bluuebunny/crossref_metadata_2025 huggingface dataset:
iPSC-Induced Neurons with the V337M MAPT Mutation are Selectively Vulnerable to Caspase-Mediated Cleavage of Tau and Apoptotic Cell Death
Authors: Theofilas Panos , Wang Chao , Butler David , Morales Dulce O. , Petersen Cathrine , Ambrose Andrew J. , Chin Brian , Yang Teddy , Khan Shireen , Ng Raymond , Kayed Rakez , Karch Celeste M. , Miller Bruce L. , Gestwicki Jason E. , Gan Li , Temple Sally , Arkin Michelle R. , Grinberg Lea T.
Published: March 2021

Background: Tau post-translational modifications (PTMs) are associated with progressive tau accumulation and neuronal loss in tauopathies, including forms of frontotemporal lobar degeneration (FTLD) and Alzheimer’s disease (AD). Tau proteolysis by caspases, including caspase-6, represents an understudied PTM that may increase neurotoxicity and tau self-aggregation. Methods: To elucidate the presence and temporal course of caspase activation, tau cleavage, and neuronal death, we generated two novel epitope (neoepitope) monoclonal antibodies (mAbs) against caspase-6 tau proteolytic sites. We evaluated tau cleavage and response to apoptotic stress in cortical neurons derived from induced pluripotent stem cells (iPSCs) with frontotemporal dementia (FTD)-causing V337M MAPT mutation. We tested the neuroprotective effect of caspase inhibitors in the induced neurons. We also demonstrated the presence of the tau neoepitopes in postmortem brains from an individual with FTD (V337M MAPT) and an individual with AD, compared to a healthy control. Results: FTLD V337M MAPT and AD postmortem brains showed positivity for both cleaved tau mAbs and active caspase-6. Relative to isogenic wild-type MAPT controls, V337M MAPT neurons cultured for 3 months showed a time-dependent increase in pathogenic tau in the form of caspase-cleaved tau and phosphorylated (p)-tau, and higher levels of tau oligomers. Accumulation of toxic tau species in V337M MAPT neurons was correlated with increased vulnerability to pro-apoptotic stress. Notably, this mutation-associated cell death was pharmacologically rescued by inhibition of effector caspases.Conclusions: Culturing iPSC-derived neurons for three months exposes age-related tau pathologies, including caspase-mediated cleavage, that are also observed in human postmortem brains with abnormal tau deposition. Neoepitope antibodies to caspase-cleaved tau may serve as biomarkers of tau pathology. Furthermore, caspases could be viable therapeutic targets for tau pathogenesis in FTLD and other tauopathies.
Simulation and refraction event of complex hyperbolic type solitary wave
in plasma and obtical fiber for the perturbed Chen-Lee-Liu equation
Authors: Yokuş Asıf , Durur Hülya , Duran Serbay
Published: March 2021

In this presented article, modified 1/G'-expansion and modified Kudryashov methods are applied to generate traveling wave solutions of perturbed Chen-Lee-Liu (CLL) equation. The similar and different aspects of the solutions produced by both analytic methods are discussed in the results and discussion section. By giving special values to the constants in the solutions obtained by analytical methods, 2D, 3D and contour graphics representing the shape of the standing wave at any time are presented. Additionally, the advantages and disadvantages of the two analytic methods are discussed and presented in the results and discussion section. Also, a solitary wave is produced by giving special values ​​to the parameters in the hyperbolic type complex traveling wave solution. Simulations are created for different values ​​of the frequency and velocity propagation parameters of the solitary wave. The values ​​of these parameters are calculated for the breakage event physically. A computer package program is used for operations such as solving complex operations, drawing graphics and systems of algebraic equations.
The Potential Value of Plasma Receptor Interacting Protein 3 for Neonatal Sepsis Diagnosis
Authors: Gao Chuchu , Feng Zongtai , Wang Lixia , Zhao Xingxing , Fu Kai , Ma Shurong , Yang Zuming , Wang Sannan , Yu Shenglin
Published: March 2021

Background: Neonatal sepsis is a systemic inflammatory response syndrome in neonates. The molecular mechanism of neonatal sepsis remains incompletely clarified. The purpose of this study was to explore the potential value of receptor interacting protein 3 (RIP3) in neonatal sepsis.Methods: 93 neonates with sepsis and 93 neonates without infectious diseases were enrolled in this study from September 2019 to March 2021. Plasma RIP3 was detected by enzyme-linked immunosorbent assay (ELISA) and assessed along with whole blood hypersensitive C-reactive protein (hs-CRP) and platelet count (PLT). Differences of RIP3, hs-CRP and PLT between the two groups were compared. Changes of the three indicators in sepsis were also observed after treatment. The diagnostic value of indicators for neonatal sepsis was evaluated by receiver operating characteristic (ROC) curve.Results: In sepsis group, RIP3 and hs-CRP levels were significantly higher than those in control group (RIP3, p ＜ 0.0001; hs-CRP, p ＜ 0.0001), and PLT level was significantly lower than that in control group (p＜0.0001). After treatment, RIP3 and hs-CRP levels among septic survivors had a significant decrease (p＜0.0001) and PLT level had a significant improvement (p=0.0028). With RIP3＞15464.72 pg/mL, CRP>3.24 mg/L, PLT<205.00×109 /L as the positive criteria, the sensitivity of the three indicators in the diagnosis of neonatal sepsis was 68.8%, 64.5%, 59.1%, and the specificity was 91.4%, 82.8%, 79.6%, respectively. The combination of RIP3, CRP and PLT showed 76.3% sensitivity and 94.6% sensitivity.Conclusions: RIP3 may attribute to the early diagnosis and understanding therapeutic effect of neonatal sepsis. The combined detection of RIP3, CRP and PLT may be more effective than individual ones in the diagnosis of neonatal sepsis.
Neuroprotection from Stem Cell-Derived Human Adipose Extracellular Vesicles Intranasally Administered 24 Hours After Stroke in Rats. 
Authors: Rohden Francieli , Teixeira Luciele Varaschini , Bernardi Luis Pedro , Lukasewicz Pâmela , Colombo Mariana , Teixeira Geciele Rodrigues , Oliveira Fernanda dos Santos de , Lima Elizabeth Obino Cirne , Guma Fátima Costa Rodrigues , Souza Diogo Onofre
Published: March 2021

Ischemic stroke is a major cause of death and disability, demanding innovative and accessible therapeutic strategies. Approaches presenting an optimal period for therapeutic intervention and new treatment administration routes are promising tools for stroke treatment. We evaluated the potential neuroprotective properties of nasally administered human adipose tissue stem cells (hAT-MSCs)-derived extracellular vesicles (EVs) obtained from healthy individuals who underwent liposuction. A single intranasal EV (200 µg/kg) was administered 24 h after a focal permanent ischemic stroke in rats. A higher tropism of EVs was observed in the peri-infarct zone surrounding the infarct core. In the same brain region, there was a significant decrease in the infarct volume, improvement of the blood-brain barrier, and re-stabilization of vascularization. In addition, EVs recovered the impairment of long-term motor and behavioral performance induced by an ischemic stroke. Surprisingly, one single intranasal EVs administration reestablished: i) front paws symmetry, ii) short- and long-term memory, and iii) anxiety-like behavior. In line with the findings, our work highlights hAT-MSC-derived EVs as a promising therapeutic strategy for stroke.
Pancreatic adenocarcinoma up-regulated factor as a target for the treatment of serous ovarian adenocarcinoma
Authors: Kim Yeon Jeong , Park Jin , Jeong Hyeon Hee , Baek Ji Eun , Hong Seung-Mo , Jeong Seong-Yun , Koh Sang Seok
Published: March 2021

Ovarian cancer is the deadliest gynecological cancer and when diagnosed at advanced stages the five-year survival rate is typically less than 30%. Pancreatic adenocarcinoma up-regulated factor (PAUF) plays a crucial role in tumor progression, angiogenesis, and immune evasion in the pancreatic tumor microenvironment. The current study aimed to characterize the potential tumorigenic role of PAUF in serous ovarian cancer as high expression of the factor is correlated with poor prognosis in epithelial ovarian cancer. Extracellular treatment with recombinant PAUF activated intracellular signal pathways that subsequently led to enhanced proliferation, migration, and invasion in various serous ovarian adenocarcinoma cell lines. A PAUF-knockout OVCAR-5 cell line demonstrated an apparent reduction in tumor incidence and delayed tumor growth in mouse xenograft experiments. Furthermore, the administration of an anti-PAUF antibody exhibited a notable therapeutic efficacy in mice bearing the OVCAR-5 cell line-derived xenograft tumors. Taken together, our results suggest that PAUF plays a role in the progression of serous ovarian adenocarcinoma and may serve as a novel therapeutic target of the disease.
Inanimate Objects and the Environment Are Far From Contributing to COVID-19 Spread
Authors: Rocha Ana Luiza Silva , Pinheiro Josilene , Nakamura Thamilin Costa , Silva José Domingos Santos da , Rocha Beatriz Gonçalves Silva , Klein Raphael Contelli , Birbrair Alexander , Amorim Jaime Henrique
Published: March 2021

It is not clear if COVID-19 can be indirectly transmitted. It is not possible to conclude the role of environment in transmission of SARS-CoV-2 without studying areas in which people transit in great amounts, such as market areas. In this work we aimed to better understand the role of environment in the spread of COVID-19. We investigated the presence of SARS-CoV-2 in inanimate objects as well as in the air and in the sewage using RT-qPCR. We studied both, a reference market area and a COVID-19 reference hospital at Barreiras city, Brazil. We collected and analyzed a total of 268 samples from mask fronts, cell phones, paper moneys, card machines, sewage, air and bedding during the ascendant phase of the epidemiological curve of COVID-19 in Barreiras. As a result, we detected the human RNAse P gene in most of samples, which indicates the presence of human cells in specimens. However, we did not detect any trace of SARS-CoV-2 in all samples analyzed. To rule out the possibility of problems in sampling method we tested detection of SARS-CoV-2 by RT-qPCR in laboratory conditions to reproduce environmental temperature and humidity. As a result, we showed detection of the virus in different conditions. We conclude that our sampling method reliable and that, strikingly, the environment and inanimate materials do not have an important role in COVID-19 transmission.
Antifreezing ionotronic skin based on flexible, transparent, and tunable ionic conductive nanocellulose hydrogels
Authors: Zhu Enwen , Xu Haiyu , Xie Yuanyuan , Song Yiheng , Liu Dongning , Gao Yujiao , Shi Zhuqun , Yang Quanling , Xiong Chuanxi
Published: March 2021

Ionic hydrogels with excellent flexibility and good conductivity have great potential in diverse electric devices. However, it remains challenging to improve the biocompatibility of ionic hydrogels. Here, natural and environment-friendly cellulose nanofiber hydrogels were prepared without adding any organic active materials. The cellulose hydrogel networks with free metal ions (Li+/Ca2+/K+) were obtained by soaking in ion aqueous solution of different concentrations in order to endow tunable conductivity, thus a new kind of transparent ionic hydrogels with both excellent sensing performance obtained by a simple, low-cost and harmless process. The free metal ions locked in the negatively charged nanocellulose network through electrostatic interaction provided adjustable conductivity and sensing performance. Hydrogels doped with 4 mol L− 1 lithium ions exhibited the best sensing performance with the conductivity of 4.36×10− 4 S cm− 1, and the current response value was as high as 127%. It was worth noting that the strain-sensitive performance of calcium ions was generally excellent even at low temperatures (-30°C). The antifreezing of the hydrogel improved its service under extreme environment. This kind of hydrogel has great application prospects in artificial intelligence products, such as human healthy monitoring equipment and soft robotics at subzero temperature.
Association of gene polymorphisms in MYH11 and TGF-β signaling with the susceptibility and clinical outcomes of Debakey type Ⅲ aortic dissection
Authors: Chang Yafei , Yuan Qinghua , Jiang Peipei , Sun Ling , Ma Yitong , Ma Xiang
Published: March 2021

Background: Myosin heavy chain 11 (MYH11) and transforming growth factor-β (TGF-β) signaling-related genes as the regulation of the structure and function of vascular smooth muscle cells (VSMCs) play a key role in the pathogenesis of aortic dissection (AD). This study aims to investigate the association of MYH11 and TGF-β signaling-related gene polymorphisms with the susceptibility of DeBakey type III AD and its clinical outcomes. Methods: A total of 159 patients with DeBakey Ⅲ AD and 305 healthy subjects were enrolled in this study. 4 SNPs (MYH11 rs115364997, rs117593370, TGFB1 rs1800469 and TGFBR1 rs1626340) were selected and analyzed. GMDR was used to evaluate gene-gene and gene-environment interactions. Patients were followed up for a median of 55.7 months. Results: MYH11 rs115364997 G carriers (OR = 1.629; 95%CI: 1.077-2.462, P = 0.020) or TGFBR1 rs1626340 A carriers (OR = 1.500; 95CI: 1.032-2.181, P = 0.033) had a higher risk of DeBakey type Ⅲ AD. MYH11, TGFB1, TGFBR1, and environment interactions are contribute to DeBakey type Ⅲ AD risk (CVC=10/10, P = 0.001). Dominant models of MYH11 rs115364997 AG+GG genotype (HR = 2.443; 95%CI:1.096-5.445, P = 0.029), TGFB1 rs1800469 AG+GG (HR = 2.303; 95%CI:1.069-4.96, P = 0.033) were associated with a higher risk of mortality in DeBakey type III AD. TGFB1 rs1800469 dominant model AG+GG genotype was associated with a higher risk of recurrence of chest pain in DeBakey type III AD (HR = 1.566; 95%CI: 1.018-2.378, P = 0.041). Conclusions: This study indicated that variations of MYH11 rs115364997 and TGFBR1 rs1626340 are associated with genetic predisposition of DeBakey type III AD. G carriers of MYH11 rs115364997 or TGFB1 rs1800469 may be the poor prognostic indicators of mortality and recurrent chest pain in DeBakey type III AD. The interactions of gene-gene and gene-environment are associated with the risk of DeBakey type III AD.
Mutation based Atom Search Optimization Algorithm for Hyperparameter Optimization of the DenseNet121 Architecture for Cervical Cancer Classification
Authors: Chitra B , Kumar S.S.
Published: March 2021

The cervical cancer patient’s death rate can be minimized by accurate and early detection of cervical cancer (CC). One of the popular techniques called the Pap test or Pap smear is widely used for the early detection of CC. The manual analysis consumed more time in the case of CC detection. The existing techniques met few shortcomings in terms of poor accuracy, more computational complexity, higher feature dimensionality, poor reliability, and higher time-consumption with poor hyperparameters optimization. Hence, the computer-aided diagnostic model provides reliable and accurate CC detection at the initial stage. In this paper, we proposed MASO optimized DenseNet 121 architecture for the early detection of cervical cancer. At first, different kinds of augmentation techniques such as horizontal flip, vertical flip, zooming, shearing, height shift, width shift, rotation, and brightness to increase the number of training samples. The Mutation based Atom Search Optimization (MASO) algorithm is established to optimize the hyperparameters in DenseNet 121 architecture suchnumber of neurons in the dense layer, learning rate value, and the batch sizes. Different kinds of performance metrics such as accuracy, specificity, sensitivity, precisions, recall, F-score, and confusion matrix evaluate the performance of MASO optimized DenseNet 121 architecture for CC detection. A single normal class with three abnormal classes namely Carcinoma, Light dysplastic, and Sever dysplastic were selected from the Hervel dataset for experimental investigation. The proposed MASO optimized DenseNet 121 architecture achieves 98.38% accuracy, 98.5% specificity, 98.83% sensitivity, 98.58% precision, 99.3% recall and 98.25% F-score values than other existing methods.
Global Evidence on the Rapid Adoption of Telemedicine in Primary Care During the First Year of the COVID-19 Pandemic: a Scoping Review Protocol.
Authors: Valdes Daniela , Alqazlan Lama , Procter Rob , Dale Jeremy
Published: March 2021

Background: Before the declaration of the COVID-19 pandemic in March 2020, primary care relied on face-to-face consultations, with relatively limited use of telemedicine. The rapid uptake that occurred following the onset of the pandemic in countries such as the United Kingdom, Canada and New Zealand prompts questions around the drivers and extent of this transformation in clinical practice at global level. The purpose of this scoping review is to explore the global evidence surrounding the rapid adoption of telemedicine in primary care settings during the first year of the COVID-19 pandemic. Methods: A draft protocol was tested through an initial search on Ovid Medline, Web of Science and Google Scholar with additional searches on the Cochrane Database. This informed the final selection of terms which will be use to search Ovid, Web of Science, Google Scholar, PROSPERO and Cochrane Library, filtering for studies from the pandemic declaration onwards. Additional grey literature reports will be sourced through simplified searches on appropriate search engines in widely spoken languages. Duplicates will be removed by screening titles. Abstracts and grey literature text extracts will be screened based on pre-set eligibility criteria by an automated tool and further screened by the lead researcher. Abstracts (and extracts in the case of grey literature) will be mapped against the domains of the Non-adoption, Abandonment, and challenges to Scale-up, Spread and Sustainability (NASSS) framework. Data will be presented in table format. Discussion: This review will map the current literature to identify current gaps in evidence related to the adoption of telemedicine after the declaration of the pandemic in March 2020. The use of simplified searches in the most spoken languages in the world is aimed at capturing more immediate non-academic reflections and experiences on this major service change at a global level.Systematic review registration: Study has been registered on Open Science Framework and can be accessed through the following URL: https://osf.io/4z5ut/
Radiation Modification and Characterization of Polyvinyl alchohol/Starch/Citric Acid/Glycerol Bioblend Film
Authors: Ghaffar Ashraf M. Abdel , Ali H. E.
Published: March 2021

The blending of polyvinyl alcohol (PVA) with starch with different content of citric acid as crosslinker and glycerol as plasticizer were performed by casting method. The hydroxyl groups of PVA and Starch react with the citric acid (1 %) and glycerol (10 vol %) to form crosslinked network. The FTIR spectral analyses show the successful preparation of the different composition of the prepared PVA/ Starch /Citric acid/Glycerol bioblend films. It is found that the prepared PVA/ Starch /Citric acid/Glycerol with composition (2:1:1/10 vol %) bioblend film characterized by higher water resistance, good mechanical and higher thermal stability than other prepared bioblend films. The using of gamma radiation improved and modified water resistance property were the water uptake at equilibrium reduced remarkably at dose of 10 kGy. Also the thermal stability increased as irradiation dose increased up to dose of 30 kGy The improved mechanical and thermal properties of the selected PVA/ Starch /Citric acid/Glycerol with composition (2:1:1/10 vol %) bioblend film were compared with LDPE and PP packaging films and found to be competitive to the these commercially packaging films which are also nonbiodegradable synthetic polymers than the prepared selected PVA/ Starch /Citric acid/Glycerol with composition (2:1:1/10 vol %) bioblend film. Hence this study can be represent potential development of low cost-effective and modified PVA/ Starch /Citric acid/Glycerol with composition (2:1:1/10 vol %) bioblend film that characterized by several advantages over the commercially available petrochemical films and can be used in different applications such as packaging industry.
A Questionnaire-based Study to Comprehensively Assess the Status Quo of Rare Disease Patients and Care-givers in China
Authors: Li Xuefeng , Liu Meiling , Li Bingzhe , Zhang Xiangyu , Zhang Shu , Lu Zijuan , Zhang Jianyong , Zhou Jincheng , Ou Li
Published: March 2021

Background: There are over 16.8 million rare disease patients in China, representing a large community that should not be neglected. To provide a basis for policy-makers to better understand the status quo of rare disease patients and care-givers in China and to devise some new policies, a comprehensive analysis of the status quo, unmet needs, difficulty caused by the rare disease is essential.Methods: A questionnaire-based study of patients and care-givers (usually family members) was performed. The questionnaire was composed of 116 questions, such as the diagnosis process, treatment access, financial burden, views on patients’ organizations, and a series of standardized tests to assess the quality of their life, including the SF-36, PHQ-9, PHQ-15, GAD-7, and PSQI. To examine the influence of age, disease type, and relationship to patients on the scores in these tests, statistical analysis with a general linear model was conducted.Findings: A total of 1,959 patients and care-givers participated in the survey, representing 104 rare diseases, such as lysosomal storage diseases, hemophilia, and muscular dystrophy diseases. The diagnosis was delayed for 1.4 ± 3.0 years, and patients experienced 1.6 ± 3.8 misdiagnoses between 3.2 ± 2.4 hospitals. The hospitals where diagnoses were made were highly concentrated in 10 large hospitals (43.8%) and 5 big cities (42.1%), indicating a significant inequality of medical resources. The disease often led to difficulty in social life, education, and employment, as well as financial burden that was seldom covered by medical insurance. A battery of standardized tests demonstrated poor health status, depression, somatization, anxiety, and sleeping issues among both patients and care-givers (p<0.05).Statistical analysis of the questionnaire also showed that poor health, anxiety, depression, somatization, and sleeping problems were more prevalent in patients than in care-givers, and more prevalent in more severe diseases (e.g., hemophilia, Dravet) or undiagnosed than in other diseases.Interpretations: This study identified the lack of rare disease awareness and legislative support as the major challenge to rare diseases in China, and makes key recommendations for policy-makers, including legislating orphan drug act, raising rare disease awareness, and protecting rights in education and employment.
Synchronisation Conditions for a Class of Non-linearly Coupled Networks using Contraction Based Strategy
Authors: CHAUHAN YASHASVI , Sharma Bharat Bhushan
Published: March 2021

This paper describes a simple and general framework for synchronisation of non-linearly coupled dynamical systems interconnected to constitute a com- plex network. The proposed methodology of attaining synchronisation of networks is based on contraction strat- egy. The paper introduces a systematic control proce- dure to achieve synchronisation of a coupled dynamical network of proposed strict-feedback like class of nonlin- ear systems. The non-linear coupling function between different systems of the network is assumed to be in the form of bidirectional links. The proposed method- ology can be applicable to any arbitrarily structure of linear/non-linear, bidirectional or unidirectional N- coupled systems in a network. The general results have been derived for coupled systems interacting through nonlinear coupling function which are interconnected in different networked topologies including Ring, Global, Star, Arbitrary etc. The analytical conditions for syn- chronisation are expressed in terms of bounds on cou- pling strength which are derived using partial contrac- tion concepts blended with graph theory results. The proposed approach is straightforwardly applied to high dimensional non-linearly coupled chaotic systems which are common in many applications. A set of representa- tive examples of coupled chaotic systems based network are simulated to verify the theoretical results.
Does Patent Foramen Ovale Presence Procure Favourable Outcomes In Patients With Severe Rheumatic Mitral Stenosis ?
Authors: Guler Gamze , Dogan Arda Can , Kalkan Ali Kemal , Demir Ali Riza , Uygur Begum , Birant Ali , Agus Hicaz Zencirkiran , Pastore Maria Concetta , Memic Kadriye , Uzun Fatih , Cameli Matteo , Erturk Mehmet
Published: March 2021

Purpose:Mitral stenosis (MS) is torelated for an extended period in patients with atrial septal defect (ASD) known as Lutembacher syndrome due to depressurizing effect. In a similar way, patients with patent foramen ovale (PFO) may have clinical benefits in severe MS. We aim to evaluate the clinical effects of PFO in rheumatic MS. Methods and Results:Transthoracic and transesophageal echocardiography records of the patients with symptomatic severe MS were screened for the period between 2008-2019 in a single center. Three-hundred-twenty symptomatic patients with severe MS were included and presence of PFO recorded. Left atrial appendix (LAA) thrombotic status was defined as clear, spontaneous echo contrast, and thrombus. Two different statistical models were used to determine the predictors of either smallest (mitral valve area) MVA at symptomatic presentation or more thrombogenic LAA. Thirty-four patients had PFO. Multivariable ordinary least square model demonstrated that increase in systolic pulmonary arterial pressure, ejection fraction and presence of PFO were associated with smaller MVA on presentation. Multivariable proportional odds logistic regression model demonstrated that advanced age, increased left atrial diameter, absence of PFO were associated with more thrombotic status whereas larger MVA was associated with decreased thrombotic status in LAA. Conclusion:Presence of PFO in severe MS results in two clinical benefits as i) being asymptomatic with smaller MVA and ii) having less LAA thrombosis probably caused by depressurizing effect on the left atrial pressure. Our study, could serve as an example for patient groups with expected symptomatic benefits from left atrium pressure offloading interventions.
Optimizing Frontline Networking Between Consultant-Led Neonatal Teams in the West Midlands: A Qualitative Report on the Utility of Modified Simulation Training. 
Authors: pillay Tilly , Clarke Lynsey , Abbott Lee , Surana Pinki , Shenvi Asha , Deshpande Sanjeev , Cookson Joanne , Nash Matthew , Fawke Joe , Rasiah Vishna , Cusack Jonathan
Published: March 2021

Background: In England neonatal care is delivered within operational delivery networks. Units within these networks are one of three designations (Neonatal Intensive Care, Local-Neonatal or Special-Care Units), based on their ability to care for babies with different degrees of illness or prematurity. With the development of network care-pathways, the most premature and sickest are triaged where possible for delivery in services linked to Neonatal Intensive Care units. This has created anxiety for teams in Local-Neonatal and Special-Care units. Less exposure to sicker babies meant limited opportunities to maintain expertise for when they do unexpectedly deliver at services linked to their own units, and thereafter require transfer for ongoing care, to Neonatal Intensive Care units. Simultaneously, Local-Neonatal and Special-Care teams develop skills in care of the less ill and premature baby which was considered of benefit to all. A need for mutual learning through networking between teams of different designations emerged.Method: An interactive programme, ‘Supporting The Sick Neonate’ was developed in the West Midlands. It focused on equal partnership between unit designations, employing high, medium and low fidelity simulation as the vehicle around which networking between units was centered. Sessions of simulation and debrief were augmented with novel networking time to enable multidirectional learning and understanding of practices. Candidates and facilitators were regarded as participants, spanning different designations. A consultant-focus was adopted to promote long term networking. Qualitative assessment of the programme over four years was captured through -graded and free text surveys.Results: 155 individuals involved in frontline neonatal care participated. 77 were consultants, supported by neonatal trainees, staff grade doctors, clinical fellows, advanced neonatal nurse practitioners and nurses in training. All were invited to participate in the qualitative survey. 79% felt that it was highly relevant; 96% agreed that for consultants this was appropriate adult learning. 98% agreed that consultant training encompassed more than bedside clinical management, including forging communication links between teams. Thematic responses around networking were positive.Conclusion: Simulation augmented with networking time with a consultant-focused model proved successful for networking and shared learning for the Neonatal fraternity in the West Midlands.
The Study of Screw Placement Parameters for Ogawa Type I Acromial Fractures by 3D Technology
Authors: Zhang Wei , Sun Zhongye , Li Weiyan , Yan Jun , Han Liren , Han Shizhang , Yang Xiaofei , Zhao Bei
Published: March 2021

Background: Acromial fractures are rare and there is no consensus on fixation, but more and more studies have reported using two screws to fix Ogawa type I acromial fractures. The objective of this study was to obtain the ideal length, diameter, insertion point and angle of the screw using a novel 3D technology. Methods: Scapula CT data of 100 human subjects were obtained to reconstruct 3D models. The transparency of 3D models was then downgraded along the axial perspective (the view perpendicular to the cross section of the acromial axial) to find the maximum translucent area. Two virtual screws were placed from the anterior edge of the acromial until they penetrated the posterior cortical bone. The largest diameters and lengths of the screw were measured, and the direction and insertion point of the screw were observed.Results: The mean maximum lengths of medial and lateral screws were 43.33±6.17mm and 39.23±6.01mm, respectively. The mean maximum diameters of medial and lateral screws were 4.71±1.23 mm and4.97±1.07mm, respectively. The study found differences in screw length, diameter and insertion point between males and females. The differences sexes in screw angle were not statistical significance.Conclusions: Using the 3D model, we demonstrated that the distal acromial can be safely placed with two screws and provide valuable guidance for screw fixation of Ogawa type I acromial fractures.
Hypoactivity, Abnormal Musculature, and Learning and Memory Defects in slc6a3 zebrafish Mutant Larvae
Authors: Jiang Yu , Geng Nan , Wang Peisong , Lu Xiaojie
Published: March 2021

Dopamine (DA) is one of the most common neurotransmitters in living organisms and is involved in the regulation of behavior, physiology, and disease. The dopamine transporter (DAT, encoded by the slc6a3 gene) re-uptakes dopamine from the synaptic cleft back into neurons, which plays a critical role in regulating dopamine signaling. Clinically, mutations in slc6a3 have been implicated in various diseases. Zebrafish are good model organisms for studying the functions of slc6a3 and dopamine. Work using the zebrafish slc6a3 mutant has previously been reported, but this mutant is not a complete loss-of-function mutant. In the present study, we knocked out the slc6a3 gene using CRISRP/Cas9 technology and obtained a zebrafish mutant with complete loss of function of slc6a3. Behavioral assessments and quantitative reverse transcription (qRT)-PCR revealed musculature injury, decreased activity, and decreased learning and memory ability in the slc6a3 mutant. This study provides a new theoretical basis for understanding the function of slc6a3 and provides a new model organism for studying the molecular pathology underscoring dopamine metabolism-related diseases. It also provides a suitable model for high-throughput screening of small-molecule drugs targeting slc6a3.
Diverse Analysis of Data Mining and Machine Learning Algorithms to Secure Computer Network
Authors: Kumar Neeraj , Kumar Upendra
Published: March 2021

Information and Communication Technologies, to a long extent, have a major influence on our social life, economy as well as on worldwide security. Holistically, computer networks embrace the Information Technology. Although the world is never free from people having malicious intents i.e. cyber criminals, network intruders etc. To counter this, Intrusion Detection System (IDS) plays a very significant role in identifying the network intrusions by performing various data analysis tasks. In order to develop robust IDS with accuracy in intrusion detection, various papers have been published over the years using different classification techniques of Data Mining (DM) and Machine Learning (ML) based hybrid approach.
The present paper is an in-depth analysis of two focal aspects of Network Intrusion Detection System that includes various pre-processing methods in the form of dimensionality reduction and an assortment of classification techniques. This paper also includes comparative algorithmic analysis of DM and ML techniques, which applied to design an intelligent IDS. An experiment al comparative analysis has been carried out in support the verdicts of this work using ‘Python’ language on ‘kddcup99’ dataset as benchmark . Experimental analysis had been done in which we had found more impact on dimensionality reduction and MLP performed well in the true classification to establish secure network. The motive behind this effort is to detect different kinds of malware as early as possible with accuracy, to provide enhanced observant among various existing techniques that may help the fascinated researchers for future potential works.
JAK2 V617F Mutational Burden and Clinical Findings Relationship in Myeloproliferative Neoplasms
Authors: Kahraman Cigdem Yuce , Sincan Gulden , Tatar Abdulgani
Published: March 2021

Background: Philadelphia-negative chronic myeloproliferative neoplasms(MPN) are associated with various genetic abnormalities. JAK2 V617F mutation is the most common one and important for diagnosis. We aimed to evaluate JAK2 mutation status and clinical parameters relationship of the MPN patients referred to our clinic.Methods and Results: We evaluate 143 JAK-2 positive patients diagnosed with polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis (PMF). JAK2 mutational burden was higher in PV and PMF than ET. Laboratory findings were different in MPN groups and higher –lower JAK2 mutational burden groups. JAK2 mutational burden was correlated with spleen size and LDH level, particularly in PMF. There was no significant difference in age, gender, jak2 mutation burden and laboratory findings in patients with and without thrombosis and bleeding. Common treatment protocols were acetylsalicylic acid (ASA) + hydroxyurea, ASA and ASA + phlebotomy and others respectively. JAK2 mutational burden, mean age and LDH level were higher significantly in the patients treated with ASA+ hydroxyurea than the patients treated with ASA.Conclusion: We speculate that if the spleen size in MPN is as large as the massive splenomegaly and the LDH level is high, the JAK2 mutation burden may tend to be higher. This relationship is more pronounced for PMF.
One-plasmid based CRISPR-Cas9 editing for gene deletion in Lactococcus lactis
Authors: Santos José Miguel Miquelão , Monteiro Gabriel António Amaro , Prazeres Duarte Miguel de França Teixeira dos , Duarte Sofia de Oliveira Dias
Published: March 2021

Lactococcus lactis strains are promising cell factories and delivery vehicles of plasmid DNA and recombinant protein for therapeutic applications. However, the limited yields of recombinant molecules obtained with these bacteria limits their wide applicability. Genome engineering of this host may solve the problem. However, the current genome editing toolbox available for L. lactis is either too laborious or incapable of large edits, limiting the scope of strain editing experiments. In this work, the basis for a one-plasmid CRISPR-Cas9 based genome editing plasmid was developed and tested. The new plasmid (pTCas9dO) adapted from the pKCcas9dO plasmid was used to delete 657 bp of the lactococcal nuclease nth of L. lactis subsp. lactis LMG19460, with the aim of improving yield and quality of plasmid DNA replicated in this strain. Although deletion mutants were successfully generated, plasmid curing was unsuccessful. Thus, further modifications are required before the plasmid is truly applicable for genome editing experiments. Unexpectedly, the generated deletion mutants generated a roughly 40% decrease in plasmid yield alongside with a decrease in the quality of produced pDNA.
The effect of mistletoe extract on tumor response in neoadjuvant chemoradiotherapy for rectal cancer
Authors: Baek Jeong-Heum , Jeon Youngbae , Han Kyoung-Won , Kim Kyung-Ok
Published: March 2021

Background

Mistletoe extract, which is usually used as a complementary agent for cancer patients, provides an anticancer effect on various malignancies. The present study aimed to evaluate the effect of mistletoe extract (Abnoba Viscum Q®) on tumor responses in neoadjuvant chemoradiotherapy for locally advanced rectal cancer.
Methods

The rectal cancer patients who underwent neoadjuvant chemoradiotherapy were analyzed from Jan 2018 to Jul 2020. In the mistletoe group (MG), the patients were administered Abnoba Viscum Q® subcutaneously during chemoradiotherapy, and it was maintained just before surgery. Patients' demographics, clinical outcomes, and histopathological outcomes were compared between chemoradiation with the MG and nonmistletoe group (NMG).
Results

A total of 52 patients were included. There were MG of 15 patients and NMG of 37 patients. Baseline demographics were statistically similar between the two groups except the CA19-9 and tumor location levels from anal verge. There was no difference in the clinical stage for both groups. We also observed better tumor response in MG in terms of TRG, T stage, and overall TNM stage. Tumor response was significantly better in MG comparing NMG in terms of pathologic complete response rate (53.3% vs 21.6%, p = 0.044), good responder of tumor regression grade (66.7% vs 32.4%, p = 0.024), T downstaging (86.7% vs 43.2%, p = 0.004), and overall downstaging (86.7% vs 56.8%, p = 0.040). The toxicities during NCRT in both groups were minimal.
Conclusion

MG treated with chemoradiation combined with mistletoe extract showed better outcomes than NMG in terms of tumor responses. This diversity in treatment may elevate the method to hope for better oncologic outcomes. Prospective and randomized studies with long-term follow-up are warranted to confirm and extend this study.
Clinical Features of Patients With Major Depressive Disorder and Bipolar Disorder Depressive Episodes With Mixed Features 
Authors: Wang Hong , Xiao Yan-Xia , Du Jing-Ge , Du Xia , Chen Lin
Published: March 2021

Background: To investigate the clinical phenomenology and clinical features of the new concept of major depressive disorder and bipolar disorder depressive episodes with mixed features.Methods: A total of 357 patients with major depressive disorder or bipolar disorder depressive episodes were assessed, we compared the differences of clinical features with or without mixed features.Results: According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria, the overall prevalence of mixed features was 9.52% (34/357) in major depressive disorder and bipolar disorder depressive episodes; specifically, the prevalence was 6.0% in major depressive disorder and 23.3% in bipolar disorder depressive episodes. Compared with the non-mixed features group, the mixed features group had more single individuals (P=0.002), earlier onset age (P=0.003), more patients with an onset age <25 years (P=0.001), and more previous incidences and prior hospitalizations (P<0.001, P=0.004, respectively), and fewer melancholic features (P=0.013).Logistic regression analysis showed that marital status (OR=0.237) and previous incidence (OR=1.478) was associated with mixed features.Conclusion: It indicates that previous incidence may be a risk factor of in patients with major depressive disorder and bipolar disorder depressive episodes with mixed features, and marital status may be a protective factor.
MVP (Micro Vascular Plug®) Embolization Experience on 104 Patients: How to Select to Proper Model and Avoid Technical Failures
Authors: Giurazza Francesco , Ierardi Anna Maria , Contegiacomo Andrea , Corvino Fabio , Carrafiello Gianpaolo , Niola Raffaella
Published: March 2021

Aim: To describe a three years experience of peripheral arterial embolization with Micro Vascular Plug (MVP) (Medtronic, USA).Materials and methods: 116 MVP have been released in 104 patients (67 males and 37 females; mean age 61.3 years). The pullback release technique was adopted in each case. The following parameters were investigated: angiographic appearance of the vascular injury, anticoagulation therapy at time of procedure, district, caliper of the target artery, course of the landing zone, additional embolics, technical and clinical success.Technical success was defined as complete embolization without deployment of additional embolics.Primary clinical success was considered as hemodynamic stability in emergency setting and resolution of the underlying vascular pathology in elective cases; secondary clinical success was considered clinical success after a second embolization session.Results: Vessel occlusion was achieved in 78 patients after MVP release, while in 26 subjects additional embolics were required; the overall technical success was 75%. Primary clinical success was 96.1%.MVP was oversized between 30% and 40% compared to the target vessel caliper; MVP-3 and MVP-5 were the most frequently adopted in this sampleNo statistical differences in terms of effectiveness were observed among patients assuming anticoagulation. A straight and longer landing zone were statistically associated with higher technical success compared to a curved and a shorter ones, respectively. No clinically adverse events directly related to MVP device occurred; in 3 cases migration was registered without clinical complications.Conclusion: MVP is a safe and effective embolic device. Oversizing is recommended. While eventual concomitant anticoagulation therapy did not influence the technical outcome, straight course and length of the landing zone are essential parameters to evaluate before deployment.
Overweight and Obesity Among The Army Personnel with Low Socio-Economic Status In Kuala Lumpur: A Cross-Sectional Study
Authors: NAR Nik Qistina , MZ Nor Afiah , Moideen M Arshil , Ahmad Rozali
Published: March 2021

Background: The prevalence of overweight and obesity in adults worldwide was 52%, which is a major public health concern. Military institutions worldwide were also plagued with this problem. 57.2% of the army personnel in Malaysia were overweight and obese, in which 52.6% had low socioeconomic status (SES). This led to negative impacts on the overall combat readiness due to the obesity-associated-diseases. This study determined the prevalence and predictors of overweight and obesity among the low SES army personnel in Kuala Lumpur.Methods: A cross-sectional study was conducted using a proportionate random sampling among 772 army personnel from low SES group in army camps in Kuala Lumpur. Online questionnaires were distributed while latest anthropometric measurements’ data were obtained from the Military Lifetime Health Record (MLHR) system. The outcome of this study was overweight and obesity (BMI of > 25kg/m2). Data were analysed using SPSS version 23.0 involving descriptive and inferential statistics.Results: The median age of the respondents was 30 (IQR=7) years. The prevalence of overweight and obese army personnel was 41.1% (95%CI:37.6-44.6). The predictors found were being married (AOR:2.026, 95%CI:1.318-3.113), secondary education (AOR:2.545, 95%CI:1.245-5.203), Lance Corporal (AOR:1.994, 95%CI:1.061-3.748), Corporal (AOR:2.814, 95%CI:1.578-5.020), Sergeant (AOR:4.174, 95%CI:2.076-8.390), past injury (AOR:1.879, 95%CI: 1.191-2.965), history of obese sibling (AOR:1.737, 95%CI:1.013-2.973), history of obese parent (AOR:3.344, 95%CI:1.965-5.688), history of obese grandparent (AOR:11.321, 95%CI:2.207-58.072), poor knowledge on dietary intake (AOR:1.524, 95%CI:1.077-2.157), less than 2 litres daily plain water intake (AOR:1.606, 95%CI:1.166-2.210).Conclusions: Knowledge on dietary intake and plain water intake are the two modifiable predictors for overweight and obesity found in this study, while the other nine predictors are non-modifiable. Understanding on issues surrounding the low SES group will help the strategic level in planning for future comprehensive interventions on overweight and obesity, specifically targeting on those predictors.
Barriers and Facilitators to COVID-19 screening at Jaipur International Airport, India.
Authors: Mantri Neha , Joshi Nitin Kumar , Bhardwaj Pankaj , Goel Akhil Dhanesh , Gupta Manoj Kumar , Singh Kuldeep , Misra Sanjeev
Published: March 2021

The authors have requested that this preprint be removed from Research Square.
Interspecific Potato Somatic Hybrids Between Solanum Malmeanum and S. Tuberosum Provide Valuable Resources for Freezing-Tolerance Breeding
Authors: Tu Wei , Dong Jianke , Zou Ying , Zhao Qinghao , Wang Haibo , Ying Jingwen , Wu Jianghai , Du Juan , Cai Xingkui , Song Botao
Published: March 2021

Freezing stress affects the geographic distribution, growth, and development of potato, resulting in loss of its yield. Solanum malmeanum , a diploid wild species with strong freezing tolerance, was fused with a freezing sensitive dihaploid S. tuberosum by somatic hybridization. In our study, 980 calli were obtained, and 248 differentiate shoots from the calli. Parental-specific SSR markers were used to analyze the chromosome composition of the randomly selected 80 regenerated plants, resulting in 51 somatic hybrids. Among them, 44 somatic hybrids were tested with ploidy analysis in the years 2016 and 2020. During subculture, the genomic ploidy levels changed due to the composition of the unstable chromosome in 56.82% of the somatic hybrids. Compared with the cultivated parent, somatic hybrids showed better freezing tolerance. After freezing-tolerant somatic hybrids were selected to backcross with cultivars, we obtained some valuable breeding resources with enhanced freezing tolerance while similar tuberization capacity close to cultivars. The correlation analysis shows that freezing tolerance has no relation with tuberization capacity, which indicates that they are controlled by independent genetic loci. In all, we successfully conducted the protoplast fusion between S. malmeanum and S. tuberosum for the first time, which provided valuable resources for freezing-tolerant breeding.