bluuebunny/crossref_metadata_2025 huggingface dataset:
Near-surface Structure of Downtown Jinan, China: Application of Ambient Noise Tomography with a Dense Seismic Array
Authors: Liang Feng , Wang Zhihui , Li Hailong , Liu Kai , Wang Tao
Published: December 2020

Urban geophysics ups the ante in the world of applied geophysics, which requires innovative thinking and seemingly off-the-wall approaches, if for no other reason than the settings. Ambient-noise-tomography (ANT) can play a pivotal role in yielding subsurfa2ce information in urban areas, which is capable of dealing with challenges related to these scenarios ( e.g., human activities and low signal-to-noise ratio). In this study, the ANT was conducted to investigate the near-surface shear-velocity structure in the surrounding area of the Baotu Spring Park in downtown Jinan, Shandong Province, China. Quiet clear Rayleigh waves have been obtained by the cross-correlation, which indicates that strong human activities, such as moving vehicles and municipal engineering constructions, can produce approximately isotropic distribution of noise sources for high-frequency signals. The direct surface-wave tomographic method with period-dependent ray-tracing was used to invert all surface-wave dispersion data in the period band 0.2-1.5 s simultaneously for 3D variations of shear-velocity (Vs) structure. Our results show a good correspondence to the geological features with thinner Quaternary sediments, the geological structural characteristic of the limestone surrounded by the igneous which has the highest velocity than that of the limestone in the study area, and several concealed faults of which specific location has been detected at depth. The results demonstrate that it is possible to successfully use ANT with high-frequency signal in an urban environment provided a detailed planning and execution is implemented.
The Development and Applications of the Helicopter-borne Transient Electromagnetic System CAS-HTEM
Authors: Wu Xin , Fang Guangyou , Xue Guoqiang , Liu Lihua , Liu Leisong , Li Jutao
Published: December 2020

Over the past decade, helicopter-borne transient electromagnetic (HTEM) systems have been rapidly developed. A new HTEM prototype (referred to as a CAS-HTEM) has been developed by the Chinese Academy of Sciences. In terms of hardware, the CAS-HTEM system uses an inflatable structure to carry the transmitting loop, which significantly reduces the weight of the system and makes it easier to transport. A dual gain receiver was innovated to extend the dynamic range of the system. In addition, an observation circuit for transmitting voltage waveform is introduced, so that the derivative waveform of transmitting current with higher SNR could be calculated. In terms of data processing, more reliable early time data could be obtained by band-limited effect removal; a weighted stacking algorithm is introduced to reduce the narrow band noise more effectively and increase the sensitivity of data to the anomaly location; a method based on τ-domain transform is used for late time signal processing. The results of the field test which was carried out in Inner Mongolia were found to be consistent with the drill data, which effectively verified the performance of this HTEM prototype.
One year follow-up and mediation in Cognitive Behavioral Therapy and Acceptance and Commitment Therapy for adult depression
Authors: A-Tjak Jacqueline G.L. , Morina Nexhmedin , Topper Maurice , Emmelkamp Paul M.G.
Published: December 2020

Background Existing therapies for depression are effective, but many patients fail to recover or relapse. To improve care for patients, more research into the effectiveness and working mechanisms of treatments is needed. We examined the long-term efficacy of Cognitive Behavioral Therapy (CBT) and Acceptance and Commitment Therapy (ACT) for Major Depressive Disorder (MDD), testing the hypothesis that CBT outperforms ACT and that both therapies work through their designated mechanisms of change.Methods We conducted a randomized controlled trial with 82 patients suffering from MDD. Data were collected before, during and after treatment, and at 12-month follow-up, assessing symptoms of depression, quality of life, dysfunctional attitudes, decentering , and experiential avoidance.Results Patients in both conditions reported significant and large reductions of depressive symptoms (d = -1.26 to -1.60) and improvement in quality of life (d = 0.91 to -1.28) 12 months following treatment. Our findings indicated no significant differences between the two interventions. Dysfunctional attitudes and decentering mediated treatment effects of depressive symptoms in both CBT and ACT, whereas experiential avoidance mediated treatment effects in ACT only. Conclusions Our results indicate that CBT is not more effective in treating depression than ACT. Both treatments seem to work through changes in dysfunctional attitudes and decentering, even though the treatments differ substantially. Change in experiential avoidance as an underlying mechanism seems to be an ACT-specific process. Further research is needed to investigate whether ACT and CBT may work differently for different groups of patients with depression.
Low levels of soluble TWEAK, indicating on-going inflammation, were associated with depression in type 1 diabetes: a cross-sectional study
Authors: Melin Eva.O. , Dereke Jonatan , Hillman Magnus
Published: December 2020

BackgroundLow levels of the soluble tumour necrosis factor-like weak inducer of apoptosis (sTWEAK) and depression are linked to cardiovascular disease. Galectin-3, inadequate glycemic control and low high-density lipoprotein (HDL)-cholesterol levels were previously linked to depression in these patients with type 1 diabetes mellitus (T1DM). The main aim was to explore whether sTWEAK was associated with depression. A secondary aim was to explore diabetes related variables associated with low sTWEAK.MethodsCross-sectional design. T1DM patients (n = 283, men 56%, age18-59 years) were consecutively recruited from one specialist diabetes clinic. Depression was defined as Hospital Anxiety and Depression Scale-Depression sub scale ≥ 8 points. Blood samples, anthropometrics and blood pressure were collected, supplemented with data from electronic health records. Enzyme linked immunosorbent assays were used to measure sTWEAK and galectin-3. Low sTWEAK was defined as < 7.2 ng/ml and high galectin-3 as ≥ 2.6 ng/ml. Multiple logistic regression analyses were performed, calibrated and validated for goodness of fit. We adjusted for age, sex, diabetes duration, galectin-3, metabolic variables, serum-creatinine, smoking, physical inactivity, medication, and cardiovascular complications. Results For 29 depressed versus 254 non-depressed patients the prevalence rates were for low sTWEAK: 93% and 68% (p = 0.003) and for high galectin-3: 34% and 13% (p = 0.005) respectively. HDL-cholesterol levels were lower for the depressed (p = 0.015). Patients with low sTWEAK versus high sTWEAK had lower usage of continuous subcutaneous insulin infusion (CSII) (6% versus 17%, p = 0.005). Low sTWEAK (adjusted odds ratio (AOR) 9.0, p = 0.006), high galectin-3 (AOR 6.3, p = 0.001), HDL-cholesterol (per mmol/l) (AOR 0.1, p = 0.006), use of antidepressants (AOR 8.4, p < 0.001), and age (per year) (AOR 1.05, p = 0.027) were associated with depression. CSII (AOR 0.3, p = 0.003) and depression (AOR 7.1, p = 0.009) were associated with low sTWEAK.ConclusionsLower levels of sTWEAK and HDL-cholesterol and higher levels of galectin-3 were independently associated with depression in T1DM. These factors might all contribute to the increased risk for cardiovascular disease and mortality previously demonstrated in patients with depression. CSII (inversely) and depression were independently associated with low sTWEAK levels.
Assessment of the Efficacy of the Far Cortical Locking Technique in Proximal Humeral Fractures: A Comparison with the Conventional Bi-cortical Locking Technique 
Authors: seo joongbae , Kim Yoenjun , Kim Kyubeom , Yoo Jae-Sung
Published: December 2020

Background Locking plate fixation is one of the treatment strategies for the management of proximal humeral fractures. However, stiffness after locking plate fixation is a clinical concern. The mechanical stiffness of the standard locking plate system may suppress the interfragmentary motion necessary to promote secondary bone healing by callus formation. The far cortical locking (FCL) technique was developed to address this limitation in 2005. FCL increases construct flexibility and promotes callus formation. Our study aimed to evaluate the clinical and radiological outcomes of the FCL technique when implemented in proximal humeral fracture management. Furthermore, we compared the surgical outcomes of FCL with those of the conventional bicortical locking (BCL) screw fixation technique.Methods Forty-five consecutive patients who had undergone locking fixation for proximal humeral fractures were included in this study. A proximal humeral locking plate (PHILOS) system with BCL screw fixation was used in the first 27 cases, and the periarticular proximal humeral locking plate with FCL screw fixation was used in the final 18 consecutive cases. Functional capacity was assessed using the constant score, American Shoulder and Elbow Surgeons (ASES) score, and range of motion. Radiographic outcomes were evaluated using the Paavolainen method of measuring the neck-shaft angle (NSA).Results No significant differences in clinical outcomes (ASES score, constant score, and range of motion)were found between the two groups. The union rate at 12 weeks was significantly higher in the FCL group (94.4%) than in the BCL group (66.7%, p=0.006). No significant differences in NSA were found between the two treatment strategies. The complication rate was not significantly different between the two groups.Conclusions When implemented in proximal humeral fractures, the FCL technique showed satisfactory clinical and radiological outcomes as compared with the conventional BCL technique. The bone union rate at 12 weeks after surgery was significantly higher in the FCL group than in the BCL group. However, no significant difference in the final bone union rate was found between the two groups.
Genetic in vivo engineering of human T lymphocytes in mouse models
Authors: Weidner Tatjana , Agarwal Shiwani , Perian Séverine , Fusil Floriane , Braun Gundula , Hartmann Jessica , Verhoeyen Els , Buchholz Christian J.
Published: December 2020

Receptor-targeting of vector particles is a key technology for cell-type specific in vivo gene delivery. Lentiviral vectors (LVs) targeted to human T cell markers enable genetic modification of T cells directly in humanized mouse models. Illustrating the example of modifying T cells with chimeric antigen receptors (CARs), we provide detailed protocols for the generation and quality check of potent CD4- and CD8-targeted LVs, the humanization of immunodeficient mice as well as the administration of the vector stocks followed by monitoring for in vivo modified T cells. By closely following the protocol, sufficient vector stock for the genetic manipulation of 10-15 humanized mice is obtained. A few weeks after administration, about 10% of T cells can be expected to convert to CAR T cells. The protocol can be easily adapted to LVs targeted to other types of receptors and/or delivering other genes of interest.
CTCF knockout in zebrafish induces alterations in regulatory landscapes and developmental gene expression
Authors: Franke Martin , Calle-Mustienes Elisa de la , Neto Ana , Acemel Rafael , Tena Juan , Santos-Pereira José , Gómez-Skarmeta José Luis
Published: December 2020

CTCF is an 11-zinc-finger DNA-binding protein that acts as a transcriptional repressor and insulator as well as an architectural protein required for 3D genome folding. CTCF mediates long-range chromatin looping and is enriched at the boundaries of topologically associating domains, which are sub-megabase chromatin structures that are believed to facilitate enhancer-promoter interactions within regulatory landscapes. Although CTCF is essential for cycling cells and developing embryos, its in vitro removal has only modest effects over gene expression, challenging the concept that CTCF-mediated chromatin interactions and topologically associated domains are a fundamental requirement for gene regulation. Here we link the loss of chromatin structure and gene regulation in an in vivo model and during animal development. We generated a ctcf knockout mutant in zebrafish that allows us to monitor the effect of CTCF loss of function during embryo patterning and organogenesis. CTCF absence leads to loss of chromatin structure in zebrafish embryos and affects the expression of thousands of genes, including many developmental genes. In addition, chromatin accessibility, both at CTCF binding sites and cis-regulatory elements, is severely compromised in ctcf mutants. Probing chromatin interactions from developmental genes at high resolution, we further demonstrate that promoters fail to fully establish long-range contacts with their associated regulatory landscapes, leading to altered gene expression patterns and disruption of developmental programs. Our results demonstrate that CTCF and topologically associating domains are essential to regulate gene expression during embryonic development, providing the structural basis for the establishment of developmental gene regulatory landscapes.
Quality of Life in Patients With End-Stage Renal Disease on Hemodialysis: A Cross-Sectional Study in Sudan
Authors: Mohamed Marwah
Published: December 2020

Background: End-stage renal disease (ESRD) is the last stage of chronic kidney disease (CKD) when renal replacement therapy (RRT) is necessary for sustaining life. Assessment of QoL of ESRD patients has become an essential tool to measure how the disease affects patients’ lives, and to develop better plans of care. Little is known about QoL in patients with CKD before RRT. This study aims to examine the various socio-demographic and other factors that affect the daily QoL of ESRD patients on haemodialysis (HD).Methods: A cross-sectional study was conducted at Dr Selma Dialysis Center, Khartoum, Sudan from September to December 2018. A total of 138 adult patients on chronic dialysis were recruited in this observational study. The QoL was assessed using the Kidney Disease Quality of Life-Short Form questionnaire (KDQoL-SF™).Results: Out of 138 enrolled patients, there were 105 patients (76.1%) had a good QoL and 33 patients (23.9%) had a poor QoL.Patients with a poor QoL had an average age of 42.8 ± 12.9 years. The good-QoL group had an average age of 46.9 ± 14.9 years. The total score of KDQoL-SF was 61.6%, while the scores for the physical and mental components were 39.3 ± 9.6 and 50.0 ± 10.6 respectively.Conclusion: This study indicated that the main factors that have a significant impact on the QoL were social status, origin, employment status, duration of the CKD, family history of kidney disease, time on HD, and Hypertension.
Effect of Aprotinin on Liver Injury After Transplantation of Extended Criteria Donor Grafts in Humans: A Retrospective Propensity Score Matched Cohort Analysis
Authors: Roehl Anna , Hein Marc , Andert Anne , Rossaint Rolf , Junge Karsten , Neumann Ulf , Kork Felix
Published: December 2020

Background: The number of patients awaiting liver transplantation still widely exceeds the number of donated organs available. Patients receiving extended criteria donor (ECD) organs are especially prone to an aggravated ischemia reperfusion syndrome during liver transplantation leading to massive hemodynamic stress and possible impairment in organ function. Previous studies have demonstrated aprotinin to ameliorate reperfusion injury and early graft survival. Methods: In this single center retrospective analysis of 84 propensity score matched patients out of 290 liver transplantation patients between 2010 and 2014 (OLT), we describe the association of aprotinin with postreperfusion syndrome (PRS), early allograft dysfunction (EAD: INR  1,6, AST/ALT >2000 within 7-10 days) and recipient survival. Results: The Incidence of PRS (52,4% vs 47,6%) and 30-day mortality did not differ (4.8 vs 0%; p=0.152) but patients treated with aprotinin suffered more often from EAD (64,3% vs 40,5%, p=0.029) compared to controls. Acceptable or poor (OR=3.3, p=0.035; OR=9.5, p=0.003) organ quality were independent predictors of EAD. Conclusion: Our data does not support the notion that aprotinin prevents nor attenuates PRS, EAD or mortality.
Halo Properties in Helium Nuclei From the Perspective of Geometrical Thermodynamics
Authors: Parker Michael , Jeynes Chris , Catford Wilton
Published: December 2020

The nuclear matter and charge radii of the helium isotopes (A=4,6,8) are calculated by quantitative geometrical thermodynamics (QGT) taking as input the symmetry of the a‑particle, the very weak binding (and hence halo nature) of the heavier helium isotopes, and a characteristic length scale given by the proton size. The results follow by considering each isotope in its ground state, with QGT representing each system as a maximum entropy configuration that conforms to the Holographic Principle. This allows key geometric parameters to be determined from the number of degrees of freedom available.QGT treats 6He as a 4He core plus a concentric neutron shell comprising a holomorphic pair of neutrons, and the 8He neutron halo is treated as a holomorphic pair of holomorphic pairs. Considering the information content of each system allows a correlation angle of 2/3 between the holomorphic entities to be inferred, and then the charge radii of the three isotopes can be calculated from the displacement of the 4He core from the centre of mass. The calculations for the charge and matter radii of 4,6,8He agree closely with observed values. Similar QGT calculation of the sizes of the self-conjugate A=4n nuclei {4He,8Be,12C,16O,20Ne,24Mg,28Si,32S,36Ar,40Ca} also agree well with experiment.
Thermodynamic Mechanism Evaluate the Feasibility of Oil Shale Pyrolysis by Topochemical Heat
Authors: Shuai Zhao , Xiaoshu LÜ , Youhong Sun , Jiandong Huang
Published: December 2020

Topochemical heat in-situ pyrolysis of oil shale is achieved by injecting high temperature nitrogen to promote oil shale pyrolysis and release heat, and then injecting air to trigger oil shale combustion in the early stage of oil shale pyrolysis, and then by injecting normal temperature air continuously to promote local oxidation of oil shale in the later stage. In order to verify the oil and gas recovery by topochemical heat method, Jilin University has chosen Fuyu City, Jilin Province, to carry out pilot project of oil shale in-situ pyrolysis by topochemical heat method. Besides, in order to infer the spontaneity, feasibility and difficulty of continuous pyrolysis of oil shale based on topochemical heat, this paper, the mechanism of solid-state pyrolysis and the thermodynamic analysis of transition state of oil shale in Fuyu area are discussed. Because the second stage of oil shale pyrolysis is the main stage of oil production. Therefore, the characteristics of Gibbs free energy, free enthalpy and free entropy of transition state in the main oil production stage of oil shale pyrolysis are obtained by calculation. The results show that in situ pyrolysis of oil shale topochemical heat can be carried out spontaneously and continuously, and the release characteristics of volatiles during pyrolysis of oil shale are described.
Relationship Between Hyperhidrosis and Hypothalamic Injury in Patients With Mild Traumatic Brain Injury
Authors: Jang Sung Ho , Kwon Hyeok Gyu
Published: December 2020

Hyperhidrosis is clinical symptom of various diseases and is an important clinical feature of paroxysmal sympathetic hyperactivity(PSH). Traumatic brain injury(TBI) is the most common condition associated with PSH, and PSH has been mainly reported in moderate and severe TBI. However, very little has been reported on PSH or hyperhidrosis in mild TBI patients. In this study, we used diffusion tensor imaging(DTI) to investigate the relationship between hyperhidrosis and hypothalamic injury in patients with mild TBI. Seven patients with hyperhidrosis after mild TBI and 21 healthy controls were recruited for this study. The Hyperhidrosis Disease Severity Scale was used for evaluation of sweating at the time of DTI scanning. The fractional anisotropy(FA) and apparent diffusion coefficient(ADC) DTI parameters were measured in the hypothalamus. In the patient group, the FA values for both sides of the hypothalamus were significantly lower than those of the control group (p<0.05). By contrast, the ADC values for both sides of the hypothalamus were significantly higher in the patient group than in the control group(p<0.05). In conclusion, we detected hypothalamic injuries in patients who showed hyperhidrosis after mild TBI. Based on the results, it appears that hyperhidrosis in patients with mild TBI is related to hypothalamic injury.
Ubiquitin-Dependent Rapid Degradation Conceals A Cell-Protective Function of Cytoplasmic SIRT3 Against Oxidative Stress
Authors: Hayashi Takashi , Matsushita Takashi , Hisahara Shin , Iwahara Naotoshi , Kuno Atsushi , Kunimoto Risa , Hosoda Ryusuke , Tanno Masaya , Shimohama Shun , Horio Yoshiyuki
Published: December 2020

SIRT3 is a NAD+-dependent protein deacetylase localized in mitochondria. Although several previous studies reported cytoplasmic and/or nuclear localization of SIRT3, extra-mitochondrial SIRT3 was obscure. We found that mitochondrial (SIRT3mt) and cytoplasmic (SIRT3ct) Sirt3 mRNAs were expressed in the mouse brain and diffuse SIRT3 immunostaining in cytoplasm was detected in cultured neural cells and neural precursor cells where SIRT3 knockdown disturbed neural precursor cell differentiation. However, overexpression of SIRT3 in COS7 cells showed that expression levels of SIRT3ct was much lower than that of SIRT3mt. SIRT3ct but not SIRT3mt was promptly degraded by the ubiquitin-dependent degradation, in which SIRT3ct degradation was mediated mainly by the ubiquitination of NH2-terminal methionine and partly by that of lysine residues. SIRT3ct expression level was significantly enhanced by the treatment of cells with staurosporine or H2O2. H2O2 promoted nuclear translocation of SIRT3ct and induced histone H3 deacetylation and superoxide dismutase 2 expression. The overexpression of SIRT3ct decreased cell death by H2O2 at similar levels achieved by that of SIRT3mt. Knockdown of Sirt3 mRNA increased cell death by amyloid-b (Ab) and the overexpression of SIRT3ct opposed the toxic function of Ab in PC12 cells. These results indicated that SIRT3ct participated in cell survival under various stress conditions.
Smoking and Family Cancer History Are Associated With Sarcomas in A Japanese Population Study
Authors: Araki Yoshihiro , Yamamoto Norio , Tanzawa Yoshikazu , Higashi Takahiro , Hayashi Katsuhiro , Takeuchi Akihiko , Miwa Shinji , Igarashi Kentaro , Makoto Endo , Kobayashi Eisuke , Tsuchiya Hiroyuki , Kawai Akira
Published: December 2020

Background: Sarcoma is a rare cancer, and it is also the cause of the development of various kinds of sarcomas, such as gene abnormalities, which has recently becoming evident due to advances of genetic testing. The approach to solve the origin of diseases is essential to elucidate both the external environmental factors and the internal genetic factors. However, the lifestyle habits, lifestyle-related diseases, personal and family cancer history of sarcoma patients remain unclear.Methods: A total of 1320 sarcoma patients were enrolled in this study. A questionnaire on lifestyle habits, life-style diseases, and the patient’s personal and family cancer history was completed at presentation. A total of 1320 controls were selected by propensity score matching for age and gender. Smoking, drinking, obesity, hypertension, dyslipidemia and diabetes mellitus were compared. In addition, we investigated the incidence of a personal and family cancer history in sarcoma patients. Results: A smoking habit was the only independent risk factor for high-grade soft tissue sarcoma development in adults ≥20 years old (n=952), excluding low-grade and intermediate malignant soft tissue tumors (Odds ratio [OR], 2.45; 95% confidence interval [CI] 1.88-3.20, p<0.001). The ORs of high-grade liposarcoma and undifferentiated pleomorphic sarcoma (UPS) were 2.56 and 3.00, respectively. Eight percent of sarcoma patients had a personal history of another cancer. Thirty percent of soft tissue sarcoma patients had a family history of cancer in a first-degree relatives (malignant peripheral nerve sheath tumor, 52%; leiomyosarcoma, 46%). Conclusions: We confirmed that a smoking habit were associated with the development of high-grade soft tissue sarcomas. A family history of cancer might be associated with certain soft tissue sarcomas, but a further investigation will be necessary.
Transcriptomic and Metabolomic Joint Analysis Reveals Distinct Flavonoid Biosynthesis Regulation for Variegated Testa Color Development in Peanut (Arachis Hypogaea L.)
Authors: Hu Mengdie , Li Jiawei , Hou Mingyu , Liu Xiaoqing , Cui Shunli , Yang Xinlei , Liu Lifeng , Jiang Xiaoxia , Mu Guojun
Published: December 2020

Peanut (Arachis hypogaea L.) is one of the important oil and economic crops, among which the variegated testa peanut is a unique member. But the molecular mechanisms underlying the pigment synthesis in variegated testa are still unclear. Differentially expressed genes (DEGs) in pigment metabolism pathway in colored area indicated there were 27 DEGs highly related to the synthesis of variegated testa color among 1,050 DEGs,which were 13 up-regulated and 14 down-regulated,consisting of 3 PALs, 1 C4H, 2 CHSs, 1 F3H, 1 F3'H, 2 DFRs, 2 LARs, 2 IAAs, 4 bHLHs and 9 MYBs. GO analysis indicated DEGs were similarly enriched in 3 branches.KEGG analysis suggested flavonoid biosynthesis is the most direct metabolic pathway for the synthesis of testa variegation. The liquid chromatography tandem mass spectrometry (LC-MS/MS) results showed that cyanidin and delphinidin were the main metabolites that caused the color difference between the colored area and the non-colored area. Through the verification of 20 DEGs via qPCR, the results were consistent with that of transcriptome sequencing in 4 comparison groups. The results in this study lay the foundation for revealing the molecular regulation mechanisms of anthocyanin synthesis in variegated testa peanut.
Health Care Providers’ Awareness on Medical Management of Children With Autism Spectrum Disorder: Cross-Sectional Study in Russia
Authors: Mukhamedshina Yana , Fayzullina Rezeda , Nigmatullina Irina , Rutland Catrin , Vasina Veronika
Published: December 2020

Background: Autism spectrum disorder (ASD) is a complex developmental range of conditions that involves difficulties with social interaction and restricted/repetitive behaviors. Unfortunately, health care providers often experience difficulties in diagnosis and management of individuals with ASD and may have no knowledge about possible ways to overcome barriers in ASD patient interactions in healthcare settings. At the same time, the provision of appropriate medical services can have positive effects on habilitative progress, functional outcome, life expectancy and quality of life for individuals with ASD.Methods: This online survey designed research study evaluated the awareness and experience of students/residents (n=247) and physicians (n=100) in medical management of children with ASD, as well as the views and experiences of caregivers of children on the autism spectrum (n=158), all based in Russia.Results: We have established that the Russian medical community has limited ASD knowledge among providers, and have suggested possible reasons for this. Based on the online survey of students/residents, non-psychiatric physicians and caregivers of children diagnosed with ASD, the main problems pertaining to medical management of individuals with ASD were identified, and possible problem solving solutions within medical practice were proposed.Conclusions: Results of this study should be considered both when implementing measures to improve healthcare practices, and in developing models of effective medical management due to start in not only in Russia but also in a number of other countries.
Knowledge and Attitudes on First aid among Advanced Level Students in Gampaha Educational Zone, Sri Lanka.
Authors: Alahakoon Prashan , Bandaranayaka Kalpani , Perera Pathirage , Wijesundara Chathura
Published: December 2020

BackgroundFirst aid is the initial care given in an emergency, to protect life and to prevent worsening of the condition of the victims, until they are undertaken by a professional medical person. It is essential to know basic first aid as a responsible person in society. The current study was conducted to assess the knowledge, attitudes and practices on first aid among advanced level students in government schools in Gampaha educational zone.MethodsA descriptive cross-sectional study was conducted among 510 grade 12 students in five randomly selected schools. A pre-tested self-administered questionnaire consisting of 25 multiple choice questions on knowledge and 10 statements formed as a Likert scale to assess attitudes. Chi-square test was used to assess the associations and a p-value <0.05 was considered as significant.ResultsStudent’s mean first aid knowledge was 57.4%±13.5% according to the score grading and 1% (n=5) were categorized as having “inadequate knowledge”, 30.6% (n=156) had “moderate knowledge”, 61.4% (n=313) were having “good knowledge” and 7.1% (n=36) were categorized as having “excellent knowledge”. Out of the sample, only 16.9% (n=86) students were previously trained in first aid. The overall attitudes towards first aid was positive and most of the students (98.8%, n=504) believed it is essential to have first aid knowledge. Their willingness to give first aid for emergencies was generally positive. There was only a slight correlation between knowledge and attitudes (r=0.134). There was a statistically significant relationship between first aid knowledge and advanced level stream (χ2=31.7, p<0.001) where biology students were more knowledgeable than students in other streams. The students who had followed health science in their O/L had a significantly higher knowledge score when compared to others (χ2=12.4, p=0.006). However, previous training on first aid and gender had no significant relationship with their knowledge (p>0.05). ConclusionsAddition of first aid as a part of the school curriculum and improving the standards of the existing first aid training programs is recommended. Further studies should be undertaken to assess the practical skills of students, as the current study mainly focused on the assessment of the theory knowledge.
Safety and Efficacy of Pediatric Sedation Protocols for Painless Diagnostic Examination in A Pediatric Emergency Room of A Single Tertiary Hospital
Authors: Park Junsung , Byun Young-Hoon , Lee Jeong-Yong , Lee Jong Seung , Ryu Jeong-Min , Choi Seung Jun
Published: December 2020

Background: Pediatric patients undergoing diagnostic tests in the pediatric emergency room are frequently sedated. Although efforts are made to prevent adverse events, no sedation protocol has specified the optimal regimen, dosage, and interval of medication to prevent adverse events. This study analyzed the safety and efficacy of sequential pediatric sedation protocols for pediatric patients undergoing diagnostic tests in the pediatric emergency room of a single tertiary medical center.Methods: The medical records of patients aged <18 years who visited the pediatric emergency room of Seoul Asan Medical Center between January and December 2019 for diagnostic testing were retrospectively reviewed. Sedation protocols consisted of 50 and 25 mg/kg chloral hydrate, 0.1 and 0.1 mg/kg midazolam, and 1 and 0.5–1 mg/kg ketamine, administered sequentially at intervals of 30, 20, 10, 10, and 10 min, respectively. Patients were assessed prior to sedation, and adverse events were investigated.Results: Of the 289 included patients, 20 (6.9%) experienced adverse events, none serious, and nine (3.1%) failed to reach the depth of sedation required to complete the test. The regimen (P=0.622) and dosage (P=0.777) of the sedatives were unrelated to the occurrence of adverse events when sedation was performed according to protocol.Conclusion: The sedation protocol used in these patients, consisting of sequential administration of minimum dosages, achieved a sufficient depth of sedation with relatively few adverse events, indicating that this protocol can be used safely and effectively for painless sedation in pediatric patients undergoing diagnostic testing.
Machine Learning-Based Prediction Model for Papillary Thyroid Carcinoma Recurrence
Authors: Park Young Min , Lee Byung-Joo
Published: December 2020

Background: This study analyzed the prognostic significance of nodal factors, including the number of metastatic LNs and LNR, in patients with PTC, and attempted to construct a disease recurrence prediction model using machine learning techniques.Methods: We retrospectively analyzed clinico-pathologic data from 1040 patients diagnosed with papillary thyroid cancer between 2003 and 2009. Results: We analyzed clinico-pathologic factors related to recurrence through logistic regression analysis. Among the factors that we included, only sex and tumor size were significantly correlated with disease recurrence. Parameters such as age, sex, tumor size, tumor multiplicity, ETE, ENE, pT, pN, ipsilateral central LN metastasis, contralateral central LNs metastasis, number of metastatic LNs, and LNR were input for construction of a machine learning prediction model. The performance of five machine learning models related to recurrence prediction was compared based on accuracy. The Decision Tree model showed the best accuracy at 95%, and the lightGBM and stacking model together showed 93% accuracy. Conclusions: We confirmed that all machine learning prediction models showed an accuracy of 90% or more for predicting disease recurrence in PTC. Large-scale multicenter clinical studies should be performed to improve the performance of our prediction models and verify their clinical effectiveness.
Separation of Phenyl Acetic Acid and 6-Aminopenicillanic Acid Applying Aqueous Two-Phase Systems Based on Copolymers and Salts
Authors: Ahsaie Farzaneh Ghazizadeh , Pazuki Gholamreza
Published: December 2020

6-Aminopenicillanic acid (6-APA) is used for synthesis of semisynthetic antibiotics. Polymer-salt aqueous two-phase systems (ATPSs) were applied for separation of 6-aminopenicillanic acid (6-APA) and phenyl acetic acid (PAA), as the products of hydrolyzation reaction of Penicillin G / Penicillin V. The binodal curves of ATPS composed of a copolymer (reverse Pluronic 10R5, Pluronic L35 and PEG-ran-PPG) and a salt (Tri-sodium citrate, tri-potassium citrate, di-potassium phosphate, sodium sulphate and magnesium sulphate) were obtained. The results show that, at a fixed PPG/PEG ratio, block copolymers have larger two-phase region compared with random copolymer. After screening on the partition coefficient of PAA and 6-APA separately, Na2SO4 was selected for studying the effect of the copolymer structure and the composition of salt and copolymer on partitioning, considering higher selectivity of PAA and 6-APA. 10R5-Na2SO4 ATPS was selected as the most appropriate system for separation of 6-APA and PAA. This system was used for separation of mixture of 6-APA and PAA. The results show that selectivity was 53 and smaller in a system, containing a mixture of 6-APA and PAA. This observation can be justified by the interaction between 6-APA and PAA. Molecular interaction between these two molecules were investigated by the Flory-Huggins interaction parameter.
Cardioprotective Effects of Exercise Training on Doxorubicin-Induced Cardiomyopathy: A Systematic Review With Meta-Analysis of Preclinical Studies
Authors: Ghignatti Paola , Nogueira Laura , Lehnen Alexandre , Leguisamo Natalia
Published: December 2020

Objective: Doxorubicin (DOX)-induced cardiotoxicity in chemotherapy is a major treatment drawback. Clinical trials on the cardioprotective effects of exercise in cancer patients have not yet been published. Thus, we conducted a systematic review and meta-analysis of preclinical studies for to assess the efficacy of exercise training on DOX-induced cardiomyopathy. Methods: We included studies with animal models of DOX-induced cardiomyopathy and exercise training from PubMed, Web of Sciences and Scopus databases. The outcome was the mean difference (MD) in fractional shortening (FS, %) assessed by echocardiography between sedentary and trained DOX-treated animals. Results: Trained DOX-treated animals improved 7.46% (95%CI 5.58 to 9.34, p<0.001) in FS vs. sedentary animals. Subgroup analyses identified a superior effect of exercise training prior to DOX exposure (MD=8.20, 95%CI 6.27 to 10.13, p=0.010). The assessment of cardiac function up to 10 days after DOX exposure and completion of exercise protocol was associated with superior effect size in FS (MD=7.13, 95%CI 5.44 to 8.81, p=0.030) vs. an echocardiography after over 4 weeks. Modality and duration of exercise, animal species, gender and cumulative DOX dose did not influence on FS. Conclusions: Exercise training is a cardioprotective approach in rodent models of DOX-induced cardiomyopathy. Exercise prior to DOX exposure exerts greater effect sizes on FS preservation.
The Evolutionary Conserved Transmembrane BAX Inhibitor Motif (TMBIM) Containing Protein Family is Essential for the Development and Survival of Drosophila Melanogaster
Authors: Zhang Li , Buhr Sebastian , Prasad Vibha , Voigt Aaron , Methner Axel
Published: December 2020

The Transmembrane BAX Inhibitor Motif (TMBIM) protein family consists of six evolutionarily conserved hydrophobic proteins that affect programmed cell death and the regulation of intracellular calcium levels. The bacterial orthologue BsYetJ is a pH-dependent calcium channel. We here identified six TMBIM family members in Drosophila melanogaster and studied the effect of their RNAi-mediated knockdown using ubiquitous and tissue-specific drivers. Mammalian TMBIM6 and TMBIM5 have obvious orthologs while this is more dubious for the other family members. Ubiquitous knockdown of family members dmTMBIM1,4,5, and 6 caused failed eclosing and tissue-specific knockdown resulted in a dramatically decreased lifespan. On the contrary, knockdown of dmTMBIM3, surprisingly, extended lifespan. Only knockdown of dmTMBIM6 increased the ER calcium levels of Pdf neurons. Neural knockdown of dmTMBIM2,3, and 4 increased ER stress, as indicated by increased Xbp1 splicing. Interestingly, TMBIM1 and TMBIM6 have a very similar expression pattern and their knockdown phenocopied each other. Also, knockdown of TMBIM1 resulted in upregulation of TMBIM6 and vice versa further suggesting a genetic interaction between these two genes. Our data demonstrate that most TMBIM proteins are essential for fly development and survival but, despite their shared protein structure, affect cell survival through different mechanisms.
Surveillance of The Major Pathogenic Arboviruses of Public Health Concern in Gabon, Central Africa: Increased Risk of West Nile Virus and Dengue Virus Infection
Authors: Ushijima Yuri , Abe Haruka , Ondo Georgelin , Bikangui Rodrigue , Loembe Marguerite , Zadeh Vahid , Essimenfane Gahell , Mbouna Armel , Bache Emmanuel , Agnandji Selidji , Lell Bertrand , Yasuda Jiro
Published: December 2020

Background: Increasing arbovirus infections have been a global burden in recent decades. Many countries have experienced the periodic emergence of arbovirus diseases. However, information on the prevalence of arboviruses is largely unknown or infrequently updated because of the lack of surveillance studies, especially in Africa. Methods: A surveillance study was conducted in Gabon, Central Africa, on arboviruses, which are a major public health concern in Africa, including: West Nile virus (WNV), dengue virus (DENV), Zika virus (ZIKV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Serological and molecular assays were performed to investigate past infection history and the current status of infection, using serum samples collected from healthy individuals and febrile patients, respectively. Results: The overall seroprevalence during 2014˗2017 was estimated to be 25.3% for WNV, 20.4% for DENV, 40.3% for ZIKV, 60.7% for YFV, 61.2% for CHIKV, and 14.3% for RVFV. No significant differences were found in the seroprevalence of any of the viruses between the male and female populations. However, a focus on the mean age in each arbovirus-seropositive individual showed a significantly younger age in WNV- and DENV-seropositive individuals than in CHIKV-seropositive individuals, indicating that WNV and DENV caused a relatively recent epidemic in the region, whereas CHIKV had actively circulated before. Of note, this indication was supported by the detection of both WNV and DENV genomes in serum samples collected from febrile patients after 2016. Conclusions: This study revealed the recent re-emergence of WNV and DENV in Gabon as well as the latest seroprevalence state of the major arboviruses, which indicated the different potential risks of virus infections and virus-specific circulation patterns. This information will be helpful for public health organizations and will enable a rapid response towards these arbovirus infections, thereby preventing future spread in the country.
Both Irbit and Long-Irbit Bind to and Coordinately Regulate Cl-/hco3-Exchanger Ae2 Activity Through Modulating the Lysosomal Degradation of Ae2.
Authors: Itoh Ryo , Hatano Naoya , Murakami Momoko , Mitsumori Kosuke , Kawasaki Satoko , Wakagi Tomoka , Kanzaki Yoshino , Kojima Hiroyuki , Kawaai Katsuhiro , Mikoshiba Katsuhiko , Hamada Koichi , Mizutani Akihiro
Published: December 2020

Anion exchanger 2 (AE2) plays crucial roles in regulating cell volume homeostasis and cell migration. We found that both IRBIT and Long-IRBIT (L-IRBIT) interact with anion exchanger 2 (AE2). The interaction occurred between the conserved AHCY-homologous domain of IRBIT/L-IRBIT and the N-terminal cytoplasmic region of AE2. Interestingly, AE2 activity was reduced in L-IRIBT KO cells, but not in IRBIT KO cells. Moreover, AE2 activity was slightly increased in IRBIT/L-IRBIT double KO cells. These changes in AE2 activity resulted from changes in the AE2 expression level of each mutant cell, and affected the regulatory volume increase and cell migration. The activity and expression level of AE2 in IRBIT/L-IRBIT double KO cells were downregulated if IRBIT, but not LIRBIT, was expressed again in the cells, and the downregulation was cancelled by the co-expression of L-IRBIT. The mRNA levels of AE2 in each KO cell did not change, and the downregulation of AE2 in L-IRBIT KO cells was inhibited by bafilomycin A1. These results indicate that IRBIT binding facilitates the lysosomal degradation of AE2, which is inhibited by coexisting L-IRBIT, suggesting a novel regulatory mode of AE2 activity through the binding of two homologous proteins with opposing functions.
Cytoskeletal interactions of eukaryotic initiation factor 6
regulate mechanical responses in cells
Authors: Keen Adam , Payne Luke , Rice Alistair , Simpson Lisa , Pang Kar Lai , Hernández Armando del Río , Reader John , Tzima Ellie
Published: December 2020

The authors have requested that this preprint be removed from Research Square.
Molecular origin of the extreme mechanical strength of an ester bond containing pathogen surface protein
Authors: Lei Hai , Ma Quan , Li Wenfei , Wen Jing , Ma Haibo , Qin Meng , Wang Wei , Cao Yi
Published: December 2020

Gram-positive bacteria can resist large mechanical perturbations during their invasion and colonization by secreting various surface proteins with intramolecular isopeptide or ester bonds. Previous studies showed that the isopeptide bond containing proteins are inextensible under mechanical load. However, compared to isopeptide bonds, ester bonds are prone to hydrolysis; it remains elusive whether ester bonds play similar roles as isopetide bonds to completely block mechanical extension, or alternatively dissipate mechanical energy by bond rupture. Here, we show that an ester bond containing protein, the C1 domain of Cpe0147, is not extensible even at forces > 2 nN. The ester bond locks the structure to a partially unfolded conformation, in which the ester bond remains largely water inaccessible. This allows the ester bond to withstand considerable mechanical forces and in turn prevent complete protein unfolding. Inspired by this design principle, we engineer a disulfide mutant resistant to mechanical unfolding under reducing conditions.
Comparative bench study evaluation of a modified snorkeling mask used during COVID-19 pandemia and standard interfaces for Non-Invasive Ventilation
Authors: Ferrone Giuliano , Spinazzola Giorgia , Costa Roberta , Piervincezi Edoardo , Gullì Antonio , Scapigliati Andrea , Antonelli Massimo , Conti Giorgio
Published: December 2020

Background

COVID-19 infection has put enormous pressure on the healthcare systems worldwide and especially on Intensive Care Units (ICUs). In this particular situation, a modified snorkeling mask into a mask for non-invasive continuous positive airway pressure (nCPAP) and non-invasive ventilation (NIV), with the help of 3D printers, has been proposed for clinical use. We designed a bench study to compare a Helmet (H), a Full face mask (RFF) and a modified full face snorkeling mask (MFF) for delivering nCPAP and NIV in pressure support mode (PSV).
Methods

A mannequin was connected to an active lung simulator. The inspiratory and expiratory variations in airways pressure observed with a high simulated effort (Pmus), were determined relative to the preset CPAP level. NIV was applied in PSV at two simulated respiratory rates and two cycling-off flow thresholds. During the bench study we measured the variables defining patient-ventilator interaction and performance.
Results

During nCPAP, the MFF presented significantly lower values of ΔPawi and ∆Pawe compared to the other interfaces tested (H and RFF). During NIV, the MFF demonstrated a better patient-ventilator interaction compared to RFF, as shown by significantly shorter Timepress and Delaytrexp (p < 0.01), but no significant differences were found in terms of Delaytrinsp and Timesync between the interfaces tested. At RR 20sim, the MFF presented the shorter ΔPtrigger (p < 0.01), moreover during all the conditions tested the MFF showed the longer PTP 200, 300 and 500 compared to RFF (p < 0.01). A major limitation of MFF is that during NIV with this interface it is possible to reach at maximum 18 cmH2O of peak inspiratory pressure. Over this pressure value, the presence of air leaks determined important asynchrony phenomena. For this reason, our test was limited to one pressure support and PEEP set (PS 10 cmH2O and PEEP 8 cmH2O).
Conclusions

The modified full face snorkeling mask can be used as an acceptable alternative to other interfaces for both nCPAP and NIV in emergency situations.