system. Conventional organoids are neither reproducible nor do they recapitulate the intricate anatomy of the neural tube. Here we describe a new protocol for recapitulating the intricate dynamics of neural tube morphogenesis using human stem cells. Our approach is reproducible, scalable, compatible with live imaging, genetic modifications, and drug screening. The protocol captures the early steps of neural development: pattering of the ectoderm into a neural plate and surface ectoderm, neural plate folding and closure, coverage by surface ectoderm, and neural crest cells differentiation and migration. This protocol opens up a way for further studies into the genetics and biophysics of the development of the human nervous system in health and disease.
Culture and Differentiation of Primary Human Tracheobronchial Epithelial Cells Using STEMCELL Technologies Pneumacult Media
Authors: Dailey Lisa A. , McCullough Shaun D.
Published: November 2021

NOTE: A PDF methods document is attached in the supplementary materials.SCOPE OF APPLICATION (LIMITATIONS)This method describes the culture and differentiation of primary human tracheobronchial epithelial cells (pHBEC). Cells used for this method can be obtained by brush biopsy during clinical bronchoscopy or purchased commercially. This method replaces the previous version described in (Dailey and McCullough, 2021a; b). Disclaimer: The contents of this article have been reviewed by the US Environmental Protection Agency and approved for publication and do not necessarily represent Agency policy. Mention of trade names or commercial products does not constitute endorsement or recommendations for use.
Experience of Danaparoid to Treat Vaccine-Induced Immune Thrombocytopenia and Thrombosis, VITT
Authors: Myllylahti Lasse , Pitkänen Hanna , Magnani Harry , Lassila Riitta
Published: November 2021

Background: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is triggered by nCOV-19 adenovirus-vectored vaccines against SARS-CoV2. Pathogenesis has been mainly related to platelet activation via PF4-reactive antibodies that activate platelets and cross-react with heparin. Data concerning optimal anticoagulation are anecdotal, and so far, there are scattered reports of danaparoid use in VITT management. Danaparoid has good efficacy and safety in treatment of heparin-induced thrombocytopenia. We report here our experience of the administration and monitoring danaparoid in VITT. Methods: We diagnosed six hospitalized cases of definite or probable VITT, based on the international diagnostic guidance. All VITT-related data were from the local electronic medical and laboratory record system and were analyzed with IBM SPSS Statistics. Results: Predominately women in their late forties developed VITT on average 24 days (range 9-59) after the first ChAdOx1 dose. Clinical presentation included single or multiple venous and/or arterial thrombosis, moderate thrombocytopenia and high D-dimer levels. After detecting PF4 antibodies subcutaneous danaparoid was our first-line antithrombotic treatment with an average duration of three weeks. The median plasma anti-FXa activity was in the lower part of the therapeutic range and during the first week of danaparoid administration clinical symptoms, platelet counts and fibrin turnover resolved or significantly improved. The average duration of hospital admission was 10 days (2-18). One patient died but the other five recovered completely. Conclusions: The clinical outcomes of our small cohort align with the earlier published reports, and support danaparoid as a rational option for the initial anticoagulation of VITT patients.
Genome-Wide Identification of Tomato Golden 2-Like Transcription Factors and Abiotic Stress Related Members Screening
Authors: Wang Ziyu , Liu Junfang , Zhao Haiyan , Sun Xuying , Wu Tairu , Pei Tong , Wang Yue , Liu Qifeng , Yang Huanhuan , Zhang He , Jiang Jingbin , Li Jingfu , Zhao Tingting , Xu Xiangyang
Published: November 2021

Background: Golden 2-Like (G2-like) transcription factors play an important role in plant development. However, the roles of these G2-like regulatory genes in response to abiotic stresses in tomato are not well understood.Results: In this study, we identified 66 putative G2-like genes in tomato (Solanum lycopersicum) and classified them into 5 groups (I to V) according to gene structure, motif composition and phylogenetic analysis. The G2-like genes were unevenly distributed across all 12 chromosomes. There were nine pairs of duplicated gene segments and four tandem duplicated SlGlk genes. Analysis of the cis-regulatory elements (CREs) showed that the promoter regions of SlGlks contain many kinds of stress- and hormone-related CREs. Based on RNA-seq, SlGlks were expressed in response to three abiotic stresses. Thirty-six differentially expressed SlGlks were identified; these genes have multiple functions according to Gene Ontology (GO) analysis and are enriched mainly in the zeatin biosynthesis pathway. Further studies exhibited that silencing SlGlk16 in tomato would reduce drought stress tolerance by earlier wilted, lower superoxide dismutase (SOD), peroxidase (POD) activities, less Pro contents and more MDA contents. Conclusion: Overall, the results of this study provide comprehensive information on G2-like transcription factors and G2-like genes that may be expressed in response to abiotic stresses.
Real-World Effectiveness and Safety of Fingolimod in Patients with Multiple Sclerosis in the Czech Republic: Results from Core and Extension Parts of the GOLEMS Study up to 48 Months
Authors: Tichá Veronika , Počíková Zuzana , Vytlačil Josef , Štěpánová Radka
Published: November 2021

Background: Fingolimod, an oral sphingosine 1-phosphate receptor immunomodulator, is approved in Europe for multiple sclerosis (MS) patients with highly active disease despite a full and adequate course of treatment with ≥1 disease-modifying therapy or patients with rapidly evolving severe relapsing–remitting MS. GOLEMS, a 12-month, national, multicenter, non-interventional, single-arm, real-world study showed a favorable benefit–risk profile of fingolimod in patients with MS in the Czech Republic. Here, we evaluated the long-term effectiveness and safety of fingolimod and its impact on disability progression and work capability for up to 48 months in patients with MS.Methods: The endpoints assessed were the incidence and severity of MS relapses in fingolimod-treated patients and the proportion of relapse-free patients up to 48 months of fingolimod treatment, change from baseline in the Expanded Disability Status Scale (EDSS) score, and change from baseline in work capability assessment. Efficacy outcomes were analyzed in the completed and efficacy sets, and safety was evaluated in all the enrolled patients.Results: Of 240 enrolled patients, 237 were included into efficacy set. Patients with a minimum of a 12-month observation period in the core study who continued fingolimod treatment, were eligible to participate in the extension phase. Of 211 patients enrolled in extension study, 155 were evaluated in the completed set. Based on analysis of 48-month period of fingolimod treatment, 95/237 patients (40.1%) in the efficacy set, 54/155 (34.8%) in the completed set were free of relapses. The majority of relapses reported were moderate in intensity. Mean EDSS score remained stable throughout 48-month study period (Baseline, 3.4; Month 48, 3.6). No significant 3 trend was observed in changes in work capability assessment or number of missed days of work. Of 240 enrolled patients, 147 (61.3%) had ≥1 treatment-emergent adverse event (AE) and 20 (8.3%) reported serious AEs. In total, 45 patients (18.8%) permanently discontinued treatment because of AEs related to study drug; two patients reported pregnancy after treatment initiation and subsequently discontinued the treatment; no deaths were reported.Conclusion: GOLEMS study demonstrated the sustained effectiveness and manageable safety profile of fingolimod under real-world conditions over 48 months in patients with MS.Trial registration: Not applicable
Effects of Advance Exposure to an Animated Surgery-Related Picture Book on Preoperative Anxiety and Anesthesia Induction in Preschool Children: A Randomized Controlled Trial
Authors: Yang Yanyan , Zhang Mazhong , Sun Ying , Peng Zhezhe , Zheng Xiaosu , Zheng Jijian
Published: November 2021

Background: Our aim was to investigate whether early surgical preparation by reading an animated picture book about procedure-related events could reduce the preoperative anxiety in preschoolers.Methods: 131 patients, aged 3-6 years and underwent elective minor surgery were randomized either to a control or a picture book group. Both groups received general information about surgery and anesthesia in pre-anesthesia clinic. Patients in study group also received a surgery-depicting picture book for them to read at home a week earlier before surgery. Child anxiety was evaluated with the modified Yale Preoperative Anxiety Scale Short Form in six observing time points before anesthesia induction, and the compliance of anesthesia induction was assessed with the Induction Compliance Checklist (ICC).Results: There were significantly lower anxiety scores in picture book group than in control group at the time of ready for intravenous cannulation in operation room [51.9 (23.6) vs. 67.2 (22.0); P = 0.001] and at the time of pre-anesthesia visit [27.8 (7.6) vs. 33.2 (13.6); P = 0.018]. No significant differences of anxiety levels were found between two groups at other observed time points: in the anesthesia outpatient clinic, in the holding area, at separation from parent to operating room (OR), and on entrance to OR (P = 0.584, 0.335, 0.228, 0.137, respectively). The percentage of children with poor induction compliance (i.e., ICC ≥ 6) was higher in control group compared with that in picture book group (38% vs.21%, P = 0.041).Conclusions: Home-reading an animated picture book to get familiar with the perioperative events earlier prior to surgery could effectively reduce the preoperative anxiety level and increase the compliance during the induction of anesthesia in preschool children.Trial registration: ChiCTR2000033583, 06/06/2020 www.chictr.org.cn.
Self-made Vitreoretinal Surgical Simulator Using Silicone Mold
Authors: Nagamoto Takashi , Kubono Hirohisa , Kawamura Mari , Suzuki Kotaro
Published: November 2021

There is no consensus on an appropriate and sustainable practice method in vitreoretinal surgery. We found a self-made vitreoretinal surgical simulator using a silicone mold that can offer various operative maneuvers and can become a solution for such a problem. We obtained a spherical silicone mold, a mannequin head, and spray material on the net market and combined them with expired surgical instruments to complete the simulator. Simulated vitrectomy was performed by vitreoretinal experts, and the practicality was verified. They reviewed that the simulated eyeball had size and rigidity very similar to the eyeball and that the intraocular practice swing seemed to be useful for the prevention of complications. The silicone material's semitransparency and open-sky structure offered them plenty of visibility. The membrane simulated by spray glue provided them with an excellent peeling sensation. These findings suggested that this simulator is suitable for practicing the basic procedures of vitreoretinal surgery. The simple shape seems to have many possibilities, and further verification at many facilities is desirable.
A Study of Dose Painting Radiotherapy Guided by Three-Dimensional Arterial Spin labeling Perfusion Magnetic Resonance Imaging for Non-Enhancing Low-Grade Gliomas
Authors: Zhu Zihong , Gong Guanzhong , Wang Lizhen , Su Ya , Qin Xiaohang , Chen Mingming , Lu Jie , Yin Yong
Published: November 2021

Background: The purpose of this study was to investigate the feasibility and dosimetric characteristics of dose painting for non-enhancing low-grade gliomas (NE-LGGs) guided by three-dimensional arterial spin labeling (3D-ASL) perfusion magnetic resonance imaging.Methods: Eighteen patients with NE-LGGs were enrolled. 3D-ASL, T2 fluid attenuated inversion recovery (T2 FLAIR) and contrast-enhanced T1-weight magnetic resonance images were obtained. The gross tumor volume (GTV) was delineated on the T2 FLAIR. The hyper-perfusion region of the GTV (GTV-ASL) was determined by 3D-ASL, and the GTV-SUB was obtained by subtracting the GTV-ASL from the GTV. The planning target volume (PTV), PTV-ASL and PTV-SUB were developed by expanding the external margins of the GTV, GTV-ASL and GTV-SUB, respectively. Three plans were established for each patient: in plan 1, the traditional homogeneous prescription dose to the PTV was 45-60 Gy; in plan 2 and plan 3, the dose to the PTV-ASL increased by 10-20% based on plan 1, without the maximum dose constraint to the PTV-ASL in plan 3. The dosimetric differences among the three plans were compared.Results: Compared with plan 1, the dose to 2% (D2%), 98% (D98%) and 50% (Dmean) of PTV-ASL volumes increased by 14.67%, 16.17% and 14.31% in plan 2 and 19.84%, 15.52% and 14.27% in plan 3, respectively (P < 0.05); the D2% of the PTV, PTV-SUB increased by 11.89% and 8.34% in plan 2, 15.89% and 8.49% in plan 3, respectively (P< 0.05). The PTV coverages were comparable among the three plans (P > 0.05). In Plan 2 and plan 3, the conformity indexs decreased by 18.60% and 12.79%; while the homogeneity indexs increased by 1.43 and 2 times (P<0.05). Compared with plan 1, the D0.1cc of brain stem and Dmax of optic chiasma slightly increased in plan 2 and plan 3, but the absolute doses met the dose constraint. The other organs at risk were similar among the three plans (P > 0.05).Conclusions: The sub-volume with hyper-perfusion for NE-LGG radiotherapy can be segmented based on the perfusion difference guided by 3D-ASL. And the radiation dose to the hyper-perfusion area increased safely by 10-20% through dose painting.
Factors Related to Nurses and Physicians’ Knowledge of and Attitudes Towards Palliative Care
Authors: Ashrafizadeh Hadis , Khanali-Mojen Leila , Barasteh Salman , Beiranvand Samira , Farahani Azam Shirinabadi , Eshaghian-dorcheh Azam , Karami Maryam , Khademi Fatemeh , Khoshnazar Tahereh Alsadat Khoubbin , Krakauer Eric , Rassouli Maryam
Published: November 2021

Background
With the increase of the elderly population, the need for palliative care has increased, which is one of the requirements of effective palliative care services, sufficient knowledge and positive attitude of nurses and physicians towards this care approach. The aim of this study was to determine the factors related to the knowledge and attitudes of nurses and physicians about palliative care.
Methods
This descriptive correlational study was performed in 2021 on 277 nurses and physicians working in selected teaching hospitals in Iran who were selected by convenience sampling method. The data collection tool was an online and researcher-made questionnaire consisting of three sections: demographics and occupation, knowledge (30 items) and attitude (37 items) that were designed and validated in the present study. To analyze the data, spss-v24 software was used for descriptive statistics tests (means and frequency tables) and inferential tests (correlation and univariate regression).
Results
The mean scores of knowledge and attitude of care providers were 19.36 ± 2.73 and 140.90 11 11.56, respectively. There was a positive relationship between knowledge and attitude variables (P-value = 0.000, r = 0.378). Meaning of relationship between the mean score of attitude and knowledge with age ranges of 31-60 and 60-51 years, level of education, workplace, work experience in palliative care, need for formal education in palliative care and need to pass palliative care course there was.
Conclusion
Based on the results of this study, the level of knowledge and attitude of palliative care providers was moderate. Therefore, in order to further promote the knowledge and attitude of nurses and physicians, it is recommended to hold theoretical and practical training courses in the form of skill and retraining courses, reviewing the curricula of general medicine and bachelor's degree in nursing.
Respiratory Syncytial Virus and Metapneumovirus Infection Have Different Clinical Presentation in Children
Authors: Montero Jonathan Illan , Berger Alice , Levy Jack , Busson Laurent , Hainaut Marc , Goetghebuer Tessa
Published: November 2021

Respiratory syncytial virus (RSV) and Human metapneumovirus (hMPV), members of Pneumoviridae family are common causes of acute respiratory tract infections (ARTI) among children. Study material includes routine nasopharyngeal samples obtained during 8-year period for hMPV and one single season for RSV in children aged 0 to 15 years at the Centre Hospitalier Universitaire (CHU) Saint Pierre in Brussels. Positive samples for RSV or hMPV identified by viral culture, lateral flow chromatography test for RSV or direct fluorescent assay for hMPV were selected retrospectively. The medical charts of these patients were reviewed. Hospitalization rate was 37% (219/591) and 39% (187/476) for hMPV and RSV respectively. Children hospitalized for RSV infection were significantly younger and more dyspneic, requiring more respiratory support, longer hospital stay and transfers in Pediatric intensive Care Units (PICU) than those hospitalized for hMPV infection. Pneumonia diagnostic and antibiotics therapies were more significantly associated with hMPV infections.In conclusion, despite their genetic similarities, RSV and hMPV present epidemiological and clinical differences in pediatric infections.
Evaluation of adrenal reserve in patients with differential thyroid cancer receiving thyroid hormone suppression therapy- case-control comparative study
Authors: Bilginer Muhammet Cuneyt , Tam Abbas Ali , Faki Sevgul , Bestepe Nagihan , Dellal Fatma Dilek , Ozdemir Didem , Topaloglu Oya , Ersoy Reyhan , Cakir Bekir
Published: November 2021

Background

Patients with differentiated thyroid cancer (DTC) are exposed to subclinical exogenous hyperthyroidism for the suppression of thyroid-stimulating hormone (TSH). In this study, we aimed to evaluate the adrenal reserve in DTC patients receiving suppression therapy.
Materials and Methods

The study included 55 DTC patients on suppression therapy and 32 healthy volunteers. Basal serum cortisol of all participants and adrenocorticotropic hormone (ACTH) of the patient group were measured. A standard-dose ACTH test (0.25 mg) was performed in patients with a basal cortisol < 14.5 mcg/dL.
Results

In the patient group, TSH was lower, free thyroxine (fT4) was higher, and free triiodothyronine (fT3) was similar to those of the control group (p < 0.01, p < 0.01, p = 0.140, respectively). The serum cortisol of the patient group was significantly lower than the control group (12.14 ± 5.12 mcg/dL vs 18.00 ± 5.56 mcg/dL, p < 0.001). 34 (61.8%) patients with DTC had a basal cortisol < 14.5 mcg/dL. Prolonged TSH suppression (≥ 5 years vs < 5 years) was associated with lower basal cortisol (7.46 ± 2.63 mcg/dL vs 9.48 ± 2.65 mcg/dL, p = 0.022). The ACTH stimulation test showed that 2 (5.8%) patients had a cortisol response < 18 mcg/dL. The rate of adrenal insufficiency was 3.6% in DTC patients. A moderate negative correlation was found between ACTH and fT3 of patients with low basal cortisol (r = − 0.358, p = 0.038)
Conclusion

Patients with DTC receiving TSH suppression therapy are at risk for adrenal insufficiency. The duration and severity of suppression might increase this possibility. Dynamic testing with synthetic ACTH can be used to reveal insufficient cortisol response in case of clinical suspicion.
Anastomotic Leakage Following Resection of the Esophagus – Introduction of an Endoscopic Scoring System
Authors: Bachmann Jeannine , Feith Marcus , Schlag Christoph , Abdelhafez Mohamed , Martignoni Marc , Friess Helmut
Published: November 2021

Background Malignant tumors of the esophagus are the sixth leading cause of cancer-related deaths worldwide. Postoperative leakage of the esophago-gastrostomy leads to mediastinal sepsis, which is still associated with a high morbidity and mortality rate. The aim of this study was to describe the endoscopic view of the different severity grades of an anastomotic leakage. MethodsPatients Between June 2016 and September 2018, 144 patients were operated upon in the Department of Surgery, University of Munich, Germany. Among these patients, 34 (23.6%) presented with a leakage of the anastomosis. EndoscopyIn this retrospective analysis the focus is to describe different patterns of leakage of the anastomosis.Results We studied 34 patients in whom post-esophagectomy leakage of the anastomosis was detected and treated with an endoluminal vacuum sponge system. The leakage healed in 26 of 29 patients (success rate 89.7%). With increasing severity of leakage, the treatment time and the in-hospital mortality correspondingly increased. Furthermore, the incidence of development of a fistula to the tracheobronchial system increased with higher grades of leakage.ConclusionsExact descriptions of leakage are necessary to compare the cases and to prove post-treatment improvement. This is, to our knowledge, the first publication to present a leakage grading score in patients after esophagectomy including reconstruction with a gastric tube. This new grading system needs to be tested in further analyses, with special focus on prospective analysis.
Role of Gasdermins in the Biogenesis of Apoptotic Cell–Derived Exosomes
Authors: Hur Jaehark , Kim Yeon Ji , Choi Da Ae , Kang Dae Wook , Kim Jaeyoung , Yoo Hyo Soon , Shahriyar Sk , Mustajab Tamanna , Kim Junho , Kim Dong Young , Chwae Yong-Joon
Published: November 2021

The gasdermins are a family of pore-forming proteins that has recently been suggested to play a central role in the pyroptosis and the release of inflammatory cytokines. Here, we describe the novel roles of gasdermins in the biogenesis of apoptotic cell–derived exosomes. In apoptotic cells, GADMA, GSDMC, GSDMD, and GSDME increased the release of ApoExos, and both their full-length and cleaved forms were localized in the exosomal membrane. GSDMB and DFNB59, on the other hand, negatively affected the release of ApoExos. The caspase-mediated cleavage of gasdermins, especially GSDME, is suggested to increase Ca2+ influx to cytosol through endosomal pores and thus increase the biogenesis of ApoExos. In addition, the GSDME-mediated biogenesis of ApoExos depended on the ESCRT-III complex and endosomal recruitment of Ca2+-dependent proteins: annexins A2 and A7, the PEF domain family proteins sorcin and grancalcin, and the Bro1 domain protein HD-PTP. Therefore, we propose that the biogenesis of ApoExos begins when gasdermin-mediated endosomal pores increase cytosolic Ca2+, continues through the recruitment of annexin-sorcin/grancalcin-HD-PTP, and is completed when the ESCRT-III complex synthesizes intraluminal vesicles in the multivesicular bodies of dying cells. Finally, we found that GSDME-bearing tumors released ApoExos to induce inflammatory responses in the in vivo 4T1 orthotropic model of breast cancer. The data presented in this study indicate that the switch from apoptosis to pyroptosis could drive the transfer of mass signals to nearby or distant living cells and tissues by way of extracellular vesicles, and that gasdermins play critical roles in that process.
Health-Related Quality of Life in Multiple System Atrophy using EQ-5D-5L: A Large Cross-Sectional Study in China
Authors: Xiao Yi , Zhang Lingyu , Wei Qianqian , Ou Ruwei , Hou Yanbing , Liu Kuncheng , Lin Junyu , Yang Tianmi , Shang HuiFang
Published: November 2021

Background Multiple system atrophy (MSA) is a rare neurodegenerative disease, featuring autonomic failure plus parkinsonism and/or cerebellar ataxia. These symptoms impact the health-related quality of life (HRQoL) of MSA. Objective We aimed to evaluate the HRQoL of MSA with a preference-based instrument, the five-level EuroQol five-dimensions questionnaire (EQ-5D-5L), for the first time.Methods EQ-5D-5L was used to evaluate the HRQoL. The result of HRQoL was displayed as heath utility index and visual analog scale (EQ-VAS) score. Specific scales were used to measure the disease severity, cognition, frontal lobe function, anxiety, depression, fatigue, and sleep disorders. The forward logistic model was used to explore the determinants of HRQoL in MSA.Results A total of 205 patients with cerebellar variant (MSA-C, 53.9%) and 175 patients with parkinsonian variant (MSA-P, 46.1%) patients were included in the study. The mean scores of the health utility index and EQ-VAS were 0.558 and 59.5, respectively. Mobility was reported by the largest proportion (92.1%) of MSA patients, followed by usual activities (88.7%), self-care (81.3%), anxiety/depression (72.1%), and pain/discomfort (53.9%). The determinants of the lower health utility index in MSA were female sex, greater total Unified Multiple System Atrophy Rating Scale (UMSARS) scores, fatigue, and Parkinson's disease-related sleep problems (PD-SP). Lower EQ-VAS score was associated with greater total UMSARS scores, fatigue, PD-SP, and anxiety symptom. MSA-P patients reported more frequent problems in pain/discomfort than MSA-C patients, while MSA-C patients reported more problems in mobility than MSA-P patients. Conclusion Patients with MSA had poor HRQoL evaluated by EQ-5D-5L. The most frequent affected problem is mobility in the Chinese MSA population. Besides the severity of MSA, fatigue, PD-SP and anxiety were determinants for poor HRQoL. Our research provides important information to improve the health status of patients with MSA.
Quantifying End User Computing Device Use Phase Greenhouse Gas Emissions Using Analytics Software
Authors: Sutton-Parker Justin
Published: November 2021

1.1 Purpose The purpose of this research is to answer the question, ‘can end user computing (EUC) use phase electricity (UPE) consumption data be captured using analytics software regardless of location?’ In doing so, the field experiment tests a proposed methodology that both addresses current barriers such as mobility and scale (Greenblatt et al., 2013) that limit the availability of EUC UPE field data (Karpagam & Yung, 2017) and challenges current methodologies that cause concomitant greenhouse gas (GHG) emissions quantification to be inaccurate by -48% to +107% (Sutton-Parker, 2020). 1.2 MethodsThis is achieved by using a distributed node based analytics software to capture both asset and use profile data sets from one hundred and eleven computer users operating in a subject organisation for 30-days. The values are then used to populate the current and popularised UPE consumption calculation data flow (Kawamoto et al, 2001; Roth eta al. 2002) in order to examine for omissions. To test for accuracy, the EUC UPE consumption of one control subject is measured using both a watt-metre and the analytics software. The rationale being that the watt-metre data is extensively proven to be accurate (Energy Star, 2017) and will therefore expose errors produced by the software in relation to power draw, on-time and resulting kilo-watt hours (kWh) values.1.3 Results and discussionFurther to the data capture period, the findings are mixed. Positively, the new method reduces complexity via the ability to compile both data sets with one tool rather than a combination of two, such as asset management and watt-metre measurement. Specifically, scale and mobility issues are overcome, also allowing for location to be deduced and therefore national electricity conversion factors to be applied when calculating scope 2 emissions. Additionally, the current methodology error range is reduced from 155% (Sutton-Parker, 2020) to 48%. Negatively, data omissions are experienced although surmountable, with the exception of monitors being excluded from the capture process. This is due to the node requiring an operating system to collect data. 1.4 ConclusionWhilst the research question is answered, the identification of energy consumption over reporting causes the analytics methodology to be arguably in need of further development. The rationale being that UPE consumption quantification is key to lifecycle assessment (LCA) and GHG accounting protocol and both require accuracy (WBCSD and WRI, 2004). It is therefore recommended that further research be undertaken to specifically address omissions and to reduce the over reporting aspect identified as caused by algorithms in the software used to calculate hardware power draw.
Effect of Bispectral Index-Guided Total Intravenous Anesthesia on Post-Anesthetic Recovery Outcomes in High-Risk Children: A Prospective, Randomized, Controlled Trial
Authors: Liu Guoliang , Li Lijing , Zhang Xuemei , Wang Xiaoxue , Hua Lei , Zheng Chao , Gao Jia , Hao Wei , Zhang Jianmin , Wang Fang
Published: November 2021

BACKGROUND TIVA is widely used in children, but few studies have attempted to evaluation of the effect of BIS-guided propofol infusion than that on conventional methods on recovery outcomes in children with higher risk factors.OBJECTIVETo evaluate the effect of bispectral index (BIS) guidance during total intravenous anesthesia on post-anesthetic recovery outcomes in children at higher risk during anesthesia. DESIGNA prospective, randomized, controlled trial. SETTING University medical centre.PATIENTSThis study enrolled 472 children (aged 1-14 years) who met the higher-risk scoring criteria and were scheduled for surgery under total intravenous anesthesia. INTERVENTIONThe children were randomly assigned to the BIS group (group B) and standard clinical practice group (group S). The BIS values in group B were maintained at 45–60. The anesthesiologist controlled the depth of anesthesia in group S according to the variation in the clinical signs of the children. MAIN OUTCOME MEASURESBIS values, heart rate (HR), mean arterial pressure (MAP), and pulse oxygen saturation at each time points, as well as the time between drug withdrawal to extubation, duration of stay in the post-anesthesia care unit (PACU), the total amount of propofol used, and postoperative adverse reactions were recorded. RESULTSThere was no significant difference in time from stopping propofol infusion to extubation and duration of PACU between the groups . There was no significant difference in BIS values between the groups at T2, T3, and T8. BIS values at T1, T4, T5, T6, and T7 in group B were lower than those in group S. There was no statistically significant difference in the HR between the groups. MAP in group B was lower than in group S at T5, T6, T7, and T8. The total amount of propofol administered in group B was higher than in group S. CONCLUSIONThe use of BIS-guided total intravenous anesthesia in higher-risk children can maintain the proper depth of anesthesia but does not prolong the time of extubation and the duration of stay in the PACU.TRIAL REGISTRATION Chictr.org.cn identifier: 24/11/2017 , ChiCTR-IOR-17013530